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NO RECOVERY NO GRANT
607
DRUGS AND THE EEG
.
THE LANCET
LONDON:SATURDAY, NOVEMBER 13, 1943
NO RECOVERY NO GRANT Mr. BEVn’s dramatic announcement early in the year that those who drop out of employment as a result of tuberculous infection are to have precisely the same chance of getting back into it as those who have suffered wounds or accidents seemed too good to be true. In one respect it was, for the MINISTER OF HEALTH has ruled that the Exchequer grant is to enable persons to give up work temporarily " for treatment which is in the interest of the public health no less than their own." Only those are eligible whose recovery is sufficiently sure to make them a realisable asset to the man-power’ of the nation in war-time. On the tuberculosis officer falls the invidious task of drawing the line. If he says " no recovery " the Exchequer says " no grant " : and the patient loses both the money and the incentive to get well. It is true that in any case- he may receive money through the local authority which can, and ultimately indeed must, provide assistance when the Exchequer refuses it ; indeed in some places it seems that such assistance is not far short of the grant. But it is not just a question of accounting; the press has been full for weeks of the bitterness (reflected in our Parliamentary column this week) which is being aroused by the distinction between recoverable and irrecoverable disease. The line is impossible to draw with any accuracy. It had to be drawn for sanatorium benefit in the unhappy period before the Public Health Act of 1921 swept it away. Tuberculosis officers are not infallible and there are borderland cases in which the encouragement of a grant might well turn the scale towards recovery. There is a feeling too that the MINISTER himself regretted the reservation, as it was not mentioned in his explanatory leaflet to the public ; moreover the premature discharge of the grantless from hospital or sanatorium must be contrary to the public health, on which he lays such stress. Do not the invidiousness and the unhappiness and the increased risk of infection outweigh any small saving of public money ?1 Unless the scheme is made comprehensive, in accordance with its first intention, shall we not drift into the position that the state only helps the sick civilian in proportion to his capacity to return the help in services rendered ?1 On the field -of battle we do not give priority treatment to the casualties who are
expected
to
fight again.
DRUGS AND THE EEG THE electro-encephalogram is an excellent, and possibly the best, physiological gauge of depression
of the highest cerebral functions. Impairment of . consciousness or increased attention is reflected in a shift of energy distribution towards the slow or fast end of the cortical frequency spectrum. Drugs which affect consciousness modify the EEG, so that the EEG gives us an objective method of studying one aspect of drug action, but the modifications are
difficult to describe without the assistance of automatic frequency analysers. The human visual ap paratus is an integrating mechanism, not an analyser ; events tend to be perceived as a whole, and the minor changes in potential distribution which most drugs produce- are readily overlooked. But-the advent of apparatus for automatic frequency analysis in America,l and now in Englandhas made the accurate assessment of changes in cortical frequency reasonably easy, and drug action on the EEG is now being studied in detail. Working with a Grass frequency analyser, GIBBS and MALTSY3 found, as was expected, that the drugs known clinically as depressants or stimulants can be sorted into the same two groups by the EEG changes they produce. Thus morphine,’Pentothal’ and phenobarbitone redistribute energy towards the slow end of the spectrum, whereas caffeine, amphetamine (’ Benzedrine ’) and adrenaline cause a shift towards the fast end. -In their effects on the EEG, therefore, the depressant drugs are comparable to normal sleep and the stimulants to attention. Of the drugs studied, pentothal, which produced the greatest clinical depression, caused the greatest shift towards the slow end of the spectrum, and adrenaline produced both the greatest clinical stimulation and the greatest shift towards the fast end, amphetamine coming next and caffeine third. In this way the activity of drugs with a similar action can readily be compared. In cases of petit mal, WILLIAMS and RUSSELL4 have studied in the EEG the effect of anticholinesterases on epileptic activity. In small doses eserine tended to prevent attacks, while in larger ones it increased their frequency and duration. ’Prostigmin,’ on the other hand, invariably increased epileptic activity as seen in the EEG, and reversed the effect of small doses of eserine. WILLIAMS 5 used the same technique to investigate the effect of other substances known to modify transmission at cholinergic endings. Intravenous injection of acetylcholine was followed by an increase of epileptic activity, and this effect was abolished by atropine. Since eserine, prostigmin, carbaminoylcholine chloride and acetycholine have a similar action on cerebral rhythms in epileptics which is abolished by atropine, it seems likely that this action is related to an alteration in the acetylcholinetransmitting mechanism in the body ; but WILLIAMS points out that the effect may be an indirect one, due to peripheral changes, since the effects of choline-like substances are so widespread and complex. CHATFIELD and DEMPSEY6 applied acetylcholine and prostigmin locally to the cortex of cats. They found that acetylcholine alone produced no change in the cortical rhythms and prostigmin a transient depression of spontaneous activity at the area of application. When prostigmin was followed by acetylcholine a characteristic series of changes occurred. There was first an increase of spontaneous activity, then an increase of low-voltage 20-30 cycle rhythms which spread over the whole cortex while the amount of 5-10 cycle rhythms decreased. The effect of a single peripheral stimulus on this preparation was to ’
1. 2. 3. 4. 5. 6.
’
Grass, A. M. and Gibbs, F. A. J. Neurophysiol. 1938, 1, 521. Walter, W. G. Electronic Engineering, June, 1943. Gibbs, F. A. and Maltby, G. L. J. Pharmacol. 1943, 78, 1. Williams, D. J. and Russell, W. R. Lancet, 1941, i, 476. Williams, D. J. J. Neurol. Psychiat. 1941, 1, 32. Chatfield, P. O. and Dempsey, E. W. Amer. J. Physiol. 1942, 135, 633.
