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Delivered at the Royal College of Pysicians, London. By Robert Bentley Todd, M.D., F.R.S. ON THE PATHOLOGY AND TREATMENT OF CONVULSIVE DISEASES

2005; Wiley; Volume: 46; Issue: 7 Linguagem: Inglês

10.1111/j.1528-1167.2005.10205.x

1528-1167

Robert B. Todd,

Epilepsy research and treatment

Theory of Epilepsy. – Phenomena essential to epilepsy – Epileptiform convulsions dependent on superficial disease of the brain – Case – Points to be explained by an adequate theory of epilepsy – Epilepsy not due to primary irritation of the spinal cord – What part or parts of the brain affected in epilepsy?– Not the Medulla oblongata, nor the Corpora Striata and Optic thalami – Affection of the hemispheric lobes explains the loss of consciousness – Can superficial irritation of these parts of the brain cause convulsions? Periodical action of the brain – Sleep – Dr. M. Hull's theory of sleep – Objections to it – The mesocephale affected in epilepsy – Experiments by the magneto-electric machine on different parts of the cerebro-spinal centre – Clonic convulsions caused by irritation of the mesocephale – Conclusion as to the parts of the brain concerned in the production of epilepsy – Inquiry into the nature of the cerebral disturbance in epilepsy – Is it inflammation? Congestion? Anaemia? Theory of the disease – Humoral view – Treatment by drugs – by discipline and regimen – Use of chloroform in epilepsy. Mr. President and Gentlemen, To frame an adequate theory of the pathology of epilepsy, is, I feel, a task of no ordinary difficulty. Although much has been done of late years towards forming exact views of the functions of the several parts of the great cerebro-spinal axis, we are still very uncertain as to the precise influence which each part has on the others, – as well above as below it, – and how far a disturbance of any one may involve the rest in a like disturbance. While such obscurity exists respecting the office of important parts of the nervous system, it is impossible not to approach the subject of the pathology of epilepsy without a feeling of hesitation and mistrust. The leading and pathognomonic features of true epilepsy are these: – loss of consciousness and sensibility, most frequently accompanied by convulsions of the kind which I have described as epileptic, i.e. of movements which consist of alternate relaxations and contractions of muscles rapidly succeeding each other: these paroxysms occurring at intervals of variable length, with something of periodicity, the patient during the interval recovering himself completely. These phenomena are most frequently ushered in without any warning whatever, so that the patient is suddenly, and on the instant, seized, rendered senseless, more or less violently convulsed, and then awakes more or less suddenly. In many instances all this is done in scarcely as much time as it takes to describe the phenomena; at other times the fit is of much longer duration. Now it must be carefully kept in view that the complete epileptic paroxysm is compounded of many phenomena, of which the primary and constant ones are the loss of consciousness, and the disturbances of sensibility which usher in the fit, or remain after it. We never meet with instances of epileptic convulsions affecting the whole system, and recurring periodically, which are not ushered in with loss of consciousness, or accompanied by it. We do, however, frequently meet with instances of the sudden loss of consciousness, lasting for a longer or shorter time, without any muscular disturbance; and this loss of consciousness is accompanied by a peculiar vacant look, – an aspect entirely devoid of all indication of intelligence, – expressive, indeed, only of the temporary abeyance of the intellectual power, and attended with a dilated condition of the pupils; – a feature of the epileptic state quite as constant, perhaps, as the loss of sensibility and consciousness, and which is very apt to remain, although in a less degree, after the fit, and throughout the entire period intervening between the fits. There are, however, certain epileptiform disturbances of motion not accompanied by loss of sensibility, which it may be as well that I should notice here, partly to draw the line of distinction between them and the true epileptic convulsions, and partly because a right appreciation of the nature and character of these pseudo-epileptic movements will assist me in the course of this discussion. These movements occur in paroxysms: they consist of alternate rapid contractions and relaxations, with, however a great tendency to muscular cramp or rigidity. If, for instance, the arm is affected, the movements will consist of rapid flexions, alternating with extensions, but in the intervals the muscles will feel firm, and more or less rigid. Sometimes, however, the reverse takes place, and a state of paralysis ensues upon a violent convulsive paroxysm. In such cases the convulsion is never general, – always partial, and confined