332 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



Experimental Results 



The various types of primarily generalized epilepsy 

 have been reproduced experimentally in animals and 

 man. 



GRAND MAL. It is easy to produce a grand mal seizure 

 in animals by any measure acting as a difTuse assault 

 on the brain and causing a sufficiently widespread 

 disorder of cerebral metabolism: l)y applying a strong 

 electric current to the whole of the brain (trans- 

 cranial electroshock), by injecting analeptic drugs 

 such as pentylenetetrazol (Metrazol), megimide, 

 picrotoxin, absinthol, by oxygen intoxication, or by 

 sudden withdrawal of sedati\es in chronic experi- 

 mental barbiturate poisoning. 



On the contrary, it is very difficult in these same 

 animals, to cause by means of minimal and localized 

 measures seizures which are generalized from the 

 onset. Thus limited electrical stimulation and mini- 

 mal glial scars developed around the site of injection 

 of aluminum hydroxide never cause generalized 

 epileptic fits, although they regularly produce seizures 

 of partial epilepsy which may become generalized 

 (84). In order to produce a grand mal seizure from the 

 onset, one needs to increase the severity and particu- 

 larly the extent of the local disturbance in these 

 experiments, to involve mid-line structures or to ad- 

 minister an agent with a generalized subliminal action. 



In man one obviously cannot produce focal experi- 

 mental cerebral lesions, but it is well established that, 

 as in other animals, various measures with a wide- 

 spread cerebral action will cause grand mal seizures: 

 electroshock treatment, pentylenetetrazol, oxygen 

 poisoning, rapid withdrawal of barbiturates (particu- 

 larlv in addicts of short-acting barbiturates), etc. All 

 these forms of experimental or accidental epilepsy 

 in man and animals are indeed comparable to spon- 

 taneous seizures of grand mal generalized from the 

 start, for they always include an immediate loss of 

 consciousness, tonic and clonic convulsions, and a 

 bilateral, synchronous and symmetrical seizure dis- 

 charge in the EEG. 



We have not regarded as grand mal seizures those 

 which are precipitated in man and animals by \arious 

 types of cerebral anoxia. These seizures are tonic, 

 lacking the clonic phase, and are accompanied by 

 depression of cerebral electrical activity and not by 

 a bisynchronous discharge. They are none the less of 

 fundamental interest for the understanding of grand 

 mal epilepsy and we shall return to the subject later. 



THEORIES OF GENERALIZED CONVULSIONS, o) Subcortical 

 theory. The idea that generalized convulsions have a 

 subcortical origin has been held by physicians ever 

 since ancient times for logical reasons which are easily 

 understood (187). In the second century A.D., Galen 

 attributed grand mal epilepsy to a 'thick humor' in 

 the middle and posterior part of the ventricles. Willis 

 in 1682 had a similar conception when he related the 

 fit to "a strong spasmodic copula distilled from the 

 blood into the brain, affecting the animal spirits which 

 lie in the middle of the brain, and causing an explo- 

 sion." This idea persists to our day since Hogner 

 [quoted by Marinesco et al. (135)] recently defended 

 the view that the epileptic discharge depends on dis- 

 tension of the third ventricle by excess formation of 

 cerebrospinal fluid, producing an excitation of the 

 centers around the ventricle. 



Experimental study of this subcortical theory was 

 begun in the middle of the eighteenth century when 

 Haller showed that generalized convulsions could be 

 proNoked h\ irritation of the white matter in the 

 depths of the brain. At the beginning of the next 

 century Flourens (1823) performed his famous experi- 

 ments on the medulla oblongata. This allowed Hall 

 (96) to formulate his theory of the medullary origin of 

 reflex epilepsy, which was taken up by Schroeder van 

 der Kolk in 1859 ('74) who concluded that "an 

 exalted sensibility and excitability of the medulla 

 oblongata is the just cause of epilepsy." As early as 

 1B38 Nothnagel provoked generalized convulsions by 

 mechanical stimulation of the medulla oijlongata, 

 and much later Binswanger (18) and Bechterew (16) 

 repeated these experiments using an electric current 

 or a needle prick. 



Stimulation experiments were not, however, the 

 only ones supporting the subcortical mechanism of 

 generalized seizures. Toward the beginning of the 

 twentieth century, a large number of ablation experi- 

 ments showed that the cerebral cortex, and the greater 

 part of the telencephalon, diencephalon and mesen- 

 cephalon, were not necessary for the experimental 

 production of generalized epilepsy. \'arious measures 

 were used in these experiments: transcranial applica- 

 tion of an electric current (89, 130, 166, 171, 191); 

 cooling of the brain (44); and injections of pentylene- 

 tetrazol (Metrazol) (14, 95, 130, 173), of insulin 

 (126, 153), of picrotoxin (36) or of a mixture of 

 chloralose and strychnine (144). Thus generalized 

 convulsions are seen in the diencephalic, the mesen- 

 cephalic and e\en in the rhombencephalic animal 



