number of instances. Cruveilhier called attention to them in the
celebrated case of the rope-dancer Lecomte. At the autopsy, the brain,
the cord, and posterior roots were found normal, but the anterior
roots, from the point of exit to where they unite with the posterior,
were greatly atrophied. In another case the anterior roots were to the
posterior in thickness, in the cervical region, in the ratio of 1:10,
while the normal ratio is 1:3; {545} in the dorsal region as 1:5, while
the normal is as 1:1½ or 2. The posterior roots, brain, and cord were
again unchanged. Up to 1876, Eulenburg had collected 26 cases in which
this alteration existed, and 19 in which it was absent. In the case of
Wood and Dercum, referred to, this atrophy of the anterior nerve-roots
existed, making 27 positive cases and 19 negative.
We come, finally, to the spinal cord as the seat of changes, and we are
met by Eulenburg's statistics, according to which, up to the date of
his article, there were 34 cases of positive disease and 15 negative.
To the former we have again to add the case of Wood and Dercum, making
35 against 15. These alterations are by no means constant as to seat
and character. Thus, Valentiner, who seems to have been the first after
Cruveilhier, in 1853, to record any, found in 1855, in the centre of
the cord, in the neighborhood of the three lowest cervical and upper
dorsal nerves, that the elements in the region of transition from gray
to white substance were obliterated, and the softened place contained
numerous compound granule-cells. Schneevogt also found a softening of
the cord from the fifth cervical to the second dorsal nerve, Frommann
described a red softening from the medulla oblongata downward,
involving chiefly the anterior and lateral columns, and especially the
commissures and the innermost parts of the anterior columns lying next
the commissure.
Luys found the gray matter in the neighborhood of the cervical
enlargement full of hyperæmic vessels, which were surrounded with
granular masses (compound granule-cells?). The same granular masses,
together with numerous corpora amylacea, were scattered throughout the
gray substance. The ganglion-cells of the anterior cornua had almost
disappeared in the part affected, and appeared to be replaced by the
granular masses. Here and there a few ganglion-cells could be
recognized in a state of retrograde metamorphosis, pigmented and bereft
of their polar prolongations. In this case the degeneration affected
principally the left anterior cornu, and it was the left side of the
body which was affected by the atrophy. The anterior roots of the
spinal nerves on the left side were also atrophied. Lockhart Clarke
found essentially the same changes in no less than six cases, and
Duménil, Schueppel, Hayem, Charcot (six or seven autopsies), Joffroy,
and lately Wood and Dercum,[23] have added others. The last two
observers found changes in the lower portion of the cervical
enlargement of the cord, and state in the report of their case that "in
the anterior cornua of the gray matter there is a marked diminution in
the number of nerve-cells. Of the three groups of these cells, the
anterior has almost entirely disappeared, the lateral group is
represented by but a few individual cells, while the internal group
seems to have undergone a less marked change. All of these cells, with
the exception of a few in the internal group, appear shrunken, and are
evidently much diminished in size. They have lost in great part their
polygonal shape, many of them being fusiform, and present but few
processes. Only in the internal group are these cells in any way
approaching the normal type, and these are few and seen in only a few
of the sections. They present the characteristic size and numerous
processes of the typical motor-cell, while they disclose a well-defined
nucleus and nucleolus. In the atrophied cells the nuclei can only be
distinguished with difficulty.
{546} "The neuroglia of the anterior cornua is increased in amount; the
vessels appear shrunken, with thickened walls and large perivascular
lymph-spaces.
"In the lumbar cord the cells in the anterior cornua appear normal: in
this respect the lumbar cord is in marked contrast with the cervical."
[Footnote 23: _Loc. cit._]
Another class of cases recorded by Gull,[24] Schueppel and Grimm,
Hallopeau and Westphal, consist in dilatation of the central spinal
canal with more or less complete destruction of the gray substance, and
in Grimm's case hyperplasia of the connective tissue in the white
substance along with increase of the axis-cylinders. The nerve-roots
were in a state of fatty degeneration, especially the finer fibres of
the anterior roots.
[Footnote 24: _Guy's Hospital Reports_, 1862.]