to one side, one arm or one leg, or both, with the side of the face. In many instances the movements are no more than twitchings, and in all, the experienced eye would readily detect the difference between the half tonic, half clonic nature, and the forcible plunging truly clonic character of the proper epileptic convulsion. Such movements as these accompany superficial irritation of the hemispheres of the brain or of the cerebellum. I have seen them most frequently in children, associated with the so–called tubercular meningitis; or, more properly, meningitis and encephalitis, excited by the presence of tubercles in the pia mater. A case of this kind came under my observation some years ago, which afforded a striking instance of these pseudo-epileptic movements, as I would call them. As the case has been made public by Mr. Dunn, the surgeon under whose care the child was, and who kindly afforded me the opportunity of seeing him, I shall refer to his clear and able account of it published in the Medico-Chirurgical Transactions for details, and content myself with mentioning those points which are most applicable to my present purpose. The boy was two years old, and of strumous habit. He had for some time been failing in health, and shown excessive perverseness of temper. On the 7th of October he awoke, as he was accustomed, between six and seven o'clock in the morning, and while amusing himself with his sister in bed, and attempting to turn over, his left hand suddenly began to take on a jerking or convulsive twitch, which did not extend beyond the wrist. Mr. Dunn saw the patient immediately, and found that these convulsive jerkings formed the only symptom exhibited by the child. He was laughing and talking, quite sensible, and in every other respect seemed perfectly well. These jerkings continued for about twenty minutes, when they subsided, and the child was free from them the whole day. The next morning, the 8th, at nine o'clock, the convulsive movements returned, and continued for half an hour. The day after this the jerkings returned again at seven o'clock in the morning, but were much slighter than before. On the 11th, the convulsive movements returned again, and were not confined to the upper extremity, but involved the leg as well, the face also, and the angle of the mouth. On the 12th and 13th, the child had two fits in the day, affecting the whole of the left side: he cried and screamed towards the termination of the fits, but he was sensible throughout them. Each fit was followed by profound sleep. Early in the morning, the 11th, Mr. Dunn was called up in consequence of a very severe paroxysm, which lasted three hours: the convulsive movements, affecting the left side from head to foot, were very severe: at times he screamed, at others he was quiet, and throughout knew all about him. Under the increased frequency and severity of these attacks, and an extension of them, though in a slight degree, to the right side, with other symptoms of irritation of the brain, the patient died, and, on examination, it was ascertained that there existed an extensive deposit of tubercular matter on the surface of the right hemisphere of the brain, the opposite to the side on which the convulsions took place, and that a slight and recent deposit had taken place on the surface of the left hemisphere, and that the cerebral substance around the tubercles was in a state of red softening, interspersed with inflammatory products, in considerable quantity. The tubercular deposits exciting inflammation of that portion of the brain which was in their immediate vicinity, no doubt gave rise to the convulsive movements on the left side, as well as to those which had begun to show themselves on the right side of the body. I would lay it down, then; that epileptiform convulsions without loss of consciousness are essentially distinct from true epilepsy, and may be developed by even a slight morbid irritation of the brain. You will see that what we have got to explain by any theory of the pathology of epilepsy, is – 1st. The sudden occurrence of complete loss of consciousness. 2nd. The sudden privation of voluntary and locomotive power, with more or less violent epileptiform convulsions. 3rd. And all this occurring at certain periods, with more or less uniform and regular intervals, during which the patient may, and frequently does, return to a condition perfectly normal. Lastly, our theory must explain why it is that these fits are so often accompanied with a maniacal state, and how it happens that their frequent repetition tends to destroy the power of the brain as the organ of the mind; and, moreover, greatly to impair the whole nervous force. It seems needless to occupy time with discussing whether, during these formidable paroxysms of epilepsy, or, as it used to be called, “falling sickness,” the muscles or the nerves are primarily affected. All the obvious phenomena point to the nervous system being chiefly engaged, and to the muscular convulsion as entirely consecutive to, and