A system of practical medicine. By American authors. Vol. 4

by Unknown

PSEUDO-HYPERTROPHIC PARALYSIS.

BY MARY PUTNAM JACOBI, M.D.

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SYNONYMS.—Hypertrophic paraplegia of infancy (Duchenne); Myo-sclerosic paralysis (Duchenne); Progressive muscular sclerosis (Jaccoud); Atrophia musculorum lipomatosa (Seidel); Lipomatous myo-atrophy (Gowers); Muscular hypertrophy (Kaulich, Griesinger); Lipomatosis musculorum luxurians progressiva (Heller); Myopachynsis lipomatosa (Uhde); Pseudo-hypertrophic paralysis (Ross); Pseudo-hypertrophy of muscles (Friedreich).

DEFINITION.—Pseudo-hypertrophic paralysis is a rare and predominantly infantile disease, characterized by a considerable increase in the volume of some or all the muscles of the lower extremities, associated with progressive diminution in their functional energy, and accompanied or followed by paresis and atrophy of the muscles of the trunk and upper limbs. Many of the hypertrophied muscles subsequently atrophy; many of the muscles in which atrophy is the most conspicuous lesion pass through a preliminary period of hypertrophy. The proximate cause of these alterations is a profound disturbance in the nutrition of the muscles, attended by great increase of their connective tissue, by wasting of the contractile substance, and by the ultimate replacement of this by fat.

HISTORY.—The honors of the discovery of this remarkable disease may be divided between Duchenne, Meryon, and Griesinger. In 1852¹ the English physician published a series of six cases, four belonging to one family, two to another; but these were described by him under the name of progressive muscular atrophy; and it was left to Duchenne, who in 1861² published as a new disease the first case observed by himself, to demonstrate the identity of Meryon's cases with his own.³ In 1868, Duchenne had collected twelve additional cases, and published an extensive monograph on the subject.⁴ But in 1865, Griesinger⁵ had excised a portion of muscle from a patient suffering with the disease, and made the first histological examination of its structure. On this account several German writers habitually refer to Griesinger as the earliest authority on the subject. Before Meryon, Partridge in 1847,⁶ and Sir Charles Bell in 1830,⁷ had described cases of pseudo-hypertrophic paralysis, but without recognizing their separate morbid entity. Bell's case is the following: "A boy at eight years of age began to experience difficulty in rising from a chair. The disease gradually progressed, till at eighteen he had to twist and jerk his body about to get upright. The muscles of the lower extremities, hips, and abdomen were debilitated and wasted. The extensor quadriceps femoris on both sides wasted, but the vasti externi had not suffered as much; a firm body, remarkably prominent, just above the knee-joint, marked the position of the vastus externus. No defect of sensibility or affection of the sphincters. The upper part of the body, shoulders, and arms were strong."⁸

¹ Lond. Med. Gaz.

² De l'Électrisation localisée.

³ Duchenne at first doubted this identity.

⁴ Archives générales, 1868.

⁵ Archiv der Heilkunde.

⁶ Lond. Med. Gaz., 1847.

⁷ Nervous System, 2d ed., 1830, p. 163.

⁸ Loc. cit. This case is quoted in an appendix to Gowers's monograph.

Autopsies.—The first was made by Meryon: the first which included microscopic examination of the spinal cord was by Cohnheim on a patient of Eulenburg's.⁹ Since then autopsies have been made in 12 genuine cases, and in 2 others frequently, though erroneously, ranked with them.¹⁰

⁹ Vhdlg. der Bul. Med. Ges., 1866, Heft 2, p. 191, quoted by Eulenburg in Ziemssen's Handbuch, Bd. xii. 2.

¹⁰ Cases of Barth and Müller.

Of cases without autopsies a collection of 80 was made by Friedreich in the monograph on pseudo-hypertrophy which accompanies his longer monograph on progressive muscular atrophy.¹¹ Mobius has increased this list to 94;¹² Gowers describes 24 cases,¹³ and refers in an appendix to 20 more—18 observed by Adams, 2 by Clifford Albutt.¹⁴ Hammond in the sixth edition of his treatise on nervous diseases, quotes 17 American cases, of which 6 were observed by himself.¹⁵ Gowers estimated that in 1879 about 220 cases had been reported, divided up among a much smaller number of families.

¹¹ Ueber Progressiv Muskel Atrophie.

¹² "Ueber Hereditare Nerven Krankheiten," Volkmann's Samml., 171.

¹³ Clinical Lecture on Pseudo-hypertrophic Paralysis, Lond., 1879.

¹⁴ Among Mobius's cases is that related by Pick in the Deutsches Archiv f. klin. Med., Bd. vi., and really a case of progressive muscular atrophy in an adult complicated by lipomatosis in the calf-muscles. Of the other cases, 6 are quoted from the Swedish, 6 are hitherto unpublished, and have been collected by the author from several clinics. There remain cases by Davidsohn, Glasgow Med. Journ., 1872 (3 cases); Berger, Schles. Gesellsch., 1875; Uhde, Arch. f. klin. Chirurg., 1873, Bd. xvi.; Huber, Deutsches Arch. für klin. Med., 1874; Brieger, ibid., 1878, Bd. xxii.; Leyden, Klinik der Ruckenmark. Krank., Bd. ii. S. 529; Schlesinger, Wien. Med. Presse, 1873.

Many other cases have been published since, but without contributing any special information on the disease. Of importance, however, are—Cornil, accompanied by autopsy, Bull. Soc. Méd. des Hôp., 1880; Donkin, followed by recovery, Brit. Med. Journ., 1882, i.; Albutt, Med. Times and Gaz., 1882; Goodridge, Brain, 1882; Barthélemy, France méd., 1880; Suckling, Med. Times and Gaz., 1885; Dowse and Crocker, Lancet, 1881.

¹⁵ These are reported by S. G. Webber, Boston Medical and Surg. Journ., Nov. 17, 1870; Wm. Pepper, Philada. Med. Times, 1871; S. Weir Mitchell, Photographic Review, 1871; C. H. Drake, Philada. Med. Times, 1874; C. T. Poore, New York Med. Journal, 1875; Steele and Kingsley of Missouri (4 cases), Philada. Med. Times, Oct., 1875; George S. Gerhardt (2 cases), Alienist and Neurologist, Jan., 1880.

I have had an opportunity of observing 3 cases of the disease—1 at the Mount Sinai Hospital; 2, brothers, in a private family.

The material at present on hand is therefore sufficient, if not to solve the problems of the disease, at least to make out a tolerably complete clinical history.

SYMPTOMS.—The early appearance of the morbid symptoms is the first striking peculiarity of the disease. Out of 88 cases whose records I have analyzed, 35 must be considered congenital, since some degree of paresis was observed from the time the child first began to walk;¹⁶ and the effort at walking was unusually late, being deferred till two, three, or even four years of age. In 21 other cases the first symptoms of the disease declared themselves between the ages of three and six¹⁷—at the age of seven 8 other cases began;¹⁸ between nine and ten, 7 cases;¹⁹ between ten and sixteen were 8 cases;²⁰ finally, in 7 cases, of which 2 are more than doubtful (cases Barth and Müller), the disease seems to have begun in adult life.²¹ Thus, 57 cases, or rather more than two-thirds of the whole number, began before the age of six.

¹⁶ These cases are the following: Meryon, Lond. Med. Gaz., 1852 (5 cases); Partridge, ibid., 1847; Duchenne, Électris. local., 1861; Kaulich, Prager Vierteljahr., 1862, quoted by Friedreich; Spielmann, Gaz. méd. de Strasbourg, 1862, quoted by Friedreich; Duchenne fils, Archives gén., 1864 ("De la Paralysie atrophique graisseuse"); Griesinger, Archiv der Heilkunde, 1864; Sigmund, Deutsches Archiv für klin. Med., Bd. i. Heft 6; Wernich, ibid., Bd. ii. Heft 2, 1866; Benedikt, Elektrotherapie, Wien, 1868; Balthazar Foster, Lancet, 1869; Barth, Archiv der Heilkunde, xii. 2, 1871; Chrostek, Oesterreich Zeitschrift für prakt. Heilkunde, No. 38, 1871, quoted by Friedreich; Pekelharing, Arch. Virch., 1882, Bd. lxxxix., quoted by Friedreich; Knoll, Wien. Medizin Jahrbuch., 1872; Friedreich, Pseudo-hypertroph. der Musc., 1878, p. 291; Duchenne, Archives gén., 1868 (7 cases); Hammond, Treatise Nerv. Dis.; Gowers, loc. cit. (5 cases); Ross, Treatise Nerv. Dis., 2, 204.

¹⁷ Cases by Eulenburg, Allgemeine Med. Central Zeitung, Berlin, 1863, quoted by Friedreich; Rinecker, Verhand. du Phys. Med. Gesellsch. zu Wurzburg, 1860, quoted by Friedreich; Heller, Deutsches Archiv f. klin. Med., Bd. i. H. 6 (2 cases); Wernich, ibid., Bd. ii., 1866; Lutz, ibid., Bd. iii., 1867; Benedikt, loc. cit. (5th and 6th cases); Russel, Med. Times and Gaz., 1869 (3d case); Duchenne, loc. cit. (2d, 3d, 6th, 12th, 13th cases); Hammond, loc. cit.; Gowers, loc. cit. (6 cases).

