A system of practical medicine. By American authors. Vol. 5

by Unknown

VASO-MOTOR AND TROPHIC NEUROSES.

BY M. ALLEN STARR, M.D., PH.D.

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DEFINITION.—In the term vaso-motor and trophic neuroses it is intended to include a number of forms of disturbance of circulation and nutrition which are caused by disorders of the nervous system. Such disturbances may occur in any part of the body. They are not to be regarded as distinct diseases, but rather as symptoms of lesions in the peripheral or central nervous system. They may present themselves in various forms, as hyperæmia or anæmia or instability of vascular tone, as atrophy or hypertrophy or disintegration of normal tissue. Their consideration cannot, however, be assigned to any previous department of this volume nor relegated to various divisions of it; partly because in some cases they are to be traced to lesions of the sympathetic system, not elsewhere considered; partly because of our ignorance as to the exact location in many cases of the lesion of which they are manifestations.

It is probable that at a future time this chapter will disappear from a system of medicine, as the chapter on ascites has disappeared, and that the symptoms under consideration will be distributed among various departments as symptoms of ascertained lesions in various organs. For the present, however, they demand a separate discussion.

It is not possible to distinguish accurately in all cases between the vaso-motor and the trophic neuroses, for while in many features they are distinct, in a large proportion of cases they occur together. But it is not possible to ascribe all trophic changes to vascular disturbance, nor all vaso-motor changes to a defect or excess of trophic action. Hence a separate consideration of these allied subjects must be given. It is always to be remembered, however, that each may give rise to the other, and that in their pathology they are closely connected. Vaso-motor disturbances manifest themselves (1) by a dilatation of the vessels, producing redness, heat, and rapid metabolism in the part affected; or (2) by a contraction of the vessels, causing pallor, coldness, and malnutrition; or (3) by an alternation of these conditions and consequent temporary disturbance of function. Trophic disturbances may occur in consequence of such increase or decrease of blood-supply, or independently of any vascular change, causing (1) an abnormal production of tissue in an organ, or (2) a decrease in the size and number of its constituent cells, or (3) an actual degeneration of the elements which make it up, after which their place may be taken by another kind of tissue. Under all these circumstances the function of the part affected will be disturbed, and symptoms will be produced which will vary with the tissue or organ involved. Hence a general consideration of these symptoms must be given. Before proceeding to a detailed consideration of these neuroses it is necessary to review the physiology of the vaso-motor and trophic systems, in order to make clear the manner in which they perform their functions. And inasmuch as the pathology of these affections is best understood by comparison with experimental lesions made by physiologists in investigating their function, it will be treated together with their physiology.

Vaso-motor Neuroses.

FIG. 56.

Vaso-motor Nerves and Ganglia accompanying the Arterioles in a Frog (Gimbert): C, arterioles; N, vaso-motor nerve; G, ganglion, from which nerves issue, situated at the point of anastomosis of several capillaries; R, fibre of Remak.

PHYSIOLOGY.—Local Vascular Tone.—Since changes in the force and frequency of the heart's action, and variations in the total amount of blood in the body, affect the body as a whole, the state of circulation in any one organ or part must be dependent upon the degree of contraction or dilatation of its own vessels. This is known as the local vascular tone. It is under the control of a system of nerve-ganglia with their subservient fibres which are found in the middle coat of all arterioles (Fig. 56). The energy expended by these ganglia is manifested by a constant moderate contraction of the circular muscular coat of the artery—a contraction which is as constantly opposed by the dilating force of the blood-pressure within the vessel. An exact equipoise between these two forces never occurs, since each varies constantly, but in a state of health one never becomes permanently excessive. Considerable variations, however, in the local vascular tone are frequently observed. Thus each organ is influenced to a certain degree by every other, since an increase of blood in one part must involve a decrease in all other parts, the total amount of blood in the vessels being constant. Alteration in the heart's action is felt more quickly in some organs than in others, and thus the general blood-pressure by its variations may cause secondarily a disturbance of local vascular tone. The variations now under consideration, however, are not of this kind. They are such as are produced by influences acting directly upon the ganglia in the vessel-walls.

Local irritation is such an influence, and it may excite the ganglia to increased activity, so producing a contraction of the vessel and consequent pallor; or it may suspend the action of the ganglia, so producing a dilatation of the vessel and consequent flushing.

Another influence is irritation acting from a distance and conveyed to the local ganglia by nerve-fibres. These nerve-fibres can be distinguished from all others by their structure, being non-medullated, and by the fact that they have an indirect course, passing from the central nervous system to the sympathetic ganglia, and from these to the local ganglia in the vessels. The impulses sent along these nerves may affect the local ganglia in one of two ways, and either cause contraction by exciting the ganglia, or dilatation by inhibiting the action of the ganglia. The result produced has determined the names given to the impulse, to the fibre transmitting it, and to the centre whence the impulse proceeds, and hence vaso-constrictors and vaso-dilators are distinguished from one another.

The history of the development of the sympathetic nervous system,¹ as well as its gross anatomy, affords distinct proof that it is not an independent system, as Bichat supposed, but is closely connected in its physiological action with the spinal cord and brain. Impulses which reach the sympathetic ganglia from a distance along the vaso-constrictor or vaso-dilator fibres originate in the central nervous system. The nervous mechanism which controls the local vascular tone is therefore a complex one, consisting not only of the set of local ganglia connected with larger sympathetic ganglia, but also of centres in the spinal cord connected with higher centres in the brain. The brain-centres in turn are complex, consisting of an automatic mechanism in the medulla regulating the action of all the subordinate parts below it, and of a series of cortical centres whose function it is to stimulate or inhibit the medullary mechanism. It therefore becomes evident that local vascular tone may be modified by local causes acting on the ganglia in the vessels—e.g. cold or heat; by changes in the sympathetic ganglia—e.g. the hyperæmia of the face in lesions of the cervical ganglia; by reflex action through the spinal cord—e.g. pallor produced by pain; by reflex action through the medulla oblongata—e.g. glycosuria following sciatica; or by conscious or unconscious impulses coming from the cortex—e.g. the blush of shame, the vaso-motor paralysis of hemiplegia.

¹ W. R. Birdsall, “Embryogeny of the Sympathetic System,” Arch. of Med., vol. i. where a bibliography of the subject is to be found.

Vaso-constrictors.—Such a mechanism, however complex in structure, would be easily comprehended if the constant manifestation of energy in the maintenance of arterial tone had its only source in the action of the local ganglia in the vessels, and was affected only occasionally by impulses from a distance, as has been thus far supposed. This, however, is not the case, as has been demonstrated by a series of experiments beginning with the brilliant researches of Claude Bernard. The classical experiments of the French physiologist were made upon the sympathetic cord in the neck of a rabbit. Division of this was found to produce a dilatation of the vessels of the ear. Irritation of the peripheral end of the divided cord produced a contraction of the vessels. Division of the spinal nerves connected with the cervical sympathetic and of their anterior roots, or irritation of the cut ends, produced effects similar in character to those caused by division or irritation of the cervical sympathetic. Destruction of the spinal cord in the lower cervical region, or division of the cord at any higher level up to the medulla, was followed by dilatation of the vessels. If the segment of the divided cord just below the section was irritated the vessels contracted. Destruction of the medulla at the calamus scriptorius and above it for three centimeters produced a general dilatation of all the vessels in the body, but division above this level had no effect. The initial congestion produced by these various experiments was accompanied by a rise of temperature in the part. It was followed after a time by a partial recovery of vascular tone, which was more complete the farther the division from the local ganglia. These facts warranted the conclusion that the energy expended by the local ganglia in holding the vessels in a state of constant moderate contraction is derived from the central nervous system, primarily from the automatic centre in the medulla, which in turn is reinforced by each of the secondary centres in the spinal cord and sympathetic ganglia; and also that while the medullary centres control the entire body, the cord and sympathetic centres control only those parts with which they are especially related. In order, therefore, to the maintenance of normal vascular tone the local ganglia must be intact, and they must be in connection with the sympathetic ganglia; these must be active, and must be connected with the spinal cord; the cord must be normal, and its tracts from the medulla must be capable of conduction; the medullary centre must be active, and not hindered or spurred by cortical impulses of a conscious or unconscious nature. Any injury to one or more of these parts will produce a vascular dilatation by interfering with the transmission of vaso-constrictor impulses from within outward, and any irritation of one or more of these parts may cause a contraction of the vessels by increasing the normal stimulus sent to the local ganglia by the vaso-constrictors.

