situated about one-half way between the terminal extremites of its two great branches; and in this fact, of the interposition of the body in the course of a nerve tract, which from the nature of the case must be a continuous tract, we have one of the most striking proofs that the function of these cell bodies may be less for the purpose of subserving sensory qualities, than for the purpose of acting as nutrient centers. We have also a proof that an axis cylinder process is not always centrifugal in the direction of its impulses. One other system of neurons must be mentioned before we close this review of modern histology, namely: the neuron that is present through the sympathetic system. These neurons are of both the types already described in structure but the fibers are not medullated. It is never to be forgotten that this sympathetic nervous system is very widely spread throughout the body and that it subserves some of the most important functions. It not only controls the entire vegetative and nutritive system contained within the cavities of the body, but it also controls that wonderful mechanism of blood supply by means of which an organ is flooded with blood, whenever it is thrown into activity. This regulation of the supply of blood to an organ during the time when it needs to increase its chemical and functional activity is one of the most delicate mechanisms of the body, and as we shall see later, an interference in this portion of the nervous mechanisms is just as serious in its consequences as an interference with the nutrition of the central nervous system.

In order that these neurons should do their work, they must have a normal structure at the outset and a normal capacity for maintaining their nutrition when in activity. It is only within two or three years that the actual structure of the neuron has been discovered. The method of staining discovered by Nissl (Internationale Rundschau, 1888, also abstracts of Nissl's work in Virchow and Saemich's Jahrbuch, 1890-1894) showed the nerve cell to be made up of a clear protoplasmic ground substance, through

which pass numerous fibrils running from one process into another, between which fibrils are disposed irregularlyshaped bodies which have the capacity to absorb staining matters and have been named the chromatin bodies, and also dumb-bell-shaped bodies which also stain. Nissl affirms that from the arrangement of these bodies in the cell, its function can be determined, that the bodies and fibrils have one arrangement in a motor cell and another in a sensory cell. This is not yet accepted.

There is also a nucleus and nucleolus in each cell and these, too, contain chromatin bodies. The fibrils of the cell have no connection with the nucleus.

When a neuron is made to work, it undergoes certain manifest changes. (Hodge, American Journal of Psychology, Volume II., page 397.) Hodge was the first to prove this, and he described alterations in the form and appearance of the cell and its nucleus consequent upon its activity. There is a general diminution in the size of the cell, a lessened power to absorb staining substances, which may be taken as an evidence of imperfect power of assimilation and nutrition, vacuolation, which may be taken as a proof of the using up of its own substance, and also changes in the appearance of the nucleus which is decreased in size and changes from a smooth and rounded to a jagged and irregular outline. As the cell becomes changed in its structure by constant work, it becomes more and more exhausted, so that finally there comes a time when it is no longer capable of sending out impulses and requires a period of rest to make up what it has lost of form and to regain a store of energy. Vas (Vas, Ueber den Bau des Chromatins in den Symphatischen Ganglien. Archiv für Mikroscopische Anatomie, 1892, Heft III, p. 375) and Mann (Gustav Mann, Journal of Anatomy and Physiology, October, 1894) have described these more exactly. Vas showed that mild stimulation of a cell caused a swelling of its body and of the nuclei and a clearing up of the central part of the cell by an apparent movement of the chromatin bodies to its periphery. Mann showed that functional activity of the

cell is accompanied by an increase in the size due to inhibition of the lymph lying in the cavity about the cell so that the cell at work fills up the cavity in which it lies. When activity goes on to the point of fatigue, then a shriveling up of the cell begins, first in the nucleus, then in the body. At the same time changes go on in the chromatin. During the period of activity the chromatin material is used up, so that a fatigued cell does not absorb staining material as does a cell at rest. While this is true of the chromatin bodies, it is not true of the dumb-bell-like bodies. These stain more deeply especially about the nucleus, so that in an exhausted cell the only stain is in and about the nucleus. These results have been reached by stimulating cells to work in living animals either by electricity or by keeping up movements, such as running or by exposing one eye to light, while the other was kept dark, and then contrasting the appearance of the cells made to work with those which were kept at rest.

