THE PHYSIOPATHOI.OGY OF EPILEPTIC SEIZURES 34 1 



FIG. 3. Schematic representation of the mechanism of pentyl- 

 enetetrazol (Metrazol) con\'ulsions. The density of the vertical 

 lines is proportional to the importance of the hypersynchronous 

 discharge of the pentylenetetrazol type. This discharge is 

 maximum at the thalamocortical level and it diminishes in 

 the mesencephalon and the metencephalon to disappear in 

 the caudal reticular formation where normal electrical activity 

 persists. It must thus be concluded that the pentylenetetrazol 

 convulsions are produced by the same mechanism as the 

 anoxic, i.e. a liberation' of the activity of the neurons of the 

 caudal reticular formation when the higher nervous centers 

 are invaded by a discharge which results in their functional 

 exclusion. 



FIG. 4. Schematic representation of the effect provoked by 

 pentylenetetrazol in an animal already heavily strychninizcd. 

 The vertical lines represent the hypersynchronous pentyl- 

 enetetrazol discharge at the thalamocortical level, while the 

 squares represent the hypersynchronous strychnine discharge 

 in the brain stem. It can be seen that the strychnine tetanus 

 which is present at this time depends exclusively on the dis- 

 charge of the caudal reticular formation without any involve- 

 ment of the diencephalic structures activated by the pentyl- 

 enetetrazol. 



versely strychnine convulsions (tetanus or raJDies 

 spasms and tonic cerebellar fits probably depend on 

 the same mechanism) do not involve the thalamo- 

 cortical system and are characterized by preservation 

 of consciousness. 



We may now attempt to apply these hypotheses to 

 the convulsions of grand mal epilepsy, believing that 

 pentylenetetrazol-induced seizures are the only ones 

 which faithfully reproduce spontaneous epilepsy in 

 man with its hypersynchronous cortical discharge and 

 its well differentiated tonic and clonic phases. A 

 grand mal seizure seems to depend on a thalamic 

 discharge which involves the nonspecific reticular 

 structures and is projected to the cortex in what may 

 be considered a generalized recruiting response trans- 

 mitted along the diffu.se cortical projection pathways. 

 Since the system responsible for recruitment is also 

 responsible for generalized epileptic discharges (66, 

 log, 163) and, since it also seems implicated in the 

 production of i)ursts of barbiturate 'sleep' (107, 143), 



one is tempted to compare the hypersynchronous dis- 

 charge of generalized epilepsy with a sort of paroxys- 

 mal 'sleep' localized to the thalamocortical system 

 and provoking a functional exclusion of this system. 

 This functional elimination may be directly responsi- 

 ble for the loss of consciousness and indirectly re- 

 sponsible for the convulsions b\ liberating the 

 underlying reticular structures. Given the antago- 

 nism which exists between the thalamic and the 

 mesencephaiorhombencephalic part of the reticular 

 formation,^ one may suppose that a momentary 

 depression of the caudal reticular system can, under 



' The recruiting as well as the augmenting responses evoked 

 by thalamic stimulation are blocked by stimulation of the 

 reticular formation (85, 147); the pyramidal discharge synchro- 

 nous with the augmenting response is suppressed during 

 reticular formation stimulation (155). Conversely, the re- 

 cruiting response is enhanced by the destruction or the barbitu- 

 rate depression of the reticular formation (iii, 124), as well 

 as many other responses induced by thalamic stimulation. 