¹⁸ Cases by Eulenburg and Cohnheim, Beitr. klin. Woch., 1865; Seidel, Atrophia Musculorum Lipomatosa, 1867; Heller, loc. cit. (2d case); Wagner, Berl. klin. Woch., 1866 (8 cases); Benedikt, loc. cit. (1st case); Duchenne, loc. cit. (9th case); Gowers, loc. cit. (7th case).

¹⁹ Seidel, loc. cit. (1st case); Coste and Gioja, Schmidt's Jahrb., Bd. xxiv. S. 176; Spielmann, Gaz. méd. de Strasbourg, 1862; Boquette, Inaug. Dissert., Berlin, 1868; Russel, loc. cit. (2d case); Rakowac, Wien. Mediz. Wochen., 1872; Brieger, Deutsches Archiv f. klin. Med., Bd. xxii., 1878; Pepper, Philada. Med. Times, 1871.

²⁰ Lutz, loc. cit. (2d case); Ross, loc. cit., p. 190 (observed when adult); Hoffmann, Inaug. Dissert., Berlin, 1867; Russel, loc. cit. (1st case); Gowers, loc. cit. (18th and 20th cases).

²¹ Benedikt, loc. cit. (2d and 3d cases); Dyce Brown, Edin. Med. Journ., 1870; Eulenburg, Archiv Virch., Bd. xlix., 1870; Martini, Centralblatt für Med. Wissensch., No. 41, 1871; Barth, Archiv der Heilkunde, xii. 2, 1871; Müller, Beit. zur path. Ruckenmarkes, 1871.

The symptoms are of three kinds: 1st, those dependent on alterations in the function of the affected muscles; 2d, changes in the appearance, consistency, and electrical reaction of these same muscles; 3d, deformities resulting from their structural alteration.

The first muscles invaded are invariably the gastrocnemii,²² and therefore uncertainty of gait is the first symptom observed. The child is usually backward in learning how to walk, even when two, three, or four years intervene between this acquisition and the first decided appearance of the disease. In the unquestionably congenital disease the act of walking is always imperfectly performed, and the original imperfection gradually deepens into a noticeable uncertainty of gait, and finally into real paresis. It is noticed that the child falls very frequently—at first only when running, afterward even while standing. He then begins to experience difficulty in going up stairs: pulls himself up by the bannisters, and usually drags one leg completely. After a while it becomes quite impossible for him to go up stairs except on his hands and knees.

²² Billroth relates an altogether exceptional case of a limited pseudo-hypertrophy with lipomatous degeneration, localized in the hamstring and adductor muscles of one thigh, in a girl seventeen years old. The only generalized lesion was an immense development of subcutaneous fat (Archiv für klin. Chir., Bd. xiii.).

Dyce Brown (Edin. Med. Journal, 1870) relates a case, also in an adult of twenty-six years, where hypertrophy of the thigh-muscles is said to have preceded by three weeks that of the calves.

These symptoms all point to failure of power in the gastrocnemii muscles, whose function it is to raise the heel from the ground in running, to steady the heel by their tension during the act of standing, and to raise the foot with considerable force during the act of going up stairs. In descending a staircase or any inclined plane great tension is required of these same muscles, and this act should therefore be even more difficult than that of ascension. But it does not seem to have been as carefully studied.

Attention is not often directed to the infirmity at this early stage, especially if the child be very young, since the apparently excellent development of the legs satisfies the parents that nothing serious can be the matter, and the falling is explained by childish awkwardness. Not infrequently, indeed, this is really due to a rachitis which has preceded the degenerative lesion, and at the early stage of the latter a diagnosis from the less severe disease is always required, and is sometimes difficult to make.

The following test may be applied in doubtful cases: The child (if old enough) is requested while standing to rise on the tips of his toes. This act necessitates a powerful effort on the part of the sural muscles, and of this, even at an early stage of degeneration, they are generally incapable.

Functional weakness may precede for several years all visible alteration of the muscles; the child may not learn to walk at all until two or even three years of age; then walks badly until five or six, when, for the first time, the calves begin to enlarge. More often the paresis precedes the hypertrophy by only a few months or weeks, or the symptoms occur simultaneously. A certain amount of hypertrophy will be overlooked; but when the calves enlarge sufficiently to render the child's stockings too tight, attention is forcibly called to the change. The enlargement is more marked at the upper part of the calf, so that the symmetry of the leg is deranged by it. Often, however, the impression of vigor conveyed by the appearance of the child's legs is with difficulty dispelled by the discovery of their functional weakness.

Eulenburg²³ affirms that the consistency of the muscle is soft and doughy, recalling, when grasped in the hand, a lipomatous tumor. This description, however, does not apply to the early stage of the disease; for then the hypertrophied muscles feel extremely hard to the touch; there is even a stony hardness (Duchenne fils); somewhat later, the hypertrophy continuing, these muscles "seem to make hernial protrusions through the skin" (Duchenne). This appearance is most marked when the subcutaneous fat is atrophied; when, as happens especially in the adult cases,²⁴ the diseased muscles are covered by a thick layer of subcutaneous fat, their protrusion is concealed. A rapid exchange of the hardness characterizing the first stage of the lesions for a lipomatous softening is of bad omen, as indicating a more rapid and irresistible march in the disease (Mobius).

²³ Ziemssen's Handbuch, Bd. xii.

²⁴ See case by Billroth, quoted p. 853, note.

At this early stage the electrical reactions of the enlarging muscles are all intact. Disturbances of sensibility, however, are not uncommon. Especially frequent are pains in the back and loins and stabbing pains in the lower limbs. These pains sometimes follow the track of the crural or sciatic nerves; at other times they appear in the joints; sometimes are limited to the affected muscles. The pains are diminished by repose and a recumbent position, but are greatly aggravated by movement. Paræsthesias, or a feeling of cold and formication, are also observed—never anæsthesia. Seidel²⁵ has found the cutaneous sensibility to be intact, as also the sense of space and pressure. The temperature sensibility has not been tested. The temperature of the affected part is, according to Eulenburg, often lowered several degrees. This statement probably refers to the advanced degree of degeneration. At an earlier stage Ord²⁶ found the temperature of the calves to be increased.

²⁵ Loc. cit., p. 32.

²⁶ Med.-Chir. Trans., 1874, 1877.

Reflex excitability is maintained, not only in this, but in the second stage of the disease, except in the patellar tendon, where it is abolished after the quadriceps extensor has been invaded. This fact may be of importance in diagnosticating paresis depending on incipient pseudo-hypertrophy from that which would be caused by a mild anterior poliomyelitis.

No symptoms of the third kind (deformity) appear in the first period of the disease. The second is ushered in either by the first perceptible degree of hypertrophy in the calves (Duchenne) or by increase of the hypertrophy, which may have already begun during the first period of paresis, and by extension of this to other muscles.

This extension of the lesion is indicated by further derangement in the functions of station and locomotion. To steady himself the child instinctively widens his base of support by placing the feet far apart, and thus straddles while walking in a manner that is highly characteristic. A second peculiarity is an oscillating movement of the trunk from side to side. The trunk is carried over to the side of the foot planted on the ground, the so-called active limb, and while the passive limb is being swung forward. A third peculiarity of attitude, already exhibited in station, but exaggerated by the act of walking, is lordosis. The lumbar portion of the spine, with the abdomen, is carried forward; the shoulders are carried backward, so that a plumb-line dropped from them falls behind the sacrum. Thus, the walk of the patient becomes highly characteristic—the feet planted so far apart; the lumbar portion of the trunk projecting forward; the body oscillating at each step from side to side.

At this stage the act of rising from a sitting or recumbent position becomes more difficult than walking. If near a support, the child always tries to draw himself up by his arms; if a fixed support be lacking, he first gets on his hands and knees, and then, grasping each thigh alternately with one hand, is enabled to get first one foot and then the other on the floor. He then seizes the thighs by successive grasps, each higher than the other, pressing back the flexed hip- and knee-joint as he does so. By this method of apparently climbing up his own thighs the patient is finally enabled to extend his body and arrive at an upright position.

This attitude of the hands, on the knees, and subsequently on the thighs, during the act of rising, is pathognomonic of pseudo-hypertrophy, for it is observed in no other disease.

Corresponding with this increased disturbance in function is the increased visible alteration in the muscles of the lower extremities. The muscles on the anterior part of the legs are not always attacked, but often become hypertrophied and paretic contemporaneously with the gastrocnemii. After these, hypertrophy of the glutæi comes next in frequency. The quadriceps extensor of the thighs may become paretic, and even perfectly paralyzed, without showing any sign of enlargement. In many cases, however, hypertrophy proceeds regularly up the limbs, and invades the thighs simultaneously with the buttocks.²⁷ The exact proportion of cases is difficult to ascertain, because the history is often imperfect, and at the time of observation the quadriceps extensor is frequently atrophied, even when it has been hypertrophied at an earlier date. The thinness of the thighs is then all the more conspicuous from the hypertrophy of the calves below and of the buttocks above. The sacro-lumbales and quadratus lumborum muscles are also frequently enlarged, next in order to the quadriceps extensor femoris, which, as seen, is rather less often hypertrophied than are the gluteal muscles.

²⁷ Cases in which the calves and thighs are alone described as hypertrophied: those by Kaulich, Griesinger, Sigmund, Wagner, Wernich (2d), Lutz (1st and 2d), Foster, Stoffella, Eulenburg (2d).

