Chapter LXXXIII: Introduction: This disease remained unnoticed until twenty years ago, (7)

[Footnote 61: Ogle, _Medico-Chirurgical Transactions_, xli. 397-440, 1858, 27 cases; Poiteau, “Le Nerf sympathetique,” _Thèse de Paris_, 1869, 19 cases; Eulenburg and Guttmann, _Die Pathologie der Sympathicus_, 1873; Nicati, _Le Paralysie du Nerf sympathique-cervicale_, 1873, 25 cases; Seeligmüller, _Inaug. Dissertation_, 1876; Mitchell, _Injuries of Nerves_; Mobius, “Pathologie der Sympathicus,” _Berlin. klin. Woch._, 1884, Nos. 15-19.]

Inasmuch as the cervical sympathetic is in close anatomical connection with the spinal cord, especially with the eighth cervical to the second dorsal segments (the so-called cilio-spinal centre of Budge), and as the functions of the sympathetic are dependent upon the integrity of the spinal cord, it is evident that any lesion of the nerves uniting it with the cord, or any lesion in the cord itself at the levels mentioned, may produce symptoms which resemble closely those of disease of the sympathetic. Thus, cervical pachymeningitis, myelitis (especially from injury of the cord, or hæmato-myelia), and diseases of the cervical vertebræ which produce either or both conditions, may cause a train of symptoms somewhat similar to those to be described.[62] A careful distinction must be made between primary and secondary disease of the sympathetic, between reflex and direct symptoms, between lesions in its substance and lesions in its governing centres in the spinal cord. The symptoms produced by affections of a reflex or central nature are rarely as numerous as those of disease of the sympathetic itself. An example of such a secondary affection is the combination of sympathetic symptoms occurring in progressive muscular atrophy. And, finally, since mental action of an emotional nature may cause flushing or pallor of the face, with profuse sweating and variations in the size of the pupil and prominence of the eyeballs, as well as palpitation or arrest of the heart, there is reason to believe that symptoms of sympathetic disease may be produced by cerebral lesions.

[Footnote 62: Ross, _Diseases of the Nervous System_, 2d ed., i. 686-688.]

PATHOLOGY.—The pathological anatomy of the cervical sympathetic is obscure. This is probably owing to the fact that the ganglia are rarely examined, and pathologists have not been familiar with their histology. Lesions of the cervical sympathetic have been described in almost every imaginable form of disease, and at one time, when many obscure conditions were blindly termed sympathetic, the records were filled with descriptions of fatty degeneration or interstitial inflammation or pigment deposit in the ganglia. As no actual symptoms of disease of the cervical {1264} sympathetic, as now understood, were present in such cases, it is impossible to believe that the lesion was other than hypothetical.

The conditions which have been observed in a few carefully-studied cases of primary disease have been—(1) A parenchymatous inflammation of the cells of the ganglia, attended by swelling, loss of nuclei, granular and fatty degeneration, and by atrophy, together with a degeneration of the fibres issuing from the cells. (2) A sclerotic process in the connective tissue in and about the ganglia and in the nerves, resulting in such an increase in the interstitial tissue as to compress and injure the cells and axis-cylinders. These may be observed together in the later stages of the disease. (3) In a number of cases the capillaries within and about the ganglia have been found dilated, tortuous, and varicose, and hemorrhages from them are not rare.

SYMPTOMS.—The symptoms of irritation of the cervical sympathetic are dilatation of the pupil, widening of the palpebral fissure, protrusion of the eyeball, pallor of the entire side of the face and head, with slight fall of local temperature and possibly an increased secretion of perspiration, and an increased frequency of the heart. It is rarely that these are all observed in any case, dilatation of the pupil with slight pallor and rapid pulse being the only signs of irritation as a rule. Such irritation is a less common occurrence than might be supposed, many lesions which produce pressure even of a slight degree on the sympathetic having caused symptoms of a suspension of its function rather than of an increased activity. This is doubtless due to the non-medullated structure of the fibres, which thus lack protection from injury.

