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EPILEPSY AND ELECTRIC DISCHARGES
271
this means induced and maintained for 1-1 hours. Most of the patients with symptoms experienced some relief and 2 of the 6 paretics had satisfactory remissions, while 3 others showed some betterment in mental condition. In 14 patients with positive tests in the cerebro-spinal fluid it was possible to make a comparison of the tests before and after the fever therapy. In 4 whose changes were of paretic type, the reversal to negative was almost complete, and in 8 others the spinal fluid tests showed substantial improvement. It will be seen that these figures, as far as they go, compare favourably with those reported from fever attained in other ways. The advantages claimed are that reactions are relatively slight, that the treatment is easily controlled, that the patients are ambulant between their bouts of fever, and that with nursing supervision the injections can be carried out in the patient’s home. If further work along these lines gives equally good results pyrexial treatment may become applicable to a number of patients who, through lack of facilities or through feebleness, would otherwise be denied this useful aid against resistant neurosyphilis.
dosage was usually needed. temperatures of 104°-106° F.
By
were
EPILEPSY AND ELECTRIC DISCHARGES AFTER an infancy as " the Berger rhythm " in the publications of academic physiology, and an adolescence as " brain waves" in the lay press, electro-encephalography is settling down to a useful maturity applied to the study of nervous diseases. In a paper just published in Brain GIBBS, GIBBS, and LENNOX of Boston maintain that their observations on electrical discharges from the brains of epileptic patients demonstrate " the pathological physiology of epilepsy to be a paroxysmal cerebral dysrhythmia."1 This confident conclusion reflects the tone of their whole paper and brings it into contrast with that of GOLLA, GRAHAM, and WALTER2 in which a more cautious attitude is expressed in the admission that " at the present stage no definite pronouncement is possible as to the significance of the delta-wave foci in epilepsy." This difference of opinion is the more interesting because there is no apparent disagreement in the observations of the two groups. Since electro-encephalography is already taking an important place in the diagnosis of epilepsy in this country, it is important to be quite clear as to what may be accepted and what must still be considered speculative in this recent work. The technique, which is analogous to electrocardiography, is much the same in all laboratories. It involves the amplification by thermionic valves of the very small bio-electric potentials of the brain as led off from electrodes on the scalp, and their registration by some sort of oscillograph. If the source of the electrical changes is to be localised at all exactly, several 1 Gibbs, F. A., Gibbs, E. L., and Lennox, W. G., Brain, 1937, p. 377. December, 2 Golla, F., Graham, S., and Walter, W. G., J. ment. Sci. 137. 1937, 83,
amplifying-recording systems must be used simultaneously, and this considerably increases the complexity and cost of the apparatus, one type of which has been described by WALTER3 in a paper on the location of cerebral tumours by this means. Being derived from orthodox and well-tried principles the technique may be considered reliable in experienced hands. The electro-encephalographic inquiry into epilepsy follows two main paths. In Boston LENNOX, F. A. and E. L. GIBBS, DAvis, and others have approached the problem of the electrical discharges associated with the epileptic seizures themselves and have not been much concerned with the precise location of the discharge that they sometimes state that it was except " frontal " or " occipital." In London GoLLA, GRAHAM, and WALTER have studied the much smaller abnormal discharges found in the majority of certain classes of epileptics in the period between seizures, and have concentrated on the location of these discharges as exactly as possible. The data accumulated by the Boston group may be summarised as follows :-
(1) The great majority of epileptic seizures, in fact all true epileptic fits, are accompanied by large rhythmic electrical changes. (2) The form of these changes is distinctive for the three main types of fit-major, minor, and epileptic
equivalent. (3) Very slight minor attacks can be detected in some patients by electro-encephalography when they are imperceptible by other means. (4) A major fit may be predicted some hours in advance when an increase is observed in the resting abnormal discharge. (5) The abnormal activity sometimes appears to start in one area of the cortex and spread to others. One patient with abnormal spikes confined to the frontal area has greatly improved following bilateral amputation of his frontal lobes." "
These facts, obtained from the study of about 400 patients, may be taken as trustworthy ; moreover they have been confirmed by other observers. The second group supply the following information :(1) Abnormal electro-encephalograms are found. between fits in about half the " patients complaining of fits." (2) The abnormality in most cases does not closely resemble the type of discharge found during fits, but is similar to the slow waves previously found near cerebral tumours and called delta waves. (3) The clinical diagnosis in the majority of epileptics showing a delta-discharge has been idiopathic epilepsy. Patients whose fits are symptomatic or hysterical give normal records. Whatever the diagnosis, abnormal records are unusual in patients over the age of 40. (4) In most cases the discharge is focal, and, although the correlation is not perfect, patients with mostly major fits have a precentral focus, those with mostly minor fits a post-central one. The commonest site for the precentral foci is in the neighbourhood of the superior frontal gyrus on either or both sides ; for the post-central foci the region of the supramarginal gyrus is common. (5) When a patient with an abnormal focus has a fit during the examination, the discharge characteristic of the fit is seen first in the region of the focus and spreads from there to other parts of the cortex.