It is evident, then, that we can now study the exact mechanical and chemical effects of nervous activity. When a stimulated cell is allowed to rest, it gradually resumes its original appearance; but the period of rest must be adequate.

During the period of reconstruction the chemical activities going on in the cell are numerous and its power of assimilation of material furnished to it by the blood must be increased. If, however, anything interferes with this increased nutrition, such as an imperfect supply of blood or a deleterious substance of any kind in the blood, then the process of building up fails to take place. If we inject a solution of absinthe into the blood of a Guinea-pig and thus produce convulsions, there is evidence throughout the motor cells of the cortex of a marked change. In the outer layer of the cell body, a granular appearance is evident, vacuoles appear and the nucleus may be shrunken, much as in the cell which has been subjected to overwork. It is not necessary that the material circulating in the blood should be

manufactured in the body itself as well as the toxic agents received from without are capable of effecting these changes in the neuron.

We see, then, that the active factors in interfering with the function and nutrition of a neuron are:

First. Exhaustion from over-work. Secondly. Defective nutrition from imperfect blood supply.

Thirdly. Active poisoning, either by substances manufactured within the body or by substances received from without, either in the nature of poisons, of infective germs, or of their products. Here we have then a provisional classification of the causes of nervous diseases; for what is true of the neuron is true of the mass of neurons making up the nervous system.

Of course, in dealing with these causes of disease we start with the supposition that they are acting upon healthy neurons. If the neuron has never developed properly, if it is weak from the start, or if it has been stunted in its growth, it is evident that it is all the more liable to succumb to any hostile influence. The hereditary and congenital predisposition to nervous disease is a factor which must not be lost sight of in studying the etiology of these affections.

Let us study these causes of nervous disease a little in detail.

I.

EXHAUSTION FROM OVER-WORK.

It is hardly necessary in this country, where every physician is constantly meeting cases of neurasthenia from over-work, to insist upon this factor in the causation of nervous diseases. The constant struggle for existence, the insatiable ambition of the majority of active workers and the constant overstraining of every energy in the attainment of wealth, position or fame, have become serious facts in American civilization and are laying the foundation not only for much distress and suffering in the present generation, but for a weakened and delicate nervous system in the next. We cannot emphasize too strongly the necessity of a proper balance between expenditure and supply of nervous energy. We realize easily enough in financial matters that a certain

reserve deposit is necessary to comfortable living and that when expenditures exactly equal receipts, one is living on the verge of bankruptcy and there is no comfort in life, no sense of security, no feeling of power. It is only when there is a substantial balance to our credit, when we feel that an extra demand can be easily met from a reserve stock, that we can go our way in comfort and avoid constant anxiety. But if, on the contrary, expenditure exceeds receipts and obligations are piling up against us, there is not only a hampering in all financial undertaking, but there is a sense of inherent weakness, which makes one less confident in all efforts and keeps one trembling on the brink of ruin.

Now what is true in regard to one's financial situation may be taken as equally true of one's stock of nervous energy. Unless there is a surplus stored up in these neurons, enabling them to do their work without immediate exhaustion, there is no sense of reserve power and no sense of confidence in results. This manifests itself in the inability for continuous attention and effort, and the morbid fears of neurasthenia. Such a reserve stock of energy can only be attained by a proper nutrition and the avoidance of over-exhaustion. That exhaustion may show itself in many different ways. It may be in the projection or in the association neurons that it becomes evident, and then the phenomenon of paralysis of voluntary effort or of arrest in the association process necessary to thinking may occur. The first of these is perhaps best mani. fested in the diseases which we call occupation neurosis. The clerk who spends his entire day in the use of his pen, the banker who has to sign his name 2000 times daily, the pianist and violinist who plays too constantly, the telegrapher who has to press his key 500,000 times in ten hours, the cigarette roller who goes through the necessary motion of making a cigarette 30,000 times daily, the sewing woman who confines her work entirely to the making of button holes and repeats a single co-ordinative movement 16,000 times a day; all these individuals are subject to a

form of exhaustion limited exclusively to the few neurons that are involved in the production of a single movement. And while every other portion of their bodies may be perfectly sound, and in every other way they may be in perfect health, they are physically incapable of reproducing this peculiar motion which their occupation has over-taxed. Nothing will cure them but rest.

