The Continuous Use of the Bromides. XBY f L. W. BAKER, M.D., superintendent family home for nervous invalids, BALDWINVILLE, MASS. (Candidate's paper before the American Neurological Society, Sept., 1888.) Reprint from The Medical Register, December 8, 1888. PHILADELPHIA: RECORDS, MCMULLIN & CO., Limited. 1888. THE CONTINUOUS USE OF THE BROMIDES. By L. W. BAKER, M.D., SUPERINTENDENT FAMILY HOME FOR NERVOUS INVALIDS, BALDWINVILLE, MASS. THE introduction of the bromides marks an epoch in the treatment of certain neuroses-notably those of a convulsive nature. The extent to which these remedies are used-and sometimes abused- leads me to offer a word in regard to their administra- tion by what Dr. Clark, of Boston, has happily termed the "continued dose," which consists in the exhibition of the drug two or more times daily in quantities sufficient to keep the blood constantly charged with the remedial agent for a longer or shorter period of time, as may be indicated. Con- cerning the physiological action of the bromides upon the nervous system there has been, and now is, some difference of opinion. Dr. Armory, a colaborer with Dr. Clark, remarks that "the action of bromide of potassium on the nervous system may be explained by its action on the capillary, arterial, or central cir- culation ; it modifies reflex action by overstimulation and subsequent paralysis of the vasomotor system, thus producing oligaemia of the tissues and nerve substances, depriving the latter of the vitalizing properties of the blood. There is probably no altera- tion of the nerve substance or cells." ("Physio. Action Bromide Potass.", p. 154.) 2 This opinion is shared by Brown-Sequard, and W. A. Hammond, while Gowers takes a different view of the subject wdien he says that "bromides are said to cause contraction of the small vessels of the brain, but it is exceedingly doubtful whether any of their influence in epilepsy is due to this action. They have, unquestionably, a direct effect on the nerve elements, diminishing, for instance, reflex action in the spinal cord, and it is probable that the mental dulness and somnolence produced by large doses are also due to a direct action on the nerve cells of the brain. If we believe that the primary change in epi- lepsy is a morbid action of the nerve-cells, it is rea- sonable to conclude that the drug does good in epi- lepsy by directly influencing them. Agents which increase reflex action-such as strychnia-are now believed to do so by lessening the resistance in the nerve centres involved. Bromide diminishes reflex action, antagonizes strychnia, and it is probable that it does so by increasing the resistance in the nerve- centres.'' ("Epilepsy,'' p. 254.) Ringer also seems to doubt the circulatory theory, while Dr. Rosenbach, in a number of experiments performed upon dogs, found that the irritability of the cortex to electrical stimulation was diminished or entirely destroyed, while that of the subjacent white substance remained unchanged. From this he concludes that the pecu- liar value of bromide of potassium in epilepsy was owing to its power of lessening the irritability of the cortical substance of the brain. (Norsk. Magazin fur Loegevidenskaken, April 15, 1884.) Between these opposing opinions it is somewhat difficult to arrive at the exact truth. It seems to me, 3 however, that each is in a measure correct. I think it has been proven that the bromides have more or less influence upon the calibre of the cerebral arte- ries, and also if the drug is given in large and long- continued doses, a condition of the brain may be pro- duced similar to that occasioned by excessive hemor- rhage, which latter, as we well know, greatly in- creases the tendency to convulsive action. In some epileptics the seizures are markedly in- creased in frequency by the continued anministration of the bromides, although at first they may have been controlled by the remedy-two such cases have come under my observation-these again improved as soon as the bromide was reduced in quantity. This seems to indicate that a condition of cerebral anaemia may be induced by this remedy. In one of these patients the administration of moderate doses of whisky at night was followed immediately by a reduction in the number of nocturnal attacks. But, while admitting the action of bromides upon the cerebral circulation, it seems to me that they have also some direct effect upon the cells of the gray matter of the brain; otherwise, it is difficult to satis- factorily account for some of the phenomena so often met with during their long continued use. The mental state of a thoroughly-bromidized person can hardly be explained alone by the effects of the drug upon the cerebral circulation. All observers, how- ever, agree that the continued use of the bromides lessens the susceptibility of the cerebral gray tissue to sensory impressions. They certainly diminish reflex action ; probably this effect is produced by their effect upon the cerebral arterioles as well as by their 4 direct influence upon the nerve-cells of the brain and spinal cord. It is this property which renders the bromides of such value in those neuroses like epilepsy, which are characterized by a sudden and excessive func- tional activity of the gray matter in some portion of the brain. This rapid liberation of