accumulate and in some cells this protoplasm appeared to be bulging out the wall of the cell, as if for the development of new processes. There were fewer leucocytes around the nucleus and none were seen around the protoplasm of the cell. After eight weeks of refeeding, the cells had approached more nearly to the normal condition, with the exception of the protoplasmic process, which still remained rudimentary.

The trace of impaired nutrition in at nerve cell remained for a considerable time after the general nutrition had been resumed. This is quite in accordance with the clinical experience of the slow recovery from conditions of nervous exhaustion, when there is no organic dis

ease.

The condition of impaired nutrition produced experimentally by starvation is quite comparable to the impaired nutrition that must follow the arrest in the blood supply. It is only recently that the dependence of many so-called nervous diseases upon disease of the blood vessels has been fully appreciated, although the statements of Heubner and of Gowers upon this subject were first put forward many years ago. Diseases of the blood vessels are certainly very common. They constitute the primary condition in a long list of syphilitic affections. They are the starting point of many cases of chronic nephritis. They are also the essential lesions in the vast majority of diseases of old age. And when we realize that hemiplegia, aphasia in its different forms, hemianopsia and hemianesthesia are usually due to a stoppage within the blood vessels produced by embolism and more frequently by thrombosis, or else are due to a rupture of the vessel wall, we see how large a part of ordinary so-called nervous disease is really secondary to a vascular affection. The various forms of cerebral softening are due to a cutting off of the blood supply; and the various conditions grouped together under the term cerebral atrophy, to which are to be traced the forms of imbecility, idiocy and paralysis of childhood are also due to disease of the blood vessels. Lately it has been shown that many spinal cord

diseases are dependent upon the same cause. Some cases of infantile spinal paralysis and many cases of myelitis, either disseminated or transverse, as well as some forms of sclerosis, are to be ascribed to defective blood supply, from a plugging of the spinal arteries. It has been recently stated that the layer of cells lining the blood vessels are really secretory cells. If this is accepted, then diseases of the tunica intima increase in importance and it is not impossible that the origin of many pathological processes may be traced to the blood vessels.

It is very easy to appreciate effects of blood stasis, such as occur in valvular disease of the heart. It is probable that much is still to be learned regarding the pathology of the capillary circulation and of the effects of stasis limited to it. Any one who has watched this circulation under the microscope, in the web of a frog's foot, has seen the sudden stoppages, the resumption of blood flow, the piling up of red corpuscles in one part, the sudden changes in the direction of the blood flow in consequence, and the very irregular and spasmodic passage of the current through these fine capillaries, and must have been impressed with the fact that temporary or permanent changes in this capillary circulation are capable of causing marked effects upon the nutrition of the cells which surround these capillaries. It is impossible for any obstruction in the blood supply to occur for any length of time without producing marked effects. It may be stated without contradiction that many neurasthenic conditions with lack of nerve energy, headache, feelings of depression, conditions of discomfort, with vertigo, inability to concentrate. the attention, insomnia, morbid fears and general nervousness, which are so common in endarteritis chronica with atheromatous or specific changes, and which constitute the prodroma of apoplexy, may be traced to such obstruction in the blood flow. It is also probable that many of the manifestations of hysteria can be best explained by a sudden suspension of nerve activity due to a spasmodic contraction of the blood vessels, either peripheral as in the retina or

acoustic nerve or extremities, producing sudden blindness, deafness, anesthesia, or within the brain as in the states of morbid intellectual and moral action so often seen in this disease, and evidently due to a lack of self-control.

It is thus evident that many organic and functional diseases of the nervous system can be traced to imperfect blood supply.

III. ACTIVE POISONING OF THE NEURON.

(A) BY POISONS PRODUCED WITHIN

THE BODY.