Vaso-dilators.—The action thus far considered has been wholly of a vaso-constrictor kind, and the dilatation which has been mentioned has been due to cessation of the constrictor energy normally passing outward. This may be termed a passive dilatation. It is the kind produced by division of any one of the sympathetic ganglia or cords. But further experiments have shown that another kind of dilatation may be produced, traceable not to a mere cessation of constrictor impulses, but to an impulse of a positive kind sent to the local ganglia and resulting in a sudden suspension of their activity. Such an impulse is really an inhibitory impulse arresting the action of the ganglia in spite of the continued stimulus sent to them from the central nervous system. Its result is a dilatation of the arteries, produced by the blood-pressure within them, which may be termed an active dilatation. Thus, Bernard found that irritation of the chorda tympani caused an immediate flow of blood to the submaxillary gland because of the dilatation of its vessels. And Dastre and Morat² have demonstrated a similar effect in the head and extremities after irritation of portions of the cervical sympathetic and of the peripheral nerves.

² See Archives de Physiologie, “Vaso-dilateurs,” 1879, 1880, 1882; Comptes rendus de l'Academie des Sciences, 1880, pp. 393 and 441.

Much confusion has arisen from the use of the term active dilatation, and many explanations of its mechanism have been offered. At first it was supposed that a system of longitudinal fibres in the vessel-wall acted as opponents to the circular constrictor fibres. This theory, originating with Stilling and Duchenne,³ has been lately revived by Anrep and Cybulski.⁴ They hold that since a vessel elongates as well as dilates with every heart-beat, its total distension is the result of two factors—viz. transverse and horizontal distension. If one of these is neutralized, they claim that the other will be increased. Longitudinal fibres in the wall by preventing elongation may thus allow the entire force of the heart to be expended in dilating the vessel. This theory has not, however, been accepted, and with that of Schiff, that contractile elements of the connective tissue surrounding the vessel-walls could pull outward the walls and thus dilate the vessel, has lapsed, because of lack of demonstration of the necessary anatomical structure in all arterioles. Another theoretical explanation, that dilatation of the arteries is caused by contraction of the veins damming back the blood, is disproved by the fact proven by Dastre and Morat, that blood-pressure increases instead of diminishing in the veins during vaso-dilator action. Legros⁵ and Onimus,⁶ noticing the normal occurrence of a peristaltic motion of centrifugal direction in the arteries of the retina, which if increased produced a certain degree of hyperæmia, attempted to explain the phenomena of dilatation by supposing a sudden increase of peristalsis. But Vulpian has proved that the peristalsis is both too slight and too slow in its effects to account for the rapid action of the vaso-dilators, and Dastre and Morat have shown that the peristalsis, not being synchronous with the heart-beat, really impedes the flow of blood. The last theory to be mentioned has a chemical basis, and is known as the theory of attraction (Brown-Séquard, Severini.) According to this, the organs, when active, manifest increased metabolism, to maintain which the blood is drawn toward them by the chemical changes in progress. This theory was based on the fact that irritation of the chorda tympani causes an increased secretion of saliva as well as a congestion of the submaxillary gland. It is now known, however, that these two acts are independent of each other, as either can be suspended while the other continues. Hence this theory too has lapsed.

³ Von Recklinghausen, Handbuch der Pathologie des Kreislaufs und der Ernahrung, 1883, where a full bibliography is to be found.

⁴ St. Petersburg Med. Wochenschrift, 1884, i. 215.

⁵ Des Nerfs vaso-moteurs, Thèse de Concours, Paris, 1873.

⁶ Des Congestions actives, Paris, 1874.

The view already stated, that vaso-dilators act by inhibiting local ganglia which cause contraction, is now accepted, especially since it is found that such inhibitory activity is constantly displayed by other parts of the nervous system, and is competent to explain the facts. The active dilatation produced by the inhibition of the action of the local ganglia is therefore to be clearly distinguished from the passive dilatation caused by the cessation of normal tonic impulses sent to them from higher centres. The former is a positive active vaso-dilator phenomenon. The latter is a negative paralytic vaso-constrictor phenomenon. The former is more effective, the dilatation being greater in degree and more permanent than the latter, and resembles exactly the dilatation produced experimentally by exhaustion of the activity of the local ganglia by over-stimulation of the constrictors.⁷

⁷ Goltz, Arch. f. d. gesammt. Physiol., xi. 92.

An important point of contrast which has been established between vaso-constrictor and vaso-dilator impulses is that while the former are constant the latter are intermittent. Hence they cannot be regarded as opponents of one another. In a normal quiescent state vaso-constrictor energy is always being supplied to counteract the continued intravascular pressure ever renewed with the cardiac systole. The vaso-dilators are inactive. In an organ thrown into functional activity an increased flow of blood at once takes place, proportionate to the work being done by the organ. Such a functional hyperæmia might be produced either by a cessation of constrictor impulses or by an inhibition of their effects. It is by the latter means and through the vaso-dilators that it is produced, and it is probably the chief function of the vaso-dilator nerves to regulate the blood-supply in accordance with the need of a part. For this reason these nerves have been supposed to pass with the motor nerves to the muscles. As few organs exist without a possible use, it is probable that vaso-dilators pass to all parts of the body, as Vulpian asserts, though they have not been demonstrated in every organ or every part.

Like the vaso-constrictors, the vaso-dilators can be traced to the spinal cord, and their centres there are governed by a general centre in the medulla, which in turn may be affected by impulses from the cortex. A destructive lesion in any part of the vaso-dilator system does not produce as marked effects as one involving the vaso-constrictor system, since the symptoms of such a lesion will only appear when the vaso-dilators are called into play. When the vaso-dilator nerve to the submaxillary gland is cut, no change is observed until by some sapid substance put in the mouth its function should be excited, when the gland is no longer found to flush with blood as in the normal state. It is by means of the vaso-dilators that erectile organs become engorged with blood. Eckhard has shown the nervi erigentes of the penis to be vaso-dilator nerves. If they are destroyed, the organs will not respond to the wonted stimulus—a symptom which, however, would only be noticed at intervals. An irritative lesion of the vaso-dilator system may produce permanent congestion of an organ or part, but this seems to be rather more rare than a congestion from paralysis of the constrictors. It is seen in injuries of the peripheral nerves.

Origin of the Vaso-motor Nerves.—The exact course of the vaso-constrictor and vaso-dilator nerves has been traced from various parts into the central nervous system by the careful experiments of Dastre and Morat,⁸ and more recently by Gaskell.⁹ It is now established that they exist as separate nerves, although they often run together, and that they usually enter the spinal cord at different levels.

⁸ See Comptes rendus Soc. de Biologie, and Arch. de Physiol., 1879-84.

⁹ W. H. Gaskell, “On the Structure and Function of the Nerves which Innervate the Vascular System,” Journ. of Physiol., Jan., 1886.

If the various spinal nerves be cut singly from above downward, and the effects noted, and if the peripheral ends be irritated and the effects noted, and if with proper care the results be analyzed and compared, it will be found that the anatomical connections of the segments of the spinal cord with the sympathetic ganglia, which are so evident at each level, are not the ones by which physiological impulses pass out at that level. The vaso-constrictors of the head, which can be traced to the superior cervical ganglion, do not come from the upper cervical region of the cord, as might be supposed from the connections of that ganglion, but from the first three dorsal nerves. They reach the ganglion through the sympathetic cord in the neck, having traversed the inferior cervical ganglion on the way. There are vaso-constrictors in the cranial cavity which accompany the third, fifth, seventh, and twelfth nerves to the eye, face, and mouth. It is still undecided whether they originate in the cord and medulla, issue in the spinal accessory nerve, and with it enter the cranium (Gaskell), or reach those nerves by way of the carotid and vertebral plexus from the inferior cervical ganglion (Dastre and Morat). The vaso-constrictors of the arm, which can be traced to the inferior cervical and upper thoracic ganglia and to the thoracic sympathetic cord, are derived from the seven upper dorsal nerves. It is true that division of the roots of the brachial plexus causes a slight dilatation of the vessels of the arm, but this is so much increased when the dorsal nerve-roots are divided that it is evident that it is through them that the constrictor fibres chiefly pass. The vaso-constrictors of the leg, which can be traced into the second and third lumbar ganglia and lumbar sympathetic cord, are derived from the five lower dorsal and first lumbar nerves, and only join the crural and sciatic nerves after passing through the abdominal sympathetic. The thoracic viscera are probably supplied partly through the branches of the inferior cervical and thoracic ganglia, and partly through the pneumogastric, the latter statement being disputed by Gaskell. The abdominal viscera are supplied partly through the splanchnic nerves, which are made up of fibres issuing from the cord in the fifth to the twelfth dorsal nerves inclusive, and partly through the pneumogastric. Thus the dorsal region of the cord is the origin of the majority of vaso-constrictor fibres in the body.

