the age of four fell out of bed, and from that time began to walk with
difficulty, and ultimately acquired a double talipes equinus. The right
leg atrophied, the left remained of tolerable thickness. At the age of
thirty-four she was admitted to an insane asylum during the incipient
stage of dementia paralytica, and death occurred two years later of
pneumonia. The autopsy showed--1st. That the calf-muscles on both sides
were converted into masses of fat, streaked with whitish-red remnants
of muscular tissue. The short muscles of the feet were atrophied; all
the other muscles of the body normal. 2d. In the brain the
blood-vessels showed a thickening of the adventitia by delicate
connective-tissue fibrillæ, between whose meshes nucleated cells were
strewed. The ependyma of the ventricles was thickened and granular, and
their cavity was filled with serous effusion. 3d. In the cord was found
diffused degeneration, especially of the lateral columns, consisting in
thickening of the interstitial connective tissue, with proliferation of
its cells; atrophy of a part of the primitive nerve-fibres with
granular degeneration of the {573} medullary sheath, and occasionally
atrophy of the axis cylinder. The adventitia of the blood-vessels was
thickened, the perivascular spaces dilated. In the central gray
substance the ganglion-cells were everywhere intact, but the
intercellular substance was thicker, and seemingly composed of a thick
net of stout, finely-granular fibres. Traces of an infantile
polio-myelitis were found in the lower part of the lumbar enlargement
(atrophy of the anterior cornua, especially the right, together with
their ganglion-cells).
[Footnote 74: _Beiträge zur pathol. des Ruckenmarkes_, 1871.]
The final lesion of importance was the obliteration of the central
canal, which was moreover surrounded by a dense ring of connective
tissue. In this case the suddenness of the original paresis, the
atrophy of the right leg, and the lesions of the lumbar cord found at
the autopsy prove that the initial disease was an acute anterior
polio-myelitis. Upon this a very localized pseudo-hypertrophy seems to
have been grafted during childhood, while in adult life a chronic
lepto-meningitis and internal hydrocephalus were certainly the cause of
the symptoms, and probably of the lesions in the cord.
That such lesions in the cord may be the consequence of chronic
hydrocephalus is well argued by Pekelharing in regard to his own
recently published case, which in some respects closely resembles that
by Müller. The patient was a boy in whom muscular paresis was
congenital, and who from birth had exhibited deficient intelligence
with an abnormally large head. At the autopsy, made at fourteen,
ventricular effusion was found in the brain, and in the cord irregular
dilatation of the central canal and great dilatation of blood-vessels
and accumulation of leucocytes in its immediate neighborhood. Some
ganglion-cells in the inner and anterior groups of the anterior cornua
were shrunken and deprived of their prolongations. The author suggests
that in this case the cerebral hydrocephalus was the primary disease;
that the central canal in the spinal cord was dilated by extension of
the effusion from the brain; that a partial reabsorption of such
effusion had caused hyperæmia ex vacuo in the tissue immediately
surrounding the canal; and that the emigration of leucocytes and
partial alteration of the ganglion-cells both resulted from this
hyperæmia.
In Müller's case the central canal and adjacent tissue were also the
part of the cord most diseased; but the canal was obliterated by
proliferation of the ependyma, not dilated. In Barth's case also[75]
the central canal of the cord was found obliterated. The patient was a
man of forty-four, who since the age of forty had suffered from
stiffness in the left ankle and difficulty of walking. After a year the
stiffness extended to the right ankle; in two years the paresis had
mounted to the thighs, and was accompanied by severe pains. Paresis and
pain then appeared in the upper extremities, which gradually atrophied.
After two years the patient was entirely confined to bed, and two years
later was unable even to sit up. Later, the muscles of the neck became
hypertrophied. No mention is made of perceptible hypertrophy in other
muscles, nor of contractions or tremors other than fibrillary. But at
the autopsy was discovered a lateral sclerosis extending the entire
length of the cord, associated with partial atrophy of the
ganglion-cells in the anterior cornua. In both the gray and white
substances the blood-vessels were dilated, and, {574} as already
stated, the central canal was obliterated. The brain was healthy. The
supinators of the upper extremities, the gastrocnemii at the lower,
were richly infiltrated with fat streaked with long bands of connective
tissue; the remaining muscles were atrophied.
