SYNONYMS.—Multiple cerebro-spinal sclerosis (also spinal and cerebral form), Insular cerebro-spinal sclerosis, Focal sclerosis, Multilocular sclerosis; Herd-sklerose (Ger.); Sclerose en plaques disseminées, Sclerose en plaques generalisées (French).
The occurrence of disseminated patches of gray degeneration in the nervous axis was observed by Cruveilhier and Türck, but they regarded the affection rather from the anatomical than the clinical standpoint, and it was left for Frerichs to recognize its important position among the chronic affections of the brain and spinal cord. The earlier German investigators who followed him were cautious in generalization, and it was not until Vulpian, Charcot, and their followers announced the discovery of infallible diagnostic criteria that disseminated sclerosis received that attention at the hands of the profession which it merits. But the more thorough researches made during the last two decades have shown that this announcement was premature. The best authorities recognize the existence of a large number of cases in which the supposed pathognomonic signs of disseminated sclerosis are absent, notwithstanding the existence of characteristic lesions, and thus the more cautious earlier investigators are justified in the reserve they had maintained.
It is in perfect harmony with the irregular location of the disease and the lack of any constant rule governing the distribution of the sclerotic foci that there is no constant clinical picture by which its existence can be accurately determined in all cases. The diagnosis of tabes dorsalis, of spastic paralysis, of amyotrophic lateral sclerosis, and of transverse myelitis rests on exact and constant signs, but that of disseminated sclerosis does not. The dictum of Charcot, that there is always intention tremor and nystagmus in disseminated sclerosis, has long been overthrown. Well-determined cases are on record by De Fleury and Westphal, and a number have been observed by myself, where there was notremor or no increased tremor with intended movement, and no nystagmus, nor any other of the pathognomonic symptoms so considered by Charcot and his followers.
The morbid process of disseminated sclerosis consists in the development of patches of sclerosed tissue, scattered apparently without any regularity or rule through the brain and spinal cord. They are the results of insidious inflammatory changes. The symptoms marking their presence may include nearly every known focal and general symptom studied by neurologists, varying with the number, size, and distribution of the foci. Usually there is some disturbance of motility, both ataxic and paretic; in the majority there is tremor, which in a large proportion of cases is of a distinctive character, and disturbance of the functions of the cranial nerves, amblyopia, color-blindness, mental enfeeblement; and, above all, apoplectiform seizures are frequent.
Some writers discriminate between cases in which the lesions are limited to, or most intense in, the spinal cord, and those in which the brain is chiefly or exclusively involved, and hence they speak of a spinal, a cerebral, and a cerebro-spinal form. This discrimination is not sufficiently supported by clinical evidence to be of any practical value. Each case is to be studied by itself during life and after death, and to be regarded as one of a series in which the lesion may be concentrated in any one segment of the cerebro-spinal axis. It seems that when the sclerotic foci are limited to or chiefly located in the spinal cord, the clinical signs are less pronounced than where the brain is seriously involved; those cases in which the symptoms are latent, or so vague that they cannot be distinguished from spinal irritation or spinal exhaustion, have been found to be of the spinal type. The cases of this character thus far observed are not sufficiently numerous to justify the creation of special subdivisions.115
115According as the formation of the sclerotic foci preponderates in a given segment of the nervous axis, the early signs of the disease may consist in disturbances of the cerebral or the spinal functions, and we may speak accordingly of a cerebral or spinal invasion type. But the principle of classification adopted by several recent writers, which would rank the spinal type among the spinal diseases, the cerebral type among the cerebral diseases, and which is compelled to erect a third category for the reception of the cerebro-spinal type under the name of cerebro-spinal diseases, is a bad one. Modern pathology recognizes the existence of affections which involve whole fibre-systems, which are intracerebral in one and intraspinal in other parts of their course, such as tabes and amyotrophic sclerosis, which would therefore have to rank among the cerebro-spinal, and not among the spinal affections, with which the authors referred to classify them.
