THE PHYSIOPATHOLOGY OF EPILEPTIC SEIZURES 



343 



discharge. This conception was held in the nineteenth 

 century by pioneers of the modern study of epilepsy 

 who from Hall (96) onwards elaborated the bulbar 

 reflex theory of generalized epilepsy and believed that 

 it depends on a "discharge produced in a reflex way in 

 the region of reticular substance of the pons and 

 medulla ..." (149) under the effect of "an exalted 

 sensibility and excitability of the medulla oblongata" 

 (174). One should not conclude, however, that 

 generalized epilepsy is merely a reflex phenomenon 

 and speak of reflex epilepsy; this unphysiological term 

 is not applicable today to any variety of epilepsy. 



The hyperexcitable state of the neurons, which is a 

 factor necessary to the production of the reticular dis- 

 charge, may depend on the existence of an 'irritative' 

 cerebral lesion lying in the neighborhood or even at a 

 distance from the brain stem. Johnson & Walker 

 (i 13-115) and KopolofT et al. (127) have shown that 

 epileptogenic lesions localized in one hemisphere are 

 always accompanied by a diffuse hyperexcitable state 

 of the neurons manifested by a general lowering of the 

 convulsant threshold. It may depend equally well on 

 a functional factor as yet undetermined, a 'humoral' 

 or 'cerebral' factor acting at the level of the synapses, 

 the axons or the cell bodies, and responsible for an 

 'epileptic predisposition' found both in man and in 

 animals. This epileptic predisposition and hyperexcit- 

 able neuronic state may be quantitatively appreciated 

 b>- determining the convulsant threshold with the 

 photopentylenetetrazol method (52). The threshold 

 is low in patients suffering from seizures generalized 

 from the start and in those whose attacks of partial 

 epilepsy pass very easily into secondary generaliza- 

 tion. 



DURATION AND TERMINATION OF DISCHARGE IN GENER- 



.'^LizED EPILEPSY. The duration and ending of a grand 

 mal seizure depend on a dual mechanism: a negative 

 process of neuronal exhaustion, and a positi\e process 

 of inhibition. 



The first of these mechanisms which may firing 

 about the cessation of the seizure, the progressive 

 fatigue and final exhaustion of the neurons, is at- 

 tributed either to the accumulation of acid metabo- 

 lites or to the fact that the reserves necessary for 

 cellular functioning have been used up, or to both 

 processes at once. The first hypothesis, "Ermiidung" 

 in the sense of Verworn (1900), has not been satis- 

 factorily demonstrated, for although the pH of the 

 motor cortex shows a tendency toward acidity during 

 the fatigue stage of a faradic seizure (42), it changes 



toward alkaline values at the end of a pentylenetetra- 

 zol-induced seizure of generalized epilepsy (i lo). 



On the other hand the .second hypothesis, 

 "Erschopfung" in the sense of \>r\vorn, has been 

 largely demonstrated. Ruf prolonged a pentylene- 

 tetrazol seizure for 30 min. by administering oxygen to 

 an experimental animal and for i hr. by giving 

 epinephrine as well as oxygen. Davis & Remond (35), 

 using a polarographic cathode method sensitive to 

 oxygen concentration, demonstrated the existence of 

 relative hypoxia in the cerebral cortex developing 

 during convulsive activity. \V'hatever may be its 

 intimate nature, the part played by neuronal exhaus- 

 tion in the electroclinical manifestations of grand mal 

 seizures is supported b\- the following considerations. 



At the beginning of a grand mal fit the EEG dis- 

 charge does not diminish in frequency, for there 

 exists an initial indefatigability. This however may be 

 apparent only if, as Rosenblueth & Cannon (168) 

 believe, hypersynchrony is still incomplete at this 

 moment and if different cortical elements are respon- 

 sible for successive convulsive waves. It may, however, 

 be real if the neurons enjoy oxygen pres.sures at the 

 onset of the seizure distinctly higher than those which 

 determine its extinction and if in addition their 

 hyperexcitability is so intense at that time that they 

 could discharge with very low ox\gen pressures. 

 Whatever the case may be, the EEG discharge of 

 sustained frequency, characteristic of the beginning 

 of the grand mal seizure, corresponds to a discharge 

 of the peripheral motor units which is equally sus- 

 tained but of much higher frequency and which 

 provokes the tetanus at the beginning of the tonic 

 phase. 



Once the seizure has lasted some seconds, progres- 

 sive slowing of the EEG discharge develops, indicating 

 increasing length of the functional refractory period 

 of the thalamocortical neurons as they fatigue. This 

 increasing state of fatigue also affects the reticulo- 

 spinal neurons and thereby converts the complete 

 tetanus into an incomplete tetanus which imprints a 

 vibratory character on the last part of the tonic 

 phase. 



At a certain point of fatigue, the functional refrac- 

 tory period has become so lengthened that the dis- 

 charge is interrupted for a short time. This, the first 

 period of extinction, appears in the EEG as an inter- 

 val of electrical silence and at the periphery as relaxa- 

 tion of the tonic phase introducing the first clonus. 

 This momentary rest permits partial recovery of 

 energy, which entails a recrudescence of the dis- 

 charge (first group of spikes) and of the muscular 



