2. Although some persons, suffering from epileptic seizures, are, in the intervals, of sound mind and body, in many the inter-paroxysmal state is characterized by certain symptoms peculiar to this condition, and independent of any form of treatment. These vary from the slightest departures from health to the most serious mental and physical disease. The general health is frequently unsatisfactory; the functions of the body being impaired in vigour, the digestion is weak, and the circulation feeble. The entire nervous system is in an unstable condition, the patient being at one time irritable and excitable, and at another depressed and despondent. There is a very common condition of so-called "nervousness" which is accompanied by headache, pains, tremors, and a variety of other subjective phenomena. The mental powers are enfeebled, the memory defective, and these intellectual alterations may exist in any degree, even to permanent and intractable forms of insanity. The physical conditions may also be changed, the nutrition of the tissues is often imperfect, the skin is pale, the muscles flabby, and the motor powers generally enfeebled, all of which may also present different degrees of severity, so as to culminate in actual paralysis.

Admitting, then, that the prolonged and excessive administration of the bromides causes a series of abnormal symptoms in the healthy individual, affecting mainly the general nutrition, the mental faculties, and the sensory and motor functions, and also that the epileptic state is itself frequently accompanied by impairment of innervation of a somewhat analogous nature, it follows that when the drug is given for the relief of the disease, care must be taken not to confound the two series of phenomena with one another. With this precaution in view, granting that the therapeutic agent beneficially controls and suppresses the convulsive seizures, we proceed to discuss whether in so doing it in any way injuriously influences the constitution of the patient. To answer this question has been found by no means easy. Comparatively few physicians have opportunities of observing cases of epilepsy in sufficient numbers to form substantial conclusions on the subject. Even in favoured circumstances it is difficult, especially in hospital practice, to ensure the regular attendance of the patient or to keep him sufficiently long under observation. The study and the recording of the facts, moreover, demand an expenditure of much time and labour. These, added to the sources of fallacy already enumerated, render the inquiry a complicated one; but it is believed that an approximation to the truth may be arrived at by the following method of investigation.

A large number of cases of epilepsy form the basis of the statistics, the great majority of whom are adults. No selection of any kind is made, and all are admitted irrespective of the cause, nature, or severity of the disease. The particulars of each having been noted, treatment by the bromides was instituted, the minimum dose being one drachm and a half daily,[G] which, if necessary, was further increased in quantity. The progress of the patient was observed at frequent and regular intervals, and if the attendance was irregular the case was excluded from the present inquiry. The result of this proceeding is an aggregate of 141 cases, all of whom have been constantly under the influence of the drug for periods varying from one to six years. These are arranged in groups according to the length of time they were under treatment. The immense mass of details thus collected, added to the varied circumstances connected with individual cases, render it impossible, in constructing a summary of the whole, to do more than select certain prominent features of interest for examination and demonstration. These in tabular form are as follows:—

Tables showing the effects of the continuous administration of the bromides in the epileptic state, in 141 cases, the condition being ascertained at the end of each period.

I. For one year (51 cases).
Physical and mental powers unaffected39, or 76.4 per cent.
Physical and mental powers impaired6, or 11.7 per cent.
Physical powers alone impaired3, or 5.9 per cent.
Mental powers alone impaired2, or 3.9 per cent.
General symptoms of neurasthenia13, or 25.4 per cent.
Bromide eruption8, or 15.6 per cent.
II. For two years (34 cases).
Physical and mental powers unaffected28, or 82.3 per cent.
Physical and mental powers impaired2, or 5.8 per cent.
Physical powers alone impaired1, or 2.9 per cent.
Mental powers alone impaired2, or 5.8 per cent.
General symptoms of neurasthenia5, or 14.7 per cent.
Bromide eruption6, or 17.6 per cent.
III. For three years (30 cases).
Physical and mental powers unaffected28, or 93.3 per cent.
Physical and mental powers impaired1, or 3.3 per cent.
Physical powers alone impaired1, or 3.3 per cent.
Mental powers alone impaired0, or 0.0 per cent.
General symptoms of neurasthenia3, or 10.0 per cent.
Bromide eruption3, or 10.0 per cent.
IV. For four years (16 cases).
Physical and mental powers unaffected12, or 75.0 per cent.
Physical and mental powers impaired0, or 0.0 per cent.
Physical powers alone impaired2, or 12.5 per cent.
Mental powers alone impaired2, or 12.5 per cent.
General symptoms of neurasthenia0, or 0.0 per cent.
Bromide eruption2, or 12.5 per cent.
V. For five years (6 cases).
Physical and mental powers unaffected6, or 100.0 per cent.
Physical and mental powers impaired0, or 0.0 per cent.
Physical powers alone impaired0, or 0.0 per cent.
Mental powers alone impaired0, or 0.0 per cent.
General symptoms of neurasthenia3, or 50.0 per cent.
Bromide eruption0, or 0.0 per cent.
VI. For six years (4 cases).
Physical and mental powers unaffected4, or 100.0 per cent.
Physical and mental powers impaired0, or 0.0 per cent.
Physical powers alone impaired0, or 0.0 per cent.
Mental powers alone impaired0, or 0.0 per cent.
General symptoms of neurasthenia2, or 50.0 per cent.
Bromide eruption0, or 0.0 per cent.