The effect of work is to use up the tissues and to produce waste products which have to be carried away and thrown off. These waste products are in themselves injurious to the organism. It has been found that if the blood from a fatigued animal is transfused into one that has rested, the latter shows every sign of fatigue. (The Insanity of Overexertion of the Brain, J. Batty Tuke, Edinburgh, 1894.) This proves that activity must give rise to products of decomposition which affect the organism as poisons. Hence a free elimination of waste products is essential to healthy recuperation after work. It is just as essential to clear away the ashes as it is to feed the fire with coal. The oppression felt by confinement in a close atmosphere, as in a badly ventilated theater or church, where the waste products of the crowd permeate the air and poison every individual, affords a proof of the constant manufacture of deleterious substances within the body, which need to be removed. I believe that much of the benefit derived from the use of mineral waters is due to the fact that they increase the elimination of these waste products.

It is unfortunate that at present so little is known in regard to the chemistry of nutrition. While general facts are at our disposal in regard to the ordinary types of nervous distress attendant upon indigestion in the stomach or intestines, or irregularities in the action of the liver or of the pancreas, or of the kidneys, yet we really have few precise statements in regard to the actual chemical disturbances produced by these diseases. A great deal has been written

has

of late about the evil effects of uric acid, especially by Haig of London. (Uric Acid in Disease, London, 2d edition, 1894.) Haig's statements do not, however, bear analysis and critical examination, as Roberts (Roberts, Lancet, 1894) and Herter (Herter, Journal of Nervous and Mental Disease, February, 1895, Review of Haig) have conclusively shown. That in many abnormal conditions an excess of uric and of indican is a constant manifestation must be admitted. But Herter is inclined to conclude that the excess of uric acid in the urine which is met with in disease is to be regarded as the result and expression of general nutritive disturbance or digestive disorders and not as the cause of disease. Horbaczewski proven that uric acid is largely derived from the nuclein in the neuclei of the body cells, in consequence of their breaking down. Now we have already seen that such a breaking down takes place in nerve cells under over-work or after starvation. Hence, the uric acid may be taken as evidence of a disintegration in nervous tissue. The researches of Herter have demonstrated that certain methods of diet, notably the milk diet alone, or a diet from which starch and sugar is rigidly excluded, have a marked effect not only in changing the general chemistry of digestion and in decreasing the proportion of uric acid and indican in the excretions, but also in producing very marked changes in many nervous symptoms, such as the symptoms common to neurasthenic patients, various forms of headaches, vertigo, inability to do mental work, general malaise and even the explosion of epilepsy.

I

In confirmation of this last named fact, I could bring forward a considerable number of interesting cases. will cite but one. A confirmed epileptic patient had for several months been under my care taking bromides daily and eating freely. Her average number of attacks was ten severe and fifty slight attacks per month. Herter found that the relation of uric acid to urea in her case was high. The following table shows this relation and the number of attacks:

I petit

I grand

I

2 petit

I 76.5 I " 85.8

25, I 28, 2 The table shows the immediate reduction in the amount of uric acid excreted to one-half and the great reduction in the number of attacks. Thus instead of fifty attacks of petit mal as in February, she had but three in April and instead of ten grand mal attacks as in February, she had but five in April. It was interesting to note that a very obstinate constipation preceded each attack in April and coincident with this. there was a temporary rise in the uric acid. The subsequent history of this patient, who is still under my care, has proven conclusively that there is a direct relation between the occurrence of attacks and a disturbance of nutritionthat autoinfection is the cause of her epilepsy. I think it may be safely said that one-third of the epileptics in the community are suffering from this type of the disease.

