Chapter M: M——, was a stout Irish woman about forty years of age. She had (25)

[Footnote 120: _Archiv für Psychiatrie_, x. p. 243.]

[Footnote 121: _Ibid._, 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 decide {878} whether 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]

[Footnote 122: Zacher, _Archiv für Psychiatrie_, xiii. p. 168; the writer, _Journal of Nervous and Mental Diseases_, April, 1877, and _Insanity, 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.[123] The peripheral limitation of vision may be for both quantitative and qualitative light-perception, but it is not, as a rule,[124] concentric as in tabes, but sector-like.

[Footnote 123: Gnauck says that the central color-blindness may become total, and the red-green blindness extend to the periphery.]

[Footnote 124: Concentric limitation of ten to thirty degrees has been noted for color-perception.]

{879} 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 Gnauck[125] as 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.

[Footnote 125: Of 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.[126] If 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,[127] a 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,[128] Siemens,[129] Schultze,[130] Zacher,[131] and Greiff,[132] {880} the 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.

[Footnote 126: Gnauck, _Neurologisches Centralblatt_, 1884, p. 315.]

[Footnote 127: _Rivista sperimentale di Freniatria e di Medicina leqale_, x. p. 227.]

[Footnote 128: _Archiv für Psychiatrie_, vii. p. 28. He designates this form sclerosis continua multiplex.]

[Footnote 129: _Ibid._, x. p. 135.]

[Footnote 130: _Ibid._, xi. p. 216.]

[Footnote 131: _Ibid._, xiii. p. 168.]

[Footnote 132: _Ibid._, 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.[133] And 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]

[Footnote 133: It 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.]

[Footnote 134: At 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.

MORBID ANATOMY.—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. {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.

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.

{888} CLINICAL HISTORY.—Impairment of motion is the most constant early feature of chronic myelitis; in the transverse form it may be as absolute as in the severest forms of acute myelitis; as a rule, however, it is rather a paresis than a paralysis. The patient is usually able to walk, manifesting the paraparetic gait: he moves along slowly, does not lift his feet, drags them along, makes short steps; in short, acts as if his limbs were heavily weighted. This difficulty of locomotion is preceded and accompanied by a tired feeling before other sensory symptoms are developed. Rigidity of the muscles, like that found in disseminated sclerosis, is a common accompaniment, and may even preponderate over the paresis to such an extent as to modify the patient's walk, rendering it spastic in character. In such cases the muscles feel hard to the touch, and the same exaggerated reflex excitability may be present as was described to be characteristic of spastic paralysis.

If, while the leg is slightly flexed on the thigh, the foot be extended,[149] so as to render the Achilles tendon and the muscles connected with it tense, and the hand while grasping the foot suddenly presses the latter to still further extension, a quick contraction occurs, which, if the pressure be renewed and kept up, recurs again and again, the succession of the involuntary movements resembling a clonic spasm. This action is termed the ankle-clonus or foot-phenomenon. Gowers has amplified this test of exaggerated reflex excitability by adding what he calls the front-tap contraction. The foot being held in the same way as stated above, the examiner strikes the muscles on the front of the leg; the calf-muscles contract and cause a brief extension movement of the foot. It is believed that the foot-clonus and the front-tap contraction are always pathological, but a few observers, notably Gnauck, leave it an open question whether it may not occur in neurotic subjects who have no organic disease. Gowers considers the foot-clonus found in hysterical women as spurious, and states that it differs from the true form in that it is not constant, being broken by voluntary contractions, and does not begin as soon as the observer applies pressure. But I have seen the form of clonus which Gowers regards as hysterical in cases of diffuse sclerosis. With regard to the front-tap contraction, its discoverer[150] admits that it may be obtained in persons in whom there is no reason to suspect organic disease. It is significant only when unequal on the two sides.

[Footnote 149: By extension the approximation of the dorsal surface to the tibial aspect of the leg—what some German writers call dorsal flexion—is meant.]