3 Walter,
W.
G., Proc. R. Soc. Med. 1937, 30, 579.
272
(6) Although the size of the focal discharge does not follow changes in the treatment of the patiente.g., by giving or withholding phenobarbitone" spontaneous " changes in the frequency of fits
associated with corresponding of the resting focus. are
These
waxing
and waning
may be accepted with the same those of the first group. They were obtained from the observation of a similar number of patients. A consideration of these undoubted facts already enables us to assess the clinical value of electroencephalography in a provisional way. It is clear that the diagnosis of epilepsy may be greatly simplified. In the first place, if a "fit can be" observed one can tell whether it is genuine or not, and in the second place, if a delta focus is found it is strongly suggestive of idiopathic epilepsy provided the possibility of cerebral tumour At any rate a or abscess has been ruled out. positive finding will exclude hystero-epilepsy and malingering, though a negative one is not conclusive, and electro-encephalography has now been used successfully for diagnostic purposes at the Hospital for Nervous Diseases, Maida Vale, for more than a year. Disappointingly little, however, has been learned about the aetiology of the disease. Although a fit may be predicted, the reason for its genesis remains obscure, and the resting delta foci found in most young idiopathic epileptics have not been satisfactorily explained. There is indeed no inductive proof that the electrical discharges are more
findings
assurance as
than adventitious signs of some more subtle cortical or subcortical condition, and if too many assumptions are made about the electro-physiology of the hemispheres, the new methods will probably produce more red herrings than facts. So far treatment too has benefited little. It is notoriously difficult to assess the value of surgery in epilepsy ; an epileptic patient is often " greatly improved " after an apparently irrelevant operation, and even after haemorrhage alone. The results of WILDER PENFIELD4 in cases where there was every indication for surgery have not been more than moderately good, and few patients will submit to bilateral amputation of the frontal lobes except to avert a catastrophe. In an oral communica. tion to the meeting of the League against Epilepsy last October, WALTER mentioned a case with a well-defined delta focus in which a craniotomy was done by Mr. WYLIE McKissocK, the focus being verified by direct leading-off under a local anaesthetic and successfully removed in two stages. We understand that the results of this operation have been so baffling that it has not yet been possible to present them for publication. None can doubt however that the exact location of the abnormal area is essential as a prelude to experimental surgery, both for the sake of the patient and to reduce the number of variables. Furthermore, when it comes to the classification of the epilepsies there is hope that electro-encephalography will help to provide a basis for the objective rearrangement of the few facts we possess.