It is well known that many of the socalled gouty manifestations of a nervous character can be temporarily relieved by great restrictions of diet, or by the administration of alkalies. The intense

headaches observed in gouty people can be avoided by eating meat and green vegetables and by drinking a quantity of water. This fact offers another proof that disturbances in the chemistry of the system are responsible for many nervous conditions. We know that in chronic nephritis, in which there is a tendency to the accumulation of urea and of other poisons in the blood, nervous manifestations are of constant occurrence, and here again the importance is apparent of limitations in diet and of such measures as will eliminate the poisonous substances from the blood, in order to remove the nervous symptoms. All these facts impress upon the observer the importance of a careful study of diet and of agents which affect digestion and also of the use of water in the treatment of many nervous conditions, which latter agent is often of vital importance, either in increasing the rapidity of chemical changes, or in washing out from the system the products of abnormal chemical action.

He

I cannot leave this subject without calling attention to the probable factor, which autointoxication plays in many mental diseases. In mild melancholia, for example, we see a constant periodicity in the symptoms. The patient is awakened early in the morning by the feeling of mental distress, anxiety and despair. He lies awake for hours. has little energy to get up, and none for work. As the day goes on he becomes brighter. In the afternoon, he can be easily interested and will undertake various things, and by evening almost all trace of the mental affection may be gone and he feels quite well and happy. Sleep comes easily, but only to be interrupted again as before by the onset of the symptoms. The only rational interpretation seems to be the development during the first hours of sleep of a poison whose action is intense-the elimination during the day of that poison-the freedom from it at night. The symptoms are due to intoxication from within, the toxine being, however, thus far unknown and not reached by antidotes.

An additional proof of the liability of the nervous system to suffer from dis

turbances in the chemistry of nutrition is afforded by the natural history of the disease myxedema. We now know that this extraordinary affection, which is attended by so many curious symptoms of a trophic nature in the skin, hair and mucous membranes, is also characterized by marked mental symptoms which may lead to active insanity, to hallucinations and to dementia. We know that all the symptoms are due to an absence of the normal secretion of the thyroid gland from the blood, and that by supplying the patient with thyroid extract of the sheep, we can entirely remove not only the physical, but also the mental symptoms, thus restoring him to health of body and of mind. The interesting fact has also become known that if too much of this thyroid extract is given to such a patient, symptoms of great nervous irritability are produced which resemble closely the symptoms of exophthalmic goiter, and the theory is now current that many of the distressing symptoms of this affection are due to an excess of thyroid secretion in the blood.

Surely these facts afford conclusive evidence that the nervous system is affected by poisons manufactured within the body; that autointoxication is a potent factor in the etiology of nervous disease.

(B) BY POISONS RECEIVED FROM WITH

OUT.

That the nervous system is particularly susceptible to the influence of certain poisons, especially lead, arsenic, mercury, strychnine, aconite, and also to alcohol, has been long known. The various forms of lead tremor and lead palsy, of mercurial tremor, of arsenical multiple neuritis and of alcoholic multiple neuritis, are so familiar that they need not detain us. It may be interesting, however, to call attention to the fact that Andriezen has recently been able to detect the series of changes going on in the cells in the cerebral cortex occurring in alcoholic insanity.

He

has shown that the first changes produced in this disease are of the nature of a softening and swelling of the proto

plasmic branches and of the fine collateral fibers of the nerve cells, that the next changes occur in the cell body and in the long apex projection, which is characteristic of the pyramidal cell of the cortex. These changes consist of a gradual disintegration and breaking up of the cell body, until finally the cell protoplasm gets vacuolated from within and this continues till the whole internal protoplasmic structure is channeled and tunneled by such holes and seams of liquefaction. Andriezen attempts to correlate these pathological changes with the clinical course of alcoholic insanity. He believes that the slowness in all processes of association, the delay of the reaction time, the diminished faculty of attention and volition and the imperfections of memory, are to be traced to the changes in the fibrils and protoplasmic processes, which interfere with the associated action of the various neurons. He believes that the dementia and the loss of muscular power, which ensue later, are to be related to the destructive process in the cell body. If this destructive process has gone on beyond. the power of regeneration the disease progresses to chronic alcoholic dementia. If, however, regeneration is possible, recovery ensues.

