Volume 5 — DISEASES OF THE NERVOUS SYSTEM. (continued 29)

⁷¹ A fall from a chair, striking on the back of the latter, while endeavoring to keep a row of books from coming down in one case, and the shock of the Ashtabula disaster in the other. The latter patient, the same one who is referred to as describing the electric-storm sensation in an earlier part of this article, had his foot amputated in consequence of that disaster; but, like one of the characters in Jacob Faithful, who felt his toes when the weather changed, though he left both legs at Aboukir, he felt the terrific pains of the disease in the absent foot as distinctly as in the other. Dumenil and Petit (Archives de Névrologie, ix. Nos. 25 and 26) relate cases in which a spinal concussion was the only ascertainable cause.

A number of toxic agents have been charged with producing tabes: thus, Bourdon maintains this of absinthe; Oppenheim attributes one case to poisoning by illuminating gas, the exposure to its influence being immediately followed by a gastric crisis, and this by a regulation tabes.⁷² It is supposed that most of the poisons acting on the cord in this or a similar way, such as arsenic, cyanogen,⁷³ barium, and chloral,⁷⁴ do not produce a spinal lesion directly, but through the medium of a secondary cachexia. Of no agent is the effect in producing tabes so well studied as ergot of rye. It had long been known that ergot-poisoning provoked certain co-ordinating, motor, and sensory disturbances, but it was left for Tuczek⁷⁵ to show that this vegetable parasite produces a lesion of the spinal cord which in its character and distribution apes typical posterior sclerosis so closely as to justify the designation of a tabes ergotica. Possibly, pellagra, which is sometimes manifested in a similar way,⁷⁶ may yet be shown to have a like influence.

⁷² Archiv für Psychiatrie, xv. p. 861.

⁷³ Bunge, Archiv für experimentelle Pathologie, xii.

⁷⁴ Transactions of the Clinical Society of London, xiii. p. 117, 1880.

⁷⁵ Archiv für Psychiatrie, xiii. p. 148.

⁷⁶ Bouchard, “Étude d'Anatomie pathologique sur un Cas de Péllagrie,” Gaz. méd. de Paris, 1864, No. 39.

Among the occasional and exceptional causes of tabes, Leyden and Jolly mention the puerperal state; Bouchut, diphtheria; and several instances are recorded in which psychical shock was responsible for the outbreak of the disease. In a small number of cases I found that mental worry and anxiety coincided with the period of presumable origin of the disease.

Age seems to have no special determining influence. It is true that most sufferers from this disease are men in the prime of life or in the period following it. But it is precisely at these periods that the exposure to the recognized causes of tabes is greatest. It seems as if there were very little liability to the development of tabes after the fiftieth and before the twenty-fifth year; still, some cases of infantile tabes have been recorded.⁷⁷

⁷⁷ Excluding the so-called family form of locomotor ataxia: 6 rather imperfectly described cases are cited by Remak (loc. cit.), and 3 additional ones related by himself. Of the latter, 2 had hereditary syphilis, and of 1 the father was both syphilitic and tabic.

In the majority of cases tabes is due to a combination of a number of the above-mentioned factors. The majority of tabic patients in the middle and wealthy classes have had syphilis, and of these, in turn, the majority have been guilty of sexual excesses or perverted sexual acts, while excesses in tobacco and of alcohol are often superadded. Among the poorer patients we find syphilis less frequently a factor, but still present, according to various estimates, in from 20 to 60 per cent. of the cases. Excesses in tobacco play a lesser, and excesses in alcohol a larger, part in the supplemental etiology than in the other class, while exposure to wet and cold and over-exertion are noted in the majority; indeed, in a fair proportion they are the only assignable causes.

DIAGNOSIS.—The recognition of advanced tabes dorsalis is one of the easiest problems of neurological differentiation. The single symptom which has given one of its names to the disease—locomotor ataxia—is so manifest in the gait that even the sufferers from the affection learn to recognize the disease in their fellow-sufferers by the peculiar walk.⁷⁸

⁷⁸ At present I have six tabic patients under treatment, who are acquainted with each other, and who have made each other's acquaintance in the singular way of addressing one another on the strength of mutual suffering at Saratoga, at the Hot Springs of Arkansas, and in New York City.

Although there are other chronic affections of the cord which manifest ataxia, such as myelitis predominating in the posterior columns, disseminated sclerosis in a similar distribution, and some partially recovered cases of acute myelitis, the gait is not exactly like that of tabes. The uncertainty may be as great, but the peculiarly stamping and throwing motions are rarely present in these affections. The clinical picture presented by the ataxic patient, aside from his gait, is equally characteristic in advanced cases. Absence of the knee-jerk and other deep reflexes, the bladder paralysis, sensory disturbance, delayed pain-conduction, trophic disturbances, and reflex iridoplegia are found in the same combination in no other chronic disorder of the cord. It is supposable that an imperfect transverse myelitis in the lumbar part of the cord might produce the reflex, ataxic, sensory, sexual, and vesical symptoms of ataxia, but the brachial symptoms found in typical tabes as well as gastric crises would be absent. The pupillary symptoms would also fail to be developed, in all probability. It is to be remembered that only fascicular cord affections can produce a clinical picture exactly like that of tabes in more than one important respect. In analyzing the individual symptoms of the early stage the more important differential features can be most practically surveyed.

The discovery of no single symptom of tabes dorsalis marks so important an epoch in its study as Westphal's observation that the knee-phenomenon is usually destroyed in it. Had this symptom not been detected, so Tuczek admits, ergotin tabes would have eluded recognition.⁷⁹ It was claimed by a majority of neurologists at first that this jerk is always abolished in tabes, but it is now recognized that there are exceptions, as is shown by cases of Hirt,⁸⁰ Westphal, and others, not to mention some well-established cases of its return during the progress of the disease.

⁷⁹ It is not to be wondered that, like most new discoveries, that of the pathological changes of the patellar reflex should have been made the basis of premature generalizations. The attempt of Shaw (Archives of Medicine) to establish a relation between disturbances of the speech-faculty and an increased knee-jerk has not met with any encouragement or confirmation, and has been rebutted by Bettencourt, Rodrigues (L'Éncephale, 1885, 2), and others.

⁸⁰ Berliner klinische Wochenschrift, 1886, 10.