The symptoms of destructive disease of the cervical sympathetic are the converse of those just mentioned, and they are all present when the part is seriously involved. The patient will then have a marked contraction of the pupil, which no longer responds to light or to irritation of the skin of the neck, but may change slightly in the act of accommodation. It resists the action of mydriatics. The vessels of the choroid and retina may be dilated, as well as those of the iris, in which case the patient will feel a sense of weariness on any long-continued attempt to use the eyes. There is no actual disturbance of vision, and the cornea is not usually flattened, as was formerly supposed. There is a noticeable narrowing of the palpebral fissure, the upper lid falling slightly as in a mild state of ptosis, and the lower lid being slightly elevated. This is due to the paralysis of the muscles of Müller in the eyelids, which are controlled by the sympathetic. It is present in 90 per cent. of the recorded cases, and in many the apparent size of the eye is reduced a half. Retraction of the eyeball is a less constant symptom, and one which develops only after the disease has existed some time. It is due partly to the paralysis of the orbital muscle of Müller, and partly to the decrease in the amount of fat in the orbit behind the eye. A marked symptom, and one which is constant, is a dilatation of the vessels of the face, conjunctiva, nasal mucous membrane, ear, and scalp. This is attended by redness, a subjective sense of heat, and an actual rise of local temperature, which may exceed that of the other side by 1.5° F., measured in the auditory meatus or nose. This vascular congestion has persisted in some cases for three years. In others it has been followed much earlier (in nine months) by a partial or complete return to the normal condition, and {1265} even when the local temperature remains higher on the affected side, the visible congestion and the sensation of heat may have disappeared. The dilatation, succeeded by the contraction (normal tone), of the vessels has led to a division of the disease into two stages, and in a few cases the affected side has become paler than the other in the second stage. In both stages the part affected is less sensitive to changes in the external temperature.

An increased secretion of tears and of perspiration has been supposed to accompany dilatation of the vessels of the skin of the head inevitably. This is not a constant symptom, as the recent cases have demonstrated. And no definite statement of the effect of disease of the cervical sympathetic on the occurrence of dryness or dampness of the face can be made, both conditions having been observed. A difference between the degree of moisture on the two sides of the face on exposure to heat is usually present. Palpitation of the heart has been an annoying symptom to the patient in many cases, and is usually associated with a marked slowing of the pulse. This was reduced from 74 to 66 in Möbius' case,[63] and remained slow for some weeks. The frequency of the heart may, however, be increased after the first period of slowing, but never reaches a very high rate (88 in the case cited). A slight atrophy of the affected side of the face has been observed in several cases, appearing after the disease has existed for some time. The muscles of the cheek feel flabby and are slightly sunken; but the condition does not approach in severity true facial hemiatrophy, nor is it sufficiently rapid to be considered due to a trophic disturbance. Changes in the secretion of saliva, dryness of the nasal mucous membrane, and symptoms referable to paralysis of the intracranial vessels, such as might be expected from the result of physiological division of the sympathetic, have only been occasionally observed. Glycosuria has been noted in a few cases.[64]

[Footnote 63: _Berlin. klin. Woch._, 1884, No. 16.]

[Footnote 64: Gerhardt, _Volkmann's Sammlung klin. Vorträge_, No. 209, “Ueber Angioneurosen,” p. 11.]

COURSE.—The course of the disease has been divided into two stages, as already mentioned, the majority of the symptoms remaining permanently from the onset. The second stage is characterized by the cessation of the dilatation of the vessels, by the appearance of retraction of the eyeball, and by the development of slight facial atrophy. In the cases where the sympathetic is extensively destroyed by the lesion no recovery is possible. When it is simply divided by a wound there has been a considerable degree of recovery, probably due to a spontaneous union of the divided ends and re-establishment of the function. From these facts the prognosis can be deduced.

DIAGNOSIS.—The symptoms are so characteristic that there is no difficulty in reaching a diagnosis. The most important point in any case is to determine the cause, care being taken to consider all the possibilities already mentioned in discussing the causation. The symptoms of lesion are always unilateral.

TREATMENT.—If the cause can be removed, an indication for treatment is afforded. Sources of reflex irritation are to be eliminated. If the sympathetic has been divided by a wound, it may be well to unite the cut ends, as in suture of other nerves, although this has not yet been attempted; otherwise there is little hope from any method of treatment. {1266} Electricity has been applied in vain, and galvanization of the sympathetic in the neck is now regarded by all good authorities as useless.

Diseases of the thoracic and abdominal sympathetic ganglia and cords have been suspected, but nothing definite is known of their symptoms or pathology; the statements which have recently been made regarding visceral neurosis not being based upon any cases in which post-mortem lesions were found.

Trophic Neuroses.

TROPHIC NERVES AND NERVOUS CENTRES.—The nutrition of the body depends upon the nutrition of the individual cells of which it is made up. Each cell has the power of appropriating from the blood such substances as will preserve its existence, enable it to perform its functions, and produce a successor. Whether this power is inherent in the cell or is controlled by the nervous system is a question upon which authorities are divided. Those who hold the first position deny the existence of trophic nervous centres and of trophic nerves from those centres to the organs and elements of the body, claiming that this hypothetical trophic system has not been demonstrated anatomically, and that the facts urged in its support are capable of another interpretation. Those who believe in the existence of a trophic system have been able to demonstrate the existence of fine peripheral nerve-fibres passing to and ending in individual cells of the skin, glands, and other organs,[65] and have brought forward a large collection of facts which merit a careful examination.[66] They are as follows:

[Footnote 65: _Bericht der Section für Dermatologie, Versammlung Deutscher aerzte_, Strasburg, 1885; _Vierteljahrschrift für Dermatologie und Syphilis_, 1885, 4 Heft, S. 683.]