[Footnote 75: _Archiv der Heilkunde_, xii. 2, 1871.]
The anatomical lesions in this case are identical with those of the
special symptom-complex described by Charcot as amyotrophic lateral
sclerosis. Certain symptoms of lateral sclerosis are wanting to
complete the clinical history, but at least as many are lacking for a
typical history of pseudo-hypertrophic paralysis. Only the muscles of
the neck hypertrophied: the gastrocnemii and adductors, primarily
atrophied, later regained some of their original size. The fatty
infiltration of the calf and muscles was unattended by
pseudo-enlargement or by retraction: it resembled a fatty substitution
due to nerve-paralysis, rather than the hyperplastic process of
pseudo-hypertrophy.
Setting aside the three foregoing cases, three remain which, together
with an unimpeachable history of pseudo-hypertrophic paralysis, show
positive lesions in the spinal cord. The first and the most famous was
made upon a patient of Gowers by Lockhart Clarke.[76] Changes were
found scattered through the entire length of the cord. "In the upper
cervical region were patches of incipient disintegration in the gray
network of the lateral portion of the cord, the lateral white columns
being healthy. Here and there in the gray substance of the anterior and
posterior cornua the intercellular matrix was wasted and disintegrated,
especially in the neighborhood of the blood-vessels and at the bottom
of the anterior median fissure. Here were accumulated globules of
myeline and other débris of nerve-tissue. The blood-vessels were
distended, their perivascular spaces enlarged. Patches of
disintegration of nerve-fibres of the lateral and posterior columns
were seen in the lower cervical and in the dorsal regions. Globules of
myeline and masses of fatty matter were at some points accumulated at
the entrance of the posterior nerve-roots, and even, to a much less
extent, adjacent to the anterior roots. The most extensive lesion
existed in the lowest part of the dorsal region. In the lateral gray
substance on each side was an area of softening containing an actual
cavity just outside each posterior vesicular column. The latter
remained undamaged.
"The anterior cornua throughout the cord were perfectly normal, though
the processes of the cells were perhaps less distinct than elsewhere.
Further, notwithstanding the spots of disintegration in the lateral
columns there was in them no change comparable to that of lateral
sclerosis."[77]
[Footnote 76: _Med.-Chir. Trans._, 1874.]
[Footnote 77: This autopsy was made on a boy of fifteen, in whom the
calves began to hypertrophy at three, and reached their maximum size at
five.]
The second post-mortem was made by Ross on a patient belonging to
Leech: "In the lumbar region of the cord the normal loose and spongy
texture of the central column was replaced by a somewhat dense and
fibrillated tissue, in which no trace of ganglion-cells could be found.
The blood-vessels were enlarged and their walls thickened. In the
anterior cornua the ganglion-cells had completely disappeared from the
median area, the anterior group, and from the margins of all the other
groups. This atrophic process extended into the dorsal and cervical
{575} region, and in the latter the central column was changed in the
manner already described."[78]
[Footnote 78: _Loc. cit._, p. 207. Patient was nine years old at time
of death; the disease had begun with paresis at two; was well developed
at nine.]
The third autopsy is recorded by Drummond in the _Lancet_ for 1881
(vol. ii.): The subject was a boy of fourteen, who never walked after
the age of six. There was found, as the author shows by some good
drawings, disintegration in the lateral gray network of fibres halfway
between the anterior and posterior horns, extending more or less
throughout the cord. In the left lumbar region the tissue had broken
down, and a cavity existed filled with serum, which bulged out the wall
of the cord, forming an apparent tumor.
Several circumstances are common to all the foregoing five cases. In
all, the patients during life had exhibited paresis and atrophy of a
large number of muscles (in Barth's case nearly all), with
pseudo-hypertrophy of some muscles of the lower extremities. In all,
the post-mortem found fatty substitution for muscular fibre in both the
atrophied and the hypertrophied muscles. Finally, in all, the lesions
found in the cord were principally grouped about the central canal.