[Footnote 150: Gowers, _The Diagnosis of the Diseases of the Spinal Cord_, 3d ed., p. 33.]

In severe cases contractures are developed in the affected muscular groups, being, as a rule, preceded by the rigidity, increased reflex excitability, and the thereon dependent phenomena above detailed. These contractures may be like those of spastic paralysis, but usually the adductors show the chief involvement, and sometimes the leg becomes flexed on the thigh and the thigh on the abdomen in such firm contraction that the patient, albeit his gross motor power is not sufficiently impaired, is unable to move about, and is confined to his bed, his heel firmly drawn up against his buttock. It is stated by Leyden that the contracted muscles occasionally become hypertrophied—an occurrence I have not been able to verify. As a rule, some muscular groups are atrophied, though {889} the limbs as a whole, particularly in those patients who are able to walk about, are fairly well nourished.

Pain in the back is a frequent accompaniment of diffuse sclerosis. It is not pronounced, but constant.

The drift of opinion to-day is to regard pain in the spinal region as not pathognomonic of organic spinal affections. It is true that pain is a frequent concomitant of neuroses, and that it is more intense and characteristic in vertebral and meningeal disease; but in denying a significance to pain in the back as an evidence of diffuse disease of the cord itself, I think many modern observers have gone to an extreme. It is particularly in diffuse sclerosis that a dull heavy sensation is experienced in the lumbo-sacral region; and in a number of my cases of slowly ascending myelitis and of tabes dorsalis the involvement of the arms was accompanied by an extension of the same pain, in one case associated with intolerable itching, to the interscapular region. It cannot be maintained that the pain corresponds in situation to the sclerotic area. It is probably, like the pain in the extremities, a symptom of irradiation, and corresponds in distribution to that of the spinal rami of the nerves arising in the affected level.

As the posterior columns are usually involved in transverse myelitis, the same lancinating and terebrating pains may occur as in tabes dorsalis. As a rule, they are not as severe, and a dull, heavy feeling, comparable to a tired or a burning sensation, is more common. A belt sensation, like that of tabes, and as in tabes corresponding to the altitude of the lesion, is a much more constant symptom than acute pains.

Cutaneous sensibility is not usually impaired to anything like the extent found in advanced tabes. It is marked in proportion to the severity of the motor paralysis; where mobility is greatly impaired, profound anæsthesia and paræsthesia will be found; where it is not much disturbed, subjective numbness, slight hyperæsthesia, or tingling and formication may be the only symptoms indicating sensory disturbance; and there are cases where even these may be wanting.

The visceral functions are not usually disturbed. In intense transverse sclerosis of the upper dorsal region I observed gastric crises, and in a second, whose lesion is of slight intensity, but probably diffused over a considerable length of the cerebro-spinal axis, there is at present pathological glycosuria. The bladder commonly shows slight impairment of expulsive as well as retaining power, the patients micturating frequently and passing the last drops of urine with difficulty. Constipation is the rule. The sexual powers are usually diminished, though rarely abolished. As with sclerotic processes generally, the sexual functions of the female, both menstrual and reproductive, are rarely disturbed.

It is not necessary to recapitulate here the symptoms which mark diffuse sclerosis at different altitudes of the cord. With this modification, that they are less intense, not apt to be associated with much atrophic degeneration, nor, as a rule, quite as abruptly demarcated in regional distribution, what was said for acute myelitis may be transferred to this form of chronic myelitis. The progress of diffuse sclerosis is slow, its development insidious, and the history of the case may extend over as long a period as that of diffuse sclerosis. Sooner or later, higher levels of the cord are involved in those cases where the primary focus was low down. {890} In this way the course of the disease may appear very rapid at one time, to become almost stationary at others. Of three deaths which occurred from the disease in my experience, one, in which there were distinct signs of involvement of the oblongata,[151] occurred from sudden paralysis of respiration; a second from a cardiac complication, which, in view of some recent revelations concerning the influence of the tabic process on the organic condition of the valves of the heart, I should be inclined to regard as not unconnected with the sclerosis; and in a third, from bed-sores of the ordinary surgical variety. The malignant bed-sore is not of frequent occurrence in this disease.