[Footnote 66: “Tropho-neurosen,” _Real Cyclopædie f. d. gesammt. Medicin_, vol. xiv., 1883; Erb, _Ziemssen's Cyclopædia_, xi. pp. 408-423.]

ATROPHY.—When a nerve is cut certain changes occur in it which are known as Wallerian degeneration.[67] This affects the peripheral end of a severed nerve, the peripheral end of a severed anterior nerve-root, and the central end of a posterior nerve-root. To maintain its integrity a motor nerve must be in direct continuity with a normal cell of the anterior cornu of the spinal cord; a sensory nerve must be in connection with the intervertebral spinal ganglion on the posterior nerve-root. Nerves which pass between two such ganglia do not degenerate when cut. The degeneration consists[68] in a coagulation of the myelin in the medullary sheath, a fatty degeneration of the coagulum, and a gradual absorption of the débris. The axis-cylinder is compressed, and finally disintegrated, by a mass of protoplasm which develops about the nuclei of the interannular segments, and after undergoing fatty degeneration its débris becomes mingled with that of the myelin, and is also absorbed. The sheath of Schwann, whose nuclei have in the mean time increased by a process of subdivision, is partly filled by the protoplasm (from which the new axis-cylinder develops if regeneration occurs), remaining as a fine {1267} thread of connective tissue when all other traces of the nerve-fibre have disappeared. There may be a proliferation of cells of the endo- and perineurium at the same time which aids in the transformation of the nerve into a connective-tissue strand. This process of degeneration involves the terminal plates by which the nerves join the muscles, but the terminations of the sensory nerves—_i.e._ tactile corpuscles—do not appear to be affected. The central end of the cut nerve may display a similar change for a distance not greater than one centimeter; it usually develops a bulbous swelling of connective tissue, and retains its conducting power indefinitely.

[Footnote 67: Waller, _Philosoph. Transactions_, 1850, ii. p. 423; _Comptes rendus de l'Acad. de Sci._, 1852-55.]

[Footnote 68: Ranvier, _Leçons sur l'Histologie de Système nerveux_, Paris, 1878; Von Recklinghausen, _Pathologie der Ernahrung_, 1883.]

Degeneration in the tracts of the spinal cord occurs after various forms of lesion,[69] and is similar in its processes to degeneration in the peripheral nerves. The increase in the connective-tissue elements is more noticeable in contrast with the parts unaffected, and from the density of the tract involved the result has been called sclerosis. The recent researches of Homen[70] have shown that the process of degeneration begins in the entire length of the affected tract, and does not proceed from the point of lesion onward, as was formerly supposed.

[Footnote 69: See Vol. V., “Myelitis—The Secondary Scleroses,” p. 892; Schültze, _Arch. für Psych._, xiv. 2.]

[Footnote 70: _Fortschritte der Medicin_, 1885, No. 9.]

When a muscle is separated from its connection with the central nervous system, either by a division of the nerve passing to it or by a destruction of the cells in the anterior cornu of the spinal cord from which that nerve arises, it undergoes an atrophy which is peculiar in being immediate and rapidly progressive, thus contrasting strongly with the gradual and slighter atrophy from disuse in cases of cerebral paralysis where the cells mentioned and the nerve-fibres are intact. There is at first a simple diminution in the number of the fibrillæ of which the muscular fibre is made up, together with an increase in the interstitial connective tissue nuclei. Then an albuminoid and fatty degeneration of the muscular elements occurs, with a proliferation of muscle-corpuscles or nuclei, and a gradual absorption of the débris. The interstitial connective tissue then increases rapidly, forming fibrous bands through the degenerated muscle which compress the few muscular fibres remaining, until as a result the muscle is transformed into a mere ribbon of connective tissue without any power of contractility.[71] As these changes go on the electrical reactions change, the three degrees of reaction of degeneration corresponding to the three stages of atrophy described.[72] These phenomena of nerve- and muscle-degeneration are observed in traumatic or idiopathic neuritis, in acute and chronic poliomyelitis anterior, in general myelitis involving the anterior cornua, and in bulbar paralysis.

[Footnote 71: Hayem, G., _Recherches sur l'Anatomie pathologique des Atrophies musculaires_, Paris, 1873; Ross, _Diseases of the Nervous System_, vol. i. p. 238.]

[Footnote 72: See Vol. V., “Electric Reactions.”]