ANNOTATIONS ADOLF LOEWY
THE recent death of Prof. Loewy at the age of 70 in Davos will recall his long association with Prof. Nathan Zuntz in Berlin. Trained in this school it is not surprising that his own interest and his personal researches were centred in the study of the physiology of the respiration in the widest sense. At the beginning of his career he took part with Zuntz in those investigations of the alkalinity of the blood which in more recent years have proved of profound importance from the point of view both of the transport of carbon dioxide in the blood and of the general theory of the regulation of the reaction of the blood. The measurement of the respiratory exchange soon attracted his attention, and in studying the influence of alteration of the composition of the inspired air he showed in 1895 that the oxygen consumption of man was practically uninfluenced by a considerable increase or reduction of the oxygen concentration in the air breathed, and from this he passed on to an investigation of the " dead space" of the pulmonary system and the bearing of this on the composition of the air in the alveoli of the lungs. It was no doubt his investigation of the influence of low atmospheric oxygen concentrations that awakened his interest in the physiology of man at high altitudes, an interest that remained unabated throughout his life, and led to the publication in collaboration with Zuntz, Muller, and Caspari of the well-known volume " Hohenklima und Bergwanderungen " (1906), the result of an expedition to the summit of Monte Rosa, as well as to his later monographs " Physiologie des
H6henklimas " (1932), and, in association with E. Wittkower, Pathology of High Altitude Climate which appeared in 1937, only a few months before his death. In addition Loewy published numerous papers on the influence on the respiratory exchange of changes of external temperature and variations of climate as well as on other problems connected with general metabolism. We recall an investigation made in collaboration with H. R. v. Schrotter in 1905an attempt to measure the output of the heart in man by an indirect method. The results of this investigation were, it is true, uncertain ; the fault lay however not so much in the difficulty of the technique as in the imperfection of existing knowledge regarding the factors governing the absorption of gases by the blood and the composition of the air in the lungs. None the less we must regard this as a pioneer experiment in an exceptionally difficult field ; many years of physiological work were to intervene before a successful adaptation of the method on which their research was based was rendered possible. Loewy also contributed important articles "
"
the blood gases and "
on the respiratory exchange Handbuch der Biochemie," and was associated with Zuntz in editing the " Lehrbuch der Physiologie des Menschen " which was first published in 1909 and ran through several editions. For the ten years 1923-33 Loewy was director of the Swiss Research Institute for Alpine Climate and Tuberculosis, and when he retired four years ago he continued to live in Davos. on
to
Oppenheimer’s
4 Penfield, W.,
449.
Arch. Neurol. Psychiat., Chicago, 1936, 36,
this means induced and maintained for 1-1 hours. Most of the patients with symptoms experienced some relief and 2 of the 6 paretics had satisfactory remissions, while 3 others showed some betterment in mental condition. In 14 patients with positive tests in the cerebro-spinal fluid it was possible to make a comparison of the tests before and after the fever therapy. In 4 whose changes were of paretic type, the reversal to negative was almost complete, and in 8 others the spinal fluid tests showed substantial improvement. It will be seen that these figures, as far as they go, compare favourably with those reported from fever attained in other ways. The advantages claimed are that reactions are relatively slight, that the treatment is easily controlled, that the patients are ambulant between their bouts of fever, and that with nursing supervision the injections can be carried out in the patient’s home. If further work along these lines gives equally good results pyrexial treatment may become applicable to a number of patients who, through lack of facilities or through feebleness, would otherwise be denied this useful aid against resistant neurosyphilis.
dosage was usually needed. temperatures of 104°-106° F.
