Semiology, clustering, periodicity and natural history of seizures in an experimental visual cortical epilepsy model

Abstract

SummaryObjectiveTo characterize a rat model of focal neocortical epilepsy for use in developing novel therapeutic strategies in a type of epilepsy that represents a significant unmet need.MethodsIntracortical tetanus toxin (TeNT) injection was used to induce epilepsy in rats. Seizures and their behavioural manifestations were evaluated with continuous video-electrocorticography telemetry.ResultsTeNT injection into rat primary visual cortex induced focal neocortical epilepsy without preceding status epilepticus. The latency to first seizure ranged from 3 to 7 days. Seizure duration was bimodal, with both short (approximately 30s) and long-lasting (>100s) seizures occurring in the same animals. Seizures were accompanied by non-motor features such as behavioural arrest, or motor seizures with or without evolution to generalized tonic-clonic seizures. Seizures were commoner during the sleep phase of a light-dark cycle. Seizure occurrence was not random, and tended to cluster with significantly higher probability of recurrence within 24 hours of a previous seizure. Across animals, the number of seizures in the first week could be used to predict the number of seizures in the following 22 days.SignificanceThe TeNT model of visual cortical epilepsy is a robust model of acquired focal neocortical epilepsy, and is well suited for preclinical evaluation of novel anti-epileptic strategies. We provide here a detailed analysis of the epilepsy phenotype, seizure activity, electrographic features, and the semiology. In addition we provide a predictive framework that can be used to reduce variation and consequently animal use in pre-clinical studies of potential treatments.Key PointsTetanus toxin injection into rat visual cortex induces focal cortical epilepsy.Electrographic seizures were associated with non-motor and motor features with or without evolution to generalized tonic-clonic seizures.Seizures could not be provoked by intermittent photic stimulation.Seizures were clustered in time and exhibited a circadian variation in frequency.The number of seizures in first week after seizure onset could be used to predict the total number of seizures in the following 