CLINICALHISTORY.—Prodromal.—Disseminated sclerosis is usually inaugurated by a long initial period in which the symptoms are not characteristic, and in which, unless there be decisive pupillary or optic-nerve symptoms present, the nature of the disease is not recognized. The patients feel weak and tired; walking is difficult, and an element of unsteadiness suggests the development of a tabic disorder. In other cases ankle-clonus is found and tremor of the foot on extension (dorsiflexion); it is discovered that the unsteadiness is due to weakness or to rigidity of the muscles, and thus the impression of a developing spastic paralysis may be created. But symptoms on the part of the cranial nerves soon show that the case is one of disseminated sclerosis. Sometimes a marked belt sensation is developed, and other forms of paræsthesia are not uncommon; nay, the symptoms of spastic paralysis and tabesdorsalis may be mingled. Diplopia of the same transitory character as in tabes usually accompanies the gradually-developing speech trouble. The reflex and mechanical excitability of the muscles is increased in all cases where the lateral column is extensively involved and the gray substance of the cord is—as it usually is in the main—intact. In some cases a slight tap on the knee when held in the position required to demonstrate the knee-jerk produces oscillatory movements of the limb; as the patient endeavors to suppress these they become more violent, extend to the trunk and head, and may eventually involve the opposite side. In those cases which show the cerebral-invasion type headache, vertigo, and speech disturbance, temporary darkening of the visual field, and loss of memory are the earliest symptoms directing attention to the existence of serious disease.
Whether the spinal or the cerebral symptoms preponderate, they continue increasing slowly and with temporary variations, which are particularly marked in the cerebral-invasion type. As a rule, the sensory disturbances are not pronounced at this time, but later, after the initial symptoms have existed for a few years, they become intense, and often extremely distressing. Those most complained of by the patient are neuralgic, lancinating, and other pains. The lancinating pains are, as a rule, not as severe as those of tabes dorsalis, but they are apt to be associated with a dull heavy pain which is located in a whole extremity, referred to the deep structures, and very persistent. This diffuse pain sometimes occupies all of the lower half of the body. As in tabes, the pain may be regarded the forerunner of anæsthesia, which rarely, however, reaches a high degree or an extensive distribution. Its distribution, like that of the other peripheral symptoms of disseminated sclerosis, is commonly irregular. Like the motor disturbance, which at this period consists in a combination of paretic and spastic—occasionally of ataxic—symptoms, it is most marked in the lower extremities.
In the majority of cases there is a peculiar tremor, which usually presents the character to which Charcot directed attention—namely, that it increases when the patient attempts to carry out a voluntary movement, and disappears, or at least diminishes, when the muscles of the part in question are at rest. This is the important symptom known as the tremor on intended movement or intention tremor. One of the time-honored means of testing it is to order the patient to take a glass of water and pass it to his mouth. While he reaches out for it some oscillatory unsteadiness is observed, but on grasping, this is increased, and on raising the glass the oscillations increase till he spills the water; if he succeeds in carrying it to his mouth, there is a clattering against the teeth, and but for the steadying aid of his mouth he would throw it aside by the violence of the disturbing movements. In incipient cases this intention tremor is best shown with delicate movements, and the more distinctly the more slowly they are performed. It has been suggested that the peculiar character of the lesion of disseminated sclerosis has some relation to the intention tremor. It is a remarkable feature of the morbid process that it leaves the axis-cylinder comparatively intact, beyond any other form of myelitis or encephalitis. The myelin, however, is destroyed, and the consequence is that the naked axis-cylinders lie in a newly-formed connective tissue, which has not the same faculty the myelin has ofisolating the nervous impulses conducted through the axis-cylinders. The result is, that when a nervous impulse, such as a voluntary movement, travels through a sclerotic focus, it may become deflected to neighboring fibres going to another muscle or muscular bundle than the one intended to be innervated. An unintended motion results; the patient makes a stronger effort, intended for the right channel, but again it slips off, to use a coarse simile, and thus a number of erroneous messages are transmitted, and an equal number of disturbing motions respond to these messages.
Whether this histological explanation be correct or not, the tremor is probably due to the lesion of the peduncular tracts of the brain. At least, this is rendered plausible for the tremor on intended movement, which indicates an interference with the transmission of voluntary impulses. Whether, as Pasternatzky116claims, the extreme muscular oscillation seen in advanced cases is due to irritation of the cortical motor fields, it is impossible to decide. No strong evidence can be adduced in favor of his view. A few cases have been described (Schüle, Jolly, and Greiff); and, in my opinion, such are far more numerous than is usually supposed, where the tremor did not have the so-called characteristic feature of ceasing in conditions of rest, claimed by Charcot, but continued as in paralysis agitans.117A collection of cases by Erb, Ordenstein, and Greiff shows clearly that with a typical dissemination of sclerotic foci in the cord the tremor on intended movement may be entirely absent, while no case is known where the crus and pons were involved to a similar extent in which it was absent. So it seems that a cerebral lesion is necessary to produce this symptom in its characteristic form.
116Jahrbücher für Psychiatrie, iii. 3, 1882.