The origin of the vaso-dilators is also to be traced to the dorsal cord. The vaso-dilators of the bucco-facial region come from the second to the fifth dorsal nerves, whence they pass to the first thoracic ganglion, and thence by the annulus of Vieussens into the cervical sympathetic cord. Those of the eye, head, and ear come from the same ganglion, but have their spinal origin in the eighth cervical and first dorsal nerves. Those of the arm are traced into the upper thoracic sympathetic cord, which they reach from the five upper dorsal and last cervical nerves. Those of the leg are traced to the first and second lumbar ganglia and the lumbar sympathetic cord, which they reach from all the dorsal nerves from the sixth downward. Gaskell holds, however, that the vaso-dilators of the extremities pass out of the cord in the cervical and lumbar plexuses and accompany the cerebro-spinal nerves. The vaso-dilators of the thorax and abdomen are supposed to pass in the pulmonary plexus and splanchnic nerves, but this is not yet fully determined.

Gaskell¹⁰ believes that vaso-motor nerves can be distinguished from motor and sensory nerves in the spinal nerve-roots by the smallness of their calibre. He finds such fine fibres only in the spinal nerve-roots between the second dorsal and second lumbar segments of the cord (in the dog), and in the three upper roots of the spinal accessory nerve. According to his account, the vaso-constrictors issue from the spinal cord in both anterior and posterior nerve-roots as medullated fibres, and pass to the sympathetic ganglia lying on the vertebræ (proximal or lateral ganglia); there they lose their medullary sheath, and either end in cells whence new fibres issue, or more probably pass directly onward as non-medullated fibres, having a connection with the unipolar cells of the ganglia only for purposes of nutrition. The number of fibres issuing from any one ganglion is much greater than the number entering it from the cord; hence it is supposed that each medullated fibre splits up into a group of non-medullated fibres; which is possible, as the researches of Ranvier have shown that each axis-cylinder is made up of numerous fibrils. Leaving these ganglia, the nerves pass either to the second series of ganglia (distal or collateral ganglia), whence they issue in plexuses to enter the vessels, or to the vessels directly, where they divide in plexuses. It is in the meshes of the plexus that the local ganglia of the vessel-walls are found. The vaso-dilators are thought to differ from the vaso-constrictors in passing directly to the distal ganglia as medullated fibres, not being connected in any way with the proximal ganglia. Gaskell makes no statement regarding their limits of origin from the cord, except to state that the nervi erigentes issue with the sacral nerves. He agrees with the view that the vaso-dilators act as inhibitory nerves upon the local ganglia.

¹⁰ Journal of Physiology, Jan., 1886.

Vaso-motor Reflexes.—Thus far, reference has been made only to fibres whose direction of transmission is centrifugal, and whose exit from the spinal cord is by the anterior nerve-roots. There are other fibres, however, through which centripetal impulses pass, and these enter the spinal cord with the posterior nerve-roots. The function of these fibres is to transmit sensory impulses inward to reflex centres, and thus set in action motor mechanisms of a vaso-constrictor or dilator kind whose effects are produced at the periphery. There are, therefore, vaso-motor reflexes, as well as skin and tendon reflexes, whose centres are in the spinal cord. These reflex acts may be excited by impulses reaching the centre not only through the vaso-motor centripetal nerves, but also through the sensory nerves of the cerebro-spinal system. The effect of changes of temperature on the circulation in the skin (if the right hand be plunged in cold water there is a fall of temperature in the left hand), the effect of pain upon the color of the face and the size of the pupil, the red cheek on the affected side in pneumonia, the occurrence of glycosuria during sciatica,—are all instances of such reflex acts. Many vaso-motor affections are produced by irritation causing reflex effects at a distance from the seat of irritation—a fact always to be kept in mind. The utility of counter-irritation to the surface in diseases of the internal organs is explained by supposing that vascular changes are produced in those organs through reflex mechanisms set in action by the local irritation. While some of these reflexes may have their central mechanism in the local ganglia, it is probable that the majority are to be traced to the spinal cord. It is believed that the sympathetic ganglia are not the seat of reflex centres.

FIG. 57.

Diagram to represent the Mode of Action of Counter-irritants applied to the Chest (Lauder Brunton). The irritation of the afferent nerves by the blister on the chest wall gives rise to a vaso-constrictor reflex in the vessels of the lung.

Since the vaso-motor nerves are connected almost exclusively with the dorsal portion of the spinal cord, it is very natural to conclude that the vaso-motor reflex centres are situated in this region; and the hypothesis has been advanced by Jacubovitch, and strongly urged by Gaskell,¹¹ that the cells of the vesicular columns of Clarke, which are peculiar to this region, are the seat of these reflex mechanisms. This hypothesis gains some support from the pathology of syringo-myelia. In this disease the gray matter surrounding the central canal and the vesicular columns are destroyed. The characteristic symptoms are vaso-motor and trophic disturbances, consisting of changes in the vascular tone, changes of local temperature, and various eruptions, in some cases going on to ulceration in the skin and mucous membranes. It is, however, undecided whether the vaso-motor centres of the cord are limited to the columns of Clarke, or are situated in the gray matter surrounding the central canal, since both these parts are destroyed in this disease.¹² That they are not located in the anterior or posterior gray cornua is determined by the fact that diseases limited exclusively to these areas do not cause vaso-motor disturbances. The situation of the various reflex centres for the various parts of the body is at different levels of the cord, as has been determined by the experiments already cited to establish the level of origin of the vaso-motor nerves. The exact location of the vaso-constrictor and vaso-dilator reflex centres for definite parts is yet to be ascertained.

¹¹ Loc. cit.

¹² See Fürstner, Arch. für Psych., xiv. 422.

Vaso-motor Tracts.—These reflex centres are connected with the medulla by tracts which lie in the lateral columns of the spinal cord,¹³ although it is not determined in which part of these columns. It is not possible as yet to separate the constrictors from the dilators in this tract, nor to determine whether it transmits impulses in both directions or only from above downward. Nor is the course of associating fibres between reflex centres at different levels known. In cases of transverse myelitis the control of the medulla is removed from the vascular centres below the lesion, and the lack of vascular tone seen in the paralyzed limbs, together with the susceptibility to local irritation, is the result of this division of the vaso-motor tracts.

¹³ “Owsjanikow and Tschirijew,” Bull. de l'Acad. de St. Petersbourg, xviii. 18.

