Seidel, "simultaneous paresis in upper and lower extremities in four
years; atrophy of arms and thighs, with hypertrophy of calves and fore
arms; in six years, primary atrophy sterno-cleido-mastoids and
pectorals; secondary atrophy of deltoids."
Further: case of Kaulich (atrophy of shoulder-muscles, including
deltoid, while triceps and biceps hypertrophied); Duchenne fils;
Eulenburg and Cohnheim; Heller (2 cases); Wagner (2d case); Wernich
(1st case); Lutz (a girl, case much resembling Eulenburg's adult case);
Roquette (atrophy of thighs as well); Hoffmann; Russel; Foster (atrophy
of muscles of forearm); Chrostek (notwithstanding hypertrophy of
tongue); Friedreich (2 cases); Duchenne (2d); Wagner (2d and 3d);
Gowers (9 cases); Ross (2 cases).]
Gowers attaches diagnostic importance to the early signs of atrophy in
the latissimus dorsi and great pectoral muscles. The time of their
invasion contrasts with that in progressive muscular atrophy, where the
process usually begins in the hands and creeps upward to the
shoulder-joint.
Neither the atrophic nor the hypertrophic process is necessarily
symmetrical on the two sides of the body, but an approximate symmetry
is usually observed. The same muscles are usually affected, and in the
same way, but not often precisely to the same degree. Fibrillary
contractions often occur in the wasting muscles, but not in those which
are hypertrophied. The electrical reactions, however, do not differ
greatly in the two states. The faradic contractility diminishes in
proportion to the diminution in the contractile mass of the muscle,
whether this be concealed by the growth of fat and connective tissue or
rendered obvious by the general wasting of the whole. But even when
contractions can be obtained, these are often abnormally feeble, and by
continual diminution in the number of contractile fibres, and increase
in the lipomatous masses overlying them, the electrical irritability is
ultimately lost. The excitability of the nerves remains intact, and
therefore response may be obtained by an indirect excitation after
direct excitation of the muscle fails to elicit one.
Eulenburg has occasionally observed one curious phenomenon in the
galvanic reaction of nerves. The anode opening contraction grows weaker
or even disappears with a progressively stronger current, and then with
a still stronger current reappears. This is due to a cross action of
the current on the excitability and on the conductibility of the nerve.
At a certain moment the increased excitability is compensated by a
corresponding increase in the resistance to conduction, and therefore
all electrical response ceases. Later, the resistance remaining the
same, the excitability is increased and the reaction reappears.
{567} The symptoms of the first order (disturbance of muscular
function) and of the third (deformity) are for a long time less
conspicuous in the upper than in the lower extremities. When the arms
begin to be paretic the patient is crippled in the characteristic
manoeuvres by which, during the earlier period of the disease, he
palliates the inefficiency of the lower limbs. When he can no longer
push up the trunk by means of his arms, he becomes unable to rise from
a sitting position at all. Further progress in the atrophy of the
erectores spinæ muscles renders even the act of sitting impossible: the
patient can only crouch, and ultimately must remain altogether
recumbent. The functions of the hands usually remain unimpaired to the
last, so that the unfortunate patient is able to amuse himself with
knitting and other light work.
Besides the paralytic cyphosis, scoliosis of a high grade is sometimes,
though infrequently, developed. It is due to the lateral oscillations
with excessive inclination of the upper portion of the trunk.[40]
[Footnote 40: Cases of scoliosis from such cause, where inequality of
muscular action cannot be invoked as a cause, help to throw light on
the real etiology of the idiopathic deformity so often attributed to
irregular muscular action.]
It is rare that any researches have been made on the nutritive
functions in pseudo-hypertrophic paralysis. Seidel[41] has analyzed the
urine in the two cases (brothers) which form the basis of his memoir.
He expected to find a marked diminution in the urea, corresponding to
the diminution in the mass and in the functional activity of the
muscles. This expectation was based on the assumption, at present
considered incorrect, that the elimination of urea is modified by
muscular contractions. In the cases examined the actual amount of urea
was considerable, rising on several occasions to 40, 43, and 69 grammes
in twenty-four hours, and offering, in the first boy, a daily average
of 41 grammes. But Scherer estimates that the average elimination of
urea in children is, per kilogramme, double that in adults; and on the
basis of this calculation the amount of urea eliminated by the patient
in question should have been 51 grammes. There was therefore a
diminution of about one-fifth.