117For several years I had been puzzled by the fact that Charcot's formula failed to correspond to the clinical picture in the majority of cases, and I registered such cases as incipient multiple sclerosis or as a connecting group between paralysis agitans and that disease.
In advanced cases of disseminated sclerosis the intention tremor becomes generalized; previously noticed, perhaps, only in one arm, it now affects all the limbs and the muscles which maintain the trunk and head in static equilibrium. The result is, that even when the patient is at rest sitting in a chair, his body, and particularly his head, are agitated by a violent and coarse tremor, which is increased on rising and walking, as well as on attempting to use the hands. Delicate mechanical occupations become impossible, and the handwriting shows a characteristic change, the forward strokes of the letters and the curvilinear back strokes, as well as the dots and crosses, registering the tremor of the hand in their peculiar irregularity.
The speech is usually rough and broken, and sometimes enunciation is impeded in a peculiar way, the patient appearing to scan his words. Krause118has found relaxation of the vocal cords in a remarkable degree to underlie the change in phonation. The scanning of speech appears to be due to impeded innervation of the lips and tongue. When the patient is told to protrude his tongue, he does so either in spasmodic instalments of movement or with a sudden jerk after delay. The same delay and apparent halting are noticed in the mimic expressions that are observedin speech. The features sometimes express an emotion opposite to the one experienced by the patient.119
118Neurologisches Centralblatt, 1885.
119This symptom is found where there are other reasons for suspecting the existence of large foci in the pons. I have observed it in one case of tumor of this region, and one of a focal disease of undetermined anatomical nature in the same location, in a remarkable form. In the former case the patient not only exhibited the facial contortions of hearty laughter when she felt as if about to break out in tears, and broke out in tears when she felt amused, with perverse regularity, but both emotional manifestations occurred simultaneously. The other case is still under observation. There was complete anarthria in the first, and nearly complete anarthria in the second case—a fact not unrelated to the inferred site of the lesion, and which may be associated with the fact that where the perverse mimic expression occurs in disseminated sclerosis the speech-disturbance often has an anarthric character.
Whether diplopia occur as an early symptom or not, nystagmic oscillation of the eyeballs is commonly found in the developed affection. This nystagmus is usually universal, noted in associated movements in every direction, and aggravated by excitement, by constrained positions, and by any act of innervation of the eye-muscles. It may be looked upon as an intention tremor of the latter, and attributed to sclerotic foci in the cerebral axis, particularly in the tegmental part of the pons varolii.
The deep reflexes are in some cases but slightly affected. Where spastic phenomena preponderate, they are exaggerated, and where the posterior root-zones are involved in the lesion, they may be, as in tabes dorsalis, diminished or absent. The nutrition of the muscles is not impaired in the early stages, and indeed most functions which depend for their proper performance on the intact condition of the gray substance, such as the power of retaining the urine, micturition, and the functions of the rectum, are properly performed at this period. The cutaneous reflexes are not markedly abnormal in the majority of cases. They sometimes become diminished in the last stages.
In cases regarded as disseminated scleroses and similar disorders approximating the combined form of sclerosis, Westphal120noticed a paradoxical muscular phenomenon which is the reverse in action of the tendon reflexes. It is best observed in the tibialis anticus: if the foot be extended (dorsiflected)—in other words, if the origin and insertion of this muscle be approximated—the muscle contracts firmly, keeping the foot in the enforced position, as if frozen into that attitude. The same occasionally occurs if the patient voluntarily extends his foot. Westphal observed the same phenomenon in the disease described by him in which the symptoms of disseminated sclerosis are present, but the corresponding lesion is not visible.121
120Archiv für Psychiatrie, x. p. 243.
121Ibid., xiv. p. 132. It is a noteworthy fact that this sign has been observed by its discoverer also in paralysis agitans.
In a number of cases the mind becomes involved. Simple dementia is the commoner condition, and some indication of passive mental enfeeblement is found sooner or later in the history of the disease in the majority of cases. In addition, there may be a morbid emotional condition, usually in the direction of depression. I have been struck by the frequent association of a melancholic state with large foci in the oblongata. When it is borne in mind that the patient exhibits tremor and speech-disturbance in addition to his mental trouble, it will be understood that with some modifications of the typical signs the case may simulate one of paretic dementia; and there are cases in which it is exceedingly difficult to decidewhether they belong to an aberrant type of disseminated sclerosis or to the sclerotic type of paretic dementia. There are some which constitute veritable connecting-links between the two affections.122
122Zacher,Archiv für Psychiatrie, xiii. p. 168; the writer,Journal of Nervous and Mental Diseases, April, 1877, andInsanity, its Classification, Diagnosis, and Treatment, p. 240.