Medullary Centres.—It has been stated already that a general vaso-motor centre with both constrictor and dilator powers is situated in the medulla. This lies in two divisions on each side of the middle line, in or just beneath the floor of the fourth ventricle, from the calamus scriptorius up to the level of the sixth nerve-nucleus. Each division governs the vascular tone of its own side of the body,¹⁴ and lesions in its region in man produce unilateral vaso-motor symptoms.¹⁵ This centre can be excited to reflex action by strong irritation locally or through the blood, in which case a general constriction or dilatation of the vessels of the entire body will ensue. It seems probable, however, that the general centre in the medulla is made up of a number of special centres, each of which governs a definite set of organs. The vascular tone of the thoracic and abdominal viscera is certainly regulated by a series of such centres. Brown-Séquard and Schiff have produced hemorrhages in the lungs, pleura, stomach, intestines, and kidneys at different times by destructive lesions of the medulla, and the well-known experiments of Bernard, in which by puncture of the medulla local hyperæmia of the liver or kidneys was caused, producing glycosuria or polyuria, confirm this view. Lesions of these parts in man produce similar effects. Charcot has shown that in cerebral hemorrhage ecchymoses may be found in the stomach, pleura, and endocardium, and that pneumonia is especially frequent upon the paralyzed side. De Jonge¹⁶ has been able to collect thirteen cases of diabetes mellitus in which a lesion of the medulla (hemorrhage or tumor) was found after death; and Flatten¹⁷ has proven the existence of similar lesions in diabetes insipidus. The connection of these centres with the liver and kidneys has been traced elsewhere.¹⁸ The medulla contains a special centre for the vaso-motor nerves of the abdomen, which are in the domain of the splanchnic nerves. This centre is excited reflexly by impulses reaching it through the depressor nerve of Cyon from the heart; so that when that organ is overburdened it may be relieved by a fall of arterial pressure produced by dilatation of the abdominal vessels. Whether the connection of the medulla with the centres in the semilunar ganglion which preside directly over these vessels is made by way of the spinal cord or by way of the pneumogastric nerve is still undetermined, though the researches of Gaskell favor the former view. Gastric and intestinal disturbances are certainly produced by nervous lesions in the medulla, but whether they are due to vascular changes is uncertain. The vomiting of mucus and blood, and the large watery evacuations which accompany mental shock or anxiety, as well as the polyuria associated with mental effort, have been ascribed to irritation of local centres in the medulla governing the gastro-intestinal and urinary organs by impulses received from the cortex above. The spleen is under the control of vaso-motor centres, since section of the splenic branches of the semilunar ganglia will produce a great enlargement of the organ, and irritation of the cut end of these branches will produce contraction.¹⁹ The medulla also contains a vaso-dilator centre for the erectile tissues of the genital organs, irritation of which by mental action or local disease causes impulses to pass to the nervi erigentes by way of the spinal cord, resulting in a flow of blood to the parts. Although a centre has been thought to exist controlling the circulation in the lungs, whose paralysis has been supposed to explain the occurrence of sudden pulmonary œdema without other known cause, no definite facts regarding it are known. That the action of the heart is under the control of the medulla is a fact too well known to require more than a mention. The physiology of the nervous control of the heart cannot be discussed here.

¹⁴ Owsjanikow, Arbeiten aus d. Physiol. Instit. zu Leipzig, 1871.

¹⁵ M. A. Starr, “Sensory Tract in Central Nervous System,” Journ. Nerv. and Ment. Dis., July, 1884, pp. 396-398.

¹⁶ Arch. f. Psych., xiii.

¹⁷ Ibid.

¹⁸ See Tyson, “Diabetes Mellitus,” Pepper's System of Medicine, Vol. I. p. 195; Edes, “Diabetes Insipidus,” ibid., Vol. IV. p. 30.

¹⁹ Tarchanoff, Pflüger's Arch., viii. p. 97; Ross, Diseases of the Nervous System, vol. i. p. 225.

While these medullary centres are certainly influenced by impulses reaching them from the cerebral hemispheres, as is evident from the vaso-motor symptoms produced by mental action—e.g. pallor from fright, blushing, etc.—it is impossible to state in what portion of the hemispheres in man the higher vaso-motor centres lie. Eulenburg and Landois locate them in the motor area in animals.²⁰ They are certainly beyond control of the will, and are wholly reflex in their action, a purely mental act in this case being the excitant of a purely physical result.²¹

²⁰ Arch. f. Path. Anat., Bd. lxviii. p. 245.

²¹ In addition to the articles already cited the reader is referred to Landois's Physiology, to Duval's article, “Vaso-moteurs,” in the Dictionnaire de Médecine et de Chirurgie, vol. xxxviii. (1885), for a summary of vaso-motor physiology, and to Gerhardt's “Ueber Angio-neurosen,” Volkmann's Sammlung klin. Vorträge, No. 209. Gaskell's researches, published in the Journal of Physiology, are the most recent and satisfactory.

PATHOGENESIS.—From this review of the physiology of the vaso-motor system it becomes evident that disturbances of vascular tone may be produced by many different causes acting upon many various parts. They may be due to local affections of the part in which the symptoms are present, as in the case of erythema²² after burns or frost-bite, or congestion of any organ after injury. They may be due to affections of the vaso-motor nerves passing to the part affected, as in the case of vascular changes due to peripheral nerve lesions.²³ They may be due to affections of the sympathetic ganglia connected with the part affected, as in the case of migraine,²⁴ sudden flushing of one ear, certain cases of polyuria,²⁵ and Basedow's disease.²⁶ They may be due to lesions in the spinal cord affecting the vaso-motor centres²⁷ or compressing the nerve-roots on their way to and from the sympathetic ganglia,²⁸ as is the case in the various forms of myelitis and in Raynaud's disease or symmetrical gangrene, and in meningitis, tumors of the cord, or Pott's disease. They may also be caused by such conditions in the cord as cut off the vaso-motor centres from the medullary centres, such as transverse myelitis from compression or traumatism.²⁹ They may be due to lesions of the medulla oblongata,³⁰ as is seen in some cases of polyuria and glycosuria,³¹ and in cases of universal erythema³² following acute fevers. They may be due to diseases of the cerebral hemispheres, as is evident from the vaso-motor symptoms occurring in hemiplegia and hysteria. Finally, they may be of a reflex origin, dependent upon some obscure source of irritation in a part quite distant from the region in which the symptoms appear.³³

²² Vol. IV. p. 511.

²³ Vol. V., “Neuritis.”

²⁴ Vol. V., “Migraine.”

²⁵ Vol. IV., “Polyuria.”

²⁶ Vol. III. p. 761.

²⁷ Vol. V., “Syringo-myelitis.”

²⁸ Vol. V., “Meningitis Spinalis.”

²⁹ Vol. V., “Transverse Myelitis.”

³⁰ Vol. V., “Medulla.”

³¹ Vol. I., “Diabetes Mellitus.”

³² Vol. IV. p. 512.

³³ Vol. V. p. 205.

The DIAGNOSIS of the seat of the lesion in many cases of vaso-motor neurosis may be made if the organ or the exact limitation of the area affected be ascertained, and the history of the case, together with the concurrent symptoms of other kinds, be considered. In some cases no organic cause can be found, and in these a reflex cause should be diligently searched for.

SYMPTOMS.—A vaso-motor affection may manifest itself either by a spasm or a paralysis of the vessels. In angiospasm the part affected becomes pale, and irritation no longer causes a vaso-motor reflex. It looks shrunken, and if the skin over it is loose it may be thrown into folds or shrivelled, presenting the appearance seen in the hands after long immersion in hot water. The lack of blood in the part arrests the processes of metabolism which are normally constant, and if the condition continues this may result in such a disturbance of nutrition that ulceration, or even gangrene, may ensue. The local anæmia, combined with the cessation of metabolism, produces a fall of temperature in the affected part, which is then more easily affected by the temperature of the air than in a normal state, so that exposure to cold is very liable to cause freezing. These conditions necessarily produce an impairment of function, so that if the affection is located in the extremities, as the fingers, they are soon rendered useless. The term digiti mortui has been applied to this state. In the surface of the body angiospasm causes cutis anserina, pallor, numbness, tingling, slight anæsthesia, and analgesia. If it occurs in a limb, the finer motions are imperfectly performed, and in time the nutrition of the muscles may be so impaired as to produce atrophy and paresis. It may even lead to gangrene. Nothnagel has recorded³⁴ five cases of sciatica in which the pain produced a reflex spasm of the vessels of the leg, which, persisting, resulted in partial paralysis, atrophy, lowering of temperature, pallor, and sensory disturbances. Ross mentions³⁵ the sudden appearance of circumscribed patches on the hands and forearms of washerwomen, in which there is a pallor, coldness, and partial anæsthesia. These may be limited to the distribution of a single nerve, and may be accompanied by trophic affections.

³⁴ Arch. f. Psych., v.

³⁵ Vol. I. p. 221.

Spasm of the veins may occur as well as of the arteries,³⁶ or independently of them. In the latter case the blood will not pass out of the capillaries. The part will then be blue, swollen, œdematous, and painful; the temperature will be lowered by increased radiation of heat, and all the sensations and functions be impaired in greater or less degree. If this continues, nutrition may suffer, and in the end gangrene develop, which will take its course and lead to the throwing off of the part. Grainger Stewart has described such a condition occurring in both hands and feet.³⁷ It may be likened to a severe form of Raynaud's disease.

³⁶ Weiss, “Symmetrische Gangrän,” Wiener Klinik, 1882.

³⁷ Grainger Stewart, An Introduction to the Study of Nervous Diseases, p. 138.