By
were
EPILEPSY AND ELECTRIC DISCHARGES AFTER an infancy as " the Berger rhythm " in the publications of academic physiology, and an adolescence as " brain waves" in the lay press, electro-encephalography is settling down to a useful maturity applied to the study of nervous diseases. In a paper just published in Brain GIBBS, GIBBS, and LENNOX of Boston maintain that their observations on electrical discharges from the brains of epileptic patients demonstrate " the pathological physiology of epilepsy to be a paroxysmal cerebral dysrhythmia."1 This confident conclusion reflects the tone of their whole paper and brings it into contrast with that of GOLLA, GRAHAM, and WALTER2 in which a more cautious attitude is expressed in the admission that " at the present stage no definite pronouncement is possible as to the significance of the delta-wave foci in epilepsy." This difference of opinion is the more interesting because there is no apparent disagreement in the observations of the two groups. Since electro-encephalography is already taking an important place in the diagnosis of epilepsy in this country, it is important to be quite clear as to what may be accepted and what must still be considered speculative in this recent work. The technique, which is analogous to electrocardiography, is much the same in all laboratories. It involves the amplification by thermionic valves of the very small bio-electric potentials of the brain as led off from electrodes on the scalp, and their registration by some sort of oscillograph. If the source of the electrical changes is to be localised at all exactly, several 1 Gibbs, F. A., Gibbs, E. L., and Lennox, W. G., Brain, 1937, p. 377. December, 2 Golla, F., Graham, S., and Walter, W. G., J. ment. Sci. 137. 1937, 83,
amplifying-recording systems must be used simultaneously, and this considerably increases the complexity and cost of the apparatus, one type of which has been described by WALTER3 in a paper on the location of cerebral tumours by this means. Being derived from orthodox and well-tried principles the technique may be considered reliable in experienced hands. The electro-encephalographic inquiry into epilepsy follows two main paths. In Boston LENNOX, F. A. and E. L. GIBBS, DAvis, and others have approached the problem of the electrical discharges associated with the epileptic seizures themselves and have not been much concerned with the precise location of the discharge that they sometimes state that it was except " frontal " or " occipital." In London GoLLA, GRAHAM, and WALTER have studied the much smaller abnormal discharges found in the majority of certain classes of epileptics in the period between seizures, and have concentrated on the location of these discharges as exactly as possible. The data accumulated by the Boston group may be summarised as follows :-
(1) The great majority of epileptic seizures, in fact all true epileptic fits, are accompanied by large rhythmic electrical changes. (2) The form of these changes is distinctive for the three main types of fit-major, minor, and epileptic
equivalent. (3) Very slight minor attacks can be detected in some patients by electro-encephalography when they are imperceptible by other means. (4) A major fit may be predicted some hours in advance when an increase is observed in the resting abnormal discharge. (5) The abnormal activity sometimes appears to start in one area of the cortex and spread to others. One patient with abnormal spikes confined to the frontal area has greatly improved following bilateral amputation of his frontal lobes." "
These facts, obtained from the study of about 400 patients, may be taken as trustworthy ; moreover they have been confirmed by other observers. The second group supply the following information :(1) Abnormal electro-encephalograms are found. between fits in about half the " patients complaining of fits." (2) The abnormality in most cases does not closely resemble the type of discharge found during fits, but is similar to the slow waves previously found near cerebral tumours and called delta waves. (3) The clinical diagnosis in the majority of epileptics showing a delta-discharge has been idiopathic epilepsy. Patients whose fits are symptomatic or hysterical give normal records. Whatever the diagnosis, abnormal records are unusual in patients over the age of 40. (4) In most cases the discharge is focal, and, although the correlation is not perfect, patients with mostly major fits have a precentral focus, those with mostly minor fits a post-central one. The commonest site for the precentral foci is in the neighbourhood of the superior frontal gyrus on either or both sides ; for the post-central foci the region of the supramarginal gyrus is common. (5) When a patient with an abnormal focus has a fit during the examination, the discharge characteristic of the fit is seen first in the region of the focus and spreads from there to other parts of the cortex.
3 Walter,
W.
G., Proc. R. Soc. Med. 1937, 30, 579.