Like tabes dorsalis, the progress of disseminated sclerosis is often marked by episodes. Some of these differ in no way from the visceral crises of posterior-column sclerosis; every form of these symptoms found with that affection may occur in the present one, while episodes involving the cerebral functions are much more common. The latter manifest themselves as apoplectiform or epileptiform seizures. They are preceded by headache and vertigo, or, if these be continuously present, by an aggravation of them; then unconsciousness develops, either accompanied by convulsions or not, and the face is flushed, the pulse full and frequent, and the temperature raised. Consciousness returns in a few hours or a day, the attack rarely lasting more than two days, and it is found that the patient is hemiplegic. But, unlike the hemiplegia found after vascular rupture, embolism, or structural cortical disease, it is rapidly recovered from.
In a case of Gnauck's an attack of scotoma scintillans, associated with a noise of thunder in the right ear and pricking pains on the right side of the face, preceded anæsthesia and the formation of a small defect of the visual field.
There is a close resemblance between these apoplectiform and epileptiform seizures and those of paretic dementia, not alone in clinical character, but also in the surprisingly complete and rapid recovery from the more serious symptoms. But just as in paretic dementia, especially in its advanced stage, each seizure leaves the patient somewhat more impaired in mind and body than he was before, so it is in disseminated sclerosis; each attack marks a step forward in the invasion of the morbid state.
Eye-trouble is much less frequently a premonitory sign of disseminated sclerosis than of tabes. A few such cases are on record. Magnan observed the development of the characteristic symptoms of disseminated sclerosis fourteen years after an amaurosis which followed typhoid; and Gnauck reports another in which first a right ptosis, and then a right amblyopia, preceded the ordinary symptoms. In exceptional cases this premonitory eye-trouble may, like that of tabes, rapidly lead to extreme amblyopia or even amaurosis. The visual disturbances are remarkable for their rapid changes. They appear within a short period, attain their maximum rapidly, and may occasionally retrograde as quickly. They develop under two forms—the central and the peripheral scotoma, or, rather, limitation of the visual or color field. The former, like the amblyopia of alcoholic and nicotine intoxication, consists in an inability to differentiate between red and green in the centre of the visual field. It never, in my experience, proceeds as far as the toxic amblyopias; that is, to the complete extinction of vision.123The peripheral limitation of vision may be for both quantitative and qualitative light-perception, but it is not, as a rule,124concentric as in tabes, but sector-like.
123Gnauck says that the central color-blindness may become total, and the red-green blindness extend to the periphery.
124Concentric limitation of ten to thirty degrees has been noted for color-perception.
The atrophy of the optic nerve in disseminated sclerosis is typically partial, in the majority of cases manifesting itself as a sharply-marked discoloration of the temporal half of the papilla. In others the nasal half of the papilla also becomes discolored, but so much less intensely that the difference between the earlier involved and later involved portions is quite easy. It is doubtful whether the subjective visual disturbance is always an indication of the extent to which the optic nerve is involved. There are good reasons for believing those amblyopias and limitations of the field of vision which show marked remissions and exacerbations to be due to some dynamic central condition involving the visual centres and tracts. Thus it has been observed that almost total amaurosis occurred after an apoplectiform attack, to disappear later on. Occasionally the amblyopia is bilateral and the optic-nerve lesion unilateral. The frequency of this affection is stated by Gnauck125as follows: In one half the cases there is diminished vision, and in half this half optic-nerve atrophy with limitation of the visual field. It is only in exceptional cases that an optic neuritis can be determined to have preceded the atrophy.
125Of 50 cases, 22 had no visual trouble, 8 showed simple diminution of perception, 5 added limitation, and 15 changes of the optic disc, a case of total atrophy and amaurosis being included in the latter.
The pupils are perfectly normal in some cases; in others myosis of the spinal type is observed; and this I found to be nearly constant in all advanced cases. Irregularity in outline and inequality exist in a small proportion, and reflex iridoplegia is found in about 10 per cent. of the cases.
Thus far, the symptoms which occur either in a majority or in a large percentage of cases have been enumerated. The typical course of disseminated sclerosis may be stated as consisting in their gradual development and intensification, covering a period of from four to twenty or more years. There are a number of cases in which so many of the symptoms regarded as typical are either absent or where some given symptom-group preponderates over the others to such an extent that they require special mention.