The knee-phenomenon is supposed to be a constant attribute of physiological man. It is difficult to elicit it in children, and frequently impossible to obtain it in young infants. It also disappears in old age, without having any special signification, except that this occurrence seems to be in direct relation to senile involution. In 2403 boys between the ages of six and thirteen years, Pelizæus⁸¹ found it absent in one only. It is customarily elicited by having the patient while sitting in a chair throw one leg over the other; hereupon the ligamentum patellæ is struck a short, quick blow. Under physiological circumstances the leg is jerked outward involuntarily after an interval of about one-fifth of a second—one that is scarcely appreciated by the eye. But if it be found absent by this mode of examination, the case is not to be regarded as one of absence of the jerk without further ado. The patient is made to sit on a table, his legs dangling down and his body leaning back, while he clenches his fists. By this means the jerk will often be produced where it appears to be impossible to evolve it by the ordinary means. It is also well to try different parts of the ligament, and when comparing both sides to strike on the corresponding spot and in the same direction. Many subjects who appear to be irresponsive will respond very well when a point on the outer edge near the tibial insertion is percussed. The elbow reflex, which has the same signification for the upper extremity that the knee-jerk has for the lower, is elicited in the same manner.

⁸¹ Archiv für Psychiatrie, xv. p. 206.

The absence of the knee-jerk is usually regarded as a suspicious circumstance in persons of middle life; and where it can be demonstrated that it has been present years previously and subsequently disappeared, it is looked upon as of grave import. I, however, published three years ago an authentic case of disappearance of the knee-jerk in a physician now in active practice in New York City who to this day enjoys excellent health and has developed no other sign of spinal disease. The knee-jerk is also abolished in a number of conditions not belonging to the domain of strictly spinal diseases, such as diphtheria, diabetes, secondary syphilis, and severe cases of intermittent fever. Of these, diabetes alone can be possibly confounded with tabes dorsalis. The difficulty of differentiating early tabes and diabetes is enhanced by the fact that on the one hand there are often ataxic symptoms with diabetes, while on the other both glycosuria and diabetes insipidus may complicate tabes. Senator, Frerichs, Rosenstein, Leval-Piquechef, Charcot, Raymond, Demange, Féré, Bernard, and T. A. McBride all recognize the occasional presence of the ataxic gait, paræsthesia, belt sensation, and even fulgurating pains, besides the abolition of the jerk, in diabetes mellitus.⁸² In pure cases of diabetes, however, I am not aware that spinal myosis or the reflex paralytic pupil has been found.

⁸² I have now under observation a case of myelitis with predominating sclerosis of the posterior columns of five years' standing in a merchant who has been under antidiabetic treatment for eleven years.

Abolition of the knee-jerk is found in all organic diseases of the spinal cord which destroy any part of the neural arch at the upper lumbar level, where the translation of the reflex occurs, whether it be in the posterior root-zones or in the gray matter of the origin of the crural nerves. Thus, acute or chronic myelitis, disseminated sclerotic foci of this level, may cause obliteration of the reflex at any time of the disease; so may acute or chronic anterior poliomyelitis, neoplasms, and amyotrophic lateral sclerosis of the anterior cornua type if the destruction of the anterior cornua be complete enough. It is also found abolished with all diseases of the peripheral nerves—traumatic and neuritic—which produce absolute motor paralysis of such nerves.

Among the sources of error possibly incurred in examining for this important symptom the presence of rheumatism is one. There is sometimes a tetanic rigidity of the joints which prevents the reflex from becoming manifest. It is also sometimes found to be absent immediately after severe epileptic attacks, according to Moeli.⁸³

⁸³ In three examinations after severe attacks of epilepsy I found it normal.

The condition of the pupil is perhaps a more constant sign of early tabes than the loss of the knee-jerk; at least it has been found well marked in cases where the jerk had not yet disappeared. It may be regarded as a rule in neuro-pathology that wherever reflex iridoplegia is at any time accompanied by other oculo-motor disturbance, it is either of spinal origin or in exceptional cases due to disease of the pons varolii. The peculiar character of the pupillary disturbance of tabes furnishes us with a criterion for distinguishing it from one affection which in common with it exhibits loss of the knee-jerk—diphtheria. In diphtheria there is also a reflex disturbance of the pupil, but it is the reverse of that of early tabes. In the latter reaction to light is lost, but the accommodative contraction power is retained; in diphtheria accommodative contraction power is lost, but reaction to light is retained.

The bladder disturbance has already been described. It is found as a marked symptom so prominently in no other systemic affection of the cord, and in few of the non-systemic forms, of sclerosis. In none of these is it associated with absence of the patellar jerk, reflex iridoplegia, and fulminating pains, as in tabes, except there be also some motor paresis. It is the combination of any two of the important initial symptoms of tabes without paralysis or atrophy that is regarded as indicative of the disease by most authorities. Thus the swaying in closing the eyes, if associated with the Argyll-Robertson pupil, is considered as sufficient to justify the diagnosis of incipient tabes, even if the knee-jerk be present and fulminating pains and bladder trouble absent. Undoubtedly, the tabic symptoms must begin somewhere. But at what point it is justifiable to give a man the alarming information that he is tabic is a question. I have a number of neurasthenic subjects now under treatment who have had reflex iridoplegia for years; in one the knee-jerk is slowly becoming extinguished; in two it has been becoming more marked after becoming less; in all the three mentioned there is slight swaying in closing the eyes and some difficulty in expelling the last drops of urine while micturating. I do not believe that such a condition justifies a positive opinion, although the surmise that they are on the road to developing tabes may turn out correct for all these and for some of those who have merely reflex iridoplegia.

Incipient tabes cannot be readily confounded with any other chronic disease of the spinal cord. Some of the cases produced by sudden refrigeration resemble a beginning myelitis. But the absence of true paralysis seems to distinguish it from the latter. In all the cases of so-called acute locomotor ataxia of myelitic origin that I can find a record of, paralytic symptoms were marked, if not throughout the disease, at least in the initial period.

Other forms of sclerosis occasionally limited to the posterior columns imitate the symptoms of tabes. It is unusual, however, for such sclerosis to be distributed through so great an extent of the posterior columns as to produce symptoms consistent with tabes in both the upper and lower extremities. And even where this condition is complied with, the typical progress so characteristic of tabes is not adhered to. As previously stated, the progress is weakened by variations in certain symptoms. Such variations are found in other forms of sclerosis, but they are not as great, trophic disturbances not so common, and visceral crises not so violent, as a rule.

The discovery of ataxic phenomena as a symptom of peripheral neuritis has added another to the long list of pseudo-tabic affections. Indeed, Dejerine, who greatly advanced our knowledge of this affection, undertook on the strength of his discovery to place tabes among the peripheral affections complicated by secondary affection of the cord. In a large number of cases of peripheral neuritis, particularly the alcoholic form described by Fischer, the static ataxia, belt sensation, bladder trouble, and reflex iridoplegia are absent. In tabes the severe pains, if influenced by deep pressure at all, are affected favorably, but in peripheral neuritis pressure on the affected nerve-trunk greatly aggravates the trouble.