[Footnote 41: _Atrophia Musculorum Lipomatosa_, Jena, 1867.]
Seidel has also examined the temperature of the diseased muscles during
their contraction either under the influence of the will or of the
faradic current. The hypertrophied gastrocnemius muscle showed a rise
of 1.5° to 2° less than a healthy gastrocnemius similarly excited. The
rise of temperature never occurred during the contraction, but during
the ten or fifteen minutes which followed it. The duration of this rise
of temperature was always longer than in the control experiment
performed on a healthy subject. The observation was the same in
hypertrophied and in atrophied muscles, and indicated a notable
diminution of heat-production in both.[42]
[Footnote 42: _Loc. cit._, p. 54.]
The mental functions are not unfrequently impaired. The defective
intelligence exhibited by several of his first patients led Duchenne to
attribute a cerebral origin to the disease. The internal hydrocephalus
discovered at the autopsy of the case so recently published by
Pekelharing suggests that this hypothesis may have been too hastily
abandoned, and that it may really prove to be correct for certain
cases. In many, however, the intelligence is intact or even precocious,
and all suspicion of cerebral lesion must be excluded.
{568} COURSE OF THE DISEASE.--As already stated, a period of paresis
may precede all signs of hypertrophy for several weeks, months, or even
years. From the time that the enlargement of the calves has once begun
about a year and a half is required before the maximum of hypertrophy
is attained. Then the disease usually remains stationary for two or
three years before the third period is ushered in by aggravation of
paralysis in the lower and by extension of paralysis, together with
hypertrophy or atrophy, to the upper limbs.
When, from complete loss of muscular power, the patient has become
permanently condemned to a recumbent position, life may nevertheless be
prolonged for ten or twelve years, with integrity of all the vegetative
functions. Death finally takes place, in all recorded cases, from some
acute pulmonary disease, whose effects are intensified by the atrophy
of the external respiratory muscles, which often extends even to the
intercostals.
The course of the disease, and consequent prognosis, is much modified
in the rare cases in which it attacks girls. Two of Duchenne's thirteen
cases were girls: in one the disease was spontaneously arrested, in the
other apparently cured. Lutz[43] relates the altogether exceptional
history of a family in which five female members were affected--two
sisters, also one step-sister, daughter of the mother by an earlier
marriage, a sister and niece of the mother, of whom a brother also was
diseased. The step-sister and niece both died at six years of age, but
the aunt lived to be forty-three (the brother to be forty-two), and one
of the girls observed by Lutz, who began to suffer at the age of six,
was twenty-eight at the time of observation: paresis had only become
marked at seventeen, and locomotion impossible at twenty-two. In the
other girl the first symptoms appeared at seventeen, and at twenty-two
were still moderate and confined to the lower extremities.
[Footnote 43: _Deutsches Archiv f. klin. Med._, Bd. iii., 1867.]
In Roquette's female case[44] the disease began at ten; in
Hoffman's,[45] at eleven and a half. These cases, with one of
Benedikt's, are the only female cases among the 88 I have analyzed.[46]
Gowers estimates 30 female cases out of a total of 220, or only 13 per
cent. of the whole.
[Footnote 44: _Inaug. Dissert._, Berlin, 1868, quoted by Friedreich.]
[Footnote 45: _Ibid._, 1867.]
[Footnote 46: This excludes the adult cases of Eulenburg, where
"progressive atrophy of the upper extremities combined with
pseudo-hypertrophy of the lower;" the case of Barth, an amyotrophic
lateral sclerosis; the case of Müller, a dementia paralytica; and the
case of Billroth, where the lesion was localized in the hamstring
muscles of one thigh.]
This great preponderance in the male sex is the first of three striking
peculiarities which distinguish the clinical history of the disease.