Still another set of observations discovers a degenerative atrophy of
the white columns only of the cord, sometimes the antero-lateral
columns and sometimes the posterior. Virchow, Friedreich, and
Swarzenski each found typical gray degeneration of the posterior
columns, in one instance recognizable by the naked eye. Atrophy of the
antero-lateral columns was noted by Frommann and Baudrimont; atrophy of
the antero-lateral columns, conjoined with inflammatory changes in the
gray substance and atrophy of ganglion-cells, by Duménil; changes in
the antero-lateral gray substance and posterior columns by Clarke.
Changes have even been found in the posterior cornua and posterior
nerve-roots in a few cases, although not confined to them.
Finally, the lesions of this singular disease have been sought also in
the sympathetic, and not without some success. Eulenburg's analysis
discovered 5 positive observations and 14 negative ones. To the
positive must be added the case of Wood and Dercum, who reported a
marked increase in the amount of connective tissue and a granular state
of the ganglion-cells without diminution in number. Among the changes
in the sympathetic were thinning of its trunk and of the two upper
ganglia observed by Swarzenski, and advanced fibrous fatty change of
the cervical and thoracic portion, with abundant hyperplasia of
connective tissue, disappearance of nerve-fibres and regressive
metamorphosis of ganglion-cells by Duménil.
PATHOGENY.--We come now to consider the relation of these changes to
the muscular atrophy which constitutes the conspicuous symptom of the
disease. There are three possible views of the pathology of this
affection. According to one, it is a muscular or myopathic disease in
the strict sense of the term. Such muscular disease may be primarily
inflammatory, a myositis--as Friedreich sought to prove in his great
work--followed by fatty metamorphosis of the sarcous substance and
subsequent absorption of the fat; or it may be a simple fatty
metamorphosis. According to a second view, it is primarily an affection
of peripheral nerves or of the anterior roots of the spinal nerves,
with secondary muscular atrophy. According to a third, it is a disease
of the spinal cord, and more particularly of the anterior cornua of the
gray matter--a poliomyelitis anterior.
A careful study of the morbid conditions as described in the various
cases reported leads me to adopt the last view. In the first place, the
number of instances of positive disease of the spinal cord exceed those
of any other seats of alteration, and although the changes do not
always involve the anterior cornua, yet it will be noted, from an
examination {547} of the foregoing paragraphs, that a decided majority
involve either the anterior cornua alone or these in connection with
the antero-lateral columns, the number of cases of disease of the
antero-lateral columns alone or of the posterior columns and posterior
nerve-roots being very limited. Again, the number of instances in which
lesions of the anterior cornua are found increases as our means of
accurate investigation improve.
If we add to these considerations the fact that the symptoms are best
explained by such a view, little more seems required to establish it.
Recalling the well-known observation of Waller, confirmed by Bernard
and others, that after section of the anterior root of a spinal nerve
the distal end wastes, while the central end remains intact, because it
is still connected with its own trophic centre, we have in this the
explanation why atrophy of the anterior roots is also so common a
symptom in progressive muscular atrophy. The fibres of the anterior
roots arise from the cells of the anterior cornua, and disease of the
latter must unfavorably influence the nutrition of the former; hence
their atrophy. This atrophy of motor nerve-filaments is continued into
the mixed nerves distributed to muscles, but is less easily
demonstrable by reason of the gradually diminishing size of the
nerve-trunks and by the fact that they are united in the mixed nerve
with the sensory fibres from the posterior roots, which do not suffer
atrophy. In consequence of the degeneration of these nerves follows
degeneration of the muscles to which they are distributed, so that the
alterations in the latter are altogether secondary.
From this point of view the disease in question is to be regarded as a
chronic form of poliomyelitis anterior, while the essential infantile
paralysis of Rilliet and Barthez would correspond to the acute form of
the disease.