This was dilated (Pekelharing) or obliterated (Müller, Barth); the
hyperæmia was always most intense in its vicinity; and it was in the
lateral gray substance adjoining, or in the gray network between it and
the lateral white columns, that patches of disintegration were
principally noted (Clarke, Ross). Negatively, the absence of any
extensive lesion of the anterior cornua is noteworthy in all the cases
but one; and here this lesion was evidently secondary to the lateral
sclerosis (Barth). On the other hand, the differences between these
cases were as numerous as the resemblances. Two resembled each other in
the presence of cerebral symptoms and of an internal hydrocephalus to
account for them (Pekelharing, Müller); in one alone was there lateral
sclerosis (Barth); in one, cavities in the lateral portion of the
central gray column (Clarke); in one, traces of an acute polio-myelitis
(Müller), Finally, in only three cases (Clarke, Ross, Drummond) was the
clinical history perfectly characteristic of the disease.
Comparing these facts with the others, equally significant, where the
autopsy in cases of pseudo-muscular hypertrophy has shown the central
nervous organs to be perfectly healthy, we should be led to
conclude--1st. That if fatty substitution in the muscles is ever to be
associated with lesions of the spinal cord, these are to be sought in
the central gray substance surrounding the central canal. 2d. That,
nevertheless, muscular lesions similar, if not in all respects
identical, can develop as the result of an idiopathic process depending
on causes at present unknown. 3d. That atrophy of muscular fibre and
replacement of it by lipomatous fat are probably determined in several
different ways, and must often be regarded as merely secondary
processes;[79] but that the muscular lesion characteristic of
pseudo-hypertrophy, considered as an idiopathic disease, is the
hyperplasia of connective tissue which originates in the perimysium
interum of the muscles. This lesion was well marked in the Ross-Leech
case, much less distinct in the three we have noted as doubtful
(Gowers).
[Footnote 79: See Leyden's remarks in his essay "Ueber Polio-myelitis
und Neuritis," _Zeitschrift für klin. Med._, 1880.]
{576} PATHOGENY.--These last conclusions, if valid, supersede the
necessity for prolonged discussion of the question whether
pseudo-hypertrophic paralysis be a peripheric disease or central
disease. By the latter term authors almost invariably mean a disease
dependent on morbid processes in the spinal cord. Hammond is almost
alone in affirming that these exist, and bases his opinion on only
three autopsies, of which two are the doubtful cases of Müller and
Barth. Mobius,[80] recognizing the frequent absence of spinal lesions,
nevertheless claims that the hereditary, frequently congenital, nature
of the disease proves that it inheres in the nervous system. Gowers,
however, points out that the exclusive inheritance through the
mother--that is, from the ovum--is a circumstance unknown in nervous
diseases. This mode of inheritance is observed in hæmophilia, which
also resembles pseudo-hypertrophy in being almost confined to males.
[Footnote 80: _Volkmann's Sammlung_, No. 171.]
The pseudo-muscular hypertrophy of children so strikingly resembles in
many particulars the progressive muscular atrophy of adults that the
theory of their essential identity could not fail to suggest itself.
Friedreich unhesitatingly advocates this theory. Many of the facts
which support it become for him additional confirmation of the
peripheric nature of the adult disease, where, nevertheless, the
anterior ganglion-cells of the cord are habitually found atrophied.[81]
[Footnote 81: According to the Friedreich theory, the lesion of the
anterior cornua is coincident with or consecutive to degeneration of
the other extremity of the nervo-muscular motor apparatus.
Lichtheim, _Arch. f. Psych._, viii., quoted in _Brain_, 1879, vol. ii.,
No. 1, quotes a case of progressive muscular atrophy with typical
changes in the muscles, but unaccompanied by the slightest change in
the nerves or nerve-roots, large ganglion-cells of the anterior cornua,
or other part of the spinal cord. The author agrees in regarding the
nearly allied pseudo-hypertrophic paralysis as a peripheric affection.
See also Hayem.]
Eulenburg thus sums up the relations between progressive muscular
atrophy and pseudo-hypertrophic paralysis: In both diseases the
fundamental muscular lesion consists in a chronic irritative process,
which starts from the interstitial connective tissue, and secondarily
affects the muscular fibre. In children, pseudo-hypertrophy of the
muscles of the lower extremities is regularly followed by primary
atrophy of many of the muscles in the upper half of the body, and
secondary atrophy in almost all. In a case of Eulenburg's the two
typical diseases seemed to coexist in the same patient, an adult woman.