The influence of the nervous system on the nutrition of the bones has also been ascertained. When a bone is developing, a lesion of the nerve to it, or of the deeper portion of the anterior cornua of the spinal cord from which these nerves arise, will modify and partly arrest its growth. This is often seen in anterior poliomyelitis and in hemiatrophy of the face occurring in children. In the adult a no less marked effect is produced, although the results are less noticeable. A condition known as {1268} osteoporosis is caused, consisting of an enlargement of the Haversian canals and an infiltration of fatty matter into them and an actual decrease in all the inorganic constituents of the bone, which loses in weight, becomes thinner and more fragile, so that spontaneous fractures may occur.[73] This condition has been noticed more frequently in diseases of the spinal cord than in neuritis; it is said to occur in locomotor ataxia. It has been found in a few cases of long-standing hemiplegia and also in dementia paralytica, no explanation of its pathogeny in these instances, however, being offered. In a case of ataxia with a lesion in the medulla which involved the nuclei of the fifth, ninth, tenth, and eleventh nerves on one side, all the teeth of the upper jaw on that side fell out within a few weeks, those in the lower jaw remaining.[74] Changes in the nutrition of the bones have also been recorded in cases of progressive muscular atrophy in the paralyzed limbs.[75]

[Footnote 73: Weir Mitchell, _Amer. Journ. of the Med. Sci._, 1873, p. 113; Charcot, _Arch. de Phys._, 1874, p. 166.]

[Footnote 74: Demange, _Rev. de Médecine_, 1882, p. 247.]

[Footnote 75: Friedreich, _Progressive Muskelatrophie_, p. 347, 1873.]

The condition of the skin and its appendages is influenced decidedly by changes in the nervous system, either in the nerves, in the spinal ganglia, or in the central gray matter. Here it is the sensory nerves which convey the trophic influence, not the motor nerves, as in the cases hitherto considered; and when the lesion producing trophic changes in the skin is central, it is situated in the posterior cornua of the spinal cord or in the gray matter near the central canal. The glossy skin seen on the fingers after injuries to the nerves is a type of such atrophy from disturbance of trophic impulses. Glossy fingers present a smooth, shining appearance, are dry from the diminution in the secretion of sweat, feel soft and satin-like to the touch from the marked thinning of the skin, and frequently show a defective or irregular growth of the nails, which may be ridged, curved, or deformed.[76] They are red and mottled from accompanying vaso-motor paralysis, and are usually hot and painful. Changes in the pigmentation of the skin and hair are recorded as a not infrequent accompaniment of severe neuralgia and as a result of great mental anxiety. Thus in several cases of supraorbital neuralgia the eyebrow on the affected side has turned white; in infraorbital neuralgia the beard has become gray; and in both the hair has been observed to fall out.[77] The sudden turning white of the hair is ascribed to a swelling of the hair by air within it.[78] In one case, frequently cited, the hair and nails fell out after a stroke of lightning.

[Footnote 76: Weir Mitchell, _Injuries of Nerves_. See also Vol. IV. p. 683.]

[Footnote 77: Seeligmüller, _Lehrbuch der Krankheiten d. Peripheren Nerven_, p. 157, 1882.]

[Footnote 78: _Arch. f. Path. Anat._, xxxv. 5, 575, Landois.]

When a gland is cut off from its nervous connection with the cord or cerebral axis by section of its nerves, its function is impaired and its nutrition suffers, so that after a time it loses weight and undergoes a progressive total atrophy. This has been proven experimentally in animals in the submaxillary gland. It has been observed in the testicle in man after division of the spermatic nerve (Nélaton) and after destruction of the spinal cord by traumatic and idiopathic myelitis (Klebs, Föster).[79] The sweat-glands are known to be under the control of a central {1269} nervous mechanism, as cases of hyperidrosis, anidrosis, and chromiodrosis prove;[80] and an atrophy of them and of the sebaceous glands has been observed[81] after nervous lesions.

[Footnote 79: Cited by Samuel, _Realcyclop., loc. cit._ See also Obolensky, _Centralblatt für med. Wissen._, 1867, 5, 497.]

[Footnote 80: See Vol. IV. pp. 583-586.]

[Footnote 81: See Vol. IV. pp. 683 _et seq._]

Progressive hemiatrophy of the face is treated elsewhere. The following case of progressive hemiatrophy of the entire body may be mentioned here: A boy, aged fourteen, dislocated his ankle, which in a few days became swollen, red, hot, and painful. The inflammation extended up the leg, but did not involve the knee, and soon subsided. After a short time the foot began to atrophy. The atrophy extended up the leg, and involved the thigh; it then progressed to the trunk and the arm, and lastly to the face on the affected side, until in the course of two years there had developed a unilateral atrophy of the entire body. Muscles, fat, and bones were all affected, but no difference in the skin or hair of the two sides was noticed. Fibrillary tremors were present in the muscles. The electric reactions were not altered, but were gradually lost. There was a hypersensitiveness to touch and to cold, but no other sensory disturbance. The boy was alive and fairly well when the case was reported.[82] It is unique.

[Footnote 82: Heuschen, _Schmidt's Jahrbuch._, vol. cxcviii. p. 130.]

