Chapter M: M——, was a stout Irish woman about forty years of age. She had (24)

SYNONYMS.—Primary lateral sclerosis. Tetanoid pseudo-paraplegia, (Seguin), Tabes dorsal spasmodique. This symptom-group was first {862} recognized by the American neurologist Seguin[86] thirteen years ago; two years later Erb[87] described it under the title at the head of this section, and about the same time Charcot[88] 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 Charcot[90] 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.

[Footnote 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_).]

[Footnote 87: “Ueber einem wenig bekannten spinalen Symptomencomplex,” _Berliner klinische Wochenschrift_, 1875, No. 26.]

[Footnote 88: “Sclérose primitive de la partie postérieure des cordons antero-lateraux,” _Gazette médicale de Paris_, 1874, pp. 38, 39.]

[Footnote 89: “Ueber primäre degeneration einzelner Rückenmarkstränge,” _Sitzungsberichte der Kaiserlichen Akademie der Wissenschaften zu Wien, Mathematisch-Naturwissenschäftliche Klasse_, Band xxi. Jahrgang 1856, p. 112.]

[Footnote 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, {863} 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]

[Footnote 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).]

[Footnote 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]

[Footnote 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 {864} 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]

[Footnote 94: “Bericht über die Thätigkeit des Jennerischen Kinderspitals,” _Wiener medizinischer Blätter_, 1884, No. 23.]

[Footnote 95: The contracture in the lower extremities, differing from the rule, was a flexion contracture.]

{865} 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 Dreschfeld[98] 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, Zacher[101] 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 disuse[102] cannot be excluded. On the other hand, the symptoms of most paretic dements presenting lateral-column {866} 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.

[Footnote 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.]

[Footnote 97: Schulz (_Deutsches Archiv für klinische Medizin_, Band xxiii.) and Strümpell (_Archiv für Psychiatrie_, x.).]

[Footnote 98: _Journal of Anatomy and Physiology_, xv. p. 510.]

[Footnote 99: _Archiv für Psychiatrie_, xv. p. 246.]

[Footnote 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.]

[Footnote 101: _Archiv für Psychiatrie_, xiii. p. 155.]

[Footnote 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 Burdach[103] 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.

[Footnote 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 {867} 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 Charcot[104] 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.

[Footnote 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 {868} 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 muscles[105] 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.

[Footnote 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 {869} 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, Zacher[106] 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. Vierordt[107] and Kahler[108] 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]

[Footnote 106: _Archiv für Psychiatrie_, xv. p. 416.]

[Footnote 107: _Ibid._, xiv. p. 397.]

[Footnote 108: _Zeitschrift für Heilkunde_, 1884, p. 109.]

[Footnote 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, {870} 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 Minor[110] 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.

[Footnote 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 {871} 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.

[Footnote 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 observed[112] 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.

[Footnote 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 {872} 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 ring[113] in shape.

[Footnote 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 {873} 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 | Early and constant. | Absent.
(Romberg symptom). | |
| |
Involvement of upper | Usually late. | Early.
extremities. | |
| |
Ataxia of tongue, | Absent or | Always developed.
eyes, and | unnoticeable. |
trunk-muscles. | |
| |
Paresis. | Rare. | Characteristic.
| |
Anæsthesia. | Present in some form. | Absent or slight.
| |
Paræsthesia. | Constant. | Rare.
| |
Sexual desire. | Becomes extinguished. | Remains unaffected.
| |
Deep reflexes. | Abolition usually | Abolition in course
| initial. | of disease.[114]
| |
Sphincters. | Involvement is | Involvement late, if
| characteristic and | at all.
| early. |
---------------------+-----------------------+---------------------

[Footnote 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 {874} 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]

[Footnote 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 {875} 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 {876} 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 Pasternatzky[116] 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.

[Footnote 116: _Jahrbücher für Psychiatrie_, iii. 3, 1882.]

[Footnote 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. Krause[118] 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 {877} in speech. The features sometimes express an emotion opposite to the one experienced by the patient.[119]

[Footnote 118: _Neurologisches Centralblatt_, 1885.]

[Footnote 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, Westphal[120] 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]