In addition, those severe forms of neuritis that lead to ataxia, abolition of deep and other reflexes, are accompanied by qualitative electrical changes and atrophic paralysis—features not found in tabes. Sometimes a disseminated neuritis will become so generalized as to cause diplopia and other evidences of ocular paralysis through the affection of the peripheral nerves, but, so far as my observations extend, not with the characteristic pupillary phenomena of tabes.

Cerebellar disease, alcoholic and hysterical neuroses, sometimes produce ataxia, and this may be associated with one or more of the other characteristic symptoms of tabes. Cerebellar ataxia is usually very different from that of tabes, as far as the locomotor element is concerned. In tabes it is the movements the patient makes which cause him to stagger; in cerebellar disease those movements made to prevent staggering are usually co-ordinated. The gait properly called cerebellar is therefore very different from that of tabes. There is, however, static ataxia in both cerebellar and posterior-column disease. In addition, the knee-jerk may be abolished in the former, heightening the resemblance: the history of the case is, however, decisive where these latter symptoms might lead to doubt. Bladder trouble in cerebellar disease is not an early feature, nor are paræsthesias and delayed pain-conduction intrinsic features, of cerebellar disease. Their presence is in favor of tabes.

Alcoholic ataxia is very rapid in its course, while tabic ataxia is exceedingly slow. In addition, the former is accompanied by atrophic paralyses as early features; if such occur in tabes, they occur late in the disease, and are not marked by degenerative electrical reactions as alcoholic ataxia is. This disorder is usually, too, accompanied by fever, which is an exceptional, and certainly never an intrinsic, feature in tabes. Discontinuing the alcoholic poison is usually followed by rapid amelioration of the ataxia. Hysterical ataxia exceptionally apes the ataxia of tabes; the presence of other hysterical phenomena, the rapid and bizarre change of the symptoms, are distinguishing features. There are cases of hysterical ataxia accompanied by concentric limitation of the field of vision.⁸⁴ The outline of the limitation is strikingly like that accompanying atrophy, but repeated examination shows a variation of a kind not found in the latter. The blind field advances in one direction to recede in another on one day, and reoccupies the latter and recedes from the former on the next.

⁸⁴ Landesberg, Journal of Nervous and Mental Diseases, vol. xiii. 2.

Ataxia after most acute diseases, such as scarlatina and typhoid, is not usually accompanied by loss of the knee-jerk, and never by reflex iridoplegia. The ataxia after diphtheria is complicated by the former, but, as already stated, the very opposite state of the pupil serves to distinguish it.

The hereditary form of tabes is frequently confounded to this day with true tabes dorsalis. The family history and age of the patient are collateral evidences of the nature of the case. In the hereditary form the sphincters, optic nerves, and the eye-muscles are not affected; in the acquired form the first and last are always involved; and this involvement occurs so early in the disease as to constitute a valuable discriminating feature. Although the locomotor ataxia is very similar in the two affections, static ataxia, the symptom manifested on closing the eyes, is not found in the hereditary form, while it is found more constantly than even the locomotor ataxia in the acquired form.

The electrical reactions in tabes are either normal or quantitatively slightly increased. This serves to distinguish it from all spinal affections accompanied by marked paralysis. In the later stages, when some atrophy results, there may be a quantitative decrease, but these are without qualitative changes. A change may occur in those exceptional cases where the anterior gray horns become involved, but we then have to deal with a true complication; and complications can be recognized only in their development and by the application of the diagnostic criteria characterizing the complicating disorder when of an independent occurrence.⁸⁵

⁸⁵ It is not impossible that many of the symptoms described as occurring in advanced tabes are due to independent focal disease. In the case of a female aged seventy years mentioned by Hirt (Berliner klinische Wochenschrift, 1885, No. 26), who developed hemiatrophy of the tongue, probably from a hemorrhage in the brain isthmus, there was no tabes, although this symptom when found with tabes is supposed to be part of the tabic symptom-group.

The TREATMENT of tabes dorsalis will be considered at the end of this article, together with that of the sclerotic processes generally. The duration and prospects of the disorder have been considered with the clinical history. In the vast majority of cases the course of the illness is progressive. A few cases have been reported, but in the only instance where an autopsy was made to test the matter it was found that the sclerosis had not been removed. It may be therefore stated that an arrest of the disease is possible, but that restitution of the nerve-elements, once destroyed, is impossible.

Spastic Spinal Paralysis.

SYNONYMS.—Primary lateral sclerosis. Tetanoid pseudo-paraplegia, (Seguin), Tabes dorsal spasmodique. This symptom-group was first recognized by the American neurologist Seguin⁸⁶ thirteen years ago; two years later Erb⁸⁷ described it under the title at the head of this section, and about the same time Charcot⁸⁸ attributed the well-marked clinical signs thus discovered on both sides of the Atlantic to a primary sclerosis of the lateral columns of the cord in that portion which is known as the crossed-pyramid tract, and whose isolated disease had been known to Türck,⁸⁹ but not clearly brought into relation with what is now regarded as one of the most remarkable and recognizable of spinal symptom-groups. Our earlier knowledge of the disease has been much confused through the discovery by Charcot⁹⁰ of the same lesion to which spastic paralysis is attributed by him, in a female who had been suffering from permanent contractures of all extremities, and which he persisted in regarding as hysterical. The only solution of the difficulty is to accept one of two alternatives—either believing that the sclerosis was in this case primary, in which case contracture cannot be regarded as hysterical, or that it was secondary to protracted disuse of the limbs, in which case it proves nothing. An additional source of confusion has been the discovery of an analogous affection, now regarded as clinically and pathologically distinct, known as amyotrophic lateral sclerosis, and of a corresponding affection of the lateral columns in a large number of cases of paretic dementia.

⁸⁶ E. C. Seguin, “Description of a Peculiar Paraplegiform Affection (tetanoid pseudo-paraplegia),” Archives of Scientific and Practical Medicine, February, 1873. Erb's statement (Ziemssen's Cyclopædia, vol. xi. 2, p. 628) that Seguin's description includes symptoms which do not properly appertain here can no longer be sustained, in view of the similar and identical symptoms which have been since attributed to the same affection and to amyotrophic lateral sclerosis by later writers. There seems to be no question that the priority of recognition of the clinical form belongs to this side of the Atlantic.

That Seguin's title was not as badly chosen as Erb implies in his first reference to it may be inferred from the fact that Strümpell, without any reference to Seguin, and evidently independently of him, uses the following language ten years later: “As also in these cases, the movements are not immaterially influenced by the ever-occurring spasms, a motor disturbance may be simulated which we feel inclined to term spastic pseudo-paralysis, or, more correctly, pseudo-paresis” (Pathologie und Therapie).