But it is often said that work never kills anyone and that worry is the thing which tells. What is the nervous mechanism at the basis of worry? We must believe from recent investigation that all emotional processes and all mental activity involving emotion are attended by a change in the caliber of the blood vessels of the brain. This is perfectly apparent in extreme cases in the blush of modesty or the flush of anger or in the pallor of fright or of extreme rage. And what is visible in these excessive manifestations is going on to a less degree all the time in every mental process, which is attended by pleasure or by pain. We have already seen that this governing power of the blood vessels resides in the neurons contained within the sympathetic system and thus it becomes at once apparent that, under nervous excitement or over-work which is attended by emotional strain or worry, not only are the neurons presiding over the voluntary activity called into play, but also the neurons which regulate the blood supply. To every practicing physician there will occur numerous examples of neurasthenic conditions in which the vaso-motor system presented the predominant symptoms; e. g., the sudden flushings, the sudden sense of rush of blood to the head or to other parts, or the sudden coldness of extremities, possibly persistent, with excessive sweating, or polyuria. All of these symptoms are evidences of an instability of vascular tone which can be traced directly to exhaustion of the neuron. One more example of a disease caused by over-work may be cited, viz.: paresis or softening of the brain; a disease which occurs chiefly in the higher classes and especially in those individuals who have manifested a high grade of mental activ

ity. The first evidence present is an evidence of exhaustion in the highest mechanism of thought. We have to believe that in various areas of the cortex are located neurons, whose function is to preside over and in a way direct the activities of other portions of the cortex, bringing them into harmony and order and directing their work in special lines. (See Flechsig, Neurologisches Centralblatt, 1894, October. See also British Medical Journal, February, 1895.) These may be considered as neurons of association and it is in these and in their numerous branches that the exhaustion first shows itself in this disease, paresis. It may be that many of the cases are to be traced as we shall see later, to poisoning by the toxic product of syphilis, but in any case it is the giving out of these higher cells of association which produce the first symptoms of the disease. Such a giving out is only a proof of exhaustion from over-work.

It is evident, therefore, that exhaustion from over-work is one of the potent causes of nervous disease, of a functional character. It may also be the cause of an organic affection. If we remember that over-work of a neuron is attended by a shrinkage in its natural size and if we accept the statement of Weigert, one of the greatest of living pathologists, that the process which we term sclerosis in the nervous system is merely a manufacture by nature of a supporting substance within the brain or cord to take the place of an atrophied nerve cell or

fiber, then we may realize the possibility that exhaustion in the domain of certain functional activities may be the actual beginning of serious organic changes in nervous structure. We certainly know that in the nervous system sclerotic processes tend to develop and to be limited to tracts of a definite single function. Thus, posterior sclerosis affects exclusively the sensory tracts of the spinal cord, while lateral sclerosis affects exclusively the motor tracts and amyotrophic lateral sclerosis invades the entire motor system from the brain to the muscles. It is true that many have supposed that this limitation of sclerotic tissue to definite regions was due to some particular poison showing a selective action upon definite parts of the nervous system; as we know that strychnine, or aconite, or conium may show such selective action. But Weigert's statement appears to me to furnish a much more rational explanation for the peculiar distribution of these sclerotic processes which have been grouped together as the system diseases. The order then of causal factors would be: First, overwork. Second, exhaustion. Third, atrophy of neurons continued for a time and then followed by a growth of connective tissue in the form of a sclerosis limited to a functional tract. Edinger (Volkmannn's Klinische Vorträge, N. F., No. 206) has recently developed this theory more fully and exhaustively than I can do at present. It will repay any careful student to read his argument.