The association of changes in the anterior roots with others in the
spinal cord may be explained either on the ground of extension by
continuity to adjacent parts, or on that of coincidence. In
illustration of the latter I may refer to a case recently reported from
Mendel's clinic[25] in Berlin, in which the symptoms of progressive
muscular atrophy were associated with those of tabes dorsalis or
progressive locomotor ataxia. Here it is not unlikely that the
coincidence is merely accidental; and this was Mendel's opinion in this
case. In other instances the involvement of other portions of the
spinal cord may be a result of an extension of the disease from its
true seat, while many cases described as progressive muscular atrophy
are not such at all, but are in part the result of other affections of
the spinal cord. It is evident, also, that this order may be reversed,
as in a case reported by Eulenburg[26] to the Berlin Medical Society.
[Footnote 25: _Philada. Medical News_, Sept. 12, 1885, p. 188.]
[Footnote 26: _Berliner klin. Wochenschr._, No. 15, April 13, 1885.]
SYMPTOMS.--The first distinctive symptom of the disease under
consideration is the muscular atrophy or wasting. However general it
may subsequently become, it is at first localized. The upper extremity
is by far the most frequently involved--7 out of 9 times in Aran's
cases. Sandahl out of 62 cases found the right upper extremity attacked
37 times, the left in 14 instances, and both in 11. In Friedreich's
statistics it occurred first in the upper 111 times out of 146, while
the lower was invaded 27 times, {548} and the lumbar muscles 8. Most
frequently it begins in some muscle or group of muscles in the right
hand, either the interossei or those of the ball of the thumb. Of the
interossei, the external interosseus is usually the first affected.
Thence it extends to the other interossei, and soon very striking
depressions make their appearance between the metacarpal bones, and the
extensor tendons on the dorsum, and the flexors in the palm become as
distinct as if dissected out. Succeeding this follows contraction of
the flexor tendons until the picture seen in Fig. 32 is produced, in
which 1 exhibits the anterior surface of the hand, and 2 the posterior.
[Illustration: FIG. 32. (1) HAND, PALMAR SURFACE. (2) DORSAL SURFACE
(after Duchenne).
_a_, Ends of the metacarpal bones; _b_, Tendons of the flexor sublimis;
_c_, Muscles of the ball of the thumb.]
Opinion is not unanimous as to whether the atrophy when beginning in
the hand involves first the thenar muscles or the interossei. Roberts,
Wachsmuth, and Friedreich say that it begins, as a rule, in the thumb;
Eulenburg, that it invariably begins in the interossei. From the
interossei it may creep up the forearm, and thence to the arm, or it
may skip the forearm and pass into the arm, although the triceps
extensor muscle is usually spared. It may come to a standstill in
either of those places, but may involve the muscle of the shoulder,
especially the deltoid. When the latter and the arm are involved, a
picture like that of Fig. 33 is produced.
[Illustration: FIG. 33. Showing Atrophy of the Right Deltoid and Arm,
and the Left Arm.]
[Illustration: FIG. 34. Showing Atrophy of the Deltoid, posterior
aspect, and the Scapular Muscles.]
Beginning most frequently in the right, both upper extremities become
sooner or later involved.
In other instances in which the upper extremities are previously
involved the atrophy begins in the shoulder, in the deltoid--here again
the right first. Succeeding the deltoid, the scapular and trapezius
muscles may be involved in any order, while a grotesqueness of effect
is often produced by reason of certain adjacent muscles retaining their
natural size or even being hypertrophied. This is particularly the case
with the anterior part of the trapezius, which is almost never
involved. With the shoulders first affected, the arm and forearm may
retain their usefulness and strength; but the power of lifting the arm
from the side, and especially of raising it above the head, is lost.
And if the patient wishes to lay hold of anything, he must swing his
arm forward with a jerk until it is brought in reach of his fingers,
and then it must often be caught up by the pathologically hooked
terminations of these.
The muscles of the trunk do, however, become at times involved--the
pectorales, the latissimi, serrati, and intercostales, and even the
{549} diaphragm and abdominal and lumbar muscles. Life is seriously
jeopardized when the intercostals and diaphragm are affected, in
consequence of interference with respiration. If the intercostals cease
to contract, the upper part of the thorax ceases to move, and if the
diaphragm is involved, the epigastric and hypogastric regions are drawn
in during inspiration, and talking and singing are interfered with.
Even a mild bronchitis is apt to be fatal in consequence of the
difficulty in expelling the secretions.