The second is its strangely-marked hereditary character. This is not,
and indeed hardly could be, shown in a direct line, since the patients
are incapable of marriage, or even die before arriving at maturity. But
several brothers in a family are usually afflicted. There was, it is
true, no trace of heredity in Duchenne's 13 cases, but this author
himself recognizes the frequency of hereditary influence in those
observed by others. Out of 81 cases analyzed by Friedreich, two or more
members of one family were attacked thirty-five times. Thus, the first
clinical report, that made by Meryon, described four brothers in one
family and two in another. Coste, Griesinger, Wernich, Benedikt, Adams,
Russel, Gowers, each relate cases of two members in one family; Heller,
Wagner, Billroth, {569} Seidel, have seen three: Moore[47] describes
three cases out of a family of seven, consisting of five boys and two
girls. Two of the cases I myself have seen were brothers. Gowers[48]
relates five cases in the families of two sisters who married two
brothers. This same writer refers to three other families in which two
brothers were affected; to a fourth family described by Clifford
Albutt, where two brothers were paralyzed, the third child dying of
Hodgkin's disease; finally, to the family of a clergyman, himself
living to the age of seventy-four, having always had large calves, and
out of whose eight children two boys and one girl were affected.
[Footnote 47: _Lancet_, 1880.]
[Footnote 48: _Loc. cit._, Appendix.]
The families invaded by this singular disease are often remarkably
large, and even where several children are affected, many others, even
boys, escape. The morbid inheritance is always through the mother,
"thus through the ovum--a condition unknown in diseases of the nervous
system" (Gowers). This peculiarity belongs to only one other disease,
hæmophilia, also almost limited to males. The third fact, which from
its all but universality is shown to be of fundamental importance, is
that the disease begins during infancy or early childhood. It has been
shown that more than two-thirds of all cases began before the age of
six. Whether there is ever an intra-uterine origin is still doubtful
(Friedreich). This early invasion, often coinciding with the first
efforts to walk or to use the muscles which are first attacked,
distinctly separates pseudo-hypertrophic paralysis from all diseases
which can be traced to definite accidents or to perversion of
functions. It implies a profound perversion of nutrition, or rather a
misdirection of developmental force.
PATHOLOGICAL ANATOMY.--The anatomical lesions of pseudo-hypertrophic
paralysis are to be sought first in the muscles, afterward in the
spinal cord, upon which so many peripheric lesions of the
nervo-muscular system have recently been shown to depend. The argument
from analogy, therefore, has of itself almost sufficed to create a
conviction that some disease of the central nervous organs must exist
as the real basis of pseudo-muscular hypertrophy.[49] Nevertheless, as
will presently be shown, the present evidence in favor of such
hypothesis is extremely small.
[Footnote 49: This conviction is fully expressed by Hammond, _loc.
cit._]
Muscular Lesions.--In the muscles, however, the anatomical changes are
profound and varied. They may be divided into three kinds--those
affecting the muscular fibre itself; those touching the connective
tissue; and, finally, the fat deposited in this.
The lesions of these different elements are variously combined with
each other in different muscles, and also at different stages of the
disease. Thus, in the muscles of the trunk and upper extremities
affected with primary atrophy the increase of fat is always moderate
and quite insufficient to compensate the wasting of the contractile
mass, while in the gastrocnemii and gluteal muscles the hypertrophied
masses are often found to consist entirely of fat, traversed by bands
of connective tissue, and indistinguishable from a lipoma.
The muscles have been examined in two ways--in the course of a general
post-mortem examination, and also during life by means of excision or
extraction by various instruments. Griesinger in 1864[50] excised a
piece {570} of the deltoid in a boy of thirteen,[51] and made on it,
with Billroth, the first microscopic examination of the diseased
muscles. Duchenne, to avoid an operation not devoid of danger for the
patient, devised his harpoon, by means of which small fragments of
muscles could be torn away. As this instrument is liable to change the
relations of the parts separated by tearing, Leech has contrived
another, in which the fragment is removed by cutting. By one method or
another of harpooning the muscular lesions have been studied during
life by Duchenne, Heller, Wernich, Russel, Eulenburg, Martini, Knoll,
Rakowac, Friedreich, Ross, Gowers, Auerbach, Hammond, Pepper, in the
cases already quoted.
[Footnote 50: _Archiv der Heilkunde_.]
[Footnote 51: The wound suppurated for a long time.]
