is visible to the naked eye on the surface of the brain and spinal
cord. Grayish maculas, sometimes elevated, more rarely a little
sunken, and occasionally showing a buff or reddish tinge, are seen on
the surface of the spinal cord, the oblongata, pons, and crura. On
making sections across the region of the spots, it is found that the
color-change is not superficial, but extends inward, involving large
parts of the transverse area of the cord or the cerebral axis; and
patches lying more deeply in their substance are revealed whose
existence could not have been suspected from a mere surface
inspection. Exceptionally, patches are found involving the entire
transverse section of the spinal cord in a length of a half to two
inches. And, similarly, in the brain nearly the entire area of the
pons or one of the crura or an entire division of the internal capsule
may be occupied by a sclerotic focus. Otherwise, they may vary from
almost microscopic dimensions to the size of a chestnut or even
larger. {881} Bourneville[135] has described cases in which the
nerve-centres appeared normal to the naked eye, while the microscope
revealed the existence of sclerotic foci. It is, however, unlikely
that the fresh brain- and cord-tissue, when the site of disseminated
sclerosis, will appear perfectly healthy to the naked eye under fairly
good illumination. Much less intense lesions than those of
disseminated sclerosis reveal their presence by changes in color and
consistency.
[Footnote 135: _Mouvement medicale_, 1869, No. 27.]
On examining the diseased spots more narrowly, they are found to be
slightly diaphanous. Usually, they are rounded or elliptical, but they
are often drawn out, as it were, in the most irregular shapes, and not
infrequently appear to be the result of a confluence of originally
remote and separate foci. In the cord they are sometimes wedge-shaped,
extending inward from the periphery. To the touch they appear
firm—sometimes not much more so than the normal tissue, contrasting
with it as hard-boiled white of egg would contrast with soft-boiled;
in advanced cases they become of almost leathery consistency, and
there are instances recorded where they actually creaked under the
knife. A clear fluid usually runs from their cut surface, and the
latter does not jut up on section like normal nerve-tissue.
The distribution of the diseased areas follows no known law. They may
be numerous and of large size in one segment of the nervous axis, and
small, few in numbers, or even absent, in others. In some altitudes of
the cord the lateral, in others the posterior, in still others the
anterior, columns are chiefly involved. The cerebrum usually contains
a larger number of foci irregularly scattered in the centrum ovale of
Vieussens, the internal capsule and its surrounding ganglia, as well
as in the corpus callosum. Throughout the nervous axis it seems that
the lesion chiefly affects the white substances, and even the roots of
the peripheral nerves, both cranial and spinal, are occasionally found
to contain small foci, gray, firm in consistency, and as distinctly
outlined as those of the central organs.
The morbid process consists in an atrophy and gradual disappearance of
the myelin, which is preceded, if not caused, by an increase of the
enveloping interstitial substance. This change is of the same
character as that found in chronic myelitis. The septa and trabeculæ
of connective tissue become thicker, formless connective substance and
fibrillar tissue, which seems to arise in, if not in part from, it,
constituting the new formation. The neuroglia-nuclei are increased,
enlarged, and develop into spider-shaped cells, whose long processes
contribute (according to some authors exclusively) to the newly-formed
fibrillar network.
While the myelin undergoes wasting, the axis-cylinders remain intact
for a long period, and even in intensely sclerosed regions they may be
found in nearly their normal number, but naked and in direct contact
with the pathological fibrillæ. Some of them become hypertrophied,
increasing to twice, thrice, and, according to Leyden, even more, of
their normal diameter. This change seems to inaugurate the last phase
of the process: the axis-cylinders, becoming sclerosed and brittle,
ultimately disappear, and no trace, or at best but doubtful traces, of
the normal nerve-tissue are left behind. The blood-vessels, following
the rule of {882} the sclerotic process, take part in it. Their walls
become thickened, richly nucleated, and the lumen becomes narrowed in
consequence. In the smaller vessels complete obliteration of the lumen
is sometimes observed.