⁸⁷ “Ueber einem wenig bekannten spinalen Symptomencomplex,” Berliner klinische Wochenschrift, 1875, No. 26.

⁸⁸ “Sclérose primitive de la partie postérieure des cordons antero-lateraux,” Gazette médicale de Paris, 1874, pp. 38, 39.

⁸⁹ “Ueber primäre degeneration einzelner Rückenmarkstränge,” Sitzungsberichte der Kaiserlichen Akademie der Wissenschaften zu Wien, Mathematisch-Naturwissenschäftliche Klasse, Band xxi. Jahrgang 1856, p. 112.

⁹⁰ Gazette hébdomadaire, 1865, 7.

CLINICAL HISTORY.—Spastic paralysis manifests itself chiefly in three symptoms: first and most noticeable, a condition of rigidity of the limbs; second, an increase of all the muscular reflexes; and third, a true motor paresis. It manifests itself in the adolescent or middle period of life, usually without any noticeable cause, beginning in the lower extremities, and, if progressive, involving the muscles of the trunk and arms. The invasion of the disease is first marked by an increase in the excursiveness of the muscular phenomena, such as the knee-jerk and the ankle-clonus. But while this reflex irritability is originally only manifested when the diagnostician applies his special tests, it soon becomes so great that the most trivial influence suffices to bring about exaggerated muscular reaction. The mere tension of a tendon in walking, the weight of the limb, the slightest change in position, suffice to produce reflex muscular tension. The muscles feel firm and stiff to the touch, as if permanently contracted, and the lower limbs, as a result of the combined contraction of special muscular groups, assume a characteristic position—namely, an extension contracture of the leg on the thigh and a flexion of the foot on the leg. In advanced cases the contracture is so extreme that it is almost or actually impossible to flex the leg and to extend (dorsiflect) the feet. This is particularly noticeable when it is attempted to overcome the strained position suddenly, while gradual traction will often succeed in relaxing the contracture. The latter procedure succeeds because sudden traction of the tendons and the reflex contraction thereby provoked are avoided by it. Gowers compares this symptom to the mechanism of a clasp-knife. When the leg is slowly extended it yields to the manipulator's influence, but as soon as it reaches full extension it remains like the blade of the knife fixed by a spring.

Although some degree of muscular weakness is experienced in the beginning of the affection—often more marked in one leg than the other—it is insufficient to account for the grave and characteristic disturbance of locomotion. This is due rather to the stiffness of the limb resulting from the morbid muscular spasm. As the limbs are rigid, the steps are short; the leg not being flexed, and consequently not being lifted from the ground, the gait consists in an awkward shuffle.⁹¹ The feet are in continuous contact with the ground, and it is observed that there is a tendency to walk on tiptoe, owing to the contracture of the gastrocnemius, in this respect resembling the pes-equinus position. In some cases it has been observed that the reflex excitability was so great that the mere need of urinating brought on a sudden tonic spasm, and there have been noted others in which the very first spasmodic phenomena occurring in the history of the case appeared while the patient emptied his bladder.⁹²

⁹¹ It was Theodore Simon, I believe, who first suggested the registration of peculiarities in gait by using sand on the floor or compelling the patient to walk over large sheets of paper with black-leaded shoes. Among the varieties of gait noted in paretic dementia by him he accurately describes that of spastic paralysis (Die Gehirnerweichung der Irren, Hamburg, 1871).

⁹² Westphal, Archiv für Psychiatrie, xv. p. 224; ibid., p. 229.

When the upper extremities are involved, the same initial muscular weakness and exaggerated reflex excitability are noted, but the contracture at the elbow, unlike that at the knee, is usually in the flexed position.

If from any cause the spastic phenomena happen to be in the background temporarily, so as to admit testing the voluntary muscular power, it is always found to be grossly impaired.⁹³

⁹³ This statement is made by Westphal, but as he considers the only pure cases of pure primary lateral sclerosis to be those associated with paretic dementia, and it is in the latter form alone that there are marked exacerbations and remissions in the spastic symptoms, it probably does not apply to uncomplicated spastic paralysis.

As the disease progresses locomotion becomes impossible; the advancing rigidity of the trunk-muscles renders sitting impossible, and the patients become bedridden. But even in this advanced stage no sensory or vegetative disturbances were noted. The cutaneous reflexes sometimes appear exaggerated, but this is not an evidence of sensory hyperexcitability, but of the increased ease with which the motor response is elicited—a feature which is also illustrated by the spasm resulting from fulness of the bladder or even from the mere act of micturition. Ataxia has never been noted in pure cases, and the uncertainty in gait sometimes noted at the onset of the disease is secondary to the motor weakness and the interference with free mobility by the, as it were, frozen state of the muscles. Occasionally the paresis becomes a veritable paralysis, but this occurrence is limited to one or several muscular groups. Cases are related in which the spastic symptoms occurred on one side, involving one arm and leg for years before involving the other. It is not improbable that these were cases of some obscure cerebral affection. Other exceptional cases in which the spastic phenomena appeared first in the arms are better authenticated.

The early occurrence of ankle-clonus in this disease heralds the appearance of apparently spontaneous clonus when the toes are put on the ground, and later on of cramps of the gastrocnemius or other muscles, which produce an exacerbation of the existing stiffness. Occasionally sudden spasms occur while the patient is at rest, and which resemble the sudden shocks which healthy persons occasionally experience when about to fall asleep.

The electrical reactions show little that can be called characteristic, and there is little unanimity among observers on this point. The majority agree that there is a slight quantitative decrease of both faradic and galvanic excitability in parallelism with the degree of paresis. In the pure form of the disease there are no other symptoms than those mentioned. Should evidences of involvement of the gray substance of the cord or the cranial nerves be added, it is a certain indication that we have to do with the similar but far from identical affection, amyotrophic lateral sclerosis.

The course of the disease is extremely slow and its development insidious. It is considered incurable, and although a few cases have been described as terminating in recovery, the most recent and reliable annals fail to make mention of any cure in a well-established case of spastic paralysis. The disease is not in itself fatal, death usually occurring from intercurrent affections.

ETIOLOGY.—Our knowledge of the causes of this disease is practically nil. It has been, like tabes dorsalis, attributed to a family tendency. Excessive sexual indulgence, over-exertion, and syphilis have been recorded as possible causes in the few cases in which an etiological assignment could be attempted. Tuczek surmises that the spastic phenomena of lathyrism, a constitutional disease analogous to pellagra and ergotism which is observed in those who live on bread prepared from a legumen grown in Italy (lathyrus bean), and which manifests itself in spastic symptoms, may be due to an affection of the pyramid tract, just as tabes ergotica is due to an affection of the posterior columns. One case of spastic paralysis of a severe nature, associated with scanning speech, in consequence of a lightning-stroke, is reported by Demme.⁹⁴ I have been able to assign a cause in but two cases of spastic paralysis. Both were in Quakers; in both there had been a history of almost incredible sexual excesses. The disease in both involved the muscles of the jaw and face. An autopsy in the one case revealed no lesion whatever.⁹⁵

⁹⁴ “Bericht über die Thätigkeit des Jennerischen Kinderspitals,” Wiener medizinischer Blätter, 1884, No. 23.