Cases of hypertrophy of calves with atrophy of thighs: those by Eulenburg (1st), Lutz (3d), Adams, Barth (2d), Knoll, Friedreich, Gowers (1st, 4th, 5th, 9th, 10th, 11th, 12th, 14th). In Rakowac's case, as also Barth's, the glutæi were also hypertrophied.

Cases of hypertrophy, calves, thighs, glutæi, and sacro-lumbales muscles: Duchenne (1st, 5th, 6th, 7th, 8th, 12th, the last being the miniature Hercules, in which all the muscles were hypertrophied except the pectorals), Heller (2 cases), Benedikt (1st, 2d, 3d, 4th; in the 5th the sacro-lumbales atrophied), Gowers (13th, 20th), Pekelharing.

Cases with hypertrophy of the calves and glutæi, with atrophy of the thighs: Berend, Duchenne fils (hypert. sacro-lumbales), Duchenne (3d, 4th, 10th).

Cases of atrophy of all but calves: Spielmann, Gowers (7th), Hammond (2 cases).

Cases of hypertrophy of calves and deltoids, atrophy of all other muscles: Ross (2 cases).

The flexor muscles of the leg are much less often affected than these; the adductors and the ileo-psoas rather more frequently. Paresis and moderate hypertrophy of the abdominal muscles, though relatively rare, are observed. Thus, from the foot up to the spinal column the morbid imminence is pronounced on the side of the extensor muscles. The liability to invasion on the part of the flexors is greatest at the foot, where dorsal flexion is early impeded, and diminishes upward toward the abdomen.

Most important for the theory of the disease is the fact that the hypertrophic appearance of the muscles is never accompanied by even a transitory period of increased strength.²⁸ Some degree of paresis usually precedes the hypertrophy, and becomes intensified when this sets in. The two symptoms, however, are by no means proportioned to one another.

²⁸ In Auerbach's case of true muscular hypertrophy the same paresis was observed.

There is another anatomical change in the muscles no less characteristic of the disease than is their hypertrophy, which contributes at least as much to the loss of muscular power. This is atrophy of the muscles, which in the lower extremities is almost invariably secondary to a stage of hypertrophy, but which occasionally in the quadriceps extensor constitutes the primary lesion. On the other hand, the calf-muscles, though occasionally retroceding from a state of exaggerated hypertrophy, never atrophy below the normal dimensions.²⁹

²⁹ Hammond relates a remarkable case where the muscles of the calves and thighs, having enlarged progressively during about two years, then began to waste, and continued to do so for three years. Then a second stage of hypertrophy set in, and continued at the time of writing (Treatise on Nervous Diseases, 6th ed., p. 508).

It not unfrequently happens that the atrophic and hypertrophic processes go on simultaneously in the same muscle, and so compensate each other that the muscle varies little or nothing from the normal size. This is especially apt to be the case with the pelvic and lumbo-spinal muscles; and thus functional disturbances will develop for which the mere appearance of the involved muscles seems to furnish no sufficient explanation.

The peculiarities which have been described in station, locomotion, and the act of rising to a vertical position nevertheless all depend on such anatomical lesions of the muscles of the back and lower extremities as render the adequate performance of their functions impossible. Thus, the widening of the base of support by straddling the legs is necessitated by weakness in all the extensor muscles of the limbs—the glutæi, quadriceps, and gastrocnemii—which by their tension should normally provide solid columns for the support of the trunk. The lordosis begins with the first difficulty experienced in steadying the heels, but is increased when the gluteals become incapable of extending the pelvis on the femurs and when the sacro-lumbales are unable to extend the vertebral column on the pelvis. The backward projection of the shoulders, effected by the extensors of the upper portion of the spine, is an instinctive compensation for the lordosis, to prevent the trunk from falling altogether forward in front of the base of support.

The lateral oscillations of the trunk have been variously explained. Duchenne attributed them to weakness of the gluteus medius. This muscle, he asserted, is normally designed to restrain the tendency of the pelvis at each step to incline toward the leg which is off the ground.³⁰ But, in reality, during the act of walking, the pelvis, and the trunk with it, are inclined toward the leg which is fixed, rotating upon the head of the femur on that side, and being slightly elevated on the opposite side, where the leg is being swung forward. This elevation assists in enabling the swinging leg to clear the ground (Ross, Hueter). The rotation is accomplished by the gluteal abductors on the active or fixed side, the femoral extremity of these muscles being fixed. Weakness of the gluteals must interfere with this rotation, and should therefore diminish lateral oscillation did this depend on the rotary movement.

³⁰ Archives gén., 1868, p. 28.

In a case examined by Ross, in which the lateral oscillation was much marked, contractions of the gluteus medius were distinctly perceptible to the hand placed just above the great trochanter. In another case, where the gluteals were entirely destroyed, the oscillation, on the contrary, was barely perceptible. Ross himself explains the phenomenon more plausibly as a simple exaggeration of what occurs in normal locomotion. In this the centre of gravity is necessarily shifted at each step from the movable to the fixed leg by the inclination of the trunk and shoulders to the side of the latter. When the legs are placed far apart the body must incline farther in order to bring the weight in the same relative position. Moreover, from the weakness of the anterior tibial muscles the dorsal flexion of the foot, which should take place at the moment the leg is lifted off the ground, is impeded or rendered impossible; and the inclination of the pelvis on one side, which necessitates its increased elevation on the other, thus favors the swinging of the leg by leaving more room between the trunk and the ground (Ross).

The curious manner in which pseudo-hypertrophic patients rise from a sitting or recumbent position has been carefully studied by Gowers, and minutely analyzed by Ross in an adult case. The act to be accomplished demands a series of extensions of the leg and pelvis on the thigh and of the vertebral column on the pelvis. As the extensor muscles are all paretic, this can only be effected by means of the muscles of the upper extremities and of the weight of the body, which the arms compel to serve as a motor force. Thus, from a recumbent position the patient rolls upon his hands and knees: then, grasping the knee, he lifts the leg upright with the foot planted on the ground. The thighs remain strongly flexed, the trunk bent forward over the thighs. The action of grasping the thighs above the knees, which is so characteristic, serves to extend them by a double mechanism. In the first place, the knee-joints are pressed slowly but directly backward. In the second place, by the intermediary of the arms the weight of the body is transferred from the upper end of the femur, above the power of the quadriceps extensor, to the lower end of the lever, near the fulcrum at the knee. Thus a lever of the third order, with the power between the fulcrum and the weight, is partly transformed into a lever of the second order, with the weight between the fulcrum and the power; and thus the enfeebled quadriceps is able to act to more advantage. Moreover, when the body inclines so far forward that the centre of gravity is carried in front of the knees, it then becomes a force applied to the upper end of the femur capable of extending the knees without any action of the quadriceps.

When extension of the knee-joints is nearly complete, extension of the pelvis on the femurs is effected by grasping the thighs alternately higher and higher. By this manoeuvre the femur is pushed back and the trunk is pushed up; and thus is compensated the incapacity of the glutæi to perform their normal action of pulling up the pelvis flexed on the femurs. Enough power remains in these muscles, however, for a long time to complete the extension when, by the pushing movement, this has been nearly effected.

During these actions the patient constantly oscillates the trunk from side to side as he transfers the centre of gravity from one foot to the other. In this, the second stage of the disease, and where the same functional disturbances may arise with very various combinations of hypertrophy and atrophy in the muscles of the lower extremities, a third set of symptoms appears—certain deformities, namely, depending on muscular shrinkage. The earliest, and often the most marked, of these is talipes equinus. The patient becomes unable to plant his heels firmly on the ground, and these are gradually drawn up higher and higher, the patient resting first on the toes, then on the anterior surfaces of the phalanges; ultimately is unable to stand at all, the foot being drawn into a line with the leg, and the astragalus not unfrequently luxated. Some authors explain this deformity by the preponderating action of the gastrocnemius. The paralysis of this muscle, which coincides with its hypertrophy, even when not quite proportioned to it, renders such an explanation highly improbable. The elevation of the heel is due to the gradual shrinkage of the muscular tissue which accompanies the pseudo-hypertrophy; and on this account the talipes is at every stage of its development irreducible.

The other possible deformities in the lower extremities are permanent flexions at the knee- or hip-joints. Both existed in the case recently described by Pekelharing.³¹ Before the disease has reached its maximum degree of development in the lower extremities, its progress has usually been marked in another manner—namely, by the invasion of the trunk and arms. In cases 19-22 of Gowers's remarkable series, where four boys out of a family of ten children were affected by the disease, the hypertrophy first involved all the muscles of the lower extremities, and then passed to the trunk and arms.³²

³¹ Loc. cit.

³² Three other boys in this family, and three girls, remained healthy.