[Footnote 151: On one occasion the patient had momentary anarthria, followed a day later by two successive periods of anarthria, lasting respectively about twenty seconds and one minute, one of which was accompanied by diplopia of equally brief duration.]

PROGNOSIS.—The disease may, as in the instances cited, lead to a fatal termination, directly or indirectly, in from three to twenty years. The average duration of life is from six to fifteen years, being greater in cases where the sclerotic process is of slight intensity, even though it be of considerable extent, than where it is of maximum or destructive severity in one area, albeit limited. I am able to say, as in the case of tabes dorsalis, that a fair number of patients suffering from this disease whom I have observed for from two to six years have not made any material progress in an unfavorable sense in that time. One cure[152] occurred in this series, of a patient manifesting extreme contractures, atrophies, bladder trouble, and ataxiform paresis, where the cause was plainly syphilis, and the histological character of the lesion is somewhat a matter of conjecture in consequence. Diffuse sclerosis of non-syphilitic origin—and this may apply also to established sclerosis in syphilitic subjects—is probably as unamenable to remedial treatment as any other sclerotic affection.

[Footnote 152: The patient went, under direction of Leonard Weber and R. H. Saunders, to Aix-la-Chapelle, where this happy result was obtained after mixed treatment had practically failed.]

The same rules of DIAGNOSIS applicable to transverse myelitis of acute onset apply, level for level, to the diagnosis of transverse myelitis of insidious development, the history of the case often furnishing the only distinguishing point between the acute and the chronic form.

The main difference between the diffuse sclerosis and acute myelitis, clinically considered, consists in the gradual development of symptoms in the former as contrasted with their rapid development in the latter disease. Acute myelitis is established within a few hours, days, or at most, in the subacute forms, a few weeks; chronic myelitis requires months and years to become a clearly-manifested disorder. It is the essential correspondence of the symptoms of both conditions, intrinsically considered, which renders it impossible to distinguish clinically and in the absence of a history of the case between some cases of acute myelitis in the secondary period and the processes which are primarily of a sclerotic character.

It is unusual to find the degeneration reaction in myelitis of slow and gradual development. Sometimes there is diminished reaction to both the faradic and galvanic currents, or the so-called middle form of degeneration reaction is obtained from atrophied muscles, the nerve presenting normal or nearly normal irritability, and the muscle increased galvanic irritability and inversion of the formula.

{891} Among the less reliable or accessible points of differentiation between the residua of acute myelitis and the chronic form is the history of the onset and the age of the patient at the time of the onset. Myelitis in young subjects is more likely to be of the acute kind; in older persons it is more apt to be chronic.

In the diagnosis of diffuse sclerosis the question of differentiation from neuroses not based on ascertainable structural disease, such as are called functional, will be most frequently raised. In differentiating between organic and functional spinal disorders all known exact signs of organic disease must be excluded before the case can be considered as appertaining to the latter group. Symptoms of hysteria, nervous exhaustion, and spinal irritation frequently coexist with diffuse sclerosis as well as with the disseminated form; and this is not surprising, for, instead, as seemed at one time to be believed, of the neurotic taint granting comparative immunity against organic disease, it is the reverse, and it is not at all uncommon to find a strongly-marked neurotic diathesis in the family history of sufferers from diffuse sclerosis. That ordinary hysteria, epilepsy, and what is vaguely called nervousness are common features in the ancestral record of the hereditary forms of spinal disease has already been stated in considering those affections.

