338 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



not fully support cither theory, believins; the matter 

 unsettled. 



Cohn (30) pointed out that the spike component 

 of the spike-wave (spike-dome) complex in man is 

 not exactly synchronous over the whole of the scalp, 

 since its beginning, measured at two homologous 

 points on the two hemispheres, could show an 

 asynchrony of the magnitude of about 5 to 20 msec. 

 Such a finding appears to lead to conflict with the 

 theory of Jasper & Droogleever-Fortuyn (109) who 

 argued that the cortical discharge in petit mal de- 

 pends on the activity of a single mid-line pacemaker 

 which projects synchronously to the two hemispheres 

 at once. Despite their discordance, one may reconcile 

 the observations of Cohn and of Jasper by taking into 

 account the anatomical relations demonstrated by 

 Nauta & VVhitlock (151). These authors showed that 

 in the anteromedial part of the thalamus, which was 

 the region stimulated by the Montreal workers, there 

 is a band of compact fibers from the brain stem 

 reticular formation going, on the one hand, to the 

 subcortical grey matter and, on the other hand, to 

 the nucleus reticularis of the thalamus which in turn 

 projects diffusely over the isocortex. These anatomical 

 facts may explain how Jasper & Droogleever-Fortuyn, 

 stimulating in the mid-line a tract of fibers with bi- 

 lateral distribution, were able to obtain a bilateral 

 and synchronous cortical discharge, whereas the spon- 

 taneous spike-and-wave discharge recorded by Cohn, 

 arising in a central but bilateral and diffuse pace 

 maker in the thalamus, may give the asynchrony which 

 he observed. It is relevant at this point to recall that it 

 was in the lateral part of the thalamus that Williams 

 (197) recorded the start of the petit mal discharge. 



IiUerpretdtioti of Experunental Results 



In the previous section we ha\e limited ourselves 

 to a presentation of experimental results with a mini- 

 mum of interpretation. In this section we shall be 

 expressing personal views in an attempt to present a 

 more general unifying conception of the physiopa- 

 thology of generalized seizures. In the first part we con- 

 sider the nature and origin of the neuronal discharge 

 responsible for a generalized seizure, taking grand 

 mal as an example. In the second we shall envisage 

 the causes of this discharge. Finally, a third part will 

 be devoted to a study of the mechanisms by which this 

 discharge is prematurely interrupted or rhythmically 

 inhibited, and which are responsible for the two vari- 

 eties of petit mal (myoclonic and 'absence' types). 

 The final aim of this section will be achieved when we 



have demonstrated the existence of a similar mecha- 

 nism in all three main varieties of generalized epilepsy. 



ORIGI.N', N.\TURE .AND PROP.AG.ATION OF NERVOUS .\C- 

 TIVHY' RESPONSIBLE FOR GENERALIZED GRAND MAL 



SEIZURE. If we envisage generalized grand mal epilepsy 

 as a group of clinical and electrical phenomena, 

 necessarily in\ol\ing convulsions, as.sociated with an 

 EEC discharge of generalized hypersynchronous 

 waves, the results which we have reviewed in the pre- 

 ceding section lead us to relate it to a reticular dis- 

 charge propagated toward the cortex, resulting in the 

 EEG manifestations, and toward the periphery, in- 

 ducing the convulsions. 



This conception of generalized epilepsy is however 

 disputable in so far as it regards the two phenomena 

 as necessarily associated, and affords them equal 

 importance, whereas the two can be dissociated and 

 only one of them corresponds to the clinical definition 

 of epilepsy. One mas try to explain grand mal epi- 

 lepsy in terms of a hypersynchronous discharge, but 

 one can not postulate the existence of hypersvn- 

 chronous discharge in an affection which (until we 

 know more about it) is characterized only by con- 

 vulsions and loss of consciousness. 



If we admit that the clinical and EEG manifesta- 

 tions of generalized epilepsy are not neces.sarily linked 

 and that the former are of greater 'medical' interest, 

 we should first of all try to explain these clinical 

 phenomena and afterward search for the factors that 

 link them to the hypersynchronous discharges by 

 which they are usually accompanied. We shall there- 

 fore examine the experimental conditions which pro- 

 voke transient generalized convulsions, whether or 

 not they are reputed to be 'epileptic', and seek to 

 delineate their precise physiopathological mechanism. 

 In the present state of knowledge, there are four con- 

 vulsive conditions which throw light on the problem. 



a) C'onvulsions with loss of con.sciousne.ss, char- 

 acterized by inten.se contractions resulting in 

 opisthotonus, preceded or followed by one or two 

 muscular jerks, are precipitated in man and in ani- 

 mals by all forms of cerebral anoxia (anoxemic anoxia 

 from insufficient partial pressure of oxygen, toxic 

 anoxia, and ischemic anoxia due to cardiac arrest 

 and fall in arterial pressure). These phenomena have 

 been studied electrophysiologically in animals by 

 Noell & Dombrowsky (152), Ward (194), Ward & 

 Wheatley (195), Ajmone-Marson & Fuortes (4) and 

 Gastaut et al. (70). The concordant results of these 

 authors may be summarized as follows. 



/) During acute anoxia, depression of electrical 