dependent on, the disturbed state of the nervous system. I would remark, however, that the enormous development of muscular force which must be produced during the convulsive paroxysm, must, in conformity with the discoveries of Matteucci, alluded to in my last lecture, have a most powerful reaction upon the nervous system. The first point, then, which should occupy our attention must be as to the part of the nervous centres which is mainly disturbed in this disease – whether the spinal cord or the encephalon; and, if the latter, whether the whole or part of it: for it cannot be admitted that the disease is one of the nerves only: the nerves, indeed, may convey irritation to the centre, and again reflect that irritation to the muscles; but it would be impossible for such an amount of irritation as would create the paroxysm of epilepsy to exist without giving rise to great disturbance of the centres. I think it cannot admit of doubt that in epilepsy the spinal cord is by no means primarily affected. That it is to a certain extent disturbed during the complete paroxysm which is accompanied by muscular convulsions, is evident; for otherwise the exciting cause of the convulsions could not reach the muscles of the limbs: but then this disturbance is secondary. The nature of the convulsions shows that the spinal cord is not primarily affected. In my former lectures I have shown that the character of the convulsion dependent on primary irritation of the spinal cord is tetanic, with more or less permanent rigidity of the muscles and opisthotonos; and this can be clearly demonstrated by experiment. But although the convulsions of epilepsy are often complicated with a good deal of tetanic spasm, they nevertheless always present features which distinguish them, in a very marked way, from the tetanic convulsions, by the alternate contraction and relaxation, – violent combined movements, resembling voluntary acts, succeeded by relaxations, to be again succeeded by violent contractions. Furthermore, if the spinal cord were affected primarily, we could not explain the sequence of the phenomena in the complete paroxysm of epilepsy. If the spinal cord were primarily disturbed in epilepsy, the sequence of the phenomena would be – first, muscular disturbance, in consequence of the state of disturbance of the cord; then impairment of consciousness, in consequence of the extension of the disturbed state of the cord to the brain. Now the natural sequence of the phenomena is – first, loss of consciousness; secondly, muscular convulsions. Moreover, the supposition of the primary existence of disturbance of the spinal cord leaves us altogether without the means of explaining the phenomena of that form of epilepsy which in its consequences to the patient is quite as formidable as that accompanied by convulsions. I mean that form which consists simply in loss of consciousness, which lasts for a variable term, and then the patient recovers himself. Lesions of the spinal cord, it is now well known, do not affect consciousness. You may have nearly the entire cord severed from the brain, and yet consciousness will be retained. A man falls from a height, and fractures his cervical vertebrae, smashing a considerable portion of the cervical region of the spinal cord: he is taken up paralysed, in both sensation and motion, at all points below the head, but consciousness is undisturbed. In the convulsive diseases confessedly spinal in their origin, – namely, in tetanus and laryngismus, – consciousness is undisturbed, or but slightly affected, however violent the convulsions may be. It seems, therefore, certain, not only that a highly disturbed state of the spinal cord will not impair consciousness, but also that that state of disturbance of the cord is not prone to extend itself to the brain, and to interrupt the functions of that organ. And these arguments applied to the ordinary spinal cord of anatomists – the intraspinal nervous mass – are equally opposed to the location of the disease in the true spinal cord of Marshall Hall, or in the sensorium commune of Prochaska. The sensorium commune of Prochaska is the spinal cord plus its intra-cranial continuation as high up as the crura cerebri. But primary irritation of this latter part produces the same phenomena as that of the spinal cord, with the addition of more or less laryngismus: therefore it is not the part first affected in the epileptic fit. It is plain, then, that the primary disturbance in the epileptic paroxysm must be located in some part of the brain. Now this organ is divisible into certain parts, each of which, there can be no doubt, enjoys a separate proper function, notwithstanding that all the parts are intimately united to each other. These parts are – First. The hemispheric lobes, consisting of the convolutions and the large mass of fibrous matter connected with them. Second. The corpora striata and the optic thalami, in intimate connection with Third. The medulla oblongata. Fourth. The corpora quadrigemina, in intimate connection