The gray substance is not involved as frequently as the white, but it
opposes no barrier to the extension of the morbid process when once
established in its neighborhood. The nerve-cells show the same
resistance which the axis-cylinder does; that is, they retain their
outline and fibre-connections a long time in the midst of the diseased
area. But eventually they become discolored, undergo hyaline or
granular disintegration, their processes shrink, and finally they
disappear.
Ribbert and Zacher consider the sclerosis of tabes and the
disseminated affection to be much more similar than Leyden and Charcot
supposed. They locate the starting-point of the morbid process in the
vascular and connective tissues; and Greiff, in harmony with this
view, finds that the foci occur most frequently in those parts of the
cord where the connective-tissue trabeculæ are most numerous, as in
the posterior columns and at the junction of the anterior and lateral
columns.
Although the morbid foci appear to the naked eye to be uniform, and to
be sharply demarcated in the normal tissue, closer examination shows
that the areas of maximum lesion are surrounded by a narrow transition
zone by which the lesion seems to mark its eccentric progress, and
occasionally a focus of intense disease lies in a diffused area of
slight changes, resembling those of diffuse myelitis. Sometimes the
cord appears to be almost continuously involved by a lesion of
moderate intensity, and a few disseminated foci in the brain alone
prove that the case belongs to this form of sclerosis.
A few years ago Greiff described what he considered a new lesion in
multiple sclerosis, under the name of disseminated vitreous
degeneration of the cerebral cortex.[136] I have been familiar with
this lesion since 1876: it can be produced at will in perfectly
healthy brains, and consists in a precipitation of leucine crystals
extracted from the brain-substance by the action of alcohol. His
accompanying figure[137] represents this artificial lesion very
accurately; and Greiff, if he fails to recognize that his vitreous
degeneration is a spurious lesion, at least identifies it with the
miliary sclerosis of Bucknill and Tuke and the spheres of Schüle,
which are now generally recognized to be the results of post-mortem
manipulations and not actual lesions.[138]
[Footnote 136: _Archiv für Psychiatrie_, xiv. p. 286.]
[Footnote 137: _Ibid._, xiv., Plate ii. Fig. 5.]
[Footnote 138: Attention was first called to the artificial nature of
these bodies by the writer in the _Journal of Nervous and Mental
Diseases_, October, 1877, and a more accurate description was given in
the _Chicago Medical Review_ of 1880, and in a demonstration before
the New York Neurological Society in 1883. In commenting on the latter
a German critic stated that the facts related had been long known in
Germany (_Neurologisches Centralblatt_, 1883, p. 283). On inquiring of
the critic what publication contained any reference to this discovery,
he frankly stated that he knew of none, but had had in mind what he
considered a tradition of the laboratory. It was in the same year that
Greiff worked at the Heidelberg laboratory under the eminent
supervision of Fürstner, and it was a few years previous that Schüle,
one of the collaborators of _Ziemssen's Cyclopædia_, had made the same
mistake. So it seems that the tradition is in some danger of expiring,
and that it would do no harm to accept the caution, even though it
travel across the Atlantic in the reverse of the usual direction. It
has been amply confirmed by Savage and Plaxton (_Journal of Mental
Science_, October, 1882, and April, 1883).]
In judging as to the nature and intensity of the inflammatory process
{883} which leads to the development of the sclerotic foci, it must be
remembered that we are acquainted thus far only with the terminal
period of the disease, when, as is to be presumed, the active
inflammatory changes have gone by or are in the background. It is very
probable that the newly-formed tissue is more nucleated in early
periods than is found in the cases which constitute the material of
pathological laboratories. In a case of protracted nervous exhaustion
accompanied by spinal irritation in an alcoholic subject who was
murdered, and whose brain and cord I had an opportunity of examining,
I found, both in the cord and brain, districts in which the white
substance showed a slight grayish discoloration and increased
consistency. Minute examination failed to show any qualitative change
in the conducting elements, but the interstitial tissue was
hypertrophied, richly nucleated, and showed Frommann's cells in
abundance.