⁹⁵ The contracture in the lower extremities, differing from the rule, was a flexion contracture.

MORBID ANATOMY AND PHYSIOLOGY.—Although Charcot's announcement that spastic paralysis is due to sclerosis of the crossed-pyramid tract was made with great positiveness, the more careful authorities have not committed themselves to his view without reservation. Their reserved position is the result of some observations which certainly show that there is no constancy between the distribution of the lesion and the distribution of the spastic paralysis;⁹⁶ while, on the other hand, characteristic spastic symptoms have been noted with purely cerebral lesions.⁹⁷ Morgan and Dreschfeld⁹⁸ publish cases in which the lesion was stated to be characteristic, but as the cell-groups in the anterior horn were found by them to have been more or less affected, it is evident they had cases of amyotrophic lateral sclerosis to deal with. In view of similar revelations in a large number of the cases that had been considered as spastic paralyses during life, and in which similar findings were found after death, Westphal,⁹⁹ one of the most critical students of the subject, concludes that thus far an anatomical basis has not been demonstrated with any constancy for the cases of spastic paralysis uncomplicated with paretic dementia. With this disease a sclerosis of the lateral column, apparently independent of the cerebral affection, is often found. It has no continuity, as a rule, with the cerebral lesion, and it may be limited to special districts of the cord. It is not usually intense enough to produce material destruction of the tract itself, and for this reason, probably, we do not find any other symptoms than a paretic weakness and an increase of the patellar and other muscular phenomena developed in the majority of paretics. In some, however, the characteristic spastic gait and muscular rigidity do develop. Westphal conjectures that if paretic dements lived as long as the sufferers from uncomplicated spastic paralysis, they would ultimately show the typical symptoms.¹⁰⁰ Numerous observations, however, show that the presence and intensity of the spastic symptoms in paretic dementia are not related to the presence and intensity of lateral-column lesion. Thus, Zacher¹⁰¹ failed to find such lesion in a case where the spastic symptoms had been well marked. It must be remembered, in drawing conclusions regarding the pathogeny of simple spastic paralysis from the lateral-cord affection and associated symptoms of paretic dementia, that the possibility of the lesion of the pyramid tract in this affection being secondary to disuse¹⁰² cannot be excluded. On the other hand, the symptoms of most paretic dements presenting lateral-column lesion differ in some respects from those of a pure spastic paralytic. There is a precedent clumsiness and helplessness of movement; the patient stumbles and trips more than is the case with the pure spastic gait; he wavers after suddenly turning around, and there is considerable tremor with intended movement. There is also more exacerbation and remission of these symptoms than is the case with true spastic paralysis, and it is observed that the exacerbations usually follow apoplectiform and epileptiform attacks, thus showing that the cerebral condition, after all, may be the determining factor.

⁹⁶ Fischer and Schultze (Archiv für Psychiatrie, xi. 3) report an impure case in which, with exquisite spastic symptoms in the neck and arms, the degeneration of the pyramid tract was limited to the dorsal part of the cord.

⁹⁷ Schulz (Deutsches Archiv für klinische Medizin, Band xxiii.) and Strümpell (Archiv für Psychiatrie, x.).

⁹⁸ Journal of Anatomy and Physiology, xv. p. 510.

⁹⁹ Archiv für Psychiatrie, xv. p. 246.

¹⁰⁰ Another feature which antagonizes the development of spastic phenomena in paretic dementia is the lesion of the posterior columns which often ensues. In proportion as this is developed it neutralizes the exaggerated knee-jerk, stiffness, and spastic gait.

¹⁰¹ Archiv für Psychiatrie, xiii. p. 155.

¹⁰² It has been claimed against this view that if this were so the degeneration of the pyramid tract should be accompanied by degeneration of the cells in the anterior horn. This claim assumes that the cells and the pyramid tract are directly continuous, but the most modern researches, those of Von Monakow, confirming an older observation of Homén's, show that a system of small cells in the lateral reticular processes is interpolated; which I can confirm. It is certainly compatible with an atrophy from disuse of the voluntary tract that the cells themselves, presiding over reflex and nutritive functions not necessarily disturbed in paretic dementia, should remain nearly intact.

There is another respect in which the two conditions differ. Spastic paralysis is usually an ascending affection, the lower extremities being involved first, the trunk next, and the upper extremities last. But in paretic dementia the spastic phenomena develop in both upper and lower extremities simultaneously, and there are universal tremors, probably of irritative origin. The lower extremities are not commonly in the extension contracture of spastic paralysis, but in the same flexed position as the arms, the adductors usually preceding the flexors in becoming rigid. If it be added to this that the lateral-column lesion in paretic dementia appears to answer all the requirements which could be made of the lesion on theoretical grounds were the case one of pure spastic paralysis—that is, that its area decreases upward—the inconsistency of the observed anatomical and clinical facts becomes strongly evident. Thus far, the attributing of spastic paralysis to a primary lesion of the pyramid tract rests in a few contested cases, on a number of doubtful analogies, and on the undoubted fact that sclerosis of this tract in the event of a myelitis is followed by pronounced spastic symptoms in all those muscles which derive their voluntary innervation from the part of the tract which lies below the level of the lesion.

The situation of this tract, which was not discovered by Türck and Flechsig, as is usually supposed, but accurately known to Burdach¹⁰³ in 1819, may be roughly stated as follows: It lies in the dorsal half of the lateral column, making up the bulk and core of this part of the column. It is separated from the pia mater by the direct cerebellar tract, and from the posterior gray horn by a narrow zone of fibres differentiated by Lissauer (see Tabes). It is connected with the lateral reticular processes, and in its cephalo-caudal course becomes gradually attenuated, giving off its fibres to these processes, thus to be exhausted in the lower part of the lumbar enlargement of the cord, where it approaches, if it does not actually reach, the surface. The fibres controlling the voluntary motions of the lower limbs, and which have a longer course to run before they reach the brain than those which mediate the voluntary control of the arms, are situated nearest the lateral boundary of the cord. Where the spastic phenomena are mainly marked in the lower limbs the sclerotic process has been found most marked in the corresponding area.

¹⁰³ Vom Bau und Leben des Gehirns. This gifted author says that the crossed-pyramid tract lies in the lateral column of the cord, behind a line corresponding to the attachment of the ligamenta denticulata and removed from the surface.

