Part 9

FOOTNOTES:

Reprinted from the "Edinburgh Medical Journal" for February and March, 1881.

For an extended experience, see the next paper.

III.

AN INQUIRY

INTO THE

EFFECTS OF THE PROLONGED

ADMINISTRATION OF THE BROMIDES

IN EPILEPSY.

The present inquiry is the result of an experience of 300 cases of epilepsy treated by myself with the bromides of potassium and ammonium. In all of these the clinical facts, as well as the progress of the malady, were carefully studied and recorded. The effects of the administration of these remedies on epileptic seizures I have already investigated and demonstrated in a somewhat elaborate series of observations. Further experience has confirmed the correctness of the general propositions then arrived at, so that they need not again be elaborated in detail.

At present it is proposed to direct attention to the effects of the prolonged administration of large doses of the bromides, and to attempt to ascertain if, while arresting or diminishing the frequency and severity of the paroxysmal symptoms, they beneficially influence the disease itself, or in any way injuriously modify the constitution of the patient. On this subject much difference of opinion and misconception prevail. It is well known that the injudicious use of the drugs leads to certain physiological phenomena which are comprised under the term "bromism." It is also generally believed that the physical and mental depression resulting from their prolonged toxic effects constitutes a condition worse than the malady for which they are exhibited. One of the objects of this article is to question the accuracy of this assertion, a true apprehension of which is the more important when we reflect how universal is this method of treatment, and the deterrent effect it exercises upon epileptic attacks. The task, like other therapeutic inquiries--especially those connected with chronic disease--is a difficult one, there being innumerable pitfalls of error between us and a sound scientific conclusion. These, however, may, I believe, in great measure be surmounted by the accumulation of facts laboriously and accurately recorded, by the intelligent study of their details, and the impartial and logical deductions which may be drawn from the data supplied. The value of a therapeutic inquiry depends, not upon the opinions and undigested experience of individuals, or by the narration of isolated cases, but upon the indisputable proofs resulting from the unbiassed analysis of a large series of accurately observed and unselected examples. The solution of the problem, if complex in all clinical affections, is especially so in epilepsy. Although the symptoms of this disease have been recognised from the earliest ages, our knowledge of its essential nature is as yet shrouded in mystery. The etiology and pathology are practically undetermined. The phenomena are not only due to a varied series of morbid conditions, but may assume a multitude of forms and degrees of severity, which may be, on the one hand, of the briefest duration, or, on the other, of a life-long permanence. The symptoms may comprise not only a diversity of physical ailments, but intellectual disturbances of the most terrible import. The malady may attack not only many whose systems are predisposed to disease, but those of the most robust constitution and with a healthy, family history. The consequences of the disorder may be comparatively innocuous, but in other circumstances may be attended with the most disastrous effects on mind and body and even on life itself. In a disease presenting such an intricate and uncertain course, it is obviously a task of the utmost difficulty to scientifically estimate the exact value of any therapeutic measures which may be adopted for its relief. The effects on one symptom, and that the most prominent, can, however, be accurately determined--namely, the paroxysmal seizures, which are definite and computable; and this has already been accomplished with tolerable precision. On the influence of the bromides on the disease itself, or on the epileptic state, we have less accurate information. In attempting to throw some light on this subject, two preliminary considerations must be recognised--1st, the physiological actions of the drug on the healthy subject; and 2nd, the inter-paroxysmal symptoms of the epileptic constitution.

1. Medicinal doses of the bromides produce in healthy persons a general diminution of nervous energy. They act as a sedative, and thus dispose to repose and sleep. If they are excessive in quantity and long continued, especially in those susceptible to their action, a series of toxic effects are produced. Various organs and functions of the body are influenced, and the results of the poison may be briefly summed up as follows:--The intellectual faculties are blunted, the memory is impaired, the ideas confused, the patient is dull, stupid, and apathetic, and has a constant tendency to somnolence. The speech is impeded and slow, and the tongue is tremulous. The special senses are weakened. The body, as a whole, is infirm, the limbs feeble, and the gait staggering and incoördinated. The reflex excitability is lowered and the sensibility diminished. The sexual powers are impaired or abolished. These symptoms may be present in a variety of degrees, and in advanced cases even imbecility or paralysis may ensue. The mucous membranes become dry and insensitive, especially those of the fauces. This is attended with various functional disorders, such as nausea, flatulence, gastric catarrh, diarrhoea, &c. The skin is pale, and the extremities are cold. The action of the heart is slow and weak. The respiration is shallow, hurried, and imperfect. The integument is frequently covered with an acne-like eruption. To these symptoms may be added a general cachexia. All these abnormal conditions, as a rule, disappear when the consumption of the poison is arrested.

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, 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 unaffected 39, or 76.4 per cent. Physical and mental powers impaired 6, or 11.7 per cent. Physical powers alone impaired 3, or 5.9 per cent. Mental powers alone impaired 2, or 3.9 per cent. General symptoms of neurasthenia 13, or 25.4 per cent. Bromide eruption 8, or 15.6 per cent.

II. For two years (34 cases).

Physical and mental powers unaffected 28, or 82.3 per cent. Physical and mental powers impaired 2, or 5.8 per cent. Physical powers alone impaired 1, or 2.9 per cent. Mental powers alone impaired 2, or 5.8 per cent. General symptoms of neurasthenia 5, or 14.7 per cent. Bromide eruption 6, or 17.6 per cent.

III. For three years (30 cases).

Physical and mental powers unaffected 28, or 93.3 per cent. Physical and mental powers impaired 1, or 3.3 per cent. Physical powers alone impaired 1, or 3.3 per cent. Mental powers alone impaired 0, or 0.0 per cent. General symptoms of neurasthenia 3, or 10.0 per cent. Bromide eruption 3, or 10.0 per cent.

IV. For four years (16 cases).

Physical and mental powers unaffected 12, or 75.0 per cent. Physical and mental powers impaired 0, or 0.0 per cent. Physical powers alone impaired 2, or 12.5 per cent. Mental powers alone impaired 2, or 12.5 per cent. General symptoms of neurasthenia 0, or 0.0 per cent. Bromide eruption 2, or 12.5 per cent.

V. For five years (6 cases).

Physical and mental powers unaffected 6, or 100.0 per cent. Physical and mental powers impaired 0, or 0.0 per cent. Physical powers alone impaired 0, or 0.0 per cent. Mental powers alone impaired 0, or 0.0 per cent. General symptoms of neurasthenia 3, or 50.0 per cent. Bromide eruption 0, or 0.0 per cent.

VI. For six years (4 cases).

Physical and mental powers unaffected 4, or 100.0 per cent. Physical and mental powers impaired 0, or 0.0 per cent. Physical powers alone impaired 0, or 0.0 per cent. Mental powers alone impaired 0, or 0.0 per cent. General symptoms of neurasthenia 2, or 50.0 per cent. Bromide eruption 0, or 0.0 per cent.