Intractability of complex partial seizure with secondary generalization: kindling studies in cats

Among many factors linked to an intractability of partial seizure secondarily generalized, changes in the brain resulting from repeated epileptic seizures are discussed mainly in light of our evidence obtained from kindling studies in cats. In addition, the literatures on biological mechanisms of the kindling effect are reviewed briefly. The evidence demonstrated and reviewed here indicates that: 1) limbic structure is not susceptible to develop generalized convulsions initially, 2) repeated attacks of limbic seizures result in a profound reduction in seizure threshold at the primary epileptogenic focus in the limbic structures, 3) once a limbic seizure developed to secondarily generalized convulsion, it seldom changes into the original partial seizure, 4) kindled events in the limbic structures are more profound and persistent than that in the cerebral cortex, and 5) repetition of focal cortical or limbic seizures may eventually produce spontaneous convulsive seizures originating in the limbic structures. These findings strongly suggest that the limbic system, rather than the cerebral cortex, is more susceptible to a lasting functional change resulted from seizure repetition, which can lead to an intractability of epilepsy with partial seizure. Lasting changes in the cell membrane including long-lasting enhancement of inositol phospholipid hydrolysis of the amygdala stimulated by excitatory amino acid appear important for development of trans-synaptic changes underlying the kindling-induced seizure susceptibility.