The muscular atrophy thus produced is generally accompanied by a
corresponding wasting and retraction of the skin, so that this
continues applied to the muscles in the usual manner. In some
instances, however, this is not the case, and in these a baggy
condition of the skin is added, which gives its subject an appearance
which has more than once rendered him valuable to the showman as the
elastic-skin man, etc. It sometimes happens, on the other hand, that
the atrophy is obscured by an accumulation between the muscle and skin
of adipose tissue, and an appearance of hypertrophy rather than atrophy
may be produced in consequence, analogous to the same state of affairs
in pseudo-hypertrophic paralysis, the relations of which disease to
progressive muscular atrophy will be considered under the head of
Diagnosis.
At almost any stage the disease may come to a standstill, and may
continue thus for many years. The time required to attain its various
degrees also varies greatly, but the spread is usually slow, requiring,
as a rule, years for its completion. A general involvement of the
voluntary muscles of the entire body is exceedingly rare.
As stated, the disease may begin in the lower extremity, but much more
rarely. It is very seldom that the same order of invasion pursued in
the upper extremity is followed in the lower--that is, beginning with
the interossei. It may begin in the thigh and involve it alone, or
extend to both {550} thighs, or both legs as well. Under these
circumstances weakness of the legs is a striking symptom, the patient
being unable to stand, often falling down or requiring a cane or
crutches to assist him. In illustration of this mode of invasion may be
related one of Roberts's cases, that of an adult woman thirty-eight
years old, a domestic servant, in whom at thirty-six was perceived a
weakness in the right thigh. She first noticed that it grew tired
sooner than the left. This gradually increased, until she was compelled
to sit much of the day, then to use a stick, and finally crutches. This
was accompanied by a gradual wasting of the thigh-muscles. Even in this
case the loss of power was greater than would have been expected from
the degree of atrophy, the loss of bulk incident to which Roberts
believed to have been in part replaced by fat. In other instances,
however, the extremest degree of atrophy has been noted where the
disease has commenced in the lower extremities.
The deformity produced by the wasting muscle is sometimes further
increased--more frequently in the earlier stages--by a painful swelling
of the joints, first mentioned by Remak, called by him neuro-paralytic
inflammation, and referred to the sympathetic. This may affect the
small (phalangeal) as well as the larger joints (shoulder and elbow).
Cases apparently beginning in the face are reported, when the distorted
expression resulting is very characteristic.
Aran first, and Roberts afterward, divided cases of the disease into
two groups, the partial and general. In the former are included those
involving the extremities only; in the latter become involved, sooner
or later, the muscles of the trunk, neck, face, mouth, pharynx (muscles
of deglutition), thorax (muscles of respiration), and even of the
abdomen. Even the tongue is reported as undergoing atrophy.
General wasting palsy, as was early observed by Roberts, is
unquestionably a rare disease, and in no case have all the muscles of
the body been found implicated in one individual, and a few seem
altogether exempted. Such are the muscles of mastication and of the
eyeball, including the levator palpebræ.
A second muscular symptom, more or less distinctive, is fibrillar
contraction. This consists in a wave-like contraction running along
small bundles of muscular fasciculi. The contractions occur
spontaneously or are excited by any slight stimulus, as a breath of air
or a dash of water, or by tapping the patient, or passing a galvanic
current through the parts, and at any stage of the disease, except that
they do not occur in muscles wholly destroyed. Sometimes they can be
felt by the patient. At other times he is wholly ignorant of them. They
are not invariably present, and often they have been observed in
muscles atrophied from other causes. They possess, however, a certain
amount of diagnostic value, especially when spontaneous.
More rare, and less destructive, are cramps, twitches, and clonic
contractions of groups of affected muscles. These, when present, are
sometimes exceedingly painful.
Coincident with the wasting of muscles is their loss of function. The
power of abducting and adducting the fingers gradually disappears, so
also that of flexion and extension, and everywhere the loss of function
goes pari passu with the atrophy. As Roberts graphically puts it, "The
tailor discovers that he cannot hold his needle; the shoemaker wonders
{551} he cannot thrust his awl; the mason finds his hammer, formerly a
plaything in his hand, now too heavy for his utmost strength; the
gentleman feels an awkwardness in handling his pen, in pulling out his
pocket handkerchief, or in putting on his hat. One man discovered his
ailment in thrusting on a horse's collar; another, a sportsman, in
bringing the fowling-piece to his shoulder."