The description of the disease in the upper half of the body may be distinctly separated from that in the lower half, on account of the remarkable differences observed in the mode of the muscular degeneration. In the lower extremities and pelvis primary pseudo-hypertrophy is the rule; atrophy is almost invariably secondary, and below the hips is rarely excessive.³³ In the upper part of the body primary atrophy is the rule for certain muscles, and succeeds rather early to the pseudo-hypertrophy which affects others. Only a few muscles habitually hypertrophy, and remain enlarged until a somewhat advanced period of the disease. The first in this group is the deltoid, which not unfrequently enlarges simultaneously with the gastrocnemii.³⁴ In one case the triceps humeri, and after that the biceps, are the next most frequently hypertrophied,³⁵ in some cases even together with atrophy of the deltoids (2d case Seidel). In exceptional cases all the muscles surrounding the shoulder-joint, especially those covering the scapula, are hypertrophied. Thus in the early case of Coste and Gioga³⁶ the latissimus dorsi and trapezius were hypertrophied, together with the deltoids, and even the muscles of mastication and the tongue. In this case not only the quadratus lumborum, but also the recti abdominis muscles, were hypertrophied. In Chrostek's case the tongue was hypertrophied, although all the shoulder-muscles, and also the sterno-cleido-mastoids, were atrophied.³⁷ In Duchenne's third case the temporal and masseter muscles were hypertrophied, while no alteration of size in any direction was observed in the arms or shoulders. In Duchenne's twelfth case all the muscles of the body, including the face, were hypertrophied, with the single exception of the pectorals. In Barth's second case, the left sterno-mastoid, the supra and infra spinali, together with the left deltoid, were hypertrophied.

³³ The quadricipites femoris, as already noticed, are not unfrequently wasted.

³⁴ See cases of Kaulich, hypertrophy of calves, thighs, deltoids; Heller, hypertrophy of all muscles of lower limbs, also of abdomen with deltoids; Benedikt (4th and 6th cases); Friedreich (1st case); Adams; Gowers (4th and 11th); Ross (2 cases); Brieger. In a case by Clarke (Med.-Chir. Trans., vol. lvii.) the deltoids were observed to be large seven years after the beginning of the disease. In a case by Duchenne the enlargement of the deltoids, by great exception, preceded that of the gastrocnemii by several months.

³⁵ Cases of hypertrophy triceps or biceps: Seidel (2d), Rinecker, Griesinger, Wagner (2d, triceps without deltoid), Knoll, Rakowac, Pekelharing, Spielmann (atrophy deltoid).

³⁶ Schmidt's Jahrb., Bd. xxiv. S. 196. Other cases are given by Wernich (hypertrophy of rhomboids), Barth, Gowers (11th).

³⁷ Oesterreich Zeitschrift f. prakt. Heilk., 1871.

In the majority of cases, however, at the time the patient came under observation all the muscles above the quadratus lumborum were atrophied, except the deltoids. In the pectoral, which has never been found hypertrophied, the wasting process always sets in the earliest, and advances to the greatest extent. The pectoral muscle is thus the exact antithesis of the gastrocnemius, while the deltoid more nearly resembles the gastrocnemius than any other muscle of the upper extremity. After the pectoral the latissimus dorsi, then the trapezius scapular muscles (including the serratus magnus), those of the arm and fore arm, the muscles of the neck, are found more or less wasted by the time the disease is fully developed. The wasting is sometimes extreme, as in a case described by Gowers, where the patient maintained a permanently crouching attitude, the spinal column being in extreme cyphosis, all its processes projecting, from the extreme emaciation of the trunk.

In Eulenburg's adult case³⁸ the atrophy began in the hands, and was regarded by him as a combination of true progressive muscular atrophy in the upper, with lipomatosis musculorum luxurians in the lower extremities.³⁹

³⁸ Virch. Arch., Bd. xlix., 1870.

³⁹ Cases of atrophy (often excepting deltoids): 1st case by Seidel, "simultaneous paresis in upper and lower extremities in four years; atrophy of arms and thighs, with hypertrophy of calves and fore arms; in six years, primary atrophy sterno-cleido-mastoids and pectorals; secondary atrophy of deltoids."

Further: case of Kaulich (atrophy of shoulder-muscles, including deltoid, while triceps and biceps hypertrophied); Duchenne fils; Eulenburg and Cohnheim; Heller (2 cases); Wagner (2d case); Wernich (1st case); Lutz (a girl, case much resembling Eulenburg's adult case); Roquette (atrophy of thighs as well); Hoffmann; Russel; Foster (atrophy of muscles of forearm); Chrostek (notwithstanding hypertrophy of tongue); Friedreich (2 cases); Duchenne (2d); Wagner (2d and 3d); Gowers (9 cases); Ross (2 cases).

Gowers attaches diagnostic importance to the early signs of atrophy in the latissimus dorsi and great pectoral muscles. The time of their invasion contrasts with that in progressive muscular atrophy, where the process usually begins in the hands and creeps upward to the shoulder-joint.

Neither the atrophic nor the hypertrophic process is necessarily symmetrical on the two sides of the body, but an approximate symmetry is usually observed. The same muscles are usually affected, and in the same way, but not often precisely to the same degree. Fibrillary contractions often occur in the wasting muscles, but not in those which are hypertrophied. The electrical reactions, however, do not differ greatly in the two states. The faradic contractility diminishes in proportion to the diminution in the contractile mass of the muscle, whether this be concealed by the growth of fat and connective tissue or rendered obvious by the general wasting of the whole. But even when contractions can be obtained, these are often abnormally feeble, and by continual diminution in the number of contractile fibres, and increase in the lipomatous masses overlying them, the electrical irritability is ultimately lost. The excitability of the nerves remains intact, and therefore response may be obtained by an indirect excitation after direct excitation of the muscle fails to elicit one.

Eulenburg has occasionally observed one curious phenomenon in the galvanic reaction of nerves. The anode opening contraction grows weaker or even disappears with a progressively stronger current, and then with a still stronger current reappears. This is due to a cross action of the current on the excitability and on the conductibility of the nerve. At a certain moment the increased excitability is compensated by a corresponding increase in the resistance to conduction, and therefore all electrical response ceases. Later, the resistance remaining the same, the excitability is increased and the reaction reappears.

The symptoms of the first order (disturbance of muscular function) and of the third (deformity) are for a long time less conspicuous in the upper than in the lower extremities. When the arms begin to be paretic the patient is crippled in the characteristic manoeuvres by which, during the earlier period of the disease, he palliates the inefficiency of the lower limbs. When he can no longer push up the trunk by means of his arms, he becomes unable to rise from a sitting position at all. Further progress in the atrophy of the erectores spinæ muscles renders even the act of sitting impossible: the patient can only crouch, and ultimately must remain altogether recumbent. The functions of the hands usually remain unimpaired to the last, so that the unfortunate patient is able to amuse himself with knitting and other light work.

Besides the paralytic cyphosis, scoliosis of a high grade is sometimes, though infrequently, developed. It is due to the lateral oscillations with excessive inclination of the upper portion of the trunk.⁴⁰

⁴⁰ Cases of scoliosis from such cause, where inequality of muscular action cannot be invoked as a cause, help to throw light on the real etiology of the idiopathic deformity so often attributed to irregular muscular action.

It is rare that any researches have been made on the nutritive functions in pseudo-hypertrophic paralysis. Seidel⁴¹ has analyzed the urine in the two cases (brothers) which form the basis of his memoir. He expected to find a marked diminution in the urea, corresponding to the diminution in the mass and in the functional activity of the muscles. This expectation was based on the assumption, at present considered incorrect, that the elimination of urea is modified by muscular contractions. In the cases examined the actual amount of urea was considerable, rising on several occasions to 40, 43, and 69 grammes in twenty-four hours, and offering, in the first boy, a daily average of 41 grammes. But Scherer estimates that the average elimination of urea in children is, per kilogramme, double that in adults; and on the basis of this calculation the amount of urea eliminated by the patient in question should have been 51 grammes. There was therefore a diminution of about one-fifth.

⁴¹ Atrophia Musculorum Lipomatosa, Jena, 1867.

Seidel has also examined the temperature of the diseased muscles during their contraction either under the influence of the will or of the faradic current. The hypertrophied gastrocnemius muscle showed a rise of 1.5° to 2° less than a healthy gastrocnemius similarly excited. The rise of temperature never occurred during the contraction, but during the ten or fifteen minutes which followed it. The duration of this rise of temperature was always longer than in the control experiment performed on a healthy subject. The observation was the same in hypertrophied and in atrophied muscles, and indicated a notable diminution of heat-production in both.⁴²

⁴² Loc. cit., p. 54.

The mental functions are not unfrequently impaired. The defective intelligence exhibited by several of his first patients led Duchenne to attribute a cerebral origin to the disease. The internal hydrocephalus discovered at the autopsy of the case so recently published by Pekelharing suggests that this hypothesis may have been too hastily abandoned, and that it may really prove to be correct for certain cases. In many, however, the intelligence is intact or even precocious, and all suspicion of cerebral lesion must be excluded.

COURSE OF THE DISEASE.—As already stated, a period of paresis may precede all signs of hypertrophy for several weeks, months, or even years. From the time that the enlargement of the calves has once begun about a year and a half is required before the maximum of hypertrophy is attained. Then the disease usually remains stationary for two or three years before the third period is ushered in by aggravation of paralysis in the lower and by extension of paralysis, together with hypertrophy or atrophy, to the upper limbs.

When, from complete loss of muscular power, the patient has become permanently condemned to a recumbent position, life may nevertheless be prolonged for ten or twelve years, with integrity of all the vegetative functions. Death finally takes place, in all recorded cases, from some acute pulmonary disease, whose effects are intensified by the atrophy of the external respiratory muscles, which often extends even to the intercostals.