These various instances of atrophy cannot be ascribed to simple disuse, since they differ markedly in their pathological changes and in the rapidity of their progress from such atrophy. Nor are they to be referred to vaso-motor disturbances, since in many cases no vascular changes are evident. Their distribution in the body often corresponds exactly with that of peripheral nerves, and they accompany nerve lesions too frequently to be explained on any theory of coincidence. There are many authorities, however, who refuse to ascribe them to a lesion of trophic nerves.[83] In regard to the degeneration of nerves it is said that each nerve axis-cylinder is a part of the nerve-cell from which it arises, and hence destruction of the cell or division of the cylinder, by disturbing the unity of existence, results in the death of the part. The fibre shares all the changes of nutrition which the nerve-cell undergoes, and if separated from it necessarily perishes. To this it is replied that trophic paths and motor paths are distinct at some points in their course, at least in the central nervous system, since each can be affected alone. Erb, who has studied this subject carefully,[84] believes that trophic are distinct from motor centres in the spinal cord, but that both impulses may be conveyed by the same axis-cylinder in the peripheral nerves—a middle ground which is widely accepted. It is now known that each axis-cylinder is made up of several fibrils, so that this theory gains probability. This would also explain the occurrence of atrophy in the muscles, the trophic centres being affected when the muscle atrophies, and unaffected when it is paralyzed without atrophy. Mayer, however, denies this explanation of the muscular atrophy, holding that the motor system, cell, nerve, and muscle-fibre, forms a nutritive as well as functional unit, and that the simple suspension of function, by interfering with the special {1270} conditions of nutrition attendant upon physiological excitement, is competent to cause a pathological change. To this it is replied that the parts of the motor system are not interdependent, since disease of the muscle does not produce degeneration of the nerve and of the cell, and the fact of a degeneration in a peripheral direction alone is evidence of central trophic influence. The attempt to ascribe trophic changes in the skin, nails, and hair to vaso-motor disturbance has been equally unsuccessful in covering all the observed cases.

[Footnote 83: See Handfield Jones, _St. George's Hospital Reports_, 1868, vol. iii. pp. 89-110; Sigmund Meyer, _Hermann's Handbuch d. Physiol._, ii. Th. 2, “Trophische Nerven,” 1879; Gowers, _Diseases of the Brain_, 1885, p. 4.]

[Footnote 84: _Arch. f. Psych._, v. S. 445, 1875; also _Ziemssen's Cyclo._, vol. xiii. p. 117 (Amer. trans.); also _Deut. Arch. f. klin. Med._, v. S. 54.]

If _d_ is destroyed, the fibres from _b_ and _c_ perish with it, and the result is paralysis and atrophy of the muscle and degeneration in the motor nerve—_e.g._ poliomyelitis anterior. If _b_ is destroyed, the muscle atrophies, and paralysis is a secondary result—_e.g._ progressive muscular atrophy. If _c_ is destroyed, the nerve degenerates, and paralysis and atrophy of the muscle are secondary results—_e.g._ neuritis with reaction of degeneration. If _a_ is destroyed, voluntary power is lost, but reflex power remains, and no atrophic changes occur—_e.g._ lateral sclerosis. If the motor nerve is cut between _d_ and _m_, the result is the same beyond the division as when the motor cell is destroyed.]

{1271} HYPERTROPHY.—Trophic changes are not limited to the process of atrophy. There are conditions of hypertrophy of supposed nervous origin. Samuel considers the hypertrophy of one testicle which attends atrophy of the other from section of its nerve as an example of this. It has been ascertained that one kidney hypertrophies when the other is atrophied or extirpated. When the spleen is removed the lymphatic glands increase in size. But these facts are capable of another explanation—viz. that increased demand upon the organ leads to its increased growth. Hypertrophy of the skin and of the tongue is seen in cretins in contrast with the deformity of the body and atrophy of the limbs. A hemihypertrophy of the face has been noticed in several cases, the counterpart of hemiatrophy; and in one case a unilateral hypertrophy of the entire body was observed.[85] The local thickening of the skin known as ichthyosis hystrix, and other hypertrophies of the skin, certain deposits of pigment, and vitiligo, have been ascribed to nervous causes. Mitchell has recorded cases of abnormal growth of the nails and hair after injuries to the nerves, and similar phenomena have followed central lesions. He has also described a thickening of the skin of the first three fingers and of the back of the hand following a wound of the brachial plexus. These conditions of the skin and its appendages indicate an abnormal activity in the cells of the affected part, a rapid metabolism and reproduction, resulting in an undue production of tissue, apparently dependent on nervous impulses reaching the cells from a distance. The insane ear may be mentioned in this connection as a trophic disturbance due to central lesion.

[Footnote 85: Ziel, _Virchow's Archiv_, xci., S. 92.]

