342 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



certain circumstances, favor a thalamocortical dis- 

 charge indirectly responsible for the seizure, so 

 explaining the part that sleep plays in inducing 

 generalized seizures. 



Finally, assuming the independence of these two 

 systems, one may postulate that a factor which can 

 precipitate thalamocortical hypersynchrony can 

 equally (and independently) precipitate h>-persyn- 

 chrony of the reticular formation. In this way there 

 may be a double reticular discharge of which one, the 

 thalamic, may be responsible for the cortical manifes- 

 tations of the seizure and the other, the mesencepha- 

 lorhombencephalic, for its peripheral manifestations. 



One therefore arrives at the following conclusions. 

 Generalized grand mal epilepsy is related to a sub- 

 cortical mechanism corresponding first to a paroxys- 

 mal discharge of the thalamic reticular system trans- 

 mitted to the cortex by the diffuse thalamocortical 

 projection pathways, which explains the loss of 

 consciousness. This discharge results in functional 

 exclusion of the thalamocortical formations, thus 

 liberating 'normal' or reinforced activity of the caudal 

 reticular system; this release, by putting into play 

 the tonicogenic reticulospinal system, explains the 

 peripheral convulsions. 



It will be noticed that this conception is closely akin 

 to that of Hughlings Jackson who related epileptic 

 seizures not only to ai^nornia! neuronal discharges 

 but to consequent liberation of other parts of the 

 brain. ° 



CAUSES OF RETICULAR DISCHARGES, THALAMIC AND 

 MESENCEPH.ALORHO.MBENCEPHALIC, RESPONSIBLE FOR 



c;r.\nd m.al EPILEPSY. In onlv a \ery small number of 



* In 1874 Hughlings Jackson wrote (104): "The principle 

 that we get over-action of lower centres from the mere re- 

 moval of the higher centres has very important applications. 

 . . . Strong epileptic discharges paralyse the nervous centre (or 

 much of it) in which they begin or through which they spread. " 

 He then applied this generalization "to the cases where the 

 discharge begins in the highest series. There is loss of use of 

 that series after a discharge beginning in it, where that dis- 

 charge has been excessive. But ob\'iously violent action (mani- 

 acal raving) could not result from this loss of use (a paralytic 

 condition) of the highest centres. That accounts only for loss 

 of consciousness. . . . That is only the patient's negative condi- 

 tion, and his condition is duplex. There is the positive element — 

 the mania — to be accounted for. My opinion is that the mania 

 is the result of over -action (morbidly increased discharge, but 

 not epileptic discharge) of the processes just below those which 

 have been put hors de combat." VVe realize that the above 

 remarks do not refer primarily to generalized giand mal 

 epilepsy, but they nevertheless exemplify some aspects of the 

 unrivalled enlightenment of Hughlings Jackson. 



epileptics has a focal or diffuse irritative lesion in the 

 reticular formation been found to be the cause of 

 generalized seizures. However, characteristic lesions 

 in these regions have been found in certain familial 

 degenerative epilepsies (of the Unverricht-Lunsborg 

 type). 



Since there are no demonstrable reticular lesions in 

 the majority of subjects with grand mal seizures 

 generalized from the start and since they are never 

 present in ca.ses of experimental generalized epilepsy, 

 the discharge responsible for these seizures no 

 doubt depends on a functional abnormality of these 

 reticular neurons. It is pcssible that this functional 

 abnormality depends on the unique anatomical 

 arrangement that is found here; numerous afferent 

 collaterals (183) arriving from many different parts 

 of the peripheral and central nervous system (fibers 

 from sensory lemnisci, the special senses, the cortex, 

 subcortical regions and cerebellum) all converge 

 toward common reticular elements and set up phe- 

 nomena of summation (146). With this spatiotem- 

 poral summation on neighboring neurons and, pro- 

 vided that these are in a hyperexcitable state (either 

 because of constitutional factors or acquired dis- 

 orders), the normal inflow of nerve impulses in the 

 reticular formation may cause sufficient synchronous 

 cellular potentials to build up an effective electrical 

 stimulus. This stimulus would entail a discharge of 

 the surrounding hyperexcitable cell bodies by direct 

 electrical spread independent of any process of 

 synaptic transmission (ephaptic phenomenon). Once 

 this process has been started, the discharge would 

 spread like an avalanche throughout the reticular 

 formation with a speed of the same order as that of 

 the transmission of the net ve impulse from neuron to 

 neuron. This theory, formulated by Gastaut (54), is 

 only a particular application of the general hypothesis 

 suggested by Moruzzi in 1950 (145): "A normal 

 neuron, by the simple fact of being subjected to a 

 bombardment of nervous activity at high frequency, 

 can enter into convulsive state. ... It is the ordinary 

 inflow of ner\e impulses which determine the fact 

 that a neuron passes from normal activity to an 

 'epileptic' state. . . . Any neuron may become 'epilep- 

 tic,' simply through the effect of bombardment of 

 nervous activity." 



In an unstable system (such as an organization of 

 hyperexcitable neurons) it is usually an external force 

 that upsets equilibrium. It is not surprising therefore 

 that a volley of impulses, converging on a center whose 

 state of tension is abnormally raised, supplies the 

 energy necessary to build up a hypersynchronous 