The course of the disease, and consequent prognosis, is much modified in the rare cases in which it attacks girls. Two of Duchenne's thirteen cases were girls: in one the disease was spontaneously arrested, in the other apparently cured. Lutz⁴³ relates the altogether exceptional history of a family in which five female members were affected—two sisters, also one step-sister, daughter of the mother by an earlier marriage, a sister and niece of the mother, of whom a brother also was diseased. The step-sister and niece both died at six years of age, but the aunt lived to be forty-three (the brother to be forty-two), and one of the girls observed by Lutz, who began to suffer at the age of six, was twenty-eight at the time of observation: paresis had only become marked at seventeen, and locomotion impossible at twenty-two. In the other girl the first symptoms appeared at seventeen, and at twenty-two were still moderate and confined to the lower extremities.

⁴³ Deutsches Archiv f. klin. Med., Bd. iii., 1867.

In Roquette's female case⁴⁴ the disease began at ten; in Hoffman's,⁴⁵ at eleven and a half. These cases, with one of Benedikt's, are the only female cases among the 88 I have analyzed.⁴⁶ Gowers estimates 30 female cases out of a total of 220, or only 13 per cent. of the whole.

⁴⁴ Inaug. Dissert., Berlin, 1868, quoted by Friedreich.

⁴⁵ Ibid., 1867.

⁴⁶ This excludes the adult cases of Eulenburg, where "progressive atrophy of the upper extremities combined with pseudo-hypertrophy of the lower;" the case of Barth, an amyotrophic lateral sclerosis; the case of Müller, a dementia paralytica; and the case of Billroth, where the lesion was localized in the hamstring muscles of one thigh.

This great preponderance in the male sex is the first of three striking peculiarities which distinguish the clinical history of the disease. The second is its strangely-marked hereditary character. This is not, and indeed hardly could be, shown in a direct line, since the patients are incapable of marriage, or even die before arriving at maturity. But several brothers in a family are usually afflicted. There was, it is true, no trace of heredity in Duchenne's 13 cases, but this author himself recognizes the frequency of hereditary influence in those observed by others. Out of 81 cases analyzed by Friedreich, two or more members of one family were attacked thirty-five times. Thus, the first clinical report, that made by Meryon, described four brothers in one family and two in another. Coste, Griesinger, Wernich, Benedikt, Adams, Russel, Gowers, each relate cases of two members in one family; Heller, Wagner, Billroth, Seidel, have seen three: Moore⁴⁷ describes three cases out of a family of seven, consisting of five boys and two girls. Two of the cases I myself have seen were brothers. Gowers⁴⁸ relates five cases in the families of two sisters who married two brothers. This same writer refers to three other families in which two brothers were affected; to a fourth family described by Clifford Albutt, where two brothers were paralyzed, the third child dying of Hodgkin's disease; finally, to the family of a clergyman, himself living to the age of seventy-four, having always had large calves, and out of whose eight children two boys and one girl were affected.

⁴⁷ Lancet, 1880.

⁴⁸ Loc. cit., Appendix.

The families invaded by this singular disease are often remarkably large, and even where several children are affected, many others, even boys, escape. The morbid inheritance is always through the mother, "thus through the ovum—a condition unknown in diseases of the nervous system" (Gowers). This peculiarity belongs to only one other disease, hæmophilia, also almost limited to males. The third fact, which from its all but universality is shown to be of fundamental importance, is that the disease begins during infancy or early childhood. It has been shown that more than two-thirds of all cases began before the age of six. Whether there is ever an intra-uterine origin is still doubtful (Friedreich). This early invasion, often coinciding with the first efforts to walk or to use the muscles which are first attacked, distinctly separates pseudo-hypertrophic paralysis from all diseases which can be traced to definite accidents or to perversion of functions. It implies a profound perversion of nutrition, or rather a misdirection of developmental force.

PATHOLOGICAL ANATOMY.—The anatomical lesions of pseudo-hypertrophic paralysis are to be sought first in the muscles, afterward in the spinal cord, upon which so many peripheric lesions of the nervo-muscular system have recently been shown to depend. The argument from analogy, therefore, has of itself almost sufficed to create a conviction that some disease of the central nervous organs must exist as the real basis of pseudo-muscular hypertrophy.⁴⁹ Nevertheless, as will presently be shown, the present evidence in favor of such hypothesis is extremely small.

⁴⁹ This conviction is fully expressed by Hammond, loc. cit.

Muscular Lesions.—In the muscles, however, the anatomical changes are profound and varied. They may be divided into three kinds—those affecting the muscular fibre itself; those touching the connective tissue; and, finally, the fat deposited in this.

The lesions of these different elements are variously combined with each other in different muscles, and also at different stages of the disease. Thus, in the muscles of the trunk and upper extremities affected with primary atrophy the increase of fat is always moderate and quite insufficient to compensate the wasting of the contractile mass, while in the gastrocnemii and gluteal muscles the hypertrophied masses are often found to consist entirely of fat, traversed by bands of connective tissue, and indistinguishable from a lipoma.

The muscles have been examined in two ways—in the course of a general post-mortem examination, and also during life by means of excision or extraction by various instruments. Griesinger in 1864⁵⁰ excised a piece of the deltoid in a boy of thirteen,⁵¹ and made on it, with Billroth, the first microscopic examination of the diseased muscles. Duchenne, to avoid an operation not devoid of danger for the patient, devised his harpoon, by means of which small fragments of muscles could be torn away. As this instrument is liable to change the relations of the parts separated by tearing, Leech has contrived another, in which the fragment is removed by cutting. By one method or another of harpooning the muscular lesions have been studied during life by Duchenne, Heller, Wernich, Russel, Eulenburg, Martini, Knoll, Rakowac, Friedreich, Ross, Gowers, Auerbach, Hammond, Pepper, in the cases already quoted.

⁵⁰ Archiv der Heilkunde.

⁵¹ The wound suppurated for a long time.

Muscular Fibre.—There are contradictory opinions in regard to the first stage of alteration in the muscular fibres. According to most observers, the fibres are seen to directly atrophy; the transverse striæ become dim and gradually disappear, and the primitive bundles shrink in diameter from loss of some of their fibrillæ (Brieger, Hammond, Pepper). Friedreich⁵² adds that the complete collapse of the contractile substance in the primitive bundles often leaves empty or shrunken sarcolemma sheaths, which swell the mass of the connective tissue. Friedreich, however, denies that the striation is modified; and its extreme fineness, commented upon by Duchenne, is considered by Ollivier⁵³ and Ranvier as devoid of pathological significance.

⁵² Loc. cit., p. 300.

⁵³ Des Atrophies musculaires, Thèse d'Agrégation.

The real size of the primitive fibres is best estimated by the method of Cohnheim, who isolated the fibres by boiling the muscular fragment from four to six hours in a mixture containing 100 c.c. of 90 per cent. alcohol and ¾ c.c. of concentrated muriatic acid. Many were found reduced to one-fifteenth or one-sixteenth their normal size.⁵⁴ Between atrophied fibres lay a peculiar striped tissue, probably composed of empty sarcolemma sheaths. Side by side with these atrophied fibres were many normal, and others grossly hypertrophied to two or even three times the normal calibre. These were only found in the hyper-voluminous muscles. Some of these exceeded the largest frog-muscle fibres. They lay in bundles of four to six between the small fibres, and seemed to be about equally distributed through the hypertrophied gastrocnemius and atrophied biceps.⁵⁵

⁵⁴ Berlin. klin. Wochensch., 1865, No. 56.

⁵⁵ Hypertrophied fibres have also been seen by Knoll (Medizin Jahrbuch., Wien, 1872), Müller, and Eulenburg.

Another alteration observed in the muscular fibres was their dichotomous and even trichotomous division. This same lesion has been seen by Friedreich in progressive muscular atrophy.

The presence of hypertrophied fibres in wasting muscles lends a special significance to the cases of true muscular hypertrophy described by Auerbach⁵⁶ and Hitzig.⁵⁷ Auerbach's observation related to a soldier aged twenty-one, whose upper arm became rather rapidly hypertrophied and paretic. In a fragment excised from the enlarged biceps the fibres were seen to have a diameter of from 96 to 180 µ. (the normal diameter being 33 to 67 µ.). The other arm was not enlarged, and yet examination of fibres obtained by means of a similar excision found them also enlarged. Auerbach suggests that this hypertrophy constituted a preliminary stage in the general process of pseudo-hypertrophic paralysis. In it, as when the excessive volume is known to depend upon the presence of non-contractile tissue, the arm, far from increasing in strength, was paretic.⁵⁸

⁵⁶ Virch. Arch., Bd. liii., 1871.

⁵⁷ Berlin. klin. Wochen., Dec. 2, 1872.

⁵⁸ Mobius (loc. cit.) declares that neither of these cases bears any relation to pseudo-hypertrophy.

Connective Tissue.—Far more conspicuous than the alterations in the contractile fibre of the muscles are those of its connective tissue. The perimysium internum, between the primitive bundles, proliferates abundantly, and the hyperplasia gradually extends correlatively with the wasting of the muscular fibres, until the hypertrophied mass is mainly composed of connective tissue. Broad bands replace the thin lamellæ normally present between the primitive bundles; the parenchyma of the muscle seems stifled in a sclerosis. It is then that it offers the feeling of stony hardness so often noticed in the clinical history.

Charcot, Knoll, Müller, and Barth describe a rich development of nuclei and of spindle-shaped cells in this new connective tissue, this being especially abundant in the neighborhood of the small vessels and in their adventitia. Eulenburg and Leyden, however, affirm that the connective tissue is unusually poor in nuclei, and thence infer that the hyperplasia is compensatory, and not due to inflammation.