a

ABORTIVE TREATMENT OF GONORRHEA.-Viceconti (British Medical Journal) draws attention to Guiard's treatment of gonorrhea by means of frequent washings out with weak solutions of permanganate of potash. He uses vessel of a capacity of about 2 liters (quarts) for holding the solution; attached to this is a rubber tube 2 meters (yards) in length, fitted with a glass cannula and tap, so arranged as to be workable by the same hand that holds the nozzle in the penis. If the inflammation is confined to the anterior urethra, only a small quantity-about 5 or 6

grammes (31 to 3jss)— is allowed to flow in, and then immediately voided. About half a liter is the utmost that should be used at one sitting. The best results are obtained with weak solutions, for example, I in 10,000, the maximum being in 5000. There should be two washings on the first, second and fourth day. On the third and last four days of the eight days' treatment only a single washing out is advised. The results obtained are very satisfactory. The stains produced by the solution may be removed by a 30 per cent. solution of bisulphite of soda.

THE cases of tubercular meningitis are not rare, yet the indefinite and rather unusual manifestations which are recorded in this instance make it one of unusual interest to me as a general practitioner and I trust that it may so impress you all.

On January 31, 1895, I was called to see a young girl, who gave the following history:

Nellie A, white, aged 12 years, 4 months, residence, Washington, D. C.

Family history.-The father and mother are living and well, though he former is of a very nervous temperament, as is also the grandmother and several immediate relatives. Several uncles and aunts have died in the past three years from tuberculosis.

Previous condition.-She was considered a bright child and up to the spring of 1894 was always well. At that time she had an attack of grippe, accompanied by much pain in the left chest. The breast was much swollen and the temperature was very high. She was never as well afterwards. In November, 1894, while at school, she received a knock on the back, and since then she has had much pain, referred to the seat of injury. Her general health has failed. rapidly and her whole nature has undergone a change. A physician saw her in December and diagnosed the case one of anemia associated with menstrual disorder, her menses having begun in November, 1893, continuing at irregular intervals. She was ordered tonics and cod liver oil, which for several weeks seemed to help her. At the first visit I was unable to make a thorough examination, but on February 2, 1895, I made the following notes in her case.

General appearance.-Tall and rather thin. Breasts developed and hair in axillae and on pubes. Anemic.

Nervous system.-Extremely irritable and cries out if touched on the body or limbs. The lower dorsal and upper lumbar region is especially sensitive and she says she has occasional pains extending from there to the sides and abdomen. Her brain is clear. Pupils equally dilated. Reflexes seemed exaggerated, though this is not certain, on account of her extreme irritability.

Respiratory system.-A physical examination of the chest shows on percussion a slightly higher note on the left side, behind and in front. On auscultation her breathing is less distinct on the left side, especially at the apex.

Digestive system. The tongue is slightly red and dry. There is anorexia and constipation with some pain on pressure over the left lumbar region.

Circulatory system.-Her heart sounds are normal. Pulse, 116. Temperature, 100.2° F.

Treatment. Rest in bed. Liquid

diet.

Salol, phenacetine and quinine in small doses; bromides also.

February 4. Pain in back and sides continues. Extremely irritable. Appetite capricious. Constipation. Sleeps very little. Will not stay in bed. Brain clear. No paralysis.

February 8. Pain in the back and sides growing progressively worse. Examination of the urine gave negative results. Chloral and hyoscine were given to produce sleep. Temperature, 100.8°. Pulse, 124.

February 10. Dr. I. S. Stone saw the patient with me this afternoon. He thinks that it is possibly some disease of the vertebrae, causing spinal irritation or abscess along the psoas muscles. Treatment changed to iodide of potash and ergot, with tonics.

February 12. She cried out almost constantly, "Oh! my poor back and