More frequently they coexist in the same family, as in the observation
by Russel, where two brothers suffered from progressive atrophy, a
third from pseudo-hypertrophic paralysis.
Pick[82] relates a case where a typical atrophy of the upper
extremities and of the trunk was accompanied by moderate hypertrophy of
the calves, with proliferation in the calf-muscles of the interstitial
fat and connective tissue. Charcot admits a special form of atrophia
musculorum lipomatosa which complicates progressive muscular atrophy,
and is associated, therefore, with atrophy of the anterior
ganglion-cells; with which, however, it has no direct connection.
[Footnote 82: "Ueber einen Fall von progressive muskel atrophie,"
_Archiv für Psych._, Bd. vi., 1876.]
The adult and infantile muscular diseases differ by the remarkable, and
sometimes even colossal, apparent development of the calf-muscles
through the excessive development in them of fat and connective {577}
tissue--by the fact that the latter disease invariably begins in the
lower extremities, and is almost peculiar to childhood, while the
progressive atrophy begins in the upper half of the body, and usually
the hands, and is as nearly exclusively limited to adult life. For both
diseases may be admitted, with Friedreich, "a congenital nutritive and
formative weakness of the striated muscle-substance" (Gowers). But, we
may add, in progressive atrophy this does not become manifest until the
muscles have been for many years subjected to the strain of constant
employment: in pseudo-hypertrophy the nutritive failure appears early
in the flagging of the developmental forces at the moment that these
are strained in muscular growth.
It would perhaps be more correct to ascribe the error of development to
a perversion of nutritive forces rather than to their weakness. For
there is no arrest in the general development of the limbs, such as
occurs after infantile spinal paralysis: the bones grow normally; the
initial lesion is hyperplasia of the connective tissue--possibly, also,
true hypertrophy of the muscular fibre. The wasting is secondary.
Perhaps the terminal nerve-plates, or else the capillary network on the
outside of the primitive bundles of muscle-fibre, does not grow in
proportion to the increasing mass, and therefore becomes insufficient
for its nutrition (Auerbach).
The question arises whether the primitive error of development does not
lie in the capillary network. Ranvier has shown that the capillaries of
muscles are specially adapted to them, being disposed in quadrangles,
at whose corners the vascular canal dilates into little pouches. It is
surmised that these pouches serve as reservoirs to hold an extra supply
of blood for the moment of contraction.[83] If such specialty of
structure be necessary for the proper accomplishment of the muscular
contraction, it is evident that any congenital defect in the
arrangement of the blood-vessels might disturb in many ways the balance
of muscular nutrition. The absence of vascular reservoirs, for
instance, would render the supply of blood during the contraction
insufficient: the contraction must then be inadequate or exhausting,
and the physiological stimulus to the growth of the muscle wanting. On
the other hand, the capillaries being, by the hypothesis, adapted to
the lower type which nourishes connective tissue, this would become
nourished at the expense of the contractile fibre, and the known
hyperplasia would result.
[Footnote 83: _Cours d'Anatomie au Collège de France_, 1880.]
That morbid vascularization exists, is shown by the peculiar mottled
appearance of the skin, which has often been interpreted as a proof of
vaso-motor paralysis (Duchenne). On such an hypothesis, further, the
curious and otherwise inexplicable relations between pseudo-hypertrophy
and hæmophilia[84] would be explained. The one or the other hereditary
disease would be due to imperfection in the blood-vessels--here of
structure, there of architecture. This imperfection could be directly
traced to the mesoblast in the embryo, in which the vascular tissues
exclusively originate. Whether we should admit the bold speculation of
His[85] that the tissues of the mesoblast are exclusively derived from
the ovum, while {578} the archiblastic tissues--the nervous, muscular,
epithelial, and glandular--come from the substance of the spermatozoa
fused with it, is beyond the scope of this paper to discuss. But were
this speculation well founded, the independent morbid tendencies of the
mesoblast would be rendered by so much the more plausible.
[Footnote 84: Part of which do not exist between pseudo-hypertrophy and
progressive atrophy, since the latter disease is not exclusively
inherited through the mother.]
[Footnote 85: _Unsere Körper Form_.]