MYXŒDEMA (cachexie pachydermique) is a disturbance of nutritive processes characterized by a production of mucin, which is deposited in all the tissues of the body, but especially in the subdermal connective tissue.[86] It is considered by the majority of authors a trophic neurosis, and is therefore considered here.

[Footnote 86: Sir William W. Gull, “On a Cretinoid State supervening in Adult Life,” _Trans. Clin. Soc. London_, 1874, vol. vii. p. 170; Ord, “On Myxœdema,” _Med.-Chir. Trans._, 1878, vol. lxi. p. 57; Mahomed, _Lancet_, 1881, ii. No. 26; Hadden, _Brain_, 1882; W. A. Hammond, _Neurological Contributions_, 1881, i. p. 36; Ballet, _Archives de Neurologie_, 1881, vol. iii. p. 30; _Schmidt's Jahrbucher_, vol. clxxxix. p. 30, and cxcviii. 264; “The Brown Lectures,” Victor Horseley, _Lancet_, Jan., 1886.]

PATHOLOGY.—In the few autopsies which have been made an increase in the connective tissue of all the organs has been found, in the meshes of which a thick, transparent, slimy substance (called animal gum), consisting of mucin, is present. This may compress and destroy the parenchyma of the organs involved. There is also found a thickening of the coats (adventitia and media) of the vessels. An atrophy of the thyroid gland has occurred in every case, and experimental extirpation of the thyroid in animals produces symptoms so nearly identical with those of myxœdema that this is considered the chief pathological feature of the disease. Whether this atrophy is due to a compression by the mucin deposited, or is due to a disease of the trophic centres of the thyroid in the medulla, or is a primary affection of the gland, remains to be determined.

ETIOLOGY.—The actual causation is unknown. Cold and mental shock have been considered exciting causes in some cases. Women are much more liable to the disease than men, and it develops after the age of forty in the majority of cases. It may occur in childhood and result in a {1272} cretinoid state. Syphilis and tuberculosis do not appear to be etiological factors.

SYMPTOMS.—The disease begins gradually, and the nervous symptoms or the local œdema may appear together or in succession. The patient notices a thickening of the skin, which becomes dry, rough, and scaly. The thickening is uniform and involves the entire body. It is most marked where the subdermal connective tissue is loose, as in the cheeks, lips, eyelids, and in all parts where the skin is thrown into folds. The hands and feet do not escape. The thickened skin is hard, and does not pit on pressure, thus differing from ordinary œdematous swelling. It appears of a waxy color, and is free from perspiration, the sweat-glands becoming atrophied from pressure. The hair may fall out or become woolly and brittle, and may change its color. In a few cases spots of pigment have appeared on various regions.[87] The nails are brittle. The teeth are carious. The mucous membranes show similar changes, and the mouth and tongue, rectum and vagina, may be so swollen as to impair their respective functions. Digestive disturbances, constipation alternating with diarrhœa, and uterine hemorrhages, which occur, are ascribed to this cause. Albumen is occasionally found in the urine, but is not a constant symptom. The nervous symptoms are constant. The patients complain of paræsthesiæ and anæsthesia of the extremities or over the entire body, and the special senses may be impaired, as well as the tactile sense. They are very liable to severe attacks of neuralgia. They suffer from subjective sensations of cold, and are easily affected by changes of temperature. Motion is interfered with; tremors occur early; movements become slow and awkward; the gait is unsteady; the voice is rough and nasal; but no true paralysis or muscular atrophy has been observed. The patella-tendon reflex is occasionally lost, but not in all cases.

[Footnote 87: Allan McLane Hamilton, _Journ. Nerv. and Ment. Dis._, 1885, April, p. 180.]

These symptoms have been ascribed to the pressure of the mucin upon the terminal filaments of the nerves, and also to changes in the central nervous system. That the latter theory is probably correct is shown by the occurrence of mental symptoms in the majority of cases. The patients become apathetic and all mental action is slowly performed. Indifference to surroundings, loss of memory, and inability to concentrate the attention may be succeeded by transient delirium, hallucinations, and occasionally by delusions of persecution, and the patient finally lapses into a state of imbecility. If the disease develops in early life, education is impossible, and the patient remains in an infantile condition.

Whether the changes in the nervous system are due to pressure by deposit of mucin (Hadden), or are due to an altered nutrition of the most delicate tissues of the body consequent upon the general metabolic derangement (Horseley), is undetermined. In experimental myxœdema the degenerative processes have been found in the nerve-cells.

There are no symptoms referable to the heart or lungs, and if cirrhosis of the kidney and liver develop, their symptoms supervene upon and are secondary to those of myxœdema. High arterial tension has been noticed in the majority of the cases.

The COURSE of the disease is a chronic one, and is progressive. There are, however, intermissions in the severity of the symptoms in some cases. Recovery does not occur.