with, and part and parcel of the mesocephale. Fifth. The cerebellum. Pursuing the method of exclusion, I hope to arrive at the determination of the part the disturbance of which gives rise to the phenomena of epilepsy, and of the epileptic paroxysm. I shall first eliminate the medulla oblongata. An affection of this part, such as could provoke convulsions, would give rise to tetanic, not to clonic, convulsions; and, in some cases, it would act so powerfully and so directly upon the muscles of respiration, that it would probably in many instances annihilate that process altogether. It is true, indeed, that a certain extent of laryngismus often complicates the epileptic convulsion; but primary disturbance of the medulla oblongata would render laryngismus a constant and necessary accompaniment of the epileptic fit, which is not the case. Primary affection of the medulla oblongata does not explain the early and constant loss of consciousness which is pathognomonic of epilepsy, and which is often its only symptom. Diseased states of the medulla oblongata show themselves in impaired deglutition, in vomiting, in altered rhythm of the respiratory movements, in an abnormal proneness to emotional excitement, but not in impaired intellectual action, nor in any affection of consciousness. We cannot admit, then, that epilepsy is due to a primary disturbance of the medulla oblongata. We come next to the Corpora Striata and Optic Thalami. These remarkable ganglia, although intimately connected with each other, are nevertheless very different in structure, and probably, also, very different in function. They are no doubt directly concerned in the development of voluntary motions and of sensation, and their intimate anatomical union is in harmony with the close connexion and interdependence of sensation and motion. They have nothing to do with intellectual operations, and therefore not with consciousness; their functions seem limited to the simple exercise of the will, or to that of the perception of some impression made on a sentient organ. If the corpus striatum or optic thalamus be diseased, you have paralysis of motion or of sensation, or both; but a sound state of intellectual power, and of the consciousness, is quite compatible with extensive disease of both of these organs, provided it does not extend beyond them. Mechanical irritation of these bodies does not produce convulsions, nor does any morbid state of them ever give rise to these disturbances of motion. It is clear, then, that these bodies can no more claim to be the seat of the primary disturbance in epilepsy, than the medulla oblongata. Has the cerebellum any share in the production of epilepsy? I think we must answer this question in the negative likewise. The cerebellum has no influence on consciousness: the absence of the cerebellum is perfectly compatible with consciousness and a certain amount of intellectual power, and these powers remain intact even where there is considerable disease of that organ. Moreover, mechanical irritations of the cerebellum do not give rise to convulsions. There remain, then, only two parts of the brain in which we can localize the primary disturbance in the epileptic paroxysms – namely, the hemispheric lobes, and the mesocephale. I will at once confess that my reflections upon this subject have led me to the conclusion that both of these parts of the brain are greatly concerned in the production of the epileptic state, and in the development of the paroxysms. First and mainly, the hemispheric lobes; secondly and consecutively, the mesocephale. You will bear in recollection that the complete epileptic paroxysm exhibits two features essentially distinct from each other: first, the loss of consciousness; secondly, the convulsions. The loss of consciousness and the other mental phenomena are dependent upon a disturbed state of the hemispheric lobes; the convulsions upon a disturbance of the mesocephale, consecutive to, and derived from, the disturbance of the hemispheric lobes. There is no point in physiology more clearly made out than that the organ which is immediately active in the manifestation of intellectual operations is the convoluted surface of the brain, and the fibrous mass connected with it – the hemispheric lobes. Every fact in comparative anatomy points to this condition. Experiment confirms it likewise. When the hemispheric lobes are removed from a pigeon, as in Flourens’ celebrated experiment, which I have more than once repeated, the animal became a mere living machine, capable only of manifesting the physical phenomena of life, exhibiting no indication of mental operation nor of consciousness: it fell into the deep unconsciousness of epilepsy. In all instances where the nutrition of the cerebral hemispheres is disturbed, the intellect suffers: you have delirium or a maniacal state; or if the disease be of a kind tending to check nutrient change, or to destroy it, you have more or less stupor. So, also, inflammatory states of the arachnoid and pia mater covering