The fact that the disease begins in the extensor muscles of the lower
extremities is probably to be explained by the rapid development of
these muscles during early childhood, and by the functional strain
imposed on them during the effort of learning to walk. It is thus
really analogous to the début of progressive atrophy in the muscles of
the hands of adults--the muscles whose functional activity is the most
incessant and the most complex during adult life.
The preponderance of the disease in males remains unexplained, unless
it be that the greater extent of muscular development in the male
necessitates a greater intensity of developmental force for the
muscles, whose deficiency, therefore, would earlier be made manifest.
DIAGNOSIS.--The diagnosis of pseudo-hypertrophic paralysis can never be
difficult in typical cases and at an advanced period of the disease.
During the early period the diagnosis rests on the gradual diminution
of force in the lower extremities, without atrophy or with apparently
excellent development of their muscles; the straddling of the legs,
lordosis, and lateral oscillation, all at first slight, but constantly
becoming more and more emphasized; the peculiar method of rising by
placing the hands on the knees and then gradually climbing up the
thighs. In the second period the enlargement of the calf or other
muscles of the lower limbs, in the third the extension of the paresis
to the upper extremities, associated with wasting of the pectorals and
usually some of the extensors of the back, confirm beyond question the
diagnosis. This may be further established by examination of small
fragments of muscular fibre removed by means of the harpoon or trocar,
and the repeated examinations, which serve, moreover, to mark the
progress of the disease.
Few diseases require to be differentiated. One very rare disease that
might be confounded with pseudo-hypertrophy is the infantile form of
progressive muscular atrophy. This is distinguished from the ordinary
form of atrophy by beginning in the muscles of the face,[86] especially
the orbicularis oris, from whose defective contractility the lips
become thick and motionless. The morbid process then progresses
downward, and is thus in notable contrast with that of
pseudo-hypertrophy, which invariably begins in the lower limbs and
extends upward, invading the face only by exception.
[Footnote 86: Duchenne has seen seventeen cases of this disease.]
It is probably after the establishment of talipes equinus and of
flexions at the knee- or hip-joint that pseudo-hypertrophy would be
most liable to be confounded with infantile atrophic paralysis. In the
latter, however, the talipes is much more rarely double, and, if
existing, is usually complicated with varus. At an advanced stage of
pseudo-hypertrophy the enlargement of the calf is apt to be confined to
its upper part, and the retraction of the lower half simulates atrophy,
even when this has not really set in. At this stage, moreover, the
thighs and gluteal regions are usually atrophied, so that the
resemblance to an atrophic paralysis may be considerable. This may be
still further increased in those rare {579} cases of extensive
polio-myelitis, where paralysis of one or more of the upper extremities
coincides with lumbar paraplegia. It is extremely rare, however, that
both arms are paralyzed and atrophied,[87] while this is the rule, with
approximative symmetry, in pseudo-hypertrophy. In the latter disease,
moreover, there are paralysis and atrophy of the muscles of the trunk
and abdomen, which is scarcely ever seen, and never to the same extent,
in atrophic paralysis. The reflex excitability is lost in the latter
disease, as also the faradic; the latter, often intact in
pseudo-hypertrophy, rarely is quite abolished. Finally, the history of
the case is generally decisive: gradual development in the one, sudden
onset, with immediate maximum intensity of paralysis, in the other;
primitive wasting of the paralyzed muscles in the spinal paralysis,
enlargement preceding the atrophy in the pseudo-hypertrophic paralysis.
[Footnote 87: A patient described by Eulenburg was affected by such
general paralysis, but recovered after five months' treatment.]
Rachitis, with its frequent polysarcia and paretic gait, might
sometimes lead to a suspicion of muscular pseudo-hypertrophy, as,
conversely, the earlier symptoms of the latter disease may be
erroneously referred to rachitis. The error is all the more facile
because children afflicted with pseudo-hypertrophy are not unfrequently
rachitic, and the symptoms of specific paralysis and muscular sclerosis
may easily seem to deepen out of those of muscular inertia and
subcutaneous fat which are due to the nutritive diathesis. The
consistency of the enlarged limbs is, however, different--soft and
flabby in rachitis, hard, even stony, in pseudo-hypertrophy. When in
the latter the subcutaneous fat is atrophied instead of increased, the
muscles seem to make hernial protrusions through the emaciated skin.