One of the commoner forms of the grave phase of hysteria is paraplegia.[153] Often muscular atrophy—which ensues from disuse—exaggeration of the deep reflexes, and retention of urine are added to the paraplegia and heighten the resemblance to an organic affection. Its development, though sometimes sudden, often occupies weeks or months, and may be preceded, exactly as in chronic myelitis, by weakness in the legs, and not infrequently by combined ataxia and weakness. It is much more difficult to discriminate here than is generally held or than is enunciated in textbooks. The sufferer from hysterical paraplegia does not always give other indications of the hysterical neurosis, and even if she did show a globus and tenderness at certain points, it is a question whether it could be called a scientific diagnosis which determined the case to be one of functional trouble on these signs alone. More than one error has been committed in this respect. In chronic myelitis retention of urine is less common than incontinence, which is the reverse of hysterical paraplegia. Pupillary symptoms do not occur with the latter affection. If there be sensory anæsthesias, they are bizarre in character or distribution, and do not usually harmonize with the distribution of the paralysis. In most cases moral influences can be exerted so as to increase the power of movement far beyond what would be possible in an organic disease; and while an electrical examination will not always yield positive results in chronic myelitis, yet no case of chronic myelitis with complete or nearly complete paraplegia but will show at least quantitative changes of such extent as to prove beyond doubt that the case is of an organic character.

[Footnote 153: I have observed for two years a stationary brachial diplegia, of undoubted hysterical origin, although the patient had never shown any ordinary hysterical manifestations, and had had no other hysterical symptom than chromatopsia, and that only for a short period. From its long duration, constancy, and the resulting atrophy of disuse it had been regarded as a case of peculiarly limited chronic myelitis.]

There is one point in which spinal and cerebral disease involving the motor tract differs in the majority of cases, which may be utilized in {892} distinguishing obscure affections of the former from those of the latter kind. In cerebral paralysis of any standing the superficial reflexes, such as the cremaster and abdominal reflexes, are usually diminished or abolished, while the deep or tendon reflexes are exaggerated. In spastic conditions due to spinal disease—say sclerosis of any kind affecting the lateral column and leaving the motor nuclei of the anterior cornua unaffected—the deep reflexes are similarly increased, but the cremaster reflex is increased also.[154] This feature of the superficial reflexes is significant in the case of cerebral disease only when unilateral.

[Footnote 154: Attention has been called, I believe, by Westphal, to the fact that the cremaster reflex may not be demonstrable when reflex excitability is at its highest, because the cremaster muscle is already in extreme spastic contraction.]

The initial period of diffuse sclerosis is sometimes confounded with rheumatism—an error less pardonable than in the case of tabes, inasmuch as in diffuse sclerosis the pains are not usually premonitory, but associated with motor paresis. It is erroneous to regard a pain as rheumatic because it is aggravated or relieved by changes in the weather. There are many subjects of myelitis who regard themselves as veritable barometers, and with more justice than most rheumatic patients.

In some cases of chronic alcoholism there are motor weakness and a gait much like that of diffuse sclerosis.[155] It is to be remembered that the solar tickling reflex is very often abolished in alcoholic subjects, and profound diminution of the normal cutaneous sensibility of the leg and feet usually coexist. But unless there is peripheral neuritis—which is an exceptional and, when present, well-marked affection—the absence of profound nutritive changes of the muscle, the presence of the alcoholic tremor, the absence of sphincter and bladder trouble, and the great variation of the symptoms from week to week, and even from day to day, serve to distinguish the alcoholic spinal neurosis from myelitis.

[Footnote 155: Wilks' alcoholic paraplegia.]

The Secondary Scleroses.

In studying the lesions underlying the symptoms of organic spinal disease, the occurrence of fascicular scleroses, secondary to such disease and due to the destructive involvement of nerve-tracts, was repeatedly noted. Türck may be regarded as the discoverer of these degenerations, and the reliability of this old observer may be inferred from the fact that one bundle of fibres liable to individual degeneration still goes by his name, and that, as far as he was able to discriminate between the various paths which secondary degenerations follow through the cerebro-spinal fibre-labyrinth, his statements have not been materially modified by more recent investigators, such as Bouchard, Vulpian, and Westphal.