In some cases, as in those of Duchenne examined by Ordonez, the sclerosis and atrophy of contractile tissue constitute the entire lesion of the muscle. Only a few fat-cells are interspersed among the bands of connective tissue or penetrate between the primitive bundles. The fatty infiltration tends constantly to increase, apparently by the same process as governs the growth of normal adipose tissue—namely, the deposit of fat in connective-tissue cells; and ultimately not only muscular fibre, but the hyperplastic connective tissue, is concealed in a yellowish glistening mass indistinguishable from a lipoma.⁵⁹

⁵⁹ See case of Billroth.

The growth of fat contributes to the apparent hypertrophy of the diseased muscles, but much less so than does the hyperplasia of connective tissue which invariably precedes it. Great rapidity of fatty infiltration marks a more rapid and irresistible progress in the disease, a lower stage of nutritive degradation. Fat-cells are found penetrating between the primitive bundles of fibres in the atrophied as well as in the hypertrophied muscles; but there the fatty substitution is always much less complete.

In contrast with this fatty infiltration true fatty degeneration of the muscular fibre is as rare in pseudo-hypertrophy as in progressive muscular atrophy. This fact is emphasized by Pepper from observation of the harpooned fragment examined by him,⁶⁰ also by Cohnheim.⁶¹ In Meryon's first case,⁶² however, the post-mortem examination of the muscular fibres found them "totally degenerated, their substance changed into a mass of granules and oil-globules, while the sarcolemma was destroyed." In Brieger's case⁶³ the fibres were filled with fat-globules.

⁶⁰ Philada. Med. Times, 1871.

⁶¹ Loc. cit.

⁶² Med.-Chir. Trans., vol. xv., 1852.

⁶³ Deutsches Archiv, Bd. xxii.

The sclerotic process which precedes the stage of fatty infiltration is far from being completed when this latter begins. Both processes, initiated nearly at the same time, continue together, and at the death of the patient may be found existing in about equal proportion, or the one markedly predominating over the other. In cases of long duration the hypertrophied muscles, as already stated, are found converted into masses of fat, divided by stripes and bands of connective tissue. With death earlier in the disease the enlargement is found to be due to masses of connective tissue englobing muscular fibres and interspersed with fat-cells.

In the wasted whitish-red muscles the proliferation of connective tissue is sometimes more, sometimes less, marked; in the pale-yellowish muscles fat accumulates by interstitial deposit, but does not overlay and conceal the remnant of muscular fibre.

Central Nervous Organs.—While the examinations of the diseased muscles have been frequent, post-mortem examinations are still relatively few, although their records are rapidly increasing. The first was made by Meryon⁶⁴ on the first of his series of six cases. Charcot has examined a case for Duchenne; Cohnheim has made a celebrated autopsy for Eulenburg;⁶⁵ Gowers and Clarke have together published a fourth.⁶⁶ The cases by Müller and Barth are still habitually—though, as we shall see, erroneously—included among the autopsies of pseudo-hypertrophic paralysis. Ross⁶⁷ and Leach have, however, a fifth indubitable case with autopsy; and more recently Cornil,⁶⁸ Brieger,⁶⁹ Bay,⁷⁰ Schultze,⁷¹ Pekelharing,⁷² and possibly Goetz and Drummond,⁷³ have all described post-mortem examinations. The data for discussion, therefore, are to be derived from 14 cases. Of these, the spinal cord was found perfectly healthy in 7, those related by Meryon, Cohnheim, Charcot, Cornil, Brieger, Bay, Schultze—all most competent observers. The cases by Barth and Müller require some special consideration, for, although rejected as irrelevant by most authors, Hammond still adduces them in proof of the central origin of pseudo-hypertrophic paralysis.

⁶⁴ Loc. cit.

⁶⁵ Loc. cit.

⁶⁶ Med.-Chir. Trans., 1874; also monograph by Gowers.

⁶⁷ Loc. cit.

⁶⁸ Union méd., 1880.

⁶⁹ Deutsches Archiv f. klin. Med., Bd. xxii. H. 2.

⁷⁰ Virch. Jahresb., 1877.

⁷¹ Virch. Arch., 1879, Bd. lxxv.

⁷² Arch. Virch., Bd. lxxxix., 11, 2, 1882.

⁷³ Quoted by Pekelharing—the first from the Aerztliches Intelligenz Blattmünchen, 1879; the second from the Lancet, 1881, vol. ii., No. 16.

Müller's case⁷⁴ is that of a woman thirty-four years of age who at the age of four fell out of bed, and from that time began to walk with difficulty, and ultimately acquired a double talipes equinus. The right leg atrophied, the left remained of tolerable thickness. At the age of thirty-four she was admitted to an insane asylum during the incipient stage of dementia paralytica, and death occurred two years later of pneumonia. The autopsy showed—1st. That the calf-muscles on both sides were converted into masses of fat, streaked with whitish-red remnants of muscular tissue. The short muscles of the feet were atrophied; all the other muscles of the body normal. 2d. In the brain the blood-vessels showed a thickening of the adventitia by delicate connective-tissue fibrillæ, between whose meshes nucleated cells were strewed. The ependyma of the ventricles was thickened and granular, and their cavity was filled with serous effusion. 3d. In the cord was found diffused degeneration, especially of the lateral columns, consisting in thickening of the interstitial connective tissue, with proliferation of its cells; atrophy of a part of the primitive nerve-fibres with granular degeneration of the medullary sheath, and occasionally atrophy of the axis cylinder. The adventitia of the blood-vessels was thickened, the perivascular spaces dilated. In the central gray substance the ganglion-cells were everywhere intact, but the intercellular substance was thicker, and seemingly composed of a thick net of stout, finely-granular fibres. Traces of an infantile polio-myelitis were found in the lower part of the lumbar enlargement (atrophy of the anterior cornua, especially the right, together with their ganglion-cells).

⁷⁴ Beiträge zur pathol. des Ruckenmarkes, 1871.

The final lesion of importance was the obliteration of the central canal, which was moreover surrounded by a dense ring of connective tissue. In this case the suddenness of the original paresis, the atrophy of the right leg, and the lesions of the lumbar cord found at the autopsy prove that the initial disease was an acute anterior polio-myelitis. Upon this a very localized pseudo-hypertrophy seems to have been grafted during childhood, while in adult life a chronic lepto-meningitis and internal hydrocephalus were certainly the cause of the symptoms, and probably of the lesions in the cord.

That such lesions in the cord may be the consequence of chronic hydrocephalus is well argued by Pekelharing in regard to his own recently published case, which in some respects closely resembles that by Müller. The patient was a boy in whom muscular paresis was congenital, and who from birth had exhibited deficient intelligence with an abnormally large head. At the autopsy, made at fourteen, ventricular effusion was found in the brain, and in the cord irregular dilatation of the central canal and great dilatation of blood-vessels and accumulation of leucocytes in its immediate neighborhood. Some ganglion-cells in the inner and anterior groups of the anterior cornua were shrunken and deprived of their prolongations. The author suggests that in this case the cerebral hydrocephalus was the primary disease; that the central canal in the spinal cord was dilated by extension of the effusion from the brain; that a partial reabsorption of such effusion had caused hyperæmia ex vacuo in the tissue immediately surrounding the canal; and that the emigration of leucocytes and partial alteration of the ganglion-cells both resulted from this hyperæmia.

In Müller's case the central canal and adjacent tissue were also the part of the cord most diseased; but the canal was obliterated by proliferation of the ependyma, not dilated. In Barth's case also⁷⁵ the central canal of the cord was found obliterated. The patient was a man of forty-four, who since the age of forty had suffered from stiffness in the left ankle and difficulty of walking. After a year the stiffness extended to the right ankle; in two years the paresis had mounted to the thighs, and was accompanied by severe pains. Paresis and pain then appeared in the upper extremities, which gradually atrophied. After two years the patient was entirely confined to bed, and two years later was unable even to sit up. Later, the muscles of the neck became hypertrophied. No mention is made of perceptible hypertrophy in other muscles, nor of contractions or tremors other than fibrillary. But at the autopsy was discovered a lateral sclerosis extending the entire length of the cord, associated with partial atrophy of the ganglion-cells in the anterior cornua. In both the gray and white substances the blood-vessels were dilated, and, as already stated, the central canal was obliterated. The brain was healthy. The supinators of the upper extremities, the gastrocnemii at the lower, were richly infiltrated with fat streaked with long bands of connective tissue; the remaining muscles were atrophied.

⁷⁵ Archiv der Heilkunde, xii. 2, 1871.

The anatomical lesions in this case are identical with those of the special symptom-complex described by Charcot as amyotrophic lateral sclerosis. Certain symptoms of lateral sclerosis are wanting to complete the clinical history, but at least as many are lacking for a typical history of pseudo-hypertrophic paralysis. Only the muscles of the neck hypertrophied: the gastrocnemii and adductors, primarily atrophied, later regained some of their original size. The fatty infiltration of the calf and muscles was unattended by pseudo-enlargement or by retraction: it resembled a fatty substitution due to nerve-paralysis, rather than the hyperplastic process of pseudo-hypertrophy.

