THE PHVSIOPATHOLOGV OF EPILEPTIC SEIZURES 



333 



which possesses nothing but the medulla and pons, 

 but they no longer occur in the spinal animal. One 

 has therefore to postulate the existence of an anatom- 

 ical structure in the brain stem, which extends to its 

 most caudal part, and which is connected with the 

 spinal inotor neurons and ai)le to transmit to them 

 convulsant impulses. Such a structure, suspected 

 by Lucciani under the name of 'common motor 

 center' may, perhaps, be identified as the brain stem 

 reticular formation, the most caudal part of which 

 furnishes crossed and direct descending pathways to 

 the motor neurons in the spinal cord. 



fe) Cortical theory. The famous experiments of Fritsch 

 & Hitzig in 1870 (51) led to the theory of the cortical 

 origin of generalized epilepsy. These authors demon- 

 strated that weak electrical stimulation applied to the 

 sigmoid gyrus in the dog provoked focal movements, 

 whereas more intense or more prolonged stimulation 

 of this region provoked generalized convulsions more 

 or less rapidly. Today we would consider this phe- 

 nomenon as a secondary (subsequent) generalization 

 and consider it entirely separate from seizures gen- 

 eralized from the start (see below). At that date, 

 however, these experiments led to doubts concerning 

 the subcortical mechanism of epileptogenesis. Thus 

 Ferrier in 1873 (47) concluded, "It is not necessary 

 to assume that the medulla oblongata is the primary 

 seat of the motor disturbance in fits." 



Only 13 years after the famous experiments of 

 Fritsch & Hitzig, Franck & Pitres (49) showed that 

 it was impossible to localize an epileptogenic center" 

 in the motor cortex only, since ablation of this region 

 did not stop convulsions provoked by its stimulation. 

 Thus it became necessary to postulate the propagation 

 of epileptogenic activity from the point stimulated to 

 the whole of the cerebral cortex or to subcortical 

 structures able to maintain convulsions. To this end, 

 Unverricht (1889) announced his 'law of irradiation', 

 conceiving an 'intracortical' conduction of the epi- 

 leptic seizure which, starting from a point on one 

 hemisphere, is propagated superficially to the whole 

 cortex. Lewandoski in 1907 (131) defended the theory 

 of transcallosal propagation, as did Erickson (43) 

 much later, although he regularly obtained general- 

 ized seizures after section of the corpus callosum. 

 Since these fits were clonic on the side opposite to 

 the stimulated hemisphere and tonic on the .same side, 

 Erickson concluded that subcortical structures play 

 an accessory part in the propagation of the epileptic 

 discharge, at least as far as the clonic component is 

 concerned. Karplus (123) on the contrary supposed 



that the spread of a discharge localized in the cortex 

 takes place mainly by subcortical pathways. He thus 

 prepared the way for later research which confirmed 

 this view, as we shall show in the section on .seizures 

 of partial epilepsy secondarih- generalized. 



In these theories of the cortical origin of generalized 

 epilepsy the authors assumed that convulsive seizures 

 depended on a discharge transmitted from the motor 

 cortex of both hemispheres to the spinal neurons by 

 way of the pyramidal tracts. This concept was vig- 

 orously attacked by Prus in 1898 (162) who showed 

 that these tracts were not essential for seizure pro- 

 duction, von Economo & Karplus confirmed this 

 work in 1910, demonstrating the persistence of tonic- 

 clonic seizures in animals after bilateral destruction 

 of the pyramidal tracts and the pes pedunculi. The 

 same kind of experiments were undertaken by Mettler 

 & Mettler in 1940 (141) who wrote, "epileptiform 

 .seizures cannot be evoked from the cortex if only the 

 pyramids are intact, but can be evoked if they alone 

 are severed," a conclusion which leaves one to .suppose 

 that extrapyramidal structures and pathways play 

 a predominant part in the mechanism of generalized 

 convulsions. 



Electrophysiological experiments soon came to 

 confirm the results of these ablation experiments. 

 Hoefer & Pool (99) showed that, during a seizure, 

 spike-discharges of cortical origin are intermittent in 

 pyramidal pathways but continuous in extrapyram- 

 idal pathways situated in the reticular formation. 

 Recently, Zanchetti & Brookhart (199) have demon- 

 strated that there is no modification in pyramidal 

 responsiveness after pentylenetetrazol has been ad- 

 ministered in doses large enough to induce 

 "spontaneous convulsive discharges". Schlag (172) 

 obtained similar results after injections of physo- 

 stigmine or acetylcholine. The two authors suggest 

 that these convulsants do not directly affect pyram- 

 idal neurons and cortical interneurons but act 

 through other neuronal structures, notably those in 

 the reticular formation. 



All these experiments indicate that, although corti- 

 cal seizures may be secondarily generalized, it is 

 unlikely that in fits that are generalized from the 

 start the primary origin is cortical with corticospinal 

 propagation. 



c) Eclectic theory nf cortual-subcortical mechanism of gen- 

 eralized conviilsion.s. Although there is agreement that 

 generalized convulsions do not necessarily depend on 

 the cerebral corte.x, some authors consider that this 

 applies only to the tonic phase. Among these one 