Angio-paralysis is more frequent than angiospasm, and may be due either to paralysis of the vaso-constrictors or to excitement of the vaso-dilators. It shows itself by a bright-red or mottled appearance of the skin, and increase of local temperature, and more rapid processes of nutrition, together with an increase of secretion if the part is a gland or a mucous membrane, and an increase of sweat if it is the skin. In the latter case an increased sensitiveness to changes of temperature, a subjective sensation of heat, and hyperæsthesia and hyperalgesia may occur. The hyperæsthesia on the paralyzed side which is present in hemiparaplegia spinalis is ascribed to the vaso-motor paralysis. But these symptoms soon give place to others. The dilatation of the vessels, which at first caused an increased flow of blood to the part, produces a slowing of the blood-current in the part, just as a river runs less rapidly where it becomes wider. The slowing of the current in the skin allows of a more complete cooling of the part as the radiation of heat and the evaporation of moisture are increased, and the slowness of the renewal of blood impairs the processes of nutrition, so that to the first stage of redness, heat, and increased metabolism there ensues a stage of blueness, cold, and defective nutrition, and the function of the part may be impaired. In this stage it usually presents a mottled appearance, and may be slightly swollen and œdematous, and the continued increase of perspiration gives it a clammy coldness to the touch. In all of these conditions severe pain, sometimes of a burning character, is a very distressing symptom (causalgia). These conditions are seen in peripheral nerve-lesions, and give rise to the appearances which have been so admirably described by Weir Mitchell.³⁸

³⁸ Injuries of Nerves.

A peculiar combination of symptoms may be mentioned here, to which Weir Mitchell has given the name of erythromelalgia.³⁹ This disease begins with tenderness and pain in the soles of the feet, which are soon followed by a marked distension of the capillary vessels. The congestion is attended by a sensation of burning pain similar to that produced by a blister. The surface is at first of a dull dusky-red color; later it appears purple. The redness is not uniformly distributed over the sole, but occurs in patches of irregular shape, being especially frequent over prominent parts exposed to pressure and friction, and the attacks seem to be brought on by long standing or walking. At first there is a rise of temperature in the affected surface, the arteries pulsate visibly, the veins are swollen, and there may be some œdema. Later, the foot is cold and pale. Sensations of touch and temperature are normal, but the part is so extremely tender that walking is impossible. There is no paralysis. One or both feet may be affected, but the patches of redness are rarely symmetrical. The hands are occasionally affected. The condition may occur in paroxysms or may remain for some time. It resists all known methods of treatment, although applications of cold relieve the burning pain to some extent and the tenderness enforces rest.

³⁹ Amer. Journ. of the Med. Sci., July, 1878.

With angio-paralysis may be classed the taches cérébrales of Trousseau no longer considered diagnostic of meningitis, but denoting a weakened condition of vaso-constrictor action in the local ganglia of the vessel-wall which may occur upon local irritation of the skin in any severe disease affecting the nutrition of the general nervous system.

Actual rupture of the capillaries in the course of vaso-motor diseases is rarely observed, although the stigmata appearing in hysterical and cataleptic patients may be ascribed to this cause. In this connection tabetic ecchymoses may be mentioned, which appear suddenly without local injury, and resemble an ordinary bruise, running a similar course. They occur only in the course of locomotor ataxia.⁴⁰

⁴⁰ Straus, Arch. de Neurologie, tome i. p. 536.

In addition to these forms of vaso-motor affections there is a condition of instability of vascular tone which manifests itself by sudden transient changes in the circulation of various organs. This is a functional affection, usually due to malnutrition. It is seen in many cases of neurasthenia and hysteria, and manifests itself by sudden flushes or pallor, alternations of heat and cold, local sweating, attacks of mental confusion, and inability to use any organ continuously from disturbance of the power of the vaso-dilators to maintain a condition of functional hyperæmia.⁴¹ Little is actually known about the causes of this state of the vascular system, although much has been written about it. (For a fuller description the article on Neurasthenia may be consulted.)

⁴¹ Anjel, Arch. für Psychiatrie, xv. 618.

Many functional derangements of the internal viscera have been ascribed to such vaso-motor instability with more or less probability,⁴² but hypothesis of this kind, however plausible, is evidently beyond confirmation. It is especially in affections of this kind that causes of reflex irritation are to be carefully sought. Cutaneous angio-neuroses, such as have just been described, may affect any part of the body. They usually appear suddenly, producing much discomfort and an impairment of function in the part if it is an extremity. They disappear as rapidly as they come. The duration of such attacks varies from a few minutes to several days. They are very liable to recur. If it is the vessels under the control of the cervical sympathetic which are affected, the symptoms will be those of migraine or of lesion of the ganglia.⁴³ If it is the vessels in the extremities which are involved, the condition of digiti mortui or erythromelalgia or symmetrical gangrene⁴⁴ may be produced.

⁴² Fox, The Influence of the Sympathetic System in Disease, London, 1885.

⁴³ See p. 1263.

⁴⁴ See p. 1257.

A singular epidemic occurred in France in 1828 and 1830 which was termed acrodynia. Many persons were suddenly seized with vomiting and purging, and soon after the onset the extremities became red or mottled in blotches, swollen and œdematous, and hot, painful, and tender. The attacks lasted from a few days to two months, and during this time the skin became thick and hard, the muscles weak and subject to spasms, and the general health was impaired. Relapses occurred in many cases, but all finally recovered, and hence the exact nature of the disease was not ascertained.

COURSE.—In any case of vaso-motor neurosis the course of the disease and its termination will depend chiefly upon its cause. If the cause is some permanent lesion of the nervous system, the condition will remain, and in this case the termination will depend upon the severity of the symptoms. Angiospasm may be so severe as to lead to gangrene ana the separation of the part affected, or may be so slight as to cause only subjective discomfort and a little pallor. Angio-paralysis may lead to an extreme degree of congestion, which is attended by heat and pain at first, later by paræsthesia and coolness, with increased liability of the part to be affected by changes in the surrounding air. This stage is succeeded by one of less marked dilatation of the vessels and a spontaneous partial recovery, although the more moderate symptoms may continue indefinitely and seriously impair the function of the part. If the cause is a temporary derangement of function in the vascular mechanism, is reflex irritation which can be removed, or is a curable organic disease, the symptoms will subside rapidly or gradually and perfect recovery may follow. If the condition is one of irritability in the vaso-motor centres, producing alternations of flashing or pallor, such as is observed in nervous exhaustion, it may recur irregularly for a considerable length of time until the causative condition can be removed.

PROGNOSIS.—The prognosis must be determined in each case by a consideration of the cause of the affection, of the nature of the symptoms, of the severity of the disease, and of the possibility of success in both symptomatic and causative treatment. In the angio-paralytic cases an eventual spontaneous relief from much of the discomfort may be promised, although the duration of the symptoms cannot be predicted.

TREATMENT.—Treatment must be directed primarily to removing or diminishing the severity of the cause. A review of the section on Pathogenesis will indicate how wide a field this may include, and the reader must be referred to the special articles which are alluded to in that place for therapeutic measures. Special diligence is to be shown in searching for a source of reflex irritation. When the cause cannot be reached, and when the symptoms are of such severity as to demand immediate attention, treatment may be directed to them.

In all conditions of vaso-motor disease it is important to shield the part from external injury; for if the vessels are dilated they are liable to rupture, and any abrasion of the surface may produce serious inflammation and ulceration; and if the vessels are contracted any injury will be repaired slowly and imperfectly on account of the anæmia, and may even hasten the approach of gangrene.

Perfect rest, bandaging with cotton, and even the application of a light splint to the extremities will be advisable in cases of angiospasm. It is desirable to retain the animal heat, inasmuch as its supply is deficient. In angio-paralysis rest in a somewhat elevated position and applications of mild evaporating lotions are indicated in the early stage; later, the limb may be bandaged. It is not advisable to attempt by tight bandaging to counteract the effect of the vascular paralysis, for the nutrition of the limb is liable to suffer and gangrene may be induced.

Massage of a part affected with vaso-motor symptoms is of great service, since the circulation can be increased in the veins, and thus indirectly in the capillaries, and the nutrition of the part can thus be favored. It is more efficacious in angio-paralysis than in angiospasm. Too rough rubbing is of course to be avoided, lest the skin be injured. All counter-irritation is to be strictly forbidden.