The progress of this affection has not been materially modified in any case by treatment. The same measures employed in sclerotic processes generally, particularly galvanism and warm baths, are recommended. It is difficult to understand what good effect ergotin, which is mentioned by a number of the German writers, can have in a disease of this nature.

Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis, so named by Charcot¹⁰⁴ and Joffroy, who first described it, consists in a disease affecting both the conducting tracts and nuclear centres of the motor system of the spinal cord and medulla oblongata, manifesting itself in a combination of atrophic and irritative phenomena on the part of the muscles. The relations between the symptoms and lesions of this disease rival in constancy and preciseness those noted in typical tabes dorsalis. As the variations in the mode of invasion and distribution of the lesion account for the widely-differing clinical types of the disease, and the advanced state of our anatomical and physiological knowledge of the cord enables us to interpret the reason of this difference, we shall invert the usual order and discuss the morbid anatomy first.

¹⁰⁴ In 1869 and 1874 (Leçons sur les Maladies de la Système nerveux) Charcot termed this, and one other form of disease associated with muscular atrophy, amyotrophic, to distinguish them from the myopathic forms. He considers amyotrophic lateral sclerosis as deuteropathic, the nuclear atrophy being secondary to the lesion of the white substance, and the progressive muscular atrophy of the type described by Duchenne and Aran as a protopathic form of the amyotrophies. Among the true myopathies he enumerates pseudo-hypertrophic paralysis, Erb's juvenile form, Duchenne's infantile form, certain mixed forms, and, without justification, Leyden's hereditary forms (report by Marie et Guivron, Progrès médicale, 1885, No. 10).

MORBID ANATOMY.—In advanced cases of amyotrophic lateral sclerosis there is found marked sclerotic degeneration of both the crossed and the uncrossed pyramid tracts; atrophy of the cells of the anterior horns; atrophy of some of the nuclei of the motor and mixed cranial nerve, particularly the hypoglossal and spinal accessory; atrophy of the anterior roots of the spinal and the roots of certain motor cranial nerves; and, finally, atrophy of the voluntary muscles. The greater part of the tract through which the voluntary impulse travels after leaving the voluntary motor-fields of the cortex is therefore continuously involved; and it would seem that there are cases (Kahler-Pick's) where the entire motor system is affected, the morbid process demarcating the course taken by the motor impulse through the cerebro-spinal fibre-labyrinth from the cortical motor-field down to the muscles.

The morbid process in the muscles consists of a narrowing of the fibres, which subsequently lose their transverse striation and undergo a granular disintegration. Sometimes a muscle disappears entirely; usually the connective-tissue elements, including the interstitial cellular and adipose tissue, undergo proliferation, so as to mask the wasting of the muscles to some extent.

The morbid process in the nervous system is also a simple degenerative process. The nerve-fibres and cells atrophy first, and the connective-tissue proliferation which marks the sclerotic change of the diseased area is a secondary process. There is still considerable dispute among authorities as to which segment of the motor-conduits the degeneration begins in. But from the great difference found in the individual cases which have become the subject of patho-anatomical studies there can be little doubt that there is no uniformity in this respect. In some cases the lesion is far advanced in the lateral columns, while the anterior horn is but slightly involved; in others the reverse is found. Sometimes the nuclei of the motor cranial nerves are the chief foci of disease; at others they are the least affected parts of the motor apparatus. As we shall see, there are differences in the clinical picture corresponding to the variations of the anatomical findings.

CLINICAL HISTORY.—In typical cases the first symptom is a tired feeling in one arm or leg, usually the former; in dextral persons the right arm, the one which is subject to the severest strain, is most frequently the first to be affected. With the increase in this tired feeling there develops actual loss of power; the muscles become wasted, and the other arm becomes involved. Often it is observed that the right leg suffers with the corresponding arm, but as a rule the lower extremities do not become involved to any marked degree within the first six months of the illness. It is then noted that a gait not unlike that of spastic paralysis is noted, but with more loss of motor power and less stiffness. There is, however, this noteworthy difference between the affection of the lower and that of the upper extremities: that atrophy and loss of power are more marked in the latter, and spastic phenomena in the former. The knee-jerk and other deep reflexes are greatly increased, and ankle-clonus is usually very well marked. As with spastic paralysis, there are no visceral or sensory disturbances. Unlike that affection, there are qualitative changes in the electrical reaction of the muscles¹⁰⁵ in amyotrophic lateral sclerosis. The degeneration reaction is found in the atrophied divisions, and particularly in such groups as those of the thenar and hypothenar eminence, which undergo complete atrophy at a comparatively early period of the disease.

¹⁰⁵ Moeli, Strümpell, Pick, and Mierzejewski describe cases in which only quantitative changes were found. They were such in which spastic phenomena preponderated at the time of the examination.

Soon after the spastic and atrophic involvements of the lower extremities, symptoms indicating the involvement of the cranial nerve-nuclei are developed, usually after the disease has lasted a year or so. Deglutition becomes difficult and speech indistinct, the general picture of a glosso-labio-laryngeal paralysis being imitated. The patient cannot pucker his lips, his lingual muscles undergo atrophy, and fibrillary and fascicular twitches are noted in the tongue and lips. But just as the atrophic affection of the muscles of the arms and legs differs from that of progressive muscular atrophy in the fact that the deep reflexes are exaggerated with amyotrophic sclerosis, so in the bulbar symptoms of the latter it is found, unlike the typical form of bulbar paralysis, that the jaw reflex is increased.