Muscular Fibre.--There are contradictory opinions in regard to the
first stage of alteration in the muscular fibres. According to most
observers, the fibres are seen to directly atrophy; the transverse
striæ become dim and gradually disappear, and the primitive bundles
shrink in diameter from loss of some of their fibrillæ (Brieger,
Hammond, Pepper). Friedreich[52] adds that the complete collapse of the
contractile substance in the primitive bundles often leaves empty or
shrunken sarcolemma sheaths, which swell the mass of the connective
tissue. Friedreich, however, denies that the striation is modified; and
its extreme fineness, commented upon by Duchenne, is considered by
Ollivier[53] and Ranvier as devoid of pathological significance.
[Footnote 52: _Loc. cit._, p. 300.]
[Footnote 53: _Des Atrophies musculaires_, Thèse d'Agrégation.]
The real size of the primitive fibres is best estimated by the method
of Cohnheim, who isolated the fibres by boiling the muscular fragment
from four to six hours in a mixture containing 100 c.c. of 90 per cent.
alcohol and ¾ c.c. of concentrated muriatic acid. Many were found
reduced to one-fifteenth or one-sixteenth their normal size.[54]
Between atrophied fibres lay a peculiar striped tissue, probably
composed of empty sarcolemma sheaths. Side by side with these atrophied
fibres were many normal, and others grossly hypertrophied to two or
even three times the normal calibre. These were only found in the
hyper-voluminous muscles. Some of these exceeded the largest
frog-muscle fibres. They lay in bundles of four to six between the
small fibres, and seemed to be about equally distributed through the
hypertrophied gastrocnemius and atrophied biceps.[55]
[Footnote 54: _Berlin. klin. Wochensch._, 1865, No. 56.]
[Footnote 55: Hypertrophied fibres have also been seen by Knoll
(_Medizin Jahrbuch._, Wien, 1872), Müller, and Eulenburg.]
Another alteration observed in the muscular fibres was their
dichotomous and even trichotomous division. This same lesion has been
seen by Friedreich in progressive muscular atrophy.
The presence of hypertrophied fibres in wasting muscles lends a special
significance to the cases of true muscular hypertrophy described by
Auerbach[56] and Hitzig.[57] Auerbach's observation related to a
soldier aged twenty-one, whose upper arm became rather rapidly
hypertrophied and paretic. In a fragment excised from the enlarged
biceps the fibres were seen to have a diameter of from 96 to 180 µ.
(the normal diameter being 33 to 67 µ.). The other arm was not
enlarged, and yet examination of fibres obtained by means of a similar
excision found them also enlarged. Auerbach suggests that this
hypertrophy constituted a preliminary stage {571} in the general
process of pseudo-hypertrophic paralysis. In it, as when the excessive
volume is known to depend upon the presence of non-contractile tissue,
the arm, far from increasing in strength, was paretic.[58]
[Footnote 56: _Virch. Arch._, Bd. liii., 1871.]
[Footnote 57: _Berlin. klin. Wochen._, Dec. 2, 1872.]
[Footnote 58: Mobius (_loc. cit._) declares that neither of these cases
bears any relation to pseudo-hypertrophy.]
Connective Tissue.--Far more conspicuous than the alterations in the
contractile fibre of the muscles are those of its connective tissue.
The perimysium internum, between the primitive bundles, proliferates
abundantly, and the hyperplasia gradually extends correlatively with
the wasting of the muscular fibres, until the hypertrophied mass is
mainly composed of connective tissue. Broad bands replace the thin
lamellæ normally present between the primitive bundles; the parenchyma
of the muscle seems stifled in a sclerosis. It is then that it offers
the feeling of stony hardness so often noticed in the clinical history.
Charcot, Knoll, Müller, and Barth describe a rich development of nuclei
and of spindle-shaped cells in this new connective tissue, this being
especially abundant in the neighborhood of the small vessels and in
their adventitia. Eulenburg and Leyden, however, affirm that the
connective tissue is unusually poor in nuclei, and thence infer that
the hyperplasia is compensatory, and not due to inflammation.
In some cases, as in those of Duchenne examined by Ordonez, the
sclerosis and atrophy of contractile tissue constitute the entire
lesion of the muscle. Only a few fat-cells are interspersed among the
bands of connective tissue or penetrate between the primitive bundles.