ETIOLOGY.—Heredity has been observed in a number of cases by Duchenne,
Erb, and Frerichs. The latter two had each an opportunity of recording
this inheritance in several members—sisters or brothers—of the same
family. In these cases the transmitted affection developed in adult
life. Dreschfeld, however, cites a case where two brothers developed
its symptoms in a marked degree in infancy. As an associated feature
it is found with some cases of congenital defect. Thus Pollak[139]
discovered disseminated sclerosis in an infant which had a defective
corpus callosum and exhibited the characteristic signs of the focal
affection side by side with the imbecility due to imperfect cerebral
development. As a rule, the disease is developed after the twentieth
year. But cases have been related (De Fleury) where the patient
developed the disease and died with an apoplectiform onset in earlier
life. One of the youngest on record is described by Hödemacker.[140]
The subject developed the disease at the seventh year, and died with
it at the fourteenth, having shown the characteristic symptoms,
besides more muscular atrophy than is common. The sclerosis in this
case belonged to the type which has been referred to as a
connecting-link between diffuse and disseminated sclerosis.
Pelizæus[141] reports five cases developing in the same family in
early life, corresponding somewhat in their relation to multiple
sclerosis of advanced life, as the family forms of tabes and spastic
paralysis correspond to the typical adult forms of those diseases. All
the cases were of males, and the ancestral taint had been present in
male members of the family, passing through the females to their
progeny without breaking out in the mothers. Each branch of this
family appeared to develop its own peculiar type of the disorder.
[Footnote 139: _Deutsches Archiv für klinische Medizin_, Bd. xxiv. p.
404.]
[Footnote 140: _Ibid._, vol. xxiii. p. 442.]
[Footnote 141: _Archiv für Psychiatrie_, xvi. p. 698.]
CAUSES.—Disseminated sclerosis may develop as a sequel of an acute
myelitis. An excellent observation of Singer,[142] in which a
unilateral optic-nerve atrophy of central origin occurred after
recovery from an acute inflammation of the cord, proves that sclerotic
foci may develop secondarily to an acute process. Westphal believes
that obstruction to the circulation, both of blood and lymph, in the
cord may act as a predisposing factor in the production of multiple
sclerosis. He rests this opinion on a case where the cord had been
compressed by a tumor, and {884} sclerotic foci of probably later date
were found in the neighboring segments of the cord.
[Footnote 142: _Prager medizinisch Wochenschrift_, 1885, No. 8.]
The myelitic affection discovered by the same observer[143] to be an
occasional sequel of typhus, smallpox, diphtheria, measles, and
erysipelas is a true disseminated sclerosis. The foci are usually very
small and very numerous. A focal sclerosis of the posterior columns of
the disseminated type has been found by Brigidi-Bandi in a case of
pellagra which presented ataxic symptoms.[144]
[Footnote 143: _Archiv für Psychiatrie_, iii. p. 376, iv.; Oertel,
_Deutsches Archiv für klinische Medizin_, viii.; Damaschino, _Gazette
médicale de Paris_, 1871, p. 505. In one case now under observation a
typical disseminated sclerosis developed in a robust young man of
thirty after typhoid fever.]
[Footnote 144: _Lo sperimentale_, December, 1879.]
Among the exciting causes, prolonged exposure to wet and cold are
acknowledged to occupy an important position. The frequent combination
of these factors with over-exertion and depressing emotions among the
poorer classes probably account for its great frequency among them. In
some cases excessive grief has been the only discoverable etiological
factor: in three of my own cases this was so prominent and connected a
feature that I could not doubt its influence, if not as a primary at
least as an exciting cause.[145] Fright has been distinctly connected
with the outbreak of the disease in a number of cases.[146] There is
considerable unanimity among observers regarding the effects of shock
and injury in producing disseminated sclerosis, usually of that
anomalous type which approximates the diffuse or fascicular form.
Railway spine is undoubtedly the mask of a disseminated inflammatory
trouble in a number of cases; the only authority of weight who opposes
this view is Charcot, and his opposition is abundantly neutralized by
a number of carefully-studied American and European cases.
