Ontogeny of feline temporal lobe epilepsy, II: Stability of spontaneous sleep epilepsy in amygdala-kindled kittens.

Abstract:  We previously described a model of spontaneous "sleep epilepsy" in kindled kittens with temporal lobe epilepsy (TLE). We now describe the postkindling course of this model from preadolescence to maturity and suggest pathophysiologic mechanisms. Spontaneous epilepsy, particularly generalized tonic-clonic convulsions (GTCs), developed 1h to 4 months after amygdala kindling and persisted to adulthood. At first, GTCs were detected only in sleep; later, convulsions also occurred during wakefulness. Two factors were consistently associated with the sequential onset of sleep and waking GTCs: seizure clusters and anatomic seizure localization. (1) Seizure clusters. Cats with infrequent or unclustered GTCs continued to exhibit "sleep epilepsy," defined by convulsions occurring exclusively during sleep. In contrast, cats with frequent seizure clusters developed recurrent or terminal convulsive status in conjunction with GTCs during waking and sleep. Severe seizure manifestations therefore appeared to contribute to the dissociation of convulsions from the sleep-wake cycle. (2) Anatomical seizure localization. Focal seizure origin appeared to differentiate sleep from waking GTCs. Onset during sleep was first recorded in the kindled amygdala, whereas onset during waking was initially detected outside the temporal lobe. Findings thus suggest secondary "kindling" of multifocal epilepsy. Secondary epileptogenesis is consistent with "transsynaptic" kindling effects. This phenomenon is defined in mature animals by rapid secondary site kindling (transfer) and subtle morphologic changes distal to the stimulating electrode. Transfer may be accentuated by youth, because kittens developed spontaneous seizure foci in previously unstimulated tissue. Moreover, multifocal interactions and diffuse cell loss were implicated as possible mechanisms. Collectively, the findings indicate complications with early onset TLE in kindled cats. Onset during youth can have an unfavorable prognosis, reflected by recurrent status epilepticus and multifocal epilepsy with convulsions distributed throughout the sleep-wake cycle.