SERUM CHOLINE ESTERASE IN BARBITURATE ADDICTION AND EPILEPSY

Abstract

1. The previously described decrease of serum choline esterase after prolonged administration of barbiturates in man was studied in epileptics after sudden withdrawal of the drug. The number of seizures then rises sharply to a maximum, while the choline esterase is still at a low level.2. The seizures become less frequent again when the choline esterase starts to rise, and usually disappear completely when the choline esterase has just reached what proves to be, in the particular individual, its highest level.3. When the drug is given, the choline esterase decreases to a minimum in about three weeks, whereas the number of seizures is minimal in a few days.4. A time sequence of the abstinence symptoms was noted, the withdrawal psychosis appearing first and wearing off when the grand mals were at their peak, whereas the latter preceded the maximal frequency of petit mal seizures.5. In an unselected group of cryptogenic (idiopathic) epileptics, when under no treatment for some time, a slightly higher average value of serum choline esterase was found than the normal average, the difference being statistically not significant. In some of the epileptics, however, much higher values were found than were ever found in normals. The possible existence of one group of epileptics, characterised by a high choline esterase, is discussed.6. After the withdrawal of the drug the narcotic effect seems to wear off more rapidly than the choline esterase increases. Thus the cholinergic system, free from narcotic and probably at a high level of activity, is left with an inadequate amount of choline esterase. This discrepancy probably accounts for the abstinence symptoms.7. Because of the relative lack of choline esterase during the period of abstinence symptoms, excessive cholinergic activity is assumed to exist. A number of indications for this are found, and its possible rôle in the production of seizures is discussed. Some diverse features, such as the peak incidence of seizures during the night, the precipitating action of alcohol in epilepsy, and some features in the electro‐encephalograms, become more understandable from this viewpoint.I am greatly indebted to Professor P. C. Cloake for his interest and helpful encouragement in this investigation. I am also very grateful to Dr. J. J. O'Reilly, Medical Superintendent of the Birrningham City Mental Hospital, Winson Green, for providing me with the necessary material from the patients under his care, for altering within limits of safety the treatment given to a number of them as this appeared important for these experiments, and for his kind help. I am also grateful to G. Hoyle and D. Marshall for valuable technical assistance.