[Footnote 145: The coincidences among these three cases were
remarkable. All three were Germans, all three musicians, two had lost
an only son. In all, the emotional manifestations were pronounced from
the initial to the advanced period of the disease.]
[Footnote 146: A Bohemian cigar-maker was startled by the sudden
firing of a pistol-shot in a dark hallway, and on arriving at the
factory, and not fully recovered from the first fright, he was again
startled by the sudden descent of an elevator and the fall of a heavy
case from it close to where he stood. From the latter moment he
trembled, and his tremor continued increasing till the last stage of
his illness was reached. This was my shortest duration, four years,
and of nuclear oblongata paralysis type.]
Hysterical and other obscure neuroses have been claimed to act as
predisposing causes. But, inasmuch as it is well established that
sclerosis is not a legitimate sequel of even the most aggravated forms
of true hysteria,[147] and, on the other hand, that disseminated
sclerosis, particularly in the early stages, may progress under the
mask of spinal irritative or other neuroses, it is reasonable to
suppose that cause and effect have been confounded by those who
advanced this view. According to Charcot, the female sex shows a
greater disposition to the disease than the male. Erb, who bases his
remarks on the surprisingly small number of nine cases, is inclined to
account for Charcot's statement on the ground that it was at a
hospital for females that Charcot made his observations. On comparing
the figures of numerous observers, it will be found that in the
experience of one the females, and of the other the males,
preponderate. {885} In my own experience the males far exceed the
females both in private and in dispensary practice. Of 22 cases with
accessible records, only 7 were females.
[Footnote 147: Charcot's observation of lateral sclerosis in
hysterical contracture, although made so long ago, has not been
confirmed, and the most careful examinations in equally severe and
protracted cases have proven altogether negative.]
Syphilis has also been assigned as a cause. The connection is not as
clear as in tabes. In the few cases where there appears to be a direct
causal relation the lesion is not typical. There are sclerotic foci,
but in addition there is a general lesion, particularly of the
posterior columns of the cord, such as is found with paretic dementia.
And it has been noted that periendymal and subendymal sclerosis is
more frequent with the cases of alleged syphilitic origin than with
those of the typical form.
DIFFERENTIAL DIAGNOSIS.—In view of what has been already stated
regarding the numerous clinical types found in disseminated sclerosis,
it is easily understood why the diagnosis of this disease is becoming
more and more uncertain: every new set of researches removes some one
or several of the old and cherished landmarks; and it may be safely
asserted that only a minority of the cases show that symptom-group
which was formerly claimed as characteristic of all. The discovery of
a series of cases by Westphal,[148] in which the typical symptom-group
of Charcot was present, but no sclerosis deserving the name found
after death, as well as the interesting experience of Seguin, who
found well-marked disseminated sclerosis in a case regarded as
hysterical intra vitam, illustrates the increasing uncertainly of our
advancing knowledge. It was believed within a few years that the
presence of cranial nerve-symptoms was a positive factor in
determining a given case to be one of disseminated sclerosis, but in
the very cases described by Westphal such symptoms were present
notwithstanding the lesion was absent. Up to this time, however, no
case has been discovered in which, optic-nerve atrophy being present
in addition to the so-called characteristic symptoms of intention
tremor, nystagmus, and scanning in speech, disseminated foci of
sclerosis were not found at the autopsy. This sign may be therefore
regarded as of the highest determining value when present; but as it
is absent in the majority of cases, its absence cannot be regarded as
decisive. The presence of pupillary symptoms also increases the
certainty of the diagnosis when added to the ordinary and general
symptoms of the disorder related above.
[Footnote 148: _Archiv für Psychiatrie_, xiv. p. 128.]
Although the difference between the tremor of typical disseminated
sclerosis and that of paralysis agitans is pathognomonic, yet the
existence of a group of cases of disseminated sclerosis, as well as of
one of cases of paralysis agitans without tremor, renders an exact
discrimination in all cases impossible. It is a question, as yet,
whether the form of paralysis agitans without tremor described by
Charcot, and which is marked by pains in the extremities, rigidity,
clumsiness, and slowness of movement, general motor weakness, a frozen
countenance, impeded speech, and mental enfeeblement, is not in
reality a diffuse or disseminated sclerosis.