the convolutions of the brain, disturb the intellectual operations, because they are so intimately connected with the hemispheric lobes, being as it were carriers of nutrition to them, that the nutrition of these membranes cannot be disturbed without perverting that of the convolutions themselves. Although it is perfectly true, that the brains of persons dead of epilepsy in its early periods will exhibit, as Foville remarks, “nothing, absolutely nothing, which differs from the normal state,” unless they have died in the attack, when the cerebral congestion which exists is, in the words of the same distinguished physician, a “feature, not of epilepsy, but of the state of asphyxia induced by it, and in which the patients have died”; still in the more advanced stages of the disease, when the patients have experienced many fits, morbid appearances are met with, and these affect the hemispheres of the brain chiefly. You have among the most common, opacities and thickening of the membranes, shrinking of the convolutions, enlargement of the sulci between them, increased subarachnoid fluid, alterations of colour and consistence of the grey and white matter of the hemispheric lobes. These alterations must be looked upon as the accumulated effects produced by the various paroxysms. Each fit does some amount of damage to the brain: in the interval the brain recovers itself to a great degree, when a new fit comes on, and new mischief is done; and so the repetition of the paroxysms leaves the brain altered as I have described it. But, observe, the alterations are not of the cerebellum, nor of the medulla oblongata, nor of the corpora striata or optic thalami, – but of the hemispheric lobes. Bouchet and Cazaurielh, who have conducted an extensive series of researches into the clinical history of epilepsy, found these alterations of the hemispheric lobes so frequent in the chronic cases, that they attribute the disease to a chronic inflammation of the cerebral lobes, which determines epilepsy if it affect the white substance, insanity if it affect the grey. I refer to these researches, not because I believe that the conclusion founded on them by their authors is correct, but because they strikingly indicate that the seat of the organic disturbance (which these authors admit to be caused by the fits) is in the hemispheric lobes. It cannot, I think, under the weight of argument which may be adduced in reference to the office of the hemispheric lobes, be doubted that an affection of these parts is capable of inducing all the phenomena of epilepsy, as far as regards consciousness and sensibility. But an important question remains: can a disturbed state of the hemispheric lobes induce or excite convulsive movements? The proper answer to this question appears to me to be this: under ordinary stimulation of the substance of the hemispheres, the fibres are incapable of exciting motion. It is not the office of these fibres to propagate the nervous force to muscles, but to other nervous centres. Their function is to establish communications between the great sheet of vesicular or grey matter which covers the convolutions of the brain, and the corpora striata, optic thalami, and mesocephale, so the changes in any of these centres may be propagated from any one to any other, or to all the rest. Hence the sections and irritations by mechanical and galvanic means to which these fibres have been subjected in the hands of various experimentalists, produce no disturbance of motion, so long as the irritation is strictly confined to them. So far, then, anatomy and experiment denote to us that of themselves these fibres of the hemispheric lobes cannot excite motion, but that they may do so through their influence upon other ganglia of the brain; and such phenomena, as I referred to at the commencement of the lecture, as a convulsive affection of the whole of one side of the body, evidently brought on by the deposition of tubercular matter on the surface of the cerebral hemisphere on the opposite side, and its consequent irritation, show that convulsive movements may be excited by a superficial lesion of the hemispheric lobes. Hence we must not deny to these lobes a certain power of exciting motion, either directly or indirectly, through their influence upon other ganglia of the brain. But it is important to remark that the influence of the hemispheres is most manifest for this purpose when the lesion is superficial; that is, when if affects the grey matter. A deposition of tubercle, such as took place in the case I described at the commencement of the lecture, would produce little or no disturbance if it took place in the white substance: it would interrupt the functions of some of the fibres; but when deposited in the vesicular matter, among the particles of the generating plate of the nervous battery, the development of the nervous force becomes seriously impaired. From all these facts, then, I infer that a disturbed state of the hemispheric lobes may undoubtedly give rise to so much of the phenomena