Electricity has been used with varying results. According to Erb,⁴⁵ moderate faradic applications contract the vessels; strong faradic applications, especially with the brush, dilate the vessels. The galvanic current at first contracts the vessels, but this is followed by a secondary dilatation, which will be greater and occur more rapidly the stronger the current used.⁴⁶ Cathodal closures contract the vessels; the anodal continuous current dilates them widely. Stabile continuous currents through a nerve dilate the vessels which the nerve supplies. Inasmuch as vaso-constrictors and vaso-dilators pass together in many nerves, and are found together in all parts, it is impossible to apply electricity to either alone. In those cases, therefore, in which it has been ascertained which set of vaso-motors is affected, it is not always possible to produce a direct effect upon that set by electrical treatment. Erb recommends, in conditions of vaso-motor spasm a trial of the galvanic current, the cathode on an indifferent point, the anode being applied over the vaso-motor centres governing the part, and also over the area of the body which is affected, and held there while a moderate continuous current is passing, interruptions being avoided; or, the cathode being placed on the neck, the anode may be applied to the nerves passing to the affected part; or a strong continuous current may be sent through the nerve, its direction being changed several times during a moderately long application. Finally, the faradic brush applied to the part or a strong faradic current sent through its nerve may relax the spasm. In any case, all these methods should be tried before electrical treatment is abandoned.

⁴⁵ Electrothérapie, 562.

⁴⁶ To this statement Lauder Brunton assents—Pharmacology, p. 250.

In vaso-motor paralysis other methods are used. The cathode is placed on the part congested, and a weak galvanic current is employed with frequent interruptions or even with changes of the pole; or the cathode may be moved about upon the reddened skin while a mild continuous current is passing. A very weak faradic current with wet electrodes, or even a weak faradic current applied with a brush, may be of service. Here, again, various methods may be tried.

If the extremities are affected, it may be well to immerse them in a basin of water which is connected with one pole of the battery, and the current directed in the manner just described, according to the case. It must be confessed that no definite results can be predicted from the use of electricity in these cases, and much more experience is needed before definite rules can be laid down. The records show that in apparently similar cases opposite methods of application have produced favorable effects, while in other cases all methods have failed. Too much reliance should not be placed in electrical treatment. Erythromelalgia is an obstinate affection, and symptomatic treatment, directed chiefly to quieting the pain by opium and allaying the sensation of burning by cool baths, must be resorted to.

Internal remedies may be tried appropriate to the condition present. In angiospasm nitrite of amyl inhaled, or nitro-glycerin ¹/100 gr. t. i. d., may give considerable relief, although both of these drugs are to be used with caution. Chloral hydrate is also of some service, and where the patient is in pain and suffers from insomnia this may fulfil several indications. In angio-paralysis ergot has been used with advantage. Oxygen inhalations are of service. Chloride of potassium may also be tried. It is evident, however, that such remedies, acting as they do upon the general arterial system, are not to be depended upon in the treatment of local conditions, since they have no selective action upon the affected part. The majority of the drugs known as sedatives and antispasmodics have been used in these conditions, but the records of individual cases show that they are not of much avail. Theoretical therapeutic measures based upon experimentation on animals have been fully discussed by Lauder Brunton,⁴⁷ but practical experience has not yet been sufficiently extensive to warrant any further statements.

⁴⁷ Pharmacology, Therapeutics, and Materia Medica, pp. 229-360. Lea Bros., 1886.

Symmetrical Gangrene.

SYNONYMS.—Local asphyxia, Asphyxie locale, Raynaud's disease; Symmetrische Gangrän.

DEFINITION.—Symmetrical gangrene is an affection of the nervous system characterized by arterial or venous spasm appearing in symmetrical parts of the body, especially in the phalanges of all the extremities, which may result in trophic changes or in gangrene. There are various stages in the disease, which have given rise to the various names by which it is known. The stage of local syncope, in which there occurs a moderate contraction of the arterioles and consequent pallor of the part, may be followed by a stage of local asphyxia, in which the complete contraction of the arterioles cuts off entirely the supply of arterial blood, and the regurgitation of venous blood produces cyanosis of the part; and this, if continued, may result in the gangrene of the part, which is then thrown off. Instead of a condition of local asphyxia, there may be a spasm of the smaller veins, resulting in a local erythema, which may go on to capillary stasis and then to gangrene. The spasm of the vessels may cease at any stage as suddenly as it began; and if this occurs in the first or second stage, no gangrene results.

HISTORY.—While isolated cases of this affection had been recorded as curiosities during the past two centuries,⁴⁸ the disease was first studied with care by Raynaud in his Thèse de Paris in 1862. He collected twenty-eight cases which had been described with accuracy or had been personally observed in the hospitals of Paris, and after a thorough analysis of the symptoms defined the disease as “a neurosis characterized by an exaggeration of the excito-motor power of the cord presiding over the vaso-motor nerves.” He called particular attention to the condition of spasm in the vessels, and proposed the name asphyxie locale to designate the peculiar appearance of the parts affected. He also noticed the resulting gangrene as a new variety of gangrene, not dependent upon embolism or upon changes of an atheromatous nature in the coats of the vessels.

⁴⁸ Schrader, 1629; Hertius, 1685; Bouquet, 1808; Moulin, 1830; Racle, 1859—cited in full by Weiss, “Symmetrische Gangrän,” Wiener Klinik, 1882.

The condition was at once recognized by others, and several cases had been reported prior to 1873, when Raynaud published a more complete article on the subject in the Dictionnaire de Médecine et de Chirurgie under the title gangrene symmétrique; in 1874 he recorded five new cases in the Archives générales de Médecine, vol. i. pp. 5 and 189.

The disease, having been thus established as a definite nervous affection, began to be noticed in other countries than France; and Billroth in Vienna,⁴⁹ Weir Mitchell,⁵⁰ Mills,⁵¹ A. McL. Hamilton,⁵² and J. C. Warren⁵³ in this country, and many other careful observers, published cases, together with more or less complete articles upon the disease. In 1882, Weiss produced a monograph⁵⁴ upon the subject containing references to all the cases which had appeared; and this is still the most complete article to be found, although the essay of R. Lauer⁵⁵ and the discussion of the disease by the Berlin Medical Society,⁵⁶ as well as the short articles of Schulz⁵⁷ and Lutz,⁵⁸ deserve mention, for they contain additional observations of cases and numerous facts not to be found elsewhere.

⁴⁹ Wiener Med. Wochensch., 1878, No. 23.

⁵⁰ Amer. Journ. of the Med. Sci., 1878, July.

⁵¹ Ibid., 1878, Oct.

⁵² N. Y. Med. Journ., 1874, Oct.

⁵³ Boston Surg. and Med. Journ., 1879, No. 3.

⁵⁴ Weiss, Wiener Klinik, 1882, “Symmetrische Gangrän;” also Zeitschrift für Prac. Heilkunde, 1882.

⁵⁵ Inaug. Dissert., Strasburg, 1884.

⁵⁶ Zeitschrift für klin. Med., vi. p. 277, 1883.

⁵⁷ Deut. Arch. f. klin. Med., xxxv. 183, 1884.

⁵⁸ Bäyr. ärzt Intell. Blatt, 1884, xxxi. 24.

SYMPTOMS.—The disease begins suddenly in all cases, and the constitutional symptoms are less prominent than the local ones. In some cases there are noticed a certain degree of mental disturbance, a condition of depression with a tendency to sigh and cry without cause, disturbed sleep with unpleasant dreams, irritability, and headache. A loss of appetite and disorders of digestion may follow, and then the local symptoms appear. In other cases, which seem to be the majority, the local condition develops without any such premonitory disturbances of the nervous and digestive systems, although these may ensue. The local symptoms first noticed may be paræsthesiæ or pain in all the extremities, usually limited to the tips of the fingers and the toes. These are continuous and severe, and are immediately followed (and occasionally preceded) by an appearance of ischæmia or of cyanosis or of erythema, in the order of frequency named.