DRUGS AND THE EEG
.
THE LANCET
LONDON:SATURDAY, NOVEMBER 13, 1943
NO RECOVERY NO GRANT Mr. BEVn’s dramatic announcement early in the year that those who drop out of employment as a result of tuberculous infection are to have precisely the same chance of getting back into it as those who have suffered wounds or accidents seemed too good to be true. In one respect it was, for the MINISTER OF HEALTH has ruled that the Exchequer grant is to enable persons to give up work temporarily " for treatment which is in the interest of the public health no less than their own." Only those are eligible whose recovery is sufficiently sure to make them a realisable asset to the man-power’ of the nation in war-time. On the tuberculosis officer falls the invidious task of drawing the line. If he says " no recovery " the Exchequer says " no grant " : and the patient loses both the money and the incentive to get well. It is true that in any case- he may receive money through the local authority which can, and ultimately indeed must, provide assistance when the Exchequer refuses it ; indeed in some places it seems that such assistance is not far short of the grant. But it is not just a question of accounting; the press has been full for weeks of the bitterness (reflected in our Parliamentary column this week) which is being aroused by the distinction between recoverable and irrecoverable disease. The line is impossible to draw with any accuracy. It had to be drawn for sanatorium benefit in the unhappy period before the Public Health Act of 1921 swept it away. Tuberculosis officers are not infallible and there are borderland cases in which the encouragement of a grant might well turn the scale towards recovery. There is a feeling too that the MINISTER himself regretted the reservation, as it was not mentioned in his explanatory leaflet to the public ; moreover the premature discharge of the grantless from hospital or sanatorium must be contrary to the public health, on which he lays such stress. Do not the invidiousness and the unhappiness and the increased risk of infection outweigh any small saving of public money ?1 Unless the scheme is made comprehensive, in accordance with its first intention, shall we not drift into the position that the state only helps the sick civilian in proportion to his capacity to return the help in services rendered ?1 On the field -of battle we do not give priority treatment to the casualties who are
expected
to
fight again.
DRUGS AND THE EEG THE electro-encephalogram is an excellent, and possibly the best, physiological gauge of depression
of the highest cerebral functions. Impairment of . consciousness or increased attention is reflected in a shift of energy distribution towards the slow or fast end of the cortical frequency spectrum. Drugs which affect consciousness modify the EEG, so that the EEG gives us an objective method of studying one aspect of drug action, but the modifications are
difficult to describe without the assistance of automatic frequency analysers. The human visual ap paratus is an integrating mechanism, not an analyser ; events tend to be perceived as a whole, and the minor changes in potential distribution which most drugs produce- are readily overlooked. But-the advent of apparatus for automatic frequency analysis in America,l and now in Englandhas made the accurate assessment of changes in cortical frequency reasonably easy, and drug action on the EEG is now being studied in detail. Working with a Grass frequency analyser, GIBBS and MALTSY3 found, as was expected, that the drugs known clinically as depressants or stimulants can be sorted into the same two groups by the EEG changes they produce. Thus morphine,’Pentothal’ and phenobarbitone redistribute energy towards the slow end of the spectrum, whereas caffeine, amphetamine (’ Benzedrine ’) and adrenaline cause a shift towards the fast end. -In their effects on the EEG, therefore, the depressant drugs are comparable to normal sleep and the stimulants to attention. Of the drugs studied, pentothal, which produced the greatest clinical depression, caused the greatest shift towards the slow end of the spectrum, and adrenaline produced both the greatest clinical stimulation and the greatest shift towards the fast end, amphetamine coming next and caffeine third. In this way the activity of drugs with a similar action can readily be compared. In cases of petit mal, WILLIAMS and RUSSELL4 have studied in the EEG the effect of anticholinesterases on epileptic activity. In small doses eserine tended to prevent attacks, while in larger ones it increased their frequency and duration. ’Prostigmin,’ on the other hand, invariably increased epileptic activity as seen in the EEG, and reversed the effect of small doses of eserine. WILLIAMS 5 used the same technique to investigate the effect of other substances known to modify transmission at cholinergic endings. Intravenous injection of acetylcholine was followed by an increase of epileptic activity, and this effect was abolished by atropine. Since eserine, prostigmin, carbaminoylcholine chloride and acetycholine have a similar action on cerebral rhythms in epileptics which is abolished by atropine, it seems likely that this action is related to an alteration in the acetylcholinetransmitting mechanism in the body ; but WILLIAMS points out that the effect may be an indirect one, due to peripheral changes, since the effects of choline-like substances are so widespread and complex. CHATFIELD and DEMPSEY6 applied acetylcholine and prostigmin locally to the cortex of cats. They found that acetylcholine alone produced no change in the cortical rhythms and prostigmin a transient depression of spontaneous activity at the area of application. When prostigmin was followed by acetylcholine a characteristic series of changes occurred. There was first an increase of spontaneous activity, then an increase of low-voltage 20-30 cycle rhythms which spread over the whole cortex while the amount of 5-10 cycle rhythms decreased. The effect of a single peripheral stimulus on this preparation was to ’
1. 2. 3. 4. 5. 6.
’
Grass, A. M. and Gibbs, F. A. J. Neurophysiol. 1938, 1, 521. Walter, W. G. Electronic Engineering, June, 1943. Gibbs, F. A. and Maltby, G. L. J. Pharmacol. 1943, 78, 1. Williams, D. J. and Russell, W. R. Lancet, 1941, i, 476. Williams, D. J. J. Neurol. Psychiat. 1941, 1, 32. Chatfield, P. O. and Dempsey, E. W. Amer. J. Physiol. 1942, 135, 633.