In the construction of the details of the above tables, care has been taken as far as possible to distinguish between the effects of the remedy and the symptoms associated with the disease, although this has not been always easy to accomplish. It has, however, been approximately arrived at by a careful study of the patient's health before treatment, as compared with his subsequent state, and those symptoms only were considered toxic which were superadded to pre-existing abnormal conditions. A general analysis of the facts thus collected shows that in the majority of cases the physical and mental powers do not appear to be injuriously affected by the prolonged use of the bromides. It is not asserted that all the individuals placed under this section were necessarily sound in mind and body. In many instances the functions of these were impaired, but there was no evidence to indicate that this was the result of the medicine taken; on the contrary, there was every reason to believe that the symptoms thus displayed were a part of the original disease, and had existed prior to treatment.

In a very small percentage of cases were both physical and mental powers unfavourably modified as a direct consequence of the use of the bromides, and even in these there is no absolute certainty that the drugs were entirely responsible for the symptoms, seeing that these might be attributed to the epileptic condition as well as to the toxic effects of the remedy. They are considered under this category, as the abnormal phenomena appeared to be augmented after treatment and improved on its temporary cessation. They mainly consisted, on the one hand, of loss of memory, dulness of apprehension, apathy, somnolence, depression of spirits, and mental debility; and on the other, of bodily languor, muscular fatigue, and general physical weakness. In no case did any of these symptoms attain an excessive or prominent position. The same conditions apply when the physical or mental powers were impaired independently of one another.

Under the heading of general phenomena of neurasthenia is included a series of indefinite subjective neurotic symptoms, without intellectual or bodily deficiencies, in which the patient complained of headache, neuralgic pains, tremors, of being easily startled and frightened, with that general instability of the nervous system to which the term neurasthenia has been given. This condition is extremely common in the epileptic, and is frequently relieved by treatment. At other times it remains persistent in spite of all medicaments, and the numbers in the tables indicate those cases conspicuous by their continuance under the use of the bromides. Those attacked by the follicular rash are seen at first to be about 16 per cent., but gradually diminishing in number as the treatment becomes chronic, and finally disappearing altogether.

In addition to the points referred to in the tables, other questions have been investigated, although on a smaller scale. For example, in persons who have been under the influence of the bromides for many years, the skin and tendon reflex action remain intact, and I have never seen a case in which the knee-jerk or plantar phenomena were absent. In only one case was the general sensibility of the skin perceptibly diminished. With regard to the effects on the sexual powers, I have not sufficient data upon which to found positive rules. This statement, however, may be made, that the prolonged use of even large doses of this drug does not of necessity abolish or even sensibly impair this function, although, no doubt, it usually does so. On examining the respiration and pulse, I have never been able to detect any characteristic abnormality.

I might record many cases in detail to prove the seemingly innocuous nature of even large and long-continued doses of the bromides in epilepsy. I shall, however, as an illustration, limit myself to a few notes on the four cases which compose Table VI., all of whom were continuously under the influence of the drugs for a period of not less than six years.