Effects of Diphenylhydantoin and Other Antiepileptic Drugs on Epileptiform Activity and Purkinje Cell Discharge Rates

Abstract

SUMMARY The effects of antiepileptic drugs on cerebellar Purkinje cell discharge rates and cerebral cortical epileptiform activity were studied in cats with penicillin foci in sensory‐motor cortex. In control experiments, extracellular microelectrode recordings of P‐cell activity revealed characteristic low‐frequency discharge rates during periods of cortical quiescence and discharge rates of 150 Hz occurring concomitant with focal cortical spike activity. P‐cell discharges abruptly ceased during development of cortical epileptiform bursts (CEB) which became generalized and maximal in both cerebral hemispheres. Following DPH (10 mg/kg i.v.) CEB frequency and duration were markedly reduced and sustained P‐cell discharge rates of 140 Hz were recorded. Following cerebellectomy in DPH‐treated animals, CEB activity intensified, was more frequent, involved both cerebral hemispheres, and was of much longer duration. Administration of DPH subsequent to cerebellectomy was less effective in reducing CEB activity. After phenobarbital (20 and 40 mg/kg i.v.) reduction of CEB activity was observed as was a consistent increase in P‐cell discharge frequency. Trimethadione (300 mg/kg i.v.) and acetazolamide (35 mg/kg i.v.) did not reduce CEB activity and no increase in P‐cell discharge rate was observed. Thus, after doses of antiepileptic drugs reducing CEB activity, cerebellar P‐cell discharge rates were increased. Conversely, P‐cell discharge rates did not increase following administration of antiepileptic drugs which did not decrease CEB activity. RÉSUMÉ Chez des chats porteurs de foyers de pénicilline dans le cortex sensorimoteur, on a étudié l'effet des drogues antiépileptiques sur la fréquence des décharges des cèllules de Purkinje dans le cervelet. Dans des conditions de contrôle, les enregistrements des cellules de Purkinje avec microélectrodes extracellulaires mettent en évidence des décharges caractéristiques de basse fréquence pendant les périodes de repos cortical et des décharges dont la fréquence est de 150 Hz en même temps que les décharges de pointes focales dans le cortex. Les décharges dans les cellules de Purkinje disparaissaient brutalement lors de l'apparition des bouffées épileptiques corticales (BEC) qui se généralisaient en augmentant d'amplitude sur les deux hémisphères. Après diphénylhydantoïne (DPH) (10 mg/kg, i.v.), la fréquence et la durée des BEC étaient nettement réduites et l'on enregistrait des décharges prolongées à 140 Hz dans les cellules de Purkinje. Après ablation du cervelet, chez les animaux traités par DPH, les BEC augmentaient en nombre, fréquence et durée et intéressaient les deux hémisphères. L'effet inhibiteur de la DPH sur les BEC était nettement moins évident après ablation du cervelet. Après phénobarbital (20 à 40 mg/kg i.v.), on observait une diminution des BEC ainsi qu'une diminution significative de la fréquence des décharges dans les cellules de Purkinje. La triméthadione (300 mg/kg i.v.) et l'acetazolamide (35 mg/kg i.v.) ne réduisaient pas les BEC et l'on n'observait pas d'aug...

Communications

“…The variations in the discharge pattern observed in these experiments could result from a change in the afferent inputs rather than a direct suppression of the spike-generating mechanism. Furthermore, the data are inconsistent with the hypothesis that the reduction of epileptiform discharge induced by diphenylhydantoin is associated with an augmentation of Purkinje cell activity (Julien & Halpern, 1972b).…”

Cerebellar Changes in Partial Seizures: Clinical Correlations of Quantitative SPECT and MRI Analysis

“…Ablation of the cerebellar vermis and the intermediate zone in cats results in an increase in the spike frequency of penicillininduced cortical lesion (13). Furthermore, there is evidence for a specific PHT-binding site on cerebellar neurons (42), and PHT has been shown to increase firing rates in Purkinje cells (43,44). Therefore, some investigators proposed that the mechanism of action of PHT phenytoin is in part due to an enhancement of cerebellar inhibition of the seizure focus (4,15).…”

Distribution of ¹⁴C-Phenytoin in Rat Purkinje Cells, Cerebellar and Cerebral Neuronal Tissue after a Single Intraperitoneal Injection

“…An increase in cerebellar Purkinje cell dis charge rates and a decrease in penicillin-induced cortical epileptiform activity have been re ported in cats following administration of phen ytoin (8,11). This is interesting, when the action mechanism of phenytoin and its possible relationship to cerebellar atrophy, and espe cially to Purkinje cell loss, are considered in patients with severe epilepsy (1,9).…”