It is not difficult to understand that disseminated sclerosis may ape other forms of spinal disease. Its symptoms depend on the location of the sclerotic foci. If these are situated chiefly in the crossed-pyramid tract, spastic phenomena will predominate, and the case may resemble a spastic paralysis.126If they be distributed in both the posterior and lateral columns, the symptoms will resemble those of a combined form of sclerosis in which the tabic and spastic signs are associated, as far as they do not, in the nature of the case, neutralize each other. This was well shown in a case of De Fleury's. Not infrequently an unusually large focus involves the entire transverse section of the cord, and the case becomes complicated by the symptoms of a transverse myelitis. In such a case, described by Rovigli,127a large transverse focus in the cord had led to ascending secondary degeneration in the column of Goll and descending degeneration of the crossed pyramid tract. In a large series, instances of which are related by Kilian,128Siemens,129Schultze,130Zacher,131and Greiff,132the disseminated foci were complicated by a diffuse lesion distributed like that of a diffuse or fascicular myelitis; and there seems to exist every connecting-link between ordinary chronic myelitis, strictly so called, and disseminated sclerosis.
126Gnauck,Neurologisches Centralblatt, 1884, p. 315.
127Rivista sperimentale di Freniatria e di Medicina leqale, x. p. 227.
128Archiv für Psychiatrie, vii. p. 28. He designates this form sclerosis continua multiplex.
129Ibid., x. p. 135.
130Ibid., xi. p. 216.
131Ibid., xiii. p. 168.
132Ibid., xiv. p. 287.
Not only does disseminated sclerosis occasionally imitate or approximate the regular (fascicular) affections of the cord, as well as diffuse cerebro-spinal affections, but it may appear under the mask of a nuclear oblongata paralysis.133And cases are on record where, in addition to the disseminated sclerosis, there occurred sclerotic atrophy of an entire hemisphere or of its capsular tracts, thus leading to a hemiplegic resemblance of the motor paralysis. In my experience the cases presenting the type of a nuclear oblongata paralysis run a more rapidly fatal course than others. The shortest history in my series, one of four years, was of such a case. A number of instances are on record by careful observers—and are probably much more numerous than is commonly suspected—where no decisive evidence of spinal or cerebral disease could be detected during life, and yet disseminated foci of sclerosis existed in the nerve-centres. In such cases the symptoms may be in the direction of simple nervous prostration, more commonly of spinal irritation. I have now under observation a case which for years had been regarded as one of spinal irritation, and which made that impression on me until I discovered the existence of optic-nerve atrophy, which was the only indication that the symptoms depended on gross structural disease.134
133It is customary to speak of symptoms referable to the oblongata as bulbar. The designation bulbus rachidicus is now obsolete, and just as we speak of a capsular hemiplegia, a pons paralysis, or a spinal hemiplegia, so we should say an oblongata paralysis, discriminating between the nuclear, the neural, and the tract affections by means of a prefix.
134At present the symptoms of disseminated sclerosis are unmistakable. Cases are mentioned by Strümpell and others in which they remained indecisive throughout.
Among the anomalous forms of disseminated sclerosis there is one which is characterized by the preponderance of paraplegia and contractures in a combination which is usually found in spinal diseases of a different type. The coexistence of dementia, however, usually enables the observer to determine that the lesion is both cerebral and spinal, although those signs which might enable him to decide the disseminated focal character may be absent.
MORBIDANATOMY.—In advanced cases of disseminated sclerosis the lesion 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.Bourneville135has 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.
135Mouvement 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 ofthe 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.136I 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 figure137represents 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
136Archiv für Psychiatrie, xiv. p. 286.
137Ibid., xiv., Plate ii. Fig. 5.
138Attention was first called to the artificial nature of these bodies by the writer in theJournal of Nervous and Mental Diseases, October, 1877, and a more accurate description was given in theChicago Medical Reviewof 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 ofZiemssen'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 processwhich 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 Pollak139discovered 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.140The 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. Pelizæus141reports 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.
139Deutsches Archiv für klinische Medizin, Bd. xxiv. p. 404.
140Ibid., vol. xxiii. p. 442.
141Archiv für Psychiatrie, xvi. p. 698.
CAUSES.—Disseminated sclerosis may develop as a sequel of an acute myelitis. An excellent observation of Singer,142in 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, andsclerotic foci of probably later date were found in the neighboring segments of the cord.
142Prager medizinisch Wochenschrift, 1885, No. 8.
The myelitic affection discovered by the same observer143to 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
143Archiv 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.
144Lo 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.145Fright has been distinctly connected with the outbreak of the disease in a number of cases.146There 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.
145The 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.
146A 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,147and, 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.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.
147Charcot'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.
DIFFERENTIALDIAGNOSIS.—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,148in 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.
148Archiv 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.