(1) The fingers may look pale and dead, presenting the appearance of the so-called digiti mortui, and may be cold, painful, and anæsthetic. If this condition is moderate in degree, a certain amount of blood will continue to flow through the contracted arterioles, and then it corresponds to the description given by Raynaud of syncope locale. If it is extreme, the part may be wholly deprived of arterial blood, and then a true local asphyxia is present. In this stage the patients usually suffer considerably, although some do not complain of pain until the next stage. The ischæmia is attended with an impairment of sensation to touch, temperature, and pain, and finer motions become clumsy on account of the subjective numbness and actual anæsthesia. At the same time, the fingers look shrunken, the skin being thrown into folds, as if the hand had been soaked in hot water, or they may appear as if frozen, the skin being hard and immovable.⁵⁹ The secretion of perspiration may be increased, and the fingers feel damp as well as cold, or it may be suspended. The local temperature is lowered. If the part is cut, little or no blood will flow. At this stage the arterial spasm may suddenly relax and the part return gradually to its normal condition, the cessation of the constriction of the arteries and the return of blood being usually accompanied by burning pain, which may last for some hours. The duration of such an attack may vary from a few moments to several days. If it continues longer, this stage is usually succeeded by the second stage, of cyanosis.

⁵⁹ Finlayson, Medical Chronicle, 1885, No. 4.

(2) The stage of cyanosis results from one of two conditions: either the arterial spasm is so complete that no blood passes into the part, in which case venous blood from lack of vis a tergo or in response to gravitation regurgitates into the capillaries, distending them and producing a state of blueness; or a venous spasm occurs, preventing the exit of blood from the part, which then becomes actively congested, and the blood in the capillaries, from want of renewal, soon becomes venous and produces the cyanotic appearance. The stage of ischæmia may be so short that it is hardly noticed, so that the patient's attention is first attracted by the swollen, blue, and extremely painful condition. The skin may be stretched, the tissue infiltrated with products of exudation, which can be pressed out, as can also the venous blood, and the surface may itch as well as be painful. Anæsthesia is rarely present in this stage, and there may even be hyperæsthesia. The part is cool from the increased radiation of heat and cessation of the processes of metabolism, the local temperature being lowered. The small vessels on the surface will be visibly injected, and capillary ecchymoses may rarely be seen. There is less liability to difficulty in movement in this stage than in the former one, as the sensations of the part are not benumbed, but if present it is due to the swelling. This condition, like that in the former stage, may cease suddenly, the recovery of the normal appearance being, as a rule, slower than after a simple ischæmia. The duration of this stage has varied from a few seconds to several days. It is usually followed by gangrene.

(3) The condition of local erythema is described here because it may lead to gangrene, and has therefore been considered by Weiss as one of the early stages of the disease. As a rule, however, it is not followed by the death of the part, and the affection in these cases is probably one of erythromelalgia rather than of symmetrical gangrene. Like the stage of ischæmia, the stage of erythema may appear suddenly. The part presents a bright-red or a mottled appearance—is hot and swollen, and painful. The vessels are visibly injected, the local temperature is raised, the secretion of sweat may or may not be increased, and the patient feels a burning sensation rather than pain. Hyperæsthesia to touch and temperature and pain is usually present, or the sensations are normal. The blood can be pressed out, but returns immediately. In this condition of hyperæmia slight injuries lead frequently to an inflammatory process, ulcers may form in the pulps of the fingers or around the nails, and the eschars may appear dark and even gangrenous; or an actual condition of gangrene may appear in the tips of the fingers, the exact method of its occurrence being a matter of dispute. The erythematous condition is much more likely to be permanent than are the other stages of the disease—another fact which has led to some hesitation in considering it a true stage. This condition of erythema may be due to a paralysis of the vaso-constrictors, the converse of the spasm occurring in ischæmia. It has also been ascribed to an irritation of the vaso-dilators; and this appears to be the more probable hypothesis.

(4) The stage of gangrene is always preceded by that of cyanosis, and the death of the tissue is due to the arrest of nutrition consequent upon a stasis of the blood. It is not necessary to invoke the injury of trophic nerves to explain its appearance. In the tips of the cyanotic fingers, on their palmar surface, beneath the epidermis, a small blister appears, filled with a dark serous fluid or with pus or blood. This soon ruptures, and a dark dry scab forms, beneath which an ulceration may go on destroying the corium, but not penetrating deeper. In the majority of cases the gangrene is limited to a small area of the pulps of the fingers, and only involves the superficial layers of the corium. The gangrenous spot is surrounded by a purple margin. When the sphacelus has separated a scar remains which is frequently insensitive. In other cases when the sphacelus is thrown off it leaves a deep ulcer, which may look as if the lost tissue had been cut out with a punch, and this gradually granulates and heals. In still other cases the entire skin of the terminal phalanx may become black and dry, presenting a true gangrenous appearance. Then a line of demarcation is formed, usually at the junction of the terminal with the middle phalanx; separation of the gangrenous part occurs, and a stump is left covered with thin, glossy skin. This extensive gangrene, involving an entire phalanx, is the exception rather than the rule.

While the gangrenous process is in progress in the tip of the finger the nails cease to grow, and may become bulbous and rigid; the epidermis elsewhere may become dry and desquamate, and ulceration around the root of the nail may take place. With the completion of the stage of gangrene, which may last from one to five weeks according to its extent, the local symptoms terminate.

It is the symmetrical distribution of the local symptoms just enumerated which is the peculiar characteristic of the disease. The fingers of both hands, the toes of both feet, symmetrically situated spots upon the back, trunk, thighs, legs, forearms, and arms (in the order of frequency named), are affected either singly or in combination. In the majority of cases fingers and toes are affected together, and a few spots are seen on the trunk. In many cases the toes escape. In a large number of cases the face has been affected, spots of cyanosis appearing on the nose or ears or lips. As a rule, the stage of gangrene only ensues in the tips of the extremities, but a few cases are recorded in which little areas of skin elsewhere have passed through all the stages of the disease. Pigmentation occurs in spots upon the body when the process does not go on to gangrene.

Among the rare symptoms which have occurred in some cases are great impairment of temperature, pain, and electric sensations in the affected extremities; swelling, pain, redness about, and effusion into, the joints; considerable loss of motion in the muscles of the hands and feet, with diminution of electric excitability, but no qualitative change; and oculo-pupillary changes ascribed to an irritation of the cervical sympathetic fibres at their origin in the spinal cord.

In addition to the constitutional symptoms mentioned, which may usher in the disease and may continue during its course, there have been observed temporary albuminuria, glycosuria, and hæmaturia. Fever never occurs as a symptom of the disease, and if present must be ascribed to some other condition. The special senses have been affected in a few cases. In one case a spastic contraction of the retinal arteries alternated with attacks of ischæmia in the extremities.⁶⁰ The intellect is usually unaffected, but Weiss observed a case in which transient aphasia occurred, which he attributes to local spasm in the arteries of the cortex. The patient could find words only after long thought, and spoke slowly and with difficulty.

⁶⁰ Raynaud, Arch. gén. de méd., 1874, p. 11; Galezowski examined the discs.

COURSE AND DURATION.—The onset of the disease is sudden. The symptoms in the first two stages may last only for a few minutes and pass off, or the disease may pass through all the stages and terminate in gangrene. It is usual for the first stage of ischæmia to last several days, varying in severity; for the second stage to last several days; and for the stage of gangrene to occupy about three weeks. The shortest duration of a single attack has been ten days, the longest five months. If the gangrene begins simultaneously in all the fingers, the duration will be shorter than if it proceeds to one after another. In one-third of the cases a recurrence of the disease within a year of the first attack has been observed, and it is probable that the proportion would have been larger had all the patients been kept under observation. In some cases three and four attacks have succeeded each other with some rapidity, some of the attacks being much less severe and shorter than others. In some cases the condition of gangrene has developed only in one out of three attacks. When the condition is one of local erythema the duration may be indefinite, the state becoming chronic and lasting for several years.

NATURE.—The nature of the disease is a matter of deduction from the study of the symptoms, no autopsies having as yet been made. As already stated, the symptoms are explained on the theory of a vaso-constrictor irritation in the stages of ischæmia and cyanosis—of a vaso-dilator irritation in the stage of erythema. Whether this irritation is the direct result of abnormal processes going on in the vaso-motor centres in the spinal cord, or is the reflex result of irritation arising elsewhere, is undetermined. Raynaud held that it must be of central origin, since in his cases galvanization of the spinal cord modified the arterial spasm. The latter observation has not been confirmed by other observers. Weiss believes that the condition may occur in response to irritation arising in the skin, in the viscera, or in the brain, and thus prefers the theory of reflex origin. This theory is adopted by several observers, who find a source for such irritation in the female genital organs in their cases.