Along with the atrophy of muscle and loss of power comes a gradually
diminishing response to electrical stimulus. Direct muscular
faradization fails first to excite contraction, and sometimes fails
completely even before voluntary mobility is lost. Indirect muscular
faradization continues longer to excite contraction, but it also
finally fails. Response to the constant current continues still longer,
but it also finally fails to elicit contractions, stronger and stronger
currents being required, until finally all fail. The galvanic
excitability of nerve-trunks is maintained for quite a long time, but
finally also disappears. Some irregularities present themselves in this
respect.
A singular electrical reaction, first described by Remak, and said by
him to be of frequent occurrence in muscular atrophy, was named by him
deplegic contraction. He describes it as follows: When the cathode or
negative pole is put below the fifth cervical vertebra, contractions
can be produced in the atrophied muscles of the arm when the anode or
positive pole is placed in an irritable zone, which extends from the
first to the fifth cervical vertebra, or, still better, in the carotid
fossa or the triangle between the lower jaw and the external ear. The
contractions always take place on the side opposite to that at which
the anode is placed, while when the electrodes are placed on the median
line they occur on both sides, although when the current is very weak
they are limited to the muscles most seriously involved. Meyer,
Drissen, and Erb confirmed Remak's statement, while Fieber, Benedikt,
and Eulenburg failed to do so. Remak interprets these contractions as
reflected from the superior cervical ganglion of the sympathetic. He
bases this view upon the fact that the patient perceived a sensation
behind the ball of the eye when the current was closed. Eulenburg, on
the other hand, regards them as genuine reflex contractions,
independent of the sympathetic, and caused either by excessive
irritability of the central reflex apparatus or by an abnormal
excitability of the muscles themselves.
Sensibility is, in many cases, unchanged, the tactile sense being as
delicate as ever, and pain, except accompanying the cramps above
described, is absent. At times, however, the atrophy is preceded by
paroxysms, which may or may not accompany the clonic contractions
referred to. It is sometimes in the course of nerve-trunks, but as
often diffuse, as though the muscles themselves were its seat. At other
times it is variously described as a soreness, an aching, or a
rheumatic pain. Accompanying advanced degrees of the atrophy, however,
there is very rarely--in 3 out of 105 cases, according to Roberts--a
slight diminution of sensibility, especially in the ends of the
fingers, while the faradic sensibility may be similarly diminished.
Modified sensations, as those of cold, numbness, and formication, may
be experienced, and reflex excitability may be increased, while the
knee-jerk is said to be absent. Unusual sensitiveness to cold is
sometimes noted, and a loss of muscular power under its influence,
which is again restored by artificial warmth.
{552} Among more inconstant symptoms, denominated vaso-motor, are, in
the early stages, fever and slight elevation in local temperature from
2° to 3° C. Fever is less frequently observed toward the termination of
the disease, and at this stage a fall of local temperature, as much as
4° C., has been noted. In the same category of vaso-motor symptoms are
classed the skin contractions already referred to, hyperidrosis or
excessive sweating, and certain very rare oculo-pupillary symptoms,
consisting mainly of contraction of the pupil and slow reaction, but
including also, in a case reported by Voisin, flattening of the cornea
on both sides and defective sight.
COMPLICATIONS.--Progressive muscular atrophy is not infrequently
associated with amyotrophic antero-lateral sclerosis and with
labio-glossal or progressive bulbar paralysis. Both affections may
result as an extension of the disease from the anterior cornua of gray
matter, the former into the antero-lateral columns, the latter into the
medulla oblongata, or the affection may be primary in either of these
two situations, and extend thence into the anterior cornua of gray
matter.
When there is also lateral sclerosis, there is rigidity of the lower
limbs in addition to the atrophy of the upper--at first temporary, but
afterward permanent. This may extend to the upper also, and the arms
become fixed in semipronation and semiflexion.