{1273} DIAGNOSIS.—The diagnosis from the accumulation of fat is made by observing the thickening of the nose, lips, fingers, and tongue, and the changes in the skin and its appendages. Scleroderma is not universal like myxœdema. In scleroderma the skin is harder and more adherent to subjacent parts, is not transparent and waxy, and the nervous symptoms are wanting. Cretinism seems to be closely allied to myxœdema, but is only observed before the age of seven and is accompanied by hypertrophy of the thyroid gland.

TREATMENT.—The treatment is only palliative. Simple nutritious diet, especially milk diet, with the use of such tonics as iron and quinine, has been found useful. The progress of the disease is hastened by exposure to cold, and in a very warm climate the symptoms may remain stationary for several years. Jaborandi or pilocarpine has been used in some cases with a moderate degree of success. Nitro-glycerin, gr. 1/100, has also been of benefit. For the paræsthesiæ and anæsthesia of the early stage the faradic brush has been applied, and for the motor weakness the faradic current, with the effect of relieving but not curing these symptoms. During the attacks of neuralgia morphine may be employed.

Inflammation.—The most important trophic disturbances are those which consist of an actual disintegration of tissue. These are very numerous. Herpes zoster, certain forms of eczema and pemphigus, lepra anæsthetica, scleroderma, acute ulceration of the fingers, perforating ulcer of the foot, acute bed-sores, keratitis with anæsthesia of the cornea, sympathetic ophthalmia, and various forms of joint disease, are examples of such trophic diseases.[88] For the discussion of the skin and eye diseases mentioned the reader is referred to special articles on those subjects. In regard to lepra anæsthetica, it may be mentioned that in this disease lesions have been found both in the sensory nerves and in the posterior cornua of the spinal cord.[89]

[Footnote 88: Leloir, “Tropho-neuroses,” _Nouveau Dictionnaire de Médecine et Chirurgie practiques_, 1885.]

[Footnote 89: Virchow, “Nerven Lepra,” _Geschwülste_, ii. 521; Tschirijew, _Travaux du Laboratoire de Vulpian_, 1879.]

I have reported[90] a case of acute ulceration of the ends of the fingers and toes occurring in an anæmic girl aged twelve, and persisting for more than a year, associated with cyanosis of the hands and feet, and with a tendency to rapid ulceration of any part of the body which happened to be exposed to pressure. The hair of the eyebrows, eyelids, and to a less extent that of the scalp, fell out during the disease. There was no local asphyxia and no appearance of gangrene; hence the case was not one of Raynaud's disease. Its symmetrical distribution, the lack of any constitutional organic disease or of any local cause for the production of the ulceration, and the anæmic and nervous condition present, all pointed to a disturbance of the central nervous system. It did not yield to treatment, either local or general or electrical. Mills has seen a similar case.[91]

[Footnote 90: _Journal Nerv. and Ment. Disease_, Feb., 1886, clinical cases.]

[Footnote 91: Mills, _Amer. Journ. Med. Sci._, Oct., 1878.]

Perforating ulcer of the foot begins on the sole, beneath any of the metatarso-phalangeal articulations, preferably the first or the fifth, or under the heel, as a small pustule under the epidermis. This ruptures, and the ulcer which results begins to extend in a direction vertical to the surface, involving the deeper tissues or even opening into the joint and destroying the bone. It appears rather like a sinus than an ulcer, and is {1274} remarkable from the fact that it is not painful and is insensitive to touch, although it may prevent the patient from walking on account of extreme tenderness. The epidermis around the sinus is thickened and insensitive, and there may be anæsthesia of the entire sole of the foot, and even of the leg, although this is due to the neuritis present, which is also the cause of the ulcer, rather than to the ulceration. The circulation is sluggish in the affected extremity; it becomes cyanotic on exposure to cold, and seems peculiarly liable to become œdematous. The œdema may go on to suppuration, and involve the articulations, and ankylosis of the smaller joints may follow. This, too, is to be traced to the neuritis. The skin of the foot becomes pigmented, and may be dry or covered with offensive sweat. As the patient cannot walk while the ulcer remains, the condition demands treatment. Rest, moist warm applications, antiseptic lotions, scraping out the sinus, and other surgical means appropriate to the treatment of ulcers and sinuses do not often prove of benefit, and in obstinate cases recourse has been had to amputation of the foot. Electrical treatment has been tried in vain.

Such perforating ulcers may occur symmetrically on both feet, and may be numerous. They also occur rarely on the hands. They have been observed not infrequently in locomotor ataxia, occurring either early or late in the disease,[92] and have appeared in patients suffering from dementia paralytica. The only constant lesion found is a degeneration of the peripheral nerve supplying the affected part.

[Footnote 92: For bibliography see Ross, _Diseases of Nervous System_, 2d ed., i. p. 256, and Blum, _Berliner klin. Wochen._, 1875, Nos. 13-15.]