The discovery by Meynert that the great cerebro-spinal tracts attain the white color which they owe to the development of myelin around their component axis-cylinders with advancing maturity, and that the tracts of noblest, and therefore most intelligent, function were the last to show this sign of maturity, was greatly extended by Flechsig, who found that each tract receives its myelin at a definite period of intra-uterine life, the lowest or the nerve-roots first; then the short or intersegmental or—as {893} the physiologist may call them—the automatic tracts; then the long or controlling tracts; and last, the associating tracts of the cerebral hemispheres which mediate the complex relations underlying mental action. It was this discovery which gave a new impulse to the study of the secondary affections of the cord and brain. The accuracy with which secondary degeneration follows the lines marked out by the normal course of the tract is as great, diminishing when the tract diminishes, changing its position or direction and decussating where the latter changes its direction or position or decussates, that it constitutes not alone an interesting subject for pathological study, but has become one of the most reliable guides of the cerebral anatomist. It is of great importance to the pathologist to be able to differentiate between the primary disease and its secondary results, and, as the controversy concerning the so-called system diseases shows, even the most studious observers are uncertain in this direction in many cases.

MORBID ANATOMY.—Secondary degeneration manifests itself by a discoloration of the affected nerve-tract, which accurately corresponds in area to the normal area of that tract. The more recent the degeneration the less pronounced is this change. In advanced cases the color may be a dark gray, in moderately old ones a reddish or yellowish gray, and in those of very recent origin no change may be visible to the naked eye. It is claimed, however, that even here a loss of translucency of the white substance, giving it a sort of cheese-like opacity, may be detected. On hardening the specimen containing the degenerated tract in Müller's fluid or a simple bichromate salt solution, the affected area, instead of appearing dark on section in contrast with the gray substance—which in such preparations appears yellowish or a light brown—contrasts with the former by its lighter tinge. This contrast is observable even in cases where the naked eye was unable to detect the change in the fresh specimen. It can be sometimes found as early as the tenth day after the primary lesion, and is apparently simultaneously developed in the whole length of the nerve-tract affected.

The minute changes characterizing secondary degeneration begin in the essential conducting elements, the axis-cylinder, which exhibits a finely granular or molecular disintegration, and disappear. According to Homén, it shows an initial swelling and a failure to stain properly before this. The myelin then follows suit: it becomes fragile, forms variously-shaped globules, and also disappears, and together with this a nuclear proliferation is noticed in the interstitial substance; fatty granule-cells are observed in large numbers, and manifest a tendency to accumulate in the perivascular districts. These cells are not permanent; their gradual diminution is accompanied by a proliferation of the interstitial tissue, which ultimately appears as a pure connective substance composed of fine fibrillæ arranged in undulating bundles. The entire process may be not inaptly compared to an hypertrophy of the interstitial substance resulting from overfeeding of its cellular elements by the morbid pabulum furnished through the disintegration of the nervous substance proper.

The disappearance of the nerve-tubes, and the formation of a new tissue in their place, which, like all tissues of the same character, undergoes shrinkage, leads to considerable deformity in the shape of the part which is the site of secondary degeneration. This is seen in the {894} accompanying figure, where in an old-standing secondary degeneration of one interolivary layer the corresponding half of the medulla is greatly reduced in diameter as compared with the other side (Fig. 34), and the entire raphé is distorted. When one side of the cord is the site of such a change a similar asymmetry results.

According as the original lesion is incompletely or completely destructive, a larger or fewer number of axis-cylinders may be found preserved in the sclerotic tissue. It is not yet determined whether in some instances these fibres may not represent an admixture from another source than are comprised in the mainly affected tract.

Secondary degenerations are classified as ascending and descending. An ascending degeneration is one which is found situated brainward of the primary lesion; a descending one is found caudad of the lesion. It was once maintained that the direction of the secondary degeneration was constant for each individual tract. This seems to be true for a few. Some tracts, particularly in the brain, degenerate on both sides of the lesion, as I showed with regard to the interolivary layer.