The duration of the disease may be stated at about three years, death usually occurring in consequence of the involvement of the cranial nerves. There are cases recorded where the disease was almost simultaneously developed in all four extremities and the tongue, reaching a high degree within a year (Mierzejewski). It is generally agreed that the reason contractures do not develop in typical cases of this kind, although the lateral column is sclerosed and spastic phenomena occur early in the disease, is the destruction of the cell-groups in the anterior horn. The reflex arch through which a reflex contracture would be mediated is broken, or rather weakened, in that part of its course which passes through these cells, and therefore a contracture is as efficiently antagonized as it would be if the posterior roots were divided. Still, in some cases a frozen attitude of the lower extremities is very well marked (Vierordt, Zacher). To reconcile these conflicting observations it has been suggested that it may be regarded as a question of speed between the progress of the pyramid-tract and the anterior-horn lesions. If the former be much in advance of the latter, spastic phenomena will preponderate and contractures be possible, to disappear with the subsequent anterior-horn lesion. But if the latter precede and preponderate, the spastic phenomena will be in the background and contractures impossible. Indeed, Zacher¹⁰⁶ suggests that there may be an ascending form in which the lesion of the pyramid tract is secondary to the nuclear atrophy, corresponding to the typical class of cases on which Charcot based his first description of the disease, and a descending form in which the pyramid tract is first affected and the nuclear cell-groups follow. Vierordt¹⁰⁷ and Kahler¹⁰⁸ express similar opinions. The latter goes so far as to suggest that progressive muscular atrophy, progressive glosso-labio-laryngeal paralysis, and amyotrophic lateral sclerosis are really due to one and the same kind of degenerative process, merely differing in location. There is certainly, as he claims, a remarkably complete chain of cases, beginning with such (1) in which spastic paralysis preponderates, passing thence to (2) those in which some muscular atrophy preponderates, then (3) those in which muscular atrophy is in the foreground and the spastic phenomena are slight, and ending with (4) the pure atrophies. A similar transition may be established on the regional principle between pure glosso-labio-laryngeal paralysis and amyotrophic lateral sclerosis, for there are cases of this affection in which the oblongata symptoms preponderate throughout, and the focus of the disease is formed there, just enough lesion being demonstrable in the pyramid tract and the spinal gray matter to prove the family relationship of what clinically appears as a spastic bulbar paralysis.¹⁰⁹

¹⁰⁶ Archiv für Psychiatrie, xv. p. 416.

¹⁰⁷ Ibid., xiv. p. 397.

¹⁰⁸ Zeitschrift für Heilkunde, 1884, p. 109.

¹⁰⁹ Such a case is described by Freund in Deutsches Archiv für klinische Medizin, xxxvii. p. 405.

PROGNOSIS.—As far as the typical cases of this disease have been studied, a fatal termination seems to be invariable. Seeligmüller reports a few cases in which the progress appeared to become arrested, but it is not clear that these were not in reality cases of some juvenile form of muscular atrophy. Not only is the affection in adults fatal, but it is so in a short period of time as compared with other spinal disorders, and particularly with the related disorder spastic paralysis. Few patients survive the third year of their illness; a number do not live to that length.

The Combined Forms of Sclerosis.

A number of cases of chronic sclerotic disease of the cord have been discovered and analyzed during the past decade, which, while they show the regularity of distribution noted in posterior and lateral scleroses, differ from them in involving at once more than one column of the spinal cord. Usually, it is the posterior column and the posterior part of the lateral column which are affected. The symptoms constitute a combination of those of tabes dorsalis and of spastic paralysis. But this combination does not represent a mere addition of symptoms; where the tendency of the two diseases conflicts, they neutralize each other. Thus the tendency of lateral sclerosis uncomplicated by posterior sclerosis is to increase the patellar jerk; when posterior sclerosis complicates it, the jerk is annihilated. The degeneration of the lateral column and the ensuing motor paresis in like manner neutralize the ataxic character of the gait by limiting its excursiveness.

The upper extremities are usually involved equally with the lower. In the cases of Kahler-Pick considerable atrophy of the muscles developed; in those of Prévost and Westphal this was not very noticeable. In a few cases, where the posterior sclerosis did not involve the lumbar part of the cord, spastic symptoms were noted in the lower extremity. In the only case of combined sclerosis now under my observation this peculiarity, noticed by Prévost, is well marked. In one of Westphal's cases there was evident mimic ataxia. The few cases of this affection observed show so many variations that it would be at present premature to attempt sketching a common clinical type. The majority of the subjects were affected between the twenty-fifth and forty-fifth years.

ETIOLOGY.—Little is known of the causes of this disease. Usually beginning insidiously, no special mode of origin can be determined. Surface chilling has been assigned in a case by Erlitzky and Rybalkin, and others are reported to have begun during pregnancy. One of Westphal's cases developed in a lithographer who had been subject to epileptoid fits.

DIAGNOSIS.—As yet we have no reliable criteria for distinguishing between a combined sclerosis and certain forms of diffused sclerosis during life. Ballet and Minor¹¹⁰ found such a sclerosis diffusely involving the posterior and lateral columns of the cord in a case where they were justified from the symptoms in expecting a combined fascicular sclerosis of these columns, and after a careful study of all similar cases collated by them in consequence of this experience, they came to the conclusion that a number of affections of different origin, but eventually involving both columns, may impose on the observer as combined fascicular sclerosis during life. Diffuse meningo-myelitis is one of these affections, and is far from uncommon, while true system or combined sclerosis is apparently a very rare disease.

¹¹⁰ Archives de Névrologie, vii. p. 44.

The Family Form of Tabes Dorsalis.

SYNONYMS.—Friedreich's disease, the Family form of locomotor ataxia, Hereditary ataxia, Hereditary tabes.

Friedreich discovered a peculiar form of co-ordinating disturbance in a number of children of the same family, which he brought into relation with a lesion of the posterior columns, and which has been since found by him and by subsequent observers to occur in other cases, always affecting several members of the same family, as in the first case observed by him. The clinical and pathological features, though resembling those of the tabes dorsalis of adults in many respects, are distinct in others, and for this reason it is generally assigned a separate place in classification.

ETIOLOGY.—The disorder is usually manifested in juvenile life, the age of the affected subjects varying from the seventh to the twenty-fifth year. The male sex preponderates in the statistics of the affection. Some neuropathic vice can always be found in the patient's immediate ancestry, and the limitation of the disease to families burdened by such a diathesis is exemplified in the fact that the ninety individual cases thus far accurately studied occurred in thirty-six families.¹¹¹ The disease type of the ancestors of the patients is usually different from that of the latter. Alcoholism in the father is one of the commonest forms, but convulsions, hysteria, and insanity are also frequent features of the family history. In a few cases tabes dorsalis, properly so called, was present in the father. In others there was consanguinity of the father and mother. In Musso's group the parents had been brother and sister, and their mother had been a melancholic dement. Three other grandchildren and six grandchildren by the incestuous marriage developed the family form of tabes. In this family the frequent experience of hereditary transmission was verified—that the neurotic taint skipped the intermediate generations.

¹¹¹ Raffaele Vizzioli, Giornale di Neuropatologia, 1885.

CLINICAL HISTORY.—Usually the first symptom is ataxia of the lower extremities; occasionally this is preceded by severe frontal headache or by vague rheumatoid pains. The inco-ordination is very similar to that of true tabes dorsalis, but swaying on closing the eyes is not noticed early in the disease, as in the latter affection. The arms soon become involved in the ataxia, but cutaneous sensibility and the muscular sense remain either intact or nearly so—a fact utilized with some success by Erb in polemicizing against the theory of Leyden that the ataxia of tabes is due to imperfect sensation. Later in the disease, usually after a few years, a peculiar speech-disturbance is noticed, which resembles the scanning of disseminated sclerosis. It depends on ataxia of the tongue and lips. This is usually associated with nystagmus. About this time the patient develops a different set of motor symptoms from those characterizing the onset of the disease; contractures, paralysis, and atrophy are found in the affected extremities; sometimes the patients cannot ascend a stair, owing to their inability to lift the feet high enough. Pes equino-varus, deformity of other joints and of the vertebral column, have been observed¹¹² to result from the associated effects of paralysis and contracture. At this stage some sensory disturbance may be developed, formication having been observed toward the close of the history in a number of cases. But the distribution of this disturbance is usually different from that of tabes dorsalis, being more intense in the trunk than in the extremities or evenly marked in the entire periphery.