Time will not permit of any further reference to the changes produced in the nervous system by this type of poisons. I must go on to speak of a more important class of poisons, whose action upon the nervous system has but recently been realized, namely, infective toxines produced by germs. It is only within the past few years that the fact has been admitted that infectious diseases of various kinds play a part in the etiology of nervous diseases. Everyone is familiar with the fact, that nervous symptoms have been very clearly recognized as constantly attendant upon the development of infectious diseases. Thus the occurrence of headache, delirium and convulsions at the onset of most acute infectious diseases and the subsequent relaxation and weakness of the muscular system and the hebetude of mind occurring in the course of these affections demonstrate the direct action

of the poison upon the neuron. It is now possible to trace a considerable number of nervous diseases directly to the invasion of the system by germs. It is known that tetanus, hydrophobia, diphtheritic paralysis, meningitis, cerebral abscess, leprous neuritis, beri-beri, many forms of multiple neuritis and some varieties of encephalitis and myelitis, are distinctly due to germ infection. It is also believed that disseminated sclerosis in some cases may be ascribed to infection and that there are many forms of neurosis and some forms of insanity which are traceable to the same cause. For the evidence in proof of these assertions, I must refer you to the discussion of the relation of infective processes to diseases of the nervous system at the last meeting of the Congress of American Physicians and Surgeons in Washington, 1894, and especially to Dr. James J. Putnam's recent article in the American Journal of the Medical Sciences, March, 1895. It has been shown that the infective agents in these diseases, whether germs or toxines, have a direct action upon the neurons and produce changes in the structure of the neuron, which remind us of the changes described already as produced by exhaustion and by imperfect nutrition.

These have been most carefully studied by Golgi in his investigations on the effects of inoculations by the toxine of rabies. He describes changes both in the cell body and in the nucleus. The body becomes shrunken, vacuolated and granular. The nucleus is crenated and the chromatic bodies are deeply stained. Golgi has also noted changes in the protoplasmic and axis cylinder processss, both being swollen at points so as to give a varicose appearance, and being in a state of granular disintegration like the cell.

If we accept the fact that infective agents may attack the nervous system to the exclusion of other parts of the body, a new light is thrown upon the clinical history of certain diseases of the nervous system, whose origin has hitherto been obscure. One of these diseases is infantile paralysis or anterior poliomyelitis. If a large number of

cases of this disease are collected, it will be found that the clinical histories fall easily into two classes showing two separate modes of onset of this affection. The small class, about one-fourth of the cases, show a sudden onset without fever or constitutional disturbances. In these one limb only, as a rule, is affected. The paralysis comes on without warning and remains quite stationary from the first. I believe these cases are to be explained by a sudden stoppage of the flow of blood in one of the small spinal arteries entering the anterior horn. The embolism or thrombosis is followed by a process of softening with destruction of the motor nerve cells and hence paralysis is permanent. The larger class, about three-fourths of the cases, presents a different history. In these the disease begins with chill or convulsions, with high fever and general constitutional symptoms, and is attended by all the signs of an acute infectious disease. In these cases the initial paralysis is often very extensive, affecting both legs or both arms or all the extremities, but later paralysis passes away, excepting in a few muscles in one limb, so that great improvement and recovery is a rule in this clinical type of the disease. These cases are well known to occur more frequently during the months of July, August and September, than in other parts of the year; a fact long ago noted by Weir Mitchell and confirmed by Gowers and myself. But the more important fact, which has only been recently established and which goes far to confirm the theory that this form of disease is a true acute infectious process, is the occurrence of this type of paralysis in the form of an epidemic. Some years ago, such an epidemic was reported in Lyons, France, and a few years later another in Stockholm, Sweden. I had occasion last summer to investigate an epidemic of this character which occurred in Vermont and through the kindness of Dr. Caverly, President of the Board of Health at Rutland, I saw a number of cases (New York Medical Record, December I, 1894). Between the 15th of July and the 20th of September, there devel