272
(6) Although the size of the focal discharge does not follow changes in the treatment of the patiente.g., by giving or withholding phenobarbitone" spontaneous " changes in the frequency of fits
associated with corresponding of the resting focus. are
These
waxing
and waning
may be accepted with the same those of the first group. They were obtained from the observation of a similar number of patients. A consideration of these undoubted facts already enables us to assess the clinical value of electroencephalography in a provisional way. It is clear that the diagnosis of epilepsy may be greatly simplified. In the first place, if a "fit can be" observed one can tell whether it is genuine or not, and in the second place, if a delta focus is found it is strongly suggestive of idiopathic epilepsy provided the possibility of cerebral tumour At any rate a or abscess has been ruled out. positive finding will exclude hystero-epilepsy and malingering, though a negative one is not conclusive, and electro-encephalography has now been used successfully for diagnostic purposes at the Hospital for Nervous Diseases, Maida Vale, for more than a year. Disappointingly little, however, has been learned about the aetiology of the disease. Although a fit may be predicted, the reason for its genesis remains obscure, and the resting delta foci found in most young idiopathic epileptics have not been satisfactorily explained. There is indeed no inductive proof that the electrical discharges are more
findings
assurance as
than adventitious signs of some more subtle cortical or subcortical condition, and if too many assumptions are made about the electro-physiology of the hemispheres, the new methods will probably produce more red herrings than facts. So far treatment too has benefited little. It is notoriously difficult to assess the value of surgery in epilepsy ; an epileptic patient is often " greatly improved " after an apparently irrelevant operation, and even after haemorrhage alone. The results of WILDER PENFIELD4 in cases where there was every indication for surgery have not been more than moderately good, and few patients will submit to bilateral amputation of the frontal lobes except to avert a catastrophe. In an oral communica. tion to the meeting of the League against Epilepsy last October, WALTER mentioned a case with a well-defined delta focus in which a craniotomy was done by Mr. WYLIE McKissocK, the focus being verified by direct leading-off under a local anaesthetic and successfully removed in two stages. We understand that the results of this operation have been so baffling that it has not yet been possible to present them for publication. None can doubt however that the exact location of the abnormal area is essential as a prelude to experimental surgery, both for the sake of the patient and to reduce the number of variables. Furthermore, when it comes to the classification of the epilepsies there is hope that electro-encephalography will help to provide a basis for the objective rearrangement of the few facts we possess.
ANNOTATIONS ADOLF LOEWY
THE recent death of Prof. Loewy at the age of 70 in Davos will recall his long association with Prof. Nathan Zuntz in Berlin. Trained in this school it is not surprising that his own interest and his personal researches were centred in the study of the physiology of the respiration in the widest sense. At the beginning of his career he took part with Zuntz in those investigations of the alkalinity of the blood which in more recent years have proved of profound importance from the point of view both of the transport of carbon dioxide in the blood and of the general theory of the regulation of the reaction of the blood. The measurement of the respiratory exchange soon attracted his attention, and in studying the influence of alteration of the composition of the inspired air he showed in 1895 that the oxygen consumption of man was practically uninfluenced by a considerable increase or reduction of the oxygen concentration in the air breathed, and from this he passed on to an investigation of the " dead space" of the pulmonary system and the bearing of this on the composition of the air in the alveoli of the lungs. It was no doubt his investigation of the influence of low atmospheric oxygen concentrations that awakened his interest in the physiology of man at high altitudes, an interest that remained unabated throughout his life, and led to the publication in collaboration with Zuntz, Muller, and Caspari of the well-known volume " Hohenklima und Bergwanderungen " (1906), the result of an expedition to the summit of Monte Rosa, as well as to his later monographs " Physiologie des
H6henklimas " (1932), and, in association with E. Wittkower, Pathology of High Altitude Climate which appeared in 1937, only a few months before his death. In addition Loewy published numerous papers on the influence on the respiratory exchange of changes of external temperature and variations of climate as well as on other problems connected with general metabolism. We recall an investigation made in collaboration with H. R. v. Schrotter in 1905an attempt to measure the output of the heart in man by an indirect method. The results of this investigation were, it is true, uncertain ; the fault lay however not so much in the difficulty of the technique as in the imperfection of existing knowledge regarding the factors governing the absorption of gases by the blood and the composition of the air in the lungs. None the less we must regard this as a pioneer experiment in an exceptionally difficult field ; many years of physiological work were to intervene before a successful adaptation of the method on which their research was based was rendered possible. Loewy also contributed important articles "
"
the blood gases and "
on the respiratory exchange Handbuch der Biochemie," and was associated with Zuntz in editing the " Lehrbuch der Physiologie des Menschen " which was first published in 1909 and ran through several editions. For the ten years 1923-33 Loewy was director of the Swiss Research Institute for Alpine Climate and Tuberculosis, and when he retired four years ago he continued to live in Davos. on
to
Oppenheimer’s
4 Penfield, W.,
449.
Arch. Neurol. Psychiat., Chicago, 1936, 36,