of the epileptic paroxysm as refers to the affection of consciousness and sensibility, and that it may, in some degree at least, contribute to the development of the convulsions. We must not forget that, in forming a theory of the pathology of epilepsy, we have to explain not a continuous state of disturbed sensation and motion, but a malady, the grand feature of which is periodical recurrence of the paroxysms, the patient being wholly or almost restored to his normal state in the intervals between the attacks. Now, it is not a little remarkable that there is no organ in the body which exhibits the same kind of periodical activity and quiescence in the performance of its functions, as the hemispheric lobes. This periodicity is manifest in the phenomena of sleep: throughout life the tendency exists that for a certain period of each day the state of sleep comes on–when intellectual acts cease, the will is not exerted, the perceptive powers remain quiescent, the channels of sensation are closed. This tendency is greatest in the early periods of life than at any other time—greatest of all in infancy, when sleep engrosses the largest portion of time: very marked in childhood, less imperious in adult life, but assuming a somewhat increased influence in second childhood – OLD AGE. It is unnecessary for me to take up time in adducing arguments in support of the assertion, that the phenomenon of sleep belongs to the brain, and especially to the hemispheric lobes. I must content myself with the statement, that the periodical recurrence of sleep is a part of the train of phenomena which belong to the normal nutrition of the brain. The diurnal variations of our planetary system are not more surely influenced by the laws which regulate them, than is the brain by that law of its nutrition which enforces that the activity of that part of it which is immediately associated with the operations of the mind should be from time to time interrupted by sleep. In hybernating animals, we have a remarkable example of the extraordinary influence of this law of the nutrition of the brain, and of the curious mastery which it exercises over all the other processes of life. When the winter sleep sets in, the breathing becomes slow, the circulation is languid, the body feeds upon the store of fat which had been laid up during a period of exertion, the chemical changes of the body are reduced in activity and complexity. It lasts a certain time, and the animal becomes gradually roused, and resumes its wonted place among the active denizens of the world. We have, indeed, in the animal economy, phenomena in some degree analogous to this alternate activity and quiescence of the brain. The heart beats with a certain rhythm, and pauses after it has accomplished its systole and diastole. Respiration exhibits a similar rhythm in its movement. So, also, perhaps, the peristaltic action of the bowels. Something like a physical explanation of these phenomena may be offered, but we know no physical cause for sleep; and, in the existing state of knowledge, we must rest content with regarding it as an ultimate fact, that it is to the peculiar economy of the brain, and to the laws which specially regulate its nutrition, that we owe the unspeakable advantage and enjoyment of “Tired Nature's sweet restorer, balmy sleep.” When these laws are impaired, there is either too much sleep, or it is almost banished from the eyes, and nature at length sinks exhausted. Dr. M. Hall, indeed, thinks that he can derive some physical explanation of the phenomena of sleep from the antagonism which he assumes to exist between what he calls the spinal system and the cerebral system. “As sleep approaches, (he says) the levator palpebrae, a muscle of voluntary motion, ceases to act; whilst the orbicularis, a muscle of true spinal action, contracts and closes the eyelids.” “Imagine,” he adds, “an event similar in its nature to take place in the muscles of the neck: volition ceasing, spinal action being energetic, certain muscles contract and compress the veins, and a degree of fullness of the neck and face, with turgidity of the eyes, is the obvious result; nay, there is even a degree of laryngismus heard in the respiration. All this is most observed in the first deep sleep.” Now, to pass over certain very decided sources of fallacy in this view, such as the assumed energetic condition of spinal action, the contraction of the orbicularis and other muscles, the distinction between a muscle of true spinal action and of cerebral action, it is plain that it involves a petitio principii, and this is expressed in the first three words of the passage I have quoted –“as sleep approaches;” and in two words of the succeeding paragraph –“volition ceasing.” The whole question is involved in these two phenomena – the approach of sleep, the abeyance of volition: if we can determine what influences the approach of sleep, to what its first beginnings are due, what determines the abeyance of volition, we need inquire no further. According to Dr.