THE PHVSIOPATHOLOGY OF EPILEPTIC SEIZURES 



337 



cal. This spike-and-vvave pattern, howexer, repeats 

 itself at intervals which are very variable and only 

 exceptionally around 3 cps. At best, it can not be re- 

 lated to any modification in alertness of the anes- 

 thetized animal. If the effect of rhythmical sensory 

 stimuli is added to that of pentylenetetrazol, it is 

 also easy to induce a spike-and-wa\'c discharge main- 

 tained at the frequency of stimulation, for example at 

 3 cps continuing for as long as desired (66). However, 

 the fact that the rhythm has to be maintained actively 

 and ceases as soon as stimulation is stopped com- 

 pletely disqualifies the phenomenon from being con- 

 sidered as a form of experimental epilepsy. The same 

 criticism may be levelled at the spike-and-wave in the 

 isocortex or allocortex which can be evoked with 

 great difficulty by rhythmical electrical stimulation of 

 the mid-line nuclei of the thalamus (12, 103, 109, 118). 



Recently Ralston & Ajmone-Marsan (163) have 

 produced in the cat EEG patterns which are very 

 close to the bilateral synchronous spike-and-wave 

 discharge of petit mal. They produced a discrete 

 irritative lesion in the nonspecific thalamic system by 

 stereotaxic injection of penicillin. As a result, fusiform 

 bursts of slow waves developed at a frequency of 3.5 to 

 5 cps, were of great amplitude and tended to appear 

 synchronously over the ipsilateral hemisphere when 

 the lesion involved the intralaminar nuclei but over 

 the two hemispheres when the lesion was in the mid- 

 line. On the basis of the topography of these thalamic 

 lesions and cortical discharges, and of the identity 

 between these discharges and those produced by 

 thalamic stimulation (either single-shock stimulation 

 provoking 'triggered' spindles, or repetitive stimula- 

 tion provoking a recruiting response), the authors 

 conclude that these discharges are 'transmitted' by 

 the nonspecific thalamocortical projection system. 

 With a sufficiently severe lesion spikes also appear, at 

 first in the thalamus and later projected to the cortex 

 where they may be grouped with the bursts of hyper- 

 synchronous waves; they may thus sometimes consti- 

 tute rhythmical spike-and-wave complexes. From 

 these observations the authors have come to believe 

 that the discharges of petit mal depend on stimulation 

 of the nonspecific thalamic system near the mid-line, 

 but that different systems are insolved in the pro- 

 duction of the spikes and of the slow waves. 



The fact that it has not Ijeen possible to reproduce 

 petit mal 'absences' in animals has not prevented 

 experimental studies on man. Thus Spiegel et al. 

 (182), Williams (197) and Kirikae et al. (125) have 

 recorded numerous episodes of 'absences' simulta- 

 neouslv in the cortex and in the thalamus. All these 



authors admit that spike-and-wa\e discharge takes 

 place in the two structures at the same time, unless it 

 occurs first in the thalamus; the British and Japanese 

 authors e\en feel that the slow wa\e in the complex is 

 essentially thalamic whereas the spike represents the 

 cortical element. Thus Williams suggests that the 

 paroxysm begins in the thalamus with a rhythm of 

 slow sinusoidal waves of which each element propa- 

 gates itself to the cortex, there to fire off a spike which, 

 in its turn transmitted to the thalamus, pro\okes there 

 another slow wave and so on. Ha\ ne li al. (98) report 

 contradictory results, for the> do not believe that 

 there is any discharge in the thalamus during petit 

 mal 'absences' with bilateral and s\nchronous spike- 

 and-wave in the cortex. 



Petit mal 'absence' also differs from the other types 

 of generalized epilepsy in its electroclinical correla- 

 tions. Loss of consciousness is undoubtedly associated 

 with the spike-and-wave discharge, since no clinical 

 petit mal seizure occurs without this particular dis- 

 charge. The reverse is quite possible, however, and 

 discharges are frequently recorded without clinical 

 manifestations. 



Although electroclinically allied to the other vari- 

 eties of generalized epilepsy, it must be admitted 

 that, from the experimental point of view, the find- 

 ings relating to petit mal "absences' are not analogous 

 to those in grand mal and myoclonus. Perhaps for 

 this reason, there is no agreement on the mechanism 

 of 'absence' and its accompanying EEG pattern, 

 Shimizu et al. (177) believe, indeed, that the petit 

 mal spike-and-wave discharge has a localized cortical 

 origin and that it is rapidly transmitted to the whole 

 of the cortex of both hemispheres by means of cor- 

 ticocortical association pathways, chiefly via the 

 corpus callosum. They base this view on their electro- 

 thalamographic findings in man, and especially on 

 the following results of animal experiments: o) intra- 

 carotid injection of pentylenetetrazol, which carries 

 it to the ipsilateral cortex, provokes a bisynchronous 

 spike-and-wa\-e pattern more easily and more often 

 than does injection via a vertebral artery, which 

 would take it to the central grey matter; H) intra- 

 carotid injection provoked only unilateral spike-and- 

 wave complexes when pentothal had been injected 

 into the other carotid. However this may be, it must 

 be admitted that this view is peculiar to the Chicago 

 school and that the majority of electroencephalog- 

 raphers accept the theory of a diencephalic pacemaker 

 mechanism in petit mal 'absences' as in the other 

 types of generalized epilepsy (105). Ingvar (103) does 