The fatty infiltration tends constantly to increase, apparently by the
same process as governs the growth of normal adipose tissue--namely,
the deposit of fat in connective-tissue cells; and ultimately not only
muscular fibre, but the hyperplastic connective tissue, is concealed in
a yellowish glistening mass indistinguishable from a lipoma.[59]
[Footnote 59: See case of Billroth.]
The growth of fat contributes to the apparent hypertrophy of the
diseased muscles, but much less so than does the hyperplasia of
connective tissue which invariably precedes it. Great rapidity of fatty
infiltration marks a more rapid and irresistible progress in the
disease, a lower stage of nutritive degradation. Fat-cells are found
penetrating between the primitive bundles of fibres in the atrophied as
well as in the hypertrophied muscles; but there the fatty substitution
is always much less complete.
In contrast with this fatty infiltration true fatty degeneration of the
muscular fibre is as rare in pseudo-hypertrophy as in progressive
muscular atrophy. This fact is emphasized by Pepper from observation of
the harpooned fragment examined by him,[60] also by Cohnheim.[61] In
Meryon's first case,[62] however, the post-mortem examination of the
muscular fibres found them "totally degenerated, their substance
changed into a mass of granules and oil-globules, while the sarcolemma
was destroyed." In Brieger's case[63] the fibres were filled with
fat-globules.
[Footnote 60: _Philada. Med. Times_, 1871.]
[Footnote 61: _Loc. cit._]
[Footnote 62: _Med.-Chir. Trans._, vol. xv., 1852.]
[Footnote 63: _Deutsches Archiv_, Bd. xxii.]
The sclerotic process which precedes the stage of fatty infiltration is
far from being completed when this latter begins. Both processes,
initiated nearly at the same time, continue together, and at the death
of the patient may be found existing in about equal proportion, or the
one {572} markedly predominating over the other. In cases of long
duration the hypertrophied muscles, as already stated, are found
converted into masses of fat, divided by stripes and bands of
connective tissue. With death earlier in the disease the enlargement is
found to be due to masses of connective tissue englobing muscular
fibres and interspersed with fat-cells.
In the wasted whitish-red muscles the proliferation of connective
tissue is sometimes more, sometimes less, marked; in the pale-yellowish
muscles fat accumulates by interstitial deposit, but does not overlay
and conceal the remnant of muscular fibre.
Central Nervous Organs.--While the examinations of the diseased muscles
have been frequent, post-mortem examinations are still relatively few,
although their records are rapidly increasing. The first was made by
Meryon[64] on the first of his series of six cases. Charcot has
examined a case for Duchenne; Cohnheim has made a celebrated autopsy
for Eulenburg;[65] Gowers and Clarke have together published a
fourth.[66] The cases by Müller and Barth are still habitually--though,
as we shall see, erroneously--included among the autopsies of
pseudo-hypertrophic paralysis. Ross[67] and Leach have, however, a
fifth indubitable case with autopsy; and more recently Cornil,[68]
Brieger,[69] Bay,[70] Schultze,[71] Pekelharing,[72] and possibly Goetz
and Drummond,[73] have all described post-mortem examinations. The data
for discussion, therefore, are to be derived from 14 cases. Of these,
the spinal cord was found perfectly healthy in 7, those related by
Meryon, Cohnheim, Charcot, Cornil, Brieger, Bay, Schultze--all most
competent observers. The cases by Barth and Müller require some special
consideration, for, although rejected as irrelevant by most authors,
Hammond still adduces them in proof of the central origin of
pseudo-hypertrophic paralysis.
[Footnote 64: _Loc. cit._]
[Footnote 65: _Loc. cit._]
[Footnote 66: _Med.-Chir. Trans._, 1874; also monograph by Gowers.]
[Footnote 67: _Loc. cit._]
[Footnote 68: _Union méd._, 1880.]
[Footnote 69: _Deutsches Archiv f. klin. Med._, Bd. xxii. H. 2.]
[Footnote 70: _Virch. Jahresb._, 1877.]
[Footnote 71: _Virch. Arch._, 1879, Bd. lxxv.]
[Footnote 72: _Arch. Virch._, Bd. lxxxix., 11, 2, 1882.]
[Footnote 73: Quoted by Pekelharing--the first from the _Aerztliches
Intelligenz Blattmünchen_, 1879; the second from the _Lancet_, 1881,
vol. ii., No. 16.]