Setting aside the three foregoing cases, three remain which, together with an unimpeachable history of pseudo-hypertrophic paralysis, show positive lesions in the spinal cord. The first and the most famous was made upon a patient of Gowers by Lockhart Clarke.⁷⁶ Changes were found scattered through the entire length of the cord. "In the upper cervical region were patches of incipient disintegration in the gray network of the lateral portion of the cord, the lateral white columns being healthy. Here and there in the gray substance of the anterior and posterior cornua the intercellular matrix was wasted and disintegrated, especially in the neighborhood of the blood-vessels and at the bottom of the anterior median fissure. Here were accumulated globules of myeline and other débris of nerve-tissue. The blood-vessels were distended, their perivascular spaces enlarged. Patches of disintegration of nerve-fibres of the lateral and posterior columns were seen in the lower cervical and in the dorsal regions. Globules of myeline and masses of fatty matter were at some points accumulated at the entrance of the posterior nerve-roots, and even, to a much less extent, adjacent to the anterior roots. The most extensive lesion existed in the lowest part of the dorsal region. In the lateral gray substance on each side was an area of softening containing an actual cavity just outside each posterior vesicular column. The latter remained undamaged.

"The anterior cornua throughout the cord were perfectly normal, though the processes of the cells were perhaps less distinct than elsewhere. Further, notwithstanding the spots of disintegration in the lateral columns there was in them no change comparable to that of lateral sclerosis."⁷⁷

⁷⁶ Med.-Chir. Trans., 1874.

⁷⁷ This autopsy was made on a boy of fifteen, in whom the calves began to hypertrophy at three, and reached their maximum size at five.

The second post-mortem was made by Ross on a patient belonging to Leech: "In the lumbar region of the cord the normal loose and spongy texture of the central column was replaced by a somewhat dense and fibrillated tissue, in which no trace of ganglion-cells could be found. The blood-vessels were enlarged and their walls thickened. In the anterior cornua the ganglion-cells had completely disappeared from the median area, the anterior group, and from the margins of all the other groups. This atrophic process extended into the dorsal and cervical region, and in the latter the central column was changed in the manner already described."⁷⁸

⁷⁸ Loc. cit., p. 207. Patient was nine years old at time of death; the disease had begun with paresis at two; was well developed at nine.

The third autopsy is recorded by Drummond in the Lancet for 1881 (vol. ii.): The subject was a boy of fourteen, who never walked after the age of six. There was found, as the author shows by some good drawings, disintegration in the lateral gray network of fibres halfway between the anterior and posterior horns, extending more or less throughout the cord. In the left lumbar region the tissue had broken down, and a cavity existed filled with serum, which bulged out the wall of the cord, forming an apparent tumor.

Several circumstances are common to all the foregoing five cases. In all, the patients during life had exhibited paresis and atrophy of a large number of muscles (in Barth's case nearly all), with pseudo-hypertrophy of some muscles of the lower extremities. In all, the post-mortem found fatty substitution for muscular fibre in both the atrophied and the hypertrophied muscles. Finally, in all, the lesions found in the cord were principally grouped about the central canal. This was dilated (Pekelharing) or obliterated (Müller, Barth); the hyperæmia was always most intense in its vicinity; and it was in the lateral gray substance adjoining, or in the gray network between it and the lateral white columns, that patches of disintegration were principally noted (Clarke, Ross). Negatively, the absence of any extensive lesion of the anterior cornua is noteworthy in all the cases but one; and here this lesion was evidently secondary to the lateral sclerosis (Barth). On the other hand, the differences between these cases were as numerous as the resemblances. Two resembled each other in the presence of cerebral symptoms and of an internal hydrocephalus to account for them (Pekelharing, Müller); in one alone was there lateral sclerosis (Barth); in one, cavities in the lateral portion of the central gray column (Clarke); in one, traces of an acute polio-myelitis (Müller), Finally, in only three cases (Clarke, Ross, Drummond) was the clinical history perfectly characteristic of the disease.

Comparing these facts with the others, equally significant, where the autopsy in cases of pseudo-muscular hypertrophy has shown the central nervous organs to be perfectly healthy, we should be led to conclude—1st. That if fatty substitution in the muscles is ever to be associated with lesions of the spinal cord, these are to be sought in the central gray substance surrounding the central canal. 2d. That, nevertheless, muscular lesions similar, if not in all respects identical, can develop as the result of an idiopathic process depending on causes at present unknown. 3d. That atrophy of muscular fibre and replacement of it by lipomatous fat are probably determined in several different ways, and must often be regarded as merely secondary processes;⁷⁹ but that the muscular lesion characteristic of pseudo-hypertrophy, considered as an idiopathic disease, is the hyperplasia of connective tissue which originates in the perimysium interum of the muscles. This lesion was well marked in the Ross-Leech case, much less distinct in the three we have noted as doubtful (Gowers).

⁷⁹ See Leyden's remarks in his essay "Ueber Polio-myelitis und Neuritis," Zeitschrift für klin. Med., 1880.

PATHOGENY.—These last conclusions, if valid, supersede the necessity for prolonged discussion of the question whether pseudo-hypertrophic paralysis be a peripheric disease or central disease. By the latter term authors almost invariably mean a disease dependent on morbid processes in the spinal cord. Hammond is almost alone in affirming that these exist, and bases his opinion on only three autopsies, of which two are the doubtful cases of Müller and Barth. Mobius,⁸⁰ recognizing the frequent absence of spinal lesions, nevertheless claims that the hereditary, frequently congenital, nature of the disease proves that it inheres in the nervous system. Gowers, however, points out that the exclusive inheritance through the mother—that is, from the ovum—is a circumstance unknown in nervous diseases. This mode of inheritance is observed in hæmophilia, which also resembles pseudo-hypertrophy in being almost confined to males.

⁸⁰ Volkmann's Sammlung, No. 171.

The pseudo-muscular hypertrophy of children so strikingly resembles in many particulars the progressive muscular atrophy of adults that the theory of their essential identity could not fail to suggest itself. Friedreich unhesitatingly advocates this theory. Many of the facts which support it become for him additional confirmation of the peripheric nature of the adult disease, where, nevertheless, the anterior ganglion-cells of the cord are habitually found atrophied.⁸¹

⁸¹ According to the Friedreich theory, the lesion of the anterior cornua is coincident with or consecutive to degeneration of the other extremity of the nervo-muscular motor apparatus.

Lichtheim, Arch. f. Psych., viii., quoted in Brain, 1879, vol. ii., No. 1, quotes a case of progressive muscular atrophy with typical changes in the muscles, but unaccompanied by the slightest change in the nerves or nerve-roots, large ganglion-cells of the anterior cornua, or other part of the spinal cord. The author agrees in regarding the nearly allied pseudo-hypertrophic paralysis as a peripheric affection. See also Hayem.

Eulenburg thus sums up the relations between progressive muscular atrophy and pseudo-hypertrophic paralysis: In both diseases the fundamental muscular lesion consists in a chronic irritative process, which starts from the interstitial connective tissue, and secondarily affects the muscular fibre. In children, pseudo-hypertrophy of the muscles of the lower extremities is regularly followed by primary atrophy of many of the muscles in the upper half of the body, and secondary atrophy in almost all. In a case of Eulenburg's the two typical diseases seemed to coexist in the same patient, an adult woman. More frequently they coexist in the same family, as in the observation by Russel, where two brothers suffered from progressive atrophy, a third from pseudo-hypertrophic paralysis.

Pick⁸² relates a case where a typical atrophy of the upper extremities and of the trunk was accompanied by moderate hypertrophy of the calves, with proliferation in the calf-muscles of the interstitial fat and connective tissue. Charcot admits a special form of atrophia musculorum lipomatosa which complicates progressive muscular atrophy, and is associated, therefore, with atrophy of the anterior ganglion-cells; with which, however, it has no direct connection.

⁸² "Ueber einen Fall von progressive muskel atrophie," Archiv für Psych., Bd. vi., 1876.

The adult and infantile muscular diseases differ by the remarkable, and sometimes even colossal, apparent development of the calf-muscles through the excessive development in them of fat and connective tissue—by the fact that the latter disease invariably begins in the lower extremities, and is almost peculiar to childhood, while the progressive atrophy begins in the upper half of the body, and usually the hands, and is as nearly exclusively limited to adult life. For both diseases may be admitted, with Friedreich, "a congenital nutritive and formative weakness of the striated muscle-substance" (Gowers). But, we may add, in progressive atrophy this does not become manifest until the muscles have been for many years subjected to the strain of constant employment: in pseudo-hypertrophy the nutritive failure appears early in the flagging of the developmental forces at the moment that these are strained in muscular growth.

It would perhaps be more correct to ascribe the error of development to a perversion of nutritive forces rather than to their weakness. For there is no arrest in the general development of the limbs, such as occurs after infantile spinal paralysis: the bones grow normally; the initial lesion is hyperplasia of the connective tissue—possibly, also, true hypertrophy of the muscular fibre. The wasting is secondary. Perhaps the terminal nerve-plates, or else the capillary network on the outside of the primitive bundles of muscle-fibre, does not grow in proportion to the increasing mass, and therefore becomes insufficient for its nutrition (Auerbach).

The question arises whether the primitive error of development does not lie in the capillary network. Ranvier has shown that the capillaries of muscles are specially adapted to them, being disposed in quadrangles, at whose corners the vascular canal dilates into little pouches. It is surmised that these pouches serve as reservoirs to hold an extra supply of blood for the moment of contraction.⁸³ If such specialty of structure be necessary for the proper accomplishment of the muscular contraction, it is evident that any congenital defect in the arrangement of the blood-vessels might disturb in many ways the balance of muscular nutrition. The absence of vascular reservoirs, for instance, would render the supply of blood during the contraction insufficient: the contraction must then be inadequate or exhausting, and the physiological stimulus to the growth of the muscle wanting. On the other hand, the capillaries being, by the hypothesis, adapted to the lower type which nourishes connective tissue, this would become nourished at the expense of the contractile fibre, and the known hyperplasia would result.

