394 TAKASHI HAYASHI AND KAZUO NAGAI 



cases while 38-9% remained unchanged or died. These resuks are quite 

 diflferent from those obtained with medication per os. 



The above facts tell us that the direct application of GABOB to the brain 

 can completely cure epilepsy of dogs in certain cases, but that it can induce 

 status epilepticus in a few cases. The important questions are: 



(1) Why and by what mechanism does directly applied GABOB cure 

 epileptics ? 



(2) Why does it in a few cases cause status epilepticus resulting in death? 



(3) Why does it have no complete action when applied indirectly per os 

 or intravenously? 



To the first question it can be stated that the completely cured cases were 

 found in the hst diagnosed as having idiopathic epilepsy, and not symptomatic 

 epilepsy. We examined the electroencephalogram of those dogs which were 

 chosen from the list, four cases of the completely cured and four cases of the 

 unchanged dogs. The results were as follows: The encephalograms of the 

 unchanged animals showed focal or multi-focal disturbances, but almost all 

 of the cured animals showed no abnormalities. Unfortunately, we have no 

 records from the time before the GABOB was introduced so that we do not 

 know whether the treatment is responsible for the absence of electrical focal 

 disturbances. 



The conclusion can be drawn, however, that symptomatic epileptic dogs 

 cannot be cured by the treatment while dogs with idiopathic epilepsy can. 

 The cure through GABOB succeeded only in the case of weak metabolic 

 changes in nerve cells which lead to diffuse multiple foci but not in cases of a 

 strong localized focus which was caused by traumatic local lesion or a cicatrix 

 of infectious adhesion. 



Concerning the second question: Since in most cases after the first treat- 

 ment with an excessive dose of GABOB introduced into the brain, epileptic 

 attacks were precipitated (although sometimes they were delayed by weeks), 

 it must be concluded that the mechanism of complete cure will not be attained 

 suddenly but that it takes several days. The fact that GABOB must be given 

 in rather large doses and that the mechanism for cure requires a certain lapse 

 of time leads us to believe that an enzyme which produces a substance that 

 causes epileptic attacks is not only inhibited but transformed or modified 

 into an inactive state by the excessive dose of oj-amino acid. If this is the case, 

 GABOB must be adsorbed by the enzyme, probably by its protein. The 

 question of the precipitation of attacks by introduction of concentrated 

 solutions of GABOB into the cerebrospinal fluid is probably related to the fact 

 that a small percentage of the dogs got worse after the injections. This prob- 

 lem must be studied in the future. 