Acute bed-sores (decubitus) develop in many cases of spinal and cerebral disease, but not in all. It is argued that anæsthesia of a part or simple pressure upon a part or irritation of an anæsthetic part will not explain their occurrence, and that they must be traced to a destruction of trophic centres in the cord or brain. No amount of attention to the position and cleanliness of the patient is thought to be sufficient to prevent them in some cases, and their progress is often so rapid as to remove them from the category of simple ulceration. Their most frequent seat is upon the buttocks, over the sacrum, on the heels, and over the scapulæ; but it is believed that in the conditions in which they appear in these places pressure on any part may cause one. They begin within a few hours after the occurrence of the lesion as irregular mottled patches of redness, in which there soon appear small or large vesicles filled with dark serum. These rupture, leaving little areas of ulcerated surface, which soon unite to form a large ulcer with softened, infiltrated, and bloody base and ragged edges. The tissues around and within the ulcer have a tendency to slough and to become gangrenous, and the process goes on rapidly until a considerable area of the surface is completely destroyed, together with the deeper structures, fat, muscles, and fasciæ, down to the bone, which may become necrosed. Acute cystitis is so frequently associated with acute bed-sore that it is traced to the same nervous cause, though here, again, another explanation is possible. The constitutional disturbance produced by these two affections may be increased by a true septicæmia, to which the patient succumbs; or metastatic abscesses may be formed, and pyæmia cause death; or, lastly, the ulcer on the back may lay bare the vertebræ and erode their ligaments, thus opening a way for the extension of suppuration to {1275} the meninges of the spinal cord. The duration may be from a few days to two weeks, and the prognosis is very grave.

Chronic bed-sores develop in a similar manner, although all the processes described occur more slowly and are much less severe. They do not show the tendency to extend so widely or so deeply, nor to become gangrenous. They remain stationary after attaining a certain size, and the tissues seem to lack all tendency to reproduction and repair. When the central lesion which they follow begins to pass away they heal; sometimes local treatment is successful; but in many cases they persist for years, always threatening the life of the patient from the possibility of their sudden aggravation or from the occurrence of the complications already mentioned in connection with the acute process.

Since neither form of decubitus occurs after lesion of the anterior cornua of the spinal cord, nor in sclerosis of the posterior or lateral columns, nor in those cases of locomotor ataxia in which extensive invasion of the posterior cornua is present, while they are particularly frequent as a complication of general myelitis, hemorrhage in the cord, and syringo-myelitis, it is argued that the trophic centres whose destruction is the cause of these bed-sores lie in the central gray matter of the cord, near to the central canal. In unilateral lesion of the cord the bed-sore occurs on the anæsthetic side of the body—_i.e._ on the side opposite to the seat of the lesion—a fact which may indicate a decussation of the trophic nerve-fibres in the cord,[93] but which has also been urged in proof of the theory that the sore is always due to irritation of an insensitive surface.

[Footnote 93: Recklinghausen believes that these cases of disturbance of nutrition can be explained by injury of anæsthetic parts in which vaso-motor disturbances of central origin exist (_Handbuch d. Path. d. Ernahrung_, pp. 236, 237).]

The treatment of bed-sores belongs to the domain of surgery, the same methods being pursued as in the case of any large ulcer. The application of electricity to the sore has been tried, but the results are not sufficiently encouraging to warrant its recommendation.

Joint affections of neurotic origin are discussed in the articles upon Locomotor Ataxia, Hemiplegia, and Hysteria.

It is evident from this review that the nervous centres have some influence upon the activity of the cells of which the body is made up, and that they control the processes of growth, function, repair, and reproduction. The facts are too numerous, too varied, and too positive to admit of any other explanation. Trophic disturbances must therefore be considered as a set of symptoms referable to various lesions of the nervous system. It is evident from the preceding discussion that they may be produced by disease of the peripheral nerves; by disease of the ganglionic cells, which nourish those nerves; by disease of the spinal cord, especially in the region of the central gray matter; and, finally, by disease of the brain. Whether in the last condition the effect is a direct one, or is produced secondarily by an irritation of the spinal centres, cannot yet be determined. There are no trophic centres as yet localized in the cerebrum, but the pathological facts already mentioned warrant the conclusion that such centres will not long elude search. Certain facts observed in cases of infantile hemiplegia point to the motor area of the cortex as the seat of trophic centres for the motor mechanisms; since it is found that when the motor cortex is destroyed in early life the bones and muscles {1276} which it controls fail to develop properly. Trophic centres for sensory mechanisms are not yet discovered. Certain investigations of Luciani recently published[94] point to the cerebellum as the part of the brain which governs the general nutrition of the body, but these need confirmation.

[Footnote 94: _Alienist and Neurologist_, July, 1885.]

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