The diagnosis of this disease, while readily made in a large number of
cases on the strength of the characteristic symptoms detailed, may be
regarded as impossible in a minority which some good authorities
incline to regard as a large one.
{886} Diffuse Sclerosis.
SYNONYMS.—Chronic myelitis, Diffuse myelitis, Simple or Diffuse spinal
sclerosis, Chronic transverse myelitis, Sclerosis stricte sic dicta
(Leyden, in part), Gray degeneration.
The various forms of sclerosis thus far considered were at one time
considered as varieties of chronic myelitis, and under different
names, founded on leading symptoms, were considered to be merely
local, and perhaps accidental, variations of one and the same morbid
process. More accurate clinical and pathological analysis has
separated from the general family of the scleroses one clearly
demarcated form after another. Tabes dorsalis, disseminated sclerosis,
amyotrophic lateral sclerosis, and the combined forms of sclerosis
have been successively isolated. Still, a large number of cases are
left which cannot be classified either with the regular affections of
the cord, limited to special systems of fibres, or with the
disseminated form last considered. They agree with the latter in that
they are not uniform; they differ from it in that they are not
multilocular. Not a few modern authors have neglected making any
provisions for these cases, while others treat of them in conjunction
with acute myelitis, of which disease it is sometimes regarded as a
sequel. The term diffuse sclerosis is here applied to those forms of
chronic myelitis which follow no special rule in their location, and
to such as are atypical and do not correspond in their symptomatology
or anatomy to the more regular forms of sclerosis. In regional
distribution the foci of diffuse sclerosis imitate those of acute
myelitis: they may be transverse, fascicular, or irregular.
MORBID ANATOMY.—In typical cases the lesion of diffuse sclerosis
constitutes a connecting-link between that of the disseminated form
and posterior sclerosis. Its naked-eye characters are the same. There
is usually more rapid destruction of the axis-cylinders, more
inflammatory vascularization, proliferation of the neuroglia-nuclei,
and pigmentary and hyaline degeneration of the nerve-cells, than in
the disseminated form.
Syphilitic inflammation of the cord extends along the lymphatic
channels, including the adventitial spaces, and leads to a diffuse
fibrous interstitial sclerosis. In one case in which I suspected
syphilis, though a fellow-observer failed to detect it after a rigid
search, I found a peculiar form of what would probably be best
designated as vesicular degeneration, according to Leyden, though
associated with a veritable sclerosis. The lymph-space in the
posterior septum showed ectasis; the blood-vessels were sclerotic, and
each was the centre of the mingled sclerotic and rarefying change. It
appears that while the interstitial tissue hypertrophied, the myelin
of adjoining nerve-tubes was pressed together till the intervening
tissue underwent pressure atrophy. The result was, the myelin-tubes
consolidated, some axis-cylinders perished, others atrophied, a few
remained, and, the myelin undergoing liquefaction, long tubular
cavities resulted, running parallel with the axis of the cord, and
exposed as round cavities on cross-section (Fig. 32). The changes in
the cells of the anterior horn in the same cord (Fig. 33) illustrate
one of the common forms of disease to which they are subjected in the
course of sclerotic disease.
[Illustration: FIG. 32.]
[Illustration: FIG. 33.]
The so-called myelitis without softening, or hyperplastic myelitis of
{887} Dujardin-Beaumetz, which is ranked by Leyden and Erb among the
acute processes, properly belongs here. It is characterized by a
proliferation of the interstitial substance, both of its cellular and
fibrillar elements. The nerve-elements proper play no part, or at best
a very slight or secondary one. In the sense that this affection
occurs after acute diseases and develops in a brief period it may be
called an acute myelitis, but both in its histological products and
its clinical features it approximates the sclerotic or chronic
inflammatory affections of the cord. As far as the clinical features
are concerned, this is particularly well shown in the disseminated
myelitis found by Westphal after acute diseases, such as the
exanthematous and continued fevers.