¹¹² H. E. Smith, Boston Medical and Surgical Journal, 1885, vol. cxiii. p. 361.

COURSE AND PROGNOSIS.—The progress of this disease is slow. It has not yet been known to be arrested by any therapeutical procedure. Death rarely occurs directly from the disease by exhaustion; more commonly life is cut short by some intercurrent affection. Unless this occurs the patients may survive the commencement of the illness from eight to forty and more years.

MORBID ANATOMY.—The sclerosis which is found to be the constant lesion underlying this disease corresponds in every character to a combined sclerosis of the pyramid tracts and the posterior columns. Usually, the crossed-pyramid tract is degenerated in its spinal course, and the uncrossed in the cervical and dorsal part, which, in many subjects at least, is its whole extent. The cerebral part of the pyramid tract is not affected. The nerve-fibres found normally in the gray substance are materially reduced, probably in dependence upon the atrophy of the great nerve-tracts.

The lesion of the posterior columns resembles that of true tabes very closely, particularly in the lumbar part of the cord. It is, however, not probable that it commences in precisely the same distribution, and if cases dying early in the disease be autopsied it will be interesting to see whether the initial sclerosis occupies identical fields—a contingency which is unlikely, owing to the profound difference in the initial symptoms of true tabes and the family form. It is claimed by Schultze that in addition to the pyramid and posterior tracts the cerebellar tract—or, rather, a large part of the periphery of the lateral column—may be sclerosed in this disease. In this way, since the direct pyramid tract in the anterior, the greater part of the border of the lateral, and the entire posterior column are degenerated, the sclerosis resembles a marginal ring¹¹³ in shape.

¹¹³ Archiv für Psychiatrie, xiv. p. 384.

Anatomically, the sclerosis of the family form of tabes resembles that form of combined sclerosis in which the lateral and posterior columns are together affected. It is probably due to a defective development of these tracts, rendering them liable to premature decrepitude or increasing their vulnerability. The latter alternative is exemplified in those cases where some acute disease of childhood, such as scarlatina or measles, acted as an exciting cause.

DIAGNOSIS.—There are two affections some of whose leading symptoms are so closely imitated by those of this disease that they may be confounded with it on first sight. These are tabes dorsalis—of which the family form is still regarded a variety, as the name indicates—and disseminated sclerosis. In the gait the former, in the nystagmus and scanning speech the latter, disorder is approximated. The distinction from true tabes has already been dilated on. (See Tabes.) The fact that relatives—usually the sisters and brothers—of the patient are affected in the same way in their youth speaks in favor of the family form. The deep reflexes are not abolished early, as in tabes, nor are anæsthesias or paræsthesias early symptoms, as in the latter. The speech-disturbance and nystagmus, which in most cases develop later in the family form, serve to distinguish it from true tabes in the advanced stage. It is at this period that the disease may resemble a disseminated sclerosis. The hereditary or family character does not aid us in making a discrimination here, as there is also a family form of the latter disease. But the absence of intention tremor, which we would assume to be present in a case of disseminated sclerosis of the cerebral type, and of optic-nerve atrophy serves to distinguish the two. Musso claims that the speech-disturbance is also different in character. There certainly is more lingual ataxia in the family form of tabes, and less of typical scanning, but I am doubtful about our ability to differentiate these characters in all cases. The following table includes the main points of difference, clinically considered, between the acquired and the family form of tabes:

Tabes Dorsalis. The Family Form.

Prodromata. Marked and constant. Absent or slight.

Static ataxia (Romberg symptom). Early and constant. Absent.

Involvement of upper extremities. Usually late. Early.

Ataxia of tongue, eyes, and trunk-muscles. Absent or unnoticeable. Always developed.

Paresis. Rare. Characteristic.

Anæsthesia. Present in some form. Absent or slight.

Paræsthesia. Constant. Rare.

Sexual desire. Becomes extinguished. Remains unaffected.

Deep reflexes. Abolition usually initial. Abolition in course of disease.¹¹⁴

Sphincters. Involvement is characteristic and early. Involvement late, if at all.

¹¹⁴ There are conflicting observations on this point.

Disseminated Sclerosis.

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 no tremor 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

¹¹⁵ According 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.

CLINICAL HISTORY.—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 tabes dorsalis 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 of isolating 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 Pasternatzky¹¹⁶ claims, 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.¹¹⁷ A 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.

¹¹⁶ Jahrbücher für Psychiatrie, iii. 3, 1882.

¹¹⁷ For 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. Krause¹¹⁸ has 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 observed in speech. The features sometimes express an emotion opposite to the one experienced by the patient.¹¹⁹

¹¹⁸ Neurologisches Centralblatt, 1885.

¹¹⁹ This 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, Westphal¹²⁰ noticed 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

¹²⁰ Archiv für Psychiatrie, x. p. 243.

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 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

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.

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

¹²⁴ Concentric 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 Gnauck¹²⁵ 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.

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 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.

¹²⁶ Gnauck, Neurologisches Centralblatt, 1884, p. 315.

¹²⁷ Rivista sperimentale di Freniatria e di Medicina leqale, x. p. 227.

¹²⁸ Archiv für Psychiatrie, vii. p. 28. He designates this form sclerosis continua multiplex.

¹²⁹ Ibid., x. p. 135.

¹³⁰ Ibid., xi. p. 216.

¹³¹ Ibid., xiii. p. 168.

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

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.

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. Bourneville¹³⁵ 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.

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 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 figure¹³⁷ 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

¹³⁶ Archiv für Psychiatrie, xiv. p. 286.

¹³⁷ Ibid., xiv., Plate ii. Fig. 5.

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 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 Pollak¹³⁹ 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. Pelizæus¹⁴¹ 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.

¹³⁹ Deutsches Archiv für klinische Medizin, Bd. xxiv. p. 404.

¹⁴⁰ Ibid., vol. xxiii. p. 442.

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 sclerotic foci of probably later date were found in the neighboring segments of the cord.

¹⁴² Prager medizinisch Wochenschrift, 1885, No. 8.

The myelitic affection discovered by the same observer¹⁴³ 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

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.