⁸³ Cours d'Anatomie au Collège de France, 1880.

That morbid vascularization exists, is shown by the peculiar mottled appearance of the skin, which has often been interpreted as a proof of vaso-motor paralysis (Duchenne). On such an hypothesis, further, the curious and otherwise inexplicable relations between pseudo-hypertrophy and hæmophilia⁸⁴ would be explained. The one or the other hereditary disease would be due to imperfection in the blood-vessels—here of structure, there of architecture. This imperfection could be directly traced to the mesoblast in the embryo, in which the vascular tissues exclusively originate. Whether we should admit the bold speculation of His⁸⁵ that the tissues of the mesoblast are exclusively derived from the ovum, while the archiblastic tissues—the nervous, muscular, epithelial, and glandular—come from the substance of the spermatozoa fused with it, is beyond the scope of this paper to discuss. But were this speculation well founded, the independent morbid tendencies of the mesoblast would be rendered by so much the more plausible.

⁸⁴ Part of which do not exist between pseudo-hypertrophy and progressive atrophy, since the latter disease is not exclusively inherited through the mother.

⁸⁵ Unsere Körper Form.

The fact that the disease begins in the extensor muscles of the lower extremities is probably to be explained by the rapid development of these muscles during early childhood, and by the functional strain imposed on them during the effort of learning to walk. It is thus really analogous to the début of progressive atrophy in the muscles of the hands of adults—the muscles whose functional activity is the most incessant and the most complex during adult life.

The preponderance of the disease in males remains unexplained, unless it be that the greater extent of muscular development in the male necessitates a greater intensity of developmental force for the muscles, whose deficiency, therefore, would earlier be made manifest.

DIAGNOSIS.—The diagnosis of pseudo-hypertrophic paralysis can never be difficult in typical cases and at an advanced period of the disease. During the early period the diagnosis rests on the gradual diminution of force in the lower extremities, without atrophy or with apparently excellent development of their muscles; the straddling of the legs, lordosis, and lateral oscillation, all at first slight, but constantly becoming more and more emphasized; the peculiar method of rising by placing the hands on the knees and then gradually climbing up the thighs. In the second period the enlargement of the calf or other muscles of the lower limbs, in the third the extension of the paresis to the upper extremities, associated with wasting of the pectorals and usually some of the extensors of the back, confirm beyond question the diagnosis. This may be further established by examination of small fragments of muscular fibre removed by means of the harpoon or trocar, and the repeated examinations, which serve, moreover, to mark the progress of the disease.

Few diseases require to be differentiated. One very rare disease that might be confounded with pseudo-hypertrophy is the infantile form of progressive muscular atrophy. This is distinguished from the ordinary form of atrophy by beginning in the muscles of the face,⁸⁶ especially the orbicularis oris, from whose defective contractility the lips become thick and motionless. The morbid process then progresses downward, and is thus in notable contrast with that of pseudo-hypertrophy, which invariably begins in the lower limbs and extends upward, invading the face only by exception.

⁸⁶ Duchenne has seen seventeen cases of this disease.

It is probably after the establishment of talipes equinus and of flexions at the knee- or hip-joint that pseudo-hypertrophy would be most liable to be confounded with infantile atrophic paralysis. In the latter, however, the talipes is much more rarely double, and, if existing, is usually complicated with varus. At an advanced stage of pseudo-hypertrophy the enlargement of the calf is apt to be confined to its upper part, and the retraction of the lower half simulates atrophy, even when this has not really set in. At this stage, moreover, the thighs and gluteal regions are usually atrophied, so that the resemblance to an atrophic paralysis may be considerable. This may be still further increased in those rare cases of extensive polio-myelitis, where paralysis of one or more of the upper extremities coincides with lumbar paraplegia. It is extremely rare, however, that both arms are paralyzed and atrophied,⁸⁷ while this is the rule, with approximative symmetry, in pseudo-hypertrophy. In the latter disease, moreover, there are paralysis and atrophy of the muscles of the trunk and abdomen, which is scarcely ever seen, and never to the same extent, in atrophic paralysis. The reflex excitability is lost in the latter disease, as also the faradic; the latter, often intact in pseudo-hypertrophy, rarely is quite abolished. Finally, the history of the case is generally decisive: gradual development in the one, sudden onset, with immediate maximum intensity of paralysis, in the other; primitive wasting of the paralyzed muscles in the spinal paralysis, enlargement preceding the atrophy in the pseudo-hypertrophic paralysis.

⁸⁷ A patient described by Eulenburg was affected by such general paralysis, but recovered after five months' treatment.

Rachitis, with its frequent polysarcia and paretic gait, might sometimes lead to a suspicion of muscular pseudo-hypertrophy, as, conversely, the earlier symptoms of the latter disease may be erroneously referred to rachitis. The error is all the more facile because children afflicted with pseudo-hypertrophy are not unfrequently rachitic, and the symptoms of specific paralysis and muscular sclerosis may easily seem to deepen out of those of muscular inertia and subcutaneous fat which are due to the nutritive diathesis. The consistency of the enlarged limbs is, however, different—soft and flabby in rachitis, hard, even stony, in pseudo-hypertrophy. When in the latter the subcutaneous fat is atrophied instead of increased, the muscles seem to make hernial protrusions through the emaciated skin.

Congenital cerebral disease, due to intra-uterine lesion, causes imperfect walking, and even contraction of the calf-muscles, which may simulate the analogous symptoms of pseudo-hypertrophic paralysis. But the trunk is bent straight forward, and not bent in lordosis; the lower extremities tend to cross in spastic paraplegia; there is no lateral oscillation of the trunk, and the faradic contractility is always preserved. The progress of the diseases suffices to decide all doubts.

TREATMENT.—The excessively bad prognosis of pseudo-hypertrophic paralysis may be inferred from the foregoing description. Duchenne claims to have had two cases brought to him at the early stage of the disease. The first (Obs. 9) was a boy attacked at the age of seven and a half with paresis of the lower extremities. He soon began to walk with a straddling gait, lordosis, and lateral oscillation. Thirty-four months later some enlargement of the calves was noticed, but the disease remained stationary for six months, when the patient was brought to Duchenne. He was treated by hydro-therapeutics, massage, and faradization of the affected muscles. Cure was complete in six months.

The second case, (Obs. 13) was a little girl six and a half years old. Paresis of the lower limbs began at the age of four and a half, and rapidly increased. The legs and thighs began to enlarge shortly after the first appearance of the paresis. Treatment began in about a year, and was conducted as in the first case, but in addition cod-liver oil and bitters were administered internally. Cure after a few months' treatment.

Duchenne refers the beneficial effect of the faradic current to a stimulating action on the vaso-motor nerves and capillary circulation, which he assumes to be paralyzed in this disease. The important point is to exert this stimulus before the hyperplasia of the connective tissue is far advanced.

Benedikt claims to have improved five cases by galvanization of the sympathetic. But the treatment was certainly based on an erroneous theory of the disease, and the alleged results must be received with caution.

Uhde⁸⁸ claims to have arrested the progress of the disease in the gastrocnemii muscles by a double tenotomy operation performed for the relief of pes equinus. The patient was a boy of eleven, in whom the disease had begun at the age of five. At the time of observation all the muscles of the legs, as also the glutæi and sacro-lumbales, were hypertrophied. The feet could not be brought to the ground, owing to retraction of the calf-muscles: standing and walking were entirely impossible, and even the power to move the limbs in a recumbent position was very much limited. Faradization during a fortnight produced no effect. Then the tendons were cut, and faradization continued. In a month the patient could execute slight movements in bed; three weeks later he could walk along the ward; and four months after the operation he could walk alone and with the soles of the feet flat on the ground. The calves were softer than before, and diminished in circumference. But as the history stops here, it is possible that the two latter changes depended on a substitution of fatty infiltration for sclerosis. By this, moreover, the muscular fibre would be less compressed, and in its temporary liberation would for a while seem to regain part of its force. The last case of alleged recovery that we have seen is by Donkin.⁸⁹

⁸⁸ Langenbeck's Archiv für Chir., Bd. xvi., 1874.

⁸⁹ Brit. Med. Journ., 1882, vol. i.

Gowers remarks⁹⁰ that treatment must be directed rather against the effects of the morbid process than against the morbid process itself, which, as a primary error of development,⁹¹ must be, to a large extent, beyond our influence. As internal remedies, Gowers recommends arsenic, phosphorus, and cod-liver oil, noting that iron and strychnine seem to have no effect.

⁹⁰ Loc. cit., p. 52.

⁹¹ Gowers says, "of the muscular tissue," but we have shown reasons why this should rather be sought in the blood-vessels of the part.

Faradization also, which is nearly always used, must have nearly always disappointed expectation, or more cures would be recorded. Systematic muscular exercises are recommended as the appropriate physiological stimulus to muscular growth. But in view of the fact that precisely those muscles are earliest and most profoundly affected which are exposed to the most strenuous influence of this stimulus, it is theoretically doubtful whether this advice be valuable.