ETIOLOGY.—The disease occurs in adult life, only two cases having been observed in persons fifty years old. It is most frequent between the ages of fifteen and thirty, although children and adults beyond the age of thirty are about equally liable. Females are more liable to it than males, four-fifths of the recorded cases having been in women. It occurs more frequently in the winter months, exposure to cold being a common exciting cause. Other exciting causes are nervous exhaustion, especially occurring in those who are predisposed to nervous diseases by heredity; general weakness from anæmia, malnutrition, or the occurrence of acute fever or exhausting disease; and mental agitation, a fright having preceded the attack in several cases. In women menstrual disorders and uterine disease have been considered as etiological factors. Occupation has something to do with its occurrence, since washerwomen, waitresses, and chambermaids are the class most often affected. In many cases, however, no cause of local irritation can be found.

DIAGNOSIS.—The diagnosis rests upon the development of vaso-motor symptoms in the extremities, situated symmetrically, going on to gangrene, in a person not afflicted with cardiac disease or with endarteritis of any kind, and not having been exposed to frost-bite or ergot-poisoning. The age of the patient, the symmetrical position of the symptoms, the persistence of the pulse in the main arteries, and the limitation of the gangrene to the tips of the extremities distinguish it readily from senile gangrene. The history of the case, the absence of itching, and the presence of pain during the arterial spasm which passes off when the spasm ceases, serve to separate it clearly from chilblains. Congenital cyanosis is produced by cardiac anomalies, and the entire body is affected. Ergot-poisoning can be ascertained by the history.

PROGNOSIS.—Life is not endangered by this disease, no fatal cases having been recorded. Recovery from an attack is certain, but the duration cannot be stated, as it will depend in any case on the character, the extent, and the severity of the symptoms. The possibility of a recurrence of the attack should be stated to the patient.

TREATMENT.—The methods of treatment have varied, and none are wholly satisfactory. If the causes can be met—e.g. anæmia, nervous exhaustion—they should be treated. If not, the disease itself may be attacked by means of electricity. Or the symptoms may be treated as they demand it. Electricity has been used by almost all observers. The faradic current produces an aggravation of all the symptoms except in the stage of erythema, and has been discarded. The galvanic current may be employed in several ways. Two methods are in use. In the first the positive pole is applied over the cervical region, and the negative pole over the lumbar region, a descending current being thus sent through the spinal cord. The current should be of moderate strength, not above twenty-five milliamperes, few patients being able to endure the strength implied in Raynaud's statement that he used sixty-four cells of a Daniel battery. The duration of the application should be ten minutes, and the electricity may be applied once daily. In the second method the anode is applied over the brachial or lumbar plexus, as the case may be, and the cathode passed over the affected extremity, the current being constant and care being taken not to break it suddenly. The strength, duration, and frequency should be the same as in the first method. From these two methods, separately or combined, Raynaud claimed to have seen favorable results. His assertions have not been confirmed by other observers who have followed his directions closely, and hence considerable doubt at present prevails as to the efficacy of the electric current. The so-called electrical application to the cervical sympathetic is certainly useless. In the stage of erythema a very weak faradic current applied to the hands in a bath may be of service.

Many observers have found that the progress of the case to recovery was quite rapid if the limb were put at rest in an elevated position, were kept warm by cotton batting or similar bandaging, and were kept clean with antiseptic lotions when the stage of gangrene set in. Massage is to be used in all cases, the limbs or affected parts being gently rubbed with the dry hand or with aromatic liniments or oils. All local injury, however, and especially counter-irritation, are to be carefully avoided. General tonic treatment, especially iron and cod-liver oil, is to be used in all cases.

The pain occurring in the early stages is often so severe as to require the use of opium or other narcotics. And when the nervous symptoms are especially aggravated, and irritability and insomnia give the patient discomfort, bromide and chloral may be employed.

Diseases of the Cervical Sympathetic.

ETIOLOGY.—Diseases of the cervical sympathetic ganglia or cord may be of two kinds—either irritative or destructive.⁶¹ They are produced by pressure upon the cervical ganglia or upon the sympathetic cord between these ganglia, by tumors, especially aneurisms, and enlarged glands; by abscesses; and by cicatrices of old wounds in the neck. They are also due to extension of inflammation from a thickened pleura in phthisis and chronic pleuritis of the apex. They may be caused by injuries, such as stab-wounds, gunshot wounds, etc. Any disease which produces marked irritation of peripheral branches of the sympathetic in the neck, or of the cerebro-spinal cervical nerves, may cause reflex phenomena resembling the symptoms of actual disease. From such phenomena it is not justifiable to conclude that the sympathetic cord and ganglia are the seat of lesions, and the only cases which will be considered here are those in which actual disease was proven to be present by an autopsy.

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.

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 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 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

⁶³ Berlin. klin. Woch., 1884, No. 16.

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. 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:

⁶⁵ Bericht der Section für Dermatologie, Versammlung Deutscher aerzte, Strasburg, 1885; Vierteljahrschrift für Dermatologie und Syphilis, 1885, 4 Heft, S. 683.

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 consists⁶⁸ 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 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.

⁶⁷ Waller, Philosoph. Transactions, 1850, ii. p. 423; Comptes rendus de l'Acad. de Sci., 1852-55.

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 Homen⁷⁰ 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.

⁶⁹ See Vol. V., “Myelitis—The Secondary Scleroses,” p. 892; Schültze, Arch. für Psych., xiv. 2.

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.

⁷¹ Hayem, G., Recherches sur l'Anatomie pathologique des Atrophies musculaires, Paris, 1873; Ross, Diseases of the Nervous System, vol. i. p. 238.

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 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

⁷³ Weir Mitchell, Amer. Journ. of the Med. Sci., 1873, p. 113; Charcot, Arch. de Phys., 1874, p. 166.

⁷⁴ Demange, Rev. de Médecine, 1882, p. 247.

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.

⁷⁶ Weir Mitchell, Injuries of Nerves. See also Vol. IV. p. 683.

⁷⁷ Seeligmüller, Lehrbuch der Krankheiten d. Peripheren Nerven, p. 157, 1882.

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 nervous mechanism, as cases of hyperidrosis, anidrosis, and chromiodrosis prove;⁸⁰ and an atrophy of them and of the sebaceous glands has been observed⁸¹ after nervous lesions.

⁷⁹ Cited by Samuel, Realcyclop., loc. cit. See also Obolensky, Centralblatt für med. Wissen., 1867, 5, 497.

⁸⁰ See Vol. IV. pp. 583-586.

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.

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 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.

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.

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.

FIG. 58.

Diagram of the Arrangement and Connection of Motor and Trophic Centres and Fibres in the Spinal Cord and Motor Nerve (after Erb): a, motor fibre of spinal cord from the brain to d, the motor cell, which is joined to the muscle m by the motor nerve; b, trophic cell in the spinal cord for the muscle, to which it is joined by the trophic fibre bʹ; c, trophic cell in the spinal cord for the motor nerve, to which it is joined by the trophic fibre cʹ; s, a fibre bringing sensory (reflex) impulses to the cell.
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.

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.

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.

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 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.

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.

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

⁸⁸ Leloir, “Tropho-neuroses,” Nouveau Dictionnaire de Médecine et Chirurgie practiques, 1885.

⁸⁹ Virchow, “Nerven Lepra,” Geschwülste, ii. 521; Tschirijew, Travaux du Laboratoire de Vulpian, 1879.

I have reported⁹⁰ 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

⁹⁰ Journal Nerv. and Ment. Disease, Feb., 1886, clinical cases.

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 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.

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 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.

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 which it controls fail to develop properly. Trophic centres for sensory mechanisms are not yet discovered. Certain investigations of Luciani recently published⁹⁴ point to the cerebellum as the part of the brain which governs the general nutrition of the body, but these need confirmation.

⁹⁴ Alienist and Neurologist, July, 1885.

CONCLUSION.—While an attempt has been made here to consider vaso-motor and trophic neuroses separately, it must be admitted that in very many conditions the two are coincident. This follows inevitably from what has been stated regarding the localization of the vaso-motor and trophic centres in the spinal cord, and regarding the course of the vaso-motor and trophic nerves from the spinal centres to the periphery. These two classes of centres and nerves lie side by side in the central and peripheral organs, and it is less surprising that they should be jointly affected than that one should ever be involved alone. In any case of lesion of the peripheral nerves or of the central nervous system they may be expected. In all cases they are to be regarded as symptoms of such lesions rather than as distinct diseases.