Prophylaxis with diphenylhydantoin and phenobarbital and alumina-gel monkey model. I. Twelve months of treatment: seizure, EEG, blood, and behavioral data.

Utilizing an alumina-gel epileptic monkey model, with instrumentation for continuous monitoring of all overt, spontaneous motor seizures, the efficacy of pharmacologic prophylactic treatment of posttraumatic epilepsy was explored. The alumina-gel model provides a relatively standardized brain trauma from monkey to monkey, resulting in virtually complete assurance that all animals will manifest, in time, electrical and clinical seizures if not treated. Thirteen rhesus monkeys were divided into two groups of 8 drug-treated and 5 placebo animals, respectively. Administration of diphenylhydantoin and phenobarbital in a combined regimen commenced within 48 hr of the alumina-gel injections. After 1 year the monkeys were withdrawn from either their drugs or placebo and followed for a subsequent 4 month period. The data for the first 12-month period indicate that anticonvulsant treatment of potentially epileptic monkeys decreased both the frequency and severity of seizures they would have had without treatment. All animals manifested an electrical focus and overt seizures, but the drug monkeys had only partial seizures whereas the placebo monkeys exhibited secondarily generalized tonic-clonic seizures. The follow-up, no-treatment data of 4 months are reported in the following paper.

Efficacy of standard anticonvulsants in monkey model with spontaneous motor seizures.

Monkeys were rendered chronically epileptic by injection of alumina gel into the pre- and postcentral gyrus. To test the validity of this primate model, the effects of diphenylhydantoin (DPH), phenobarbital, and primidone on spontaneous seizures evaluated for 8 months with a Latin-Squar experimental design. All three drugs were effective, the frequency of seizures being reduced by at least one-half during 6 weeks with treatment as compared with 6 weeks without. In most monkeys the frequency and severity of seizures were correlated to the number of interictal spikes in the EEG, and were inversely related to the level of drug in plasma. During withdrawal of phenobarbital and primidone, epileptic activity increased over that during control periods. Side effects were minimal with all three drugs. Patterns of behavior, although they differed from one monkey to the next, exhibited trends specific to each drug but particularly DPH. The seizures of some animals seemed to be related to the sleep-waking cycle.