energy, giving rise to an epileptic paroxysm, may be due to a sud- den diminution of inhibitory power in the nerve- centres, or to an excessive generation of nerve force within the affected cells. Some of the failures in the treatment of epilepsy may possibly be due to lack of appreciation of these two classes, as, for instance, in those cases of convulsions due to any cause which lowers the general bodily health. In this event, there is more or less depression of nerve force, with a corresponding deficiency in the controlling power of the nerve-cells. In such cases, better results will follow the restorative and tonic plan of treatment than by the use of the bromides. "It is in these cases,'' says Dr. Pepper,where there is anaemia, defective nutrition, and neuras- thenia, that cod-liver oil, strychnine, arsenic, and quinine, are so valuable.'' A similar condition of feeble control is generally present during childhood, at which period of life there is an inherent weakness of inhibitory power rather than excessive development of nervous en- ergy. The peculiar instability of the brain-cells in young children is really the predisposing cause of most of their nervous diseases. This susceptibility is often increased by influences which have been de- rived from a previous generation. "Nervous chil- dren," so-called, are now met with with increasing frequency, and are often treated by continued doses of the bromides, upon the theory that there is an abnormal generation of nerve force. At times, it is undoubtedly wise to diminish reflex action and peri- pheral sensibility with the aid of these remedies, but it seems to me of more importance to increase the nutrition of the cerebral centres by the administra- tion of a nerve food like cod-liver oil. Nervousness is really a condition of nervelessness, and I have often had occasion to test the superiority of cod-liver oil over the bromides in the treatment of certain nervous disorders of childhood as well as in other conditions of deficient nerve power. In another class of patients there seems to be really an excessive production of nerve force which is suffi- cient to overcome the normal inhibitory power of the brain-cells. The exciting cause of this sudden in- crease of functional nervous activity is often beyond our powers of detection; at other times, it is mani- festly due to some excentric irritation, which is often sufficient to establish the convulsive habit, which may even continue long after the removal of the exciting cause. It is in these and similar cases of abnormal irrita- bility of the motor tract that the continued use of the bromides is generally so beneficial, owing to their power of diminishing reflex action, as well as for their anaesthetic effect upon the sensory nerve endings; this latter property renders them of value in various conditions of hyperaesthesia of the peripheral nerves. The continued use of the bromides, like other al- kalies, increases tissue waste, the liability to emacia- 5 6 tion during their administration must therefore be guarded against by a liberal, easily-digested diet, combined with the restorative plan of treatment. The irritant effect of the bromides upon the mucous membrane of the stomach, spoken of by authors, I have never met with, owing, perhaps, to my practice of always administering them largely diluted with water. Phthisis is said to be of common occurrence among epileptics. When this occurs it is a question in my mind if the continued use of large doses of the bro- mides is not a more prominent factor in the produc- tion of this result than the disease for which they are used. In one case which came under my observation there was considerable emaciation and cough, with prolonged expiration at the apex of the right lung, which rapidly disappeared upon the suspension of the bromides and the administration of cod-liver oil. The susceptibility to the toxic effects of the bro- mides varies greatly in different individuals. I have known sixty grains daily produce bromism in a young lady of sixteen, while I have given one hun- dred grains daily to a girl of ten without the slight- est ill effect. In majiy cases of epilepsy it will be found necessary to keep the patient continuously on the border line of bromism in order to control the attacks. It does not, however, seem to me wise to keep him in a state of hebetude by massive doses ot the drug simply for the sake of preventing a few convulsions. The destructive effect of the remedy in such cases more than counterbalances any good which it can accomplish. The phenomena of bromism have been admirably 7 described by Dr. Seguin and others, and are, of course, familiar to every neurologist. Certain pecu- liar mental disturbances are now and then met with during the continued use of the bromides, which are worth a moment's attention. I have met with at least one case in which distinct hallucinations of vision were present, and which disappeared as soon as the drug was reduced in quantity. Dr. Wm. A. Hammond insists that the mental derangements which sometimes follow the administration of large doses of the bromides are due to cerebral anaemia. (Quar. Journal Psycological Medicine, 1869, p. 60-61.) In certain cases, aside from the peculiar mental man- ifestations of epilepsy, it will be noticed that the pa- tient is gradually becoming more peevish, more irri- table, and intolerant of control. Such a condition is, I think, usually indicative of an impaired nutrition of the brain-cells, requiring the administration of cod- liver oil for its relief; indeed, I think it will be found that this is a remedy of great value in most cases of epilepsy, not alone for its assistance in preventing general tissue waste, but also for its effect as a direct brain food. I have elsewhere (Medico-Legal Journal, December, 1886) referred to another mental condition sometimes met with during the continued administration of the bromides which, so far as I know, has attracted but little attention. Occasionally cases of epilepsy are met with in which the cessation of convulsive attacks is followed by more or less mental disturbance, when this occurs, it is generally regarded as due to the medicine taken, which is consequently discontinued, with the result of the continuance of the attacks with 8 their accustomed frequency. In those patients ex- hibiting this condition, which have come under my observation, a different view has been taken, as illus- trated by the following cases : A young gentleman, eighteen years of age, having several convulsions daily, was sent to me with the request that I abstain from the use of the bromides in treating him, as previous attempts in the use of these remedies had caused insanity. After watching him carefully for several days, I decided to resume the bromide in doses of about fifty grains daily, at least temporarily. The convulsions at once ceased, and have not since returned for a period of now over three years. Mental excitement, however, soon ap- peared, accompanied by sleeplessness and by the most violent exhibitions of temper, and intolerance of any attempts of control, the slightest cause being sufficient to excite a paroxysm of noisy rage, although no de- lusions were present. Notwithstanding the mental disturbance, the original plan of treatment was steadily followed, combined with treatment intended to allay the mental excitement. A few months' perseverance in this line accomplished the desired result, and his mind gradually returned to its normal condition. He always has been, and will be feeble-minded, but there has since been no tendency to any mental convulsion. Another case was a young lady, who was sent to me from New Jersey. On her arrival she was maniacal, had various delusions, and was quite difficult to man- age. She was then undoubtedly in a state of bromism, which for a time gradually grew worse. This patient was under my care for nearly two years, and during this time the bromide treatment was occasionally 9 suspended for varying intervals of time, with the immediate effect of increasing the frequency of the attacks, while the mental condition improved. A return to treatment intended to allay the convulsive tendency was always' followed by a return of the mental disturbances, although with lessened severity; still this plan was patiently followed in connection with nerve tonics, nourishing food, and outdoor exer- cise, with the ultimate result of an improvement in the mental condition, and of lessened frequency of the convulsive seizures. Another patient, a young lady of twenty-five, had for years a weekly convulsion, preceded for hours by an indescribable, dreamy feeling. These attacks were at once almost entirely controlled by treatment, but considerable mental confusion soon supervened, and she was unable to perform mental acts which had pre- viously given her no trouble, she could not read with comfort, could not write connectedly, and the peculiar aura, instead of being paroxysmal, was con- stantly present. The anti-convulsive treatment was, however, continued notwithstanding these symptoms, and she has since completely regained her normal mental condition, and is now better than she has been for years. These examples are, I think, sufficient to indicate that the use of the bromides should not be too readily abandoned when mental disturbances follow the cessa- tion of convulsive seizures. In these cases the brain has become accustomed to excessive discharges of nerve-force, which occasion muscular convulsions. When this tendency is con- trolled by treatment, the eqilibrium of the nervous 10 centres is for a time destroyed, the discharge then becomes mental, rather than motor, and there ensues a convulsion of ideas rather than a convulsion of muscles. If the anti - epileptic treatment is com- bined with cod-liver oil, phosphorous, and other nerve tonics, the brain will, I think, gradually return to the condition in which it was before the attacks were controlled. Of course, in these cases it is important to distin- guish between this condition and that which is occa- sionally produced by large doses of bromide of potas- sium, but, in the majority of instances, I think it will be found that the mental disturbance is due to the cessation of convulsive attacks rather than to the effects of the drug. In the cases above quoted only comparativelv small doses of bromide were used, the average dose being about forty-five grains daily. Many of these patients will, however, need to be re- moved from home, and treated for a while away from home surroundings. They should not be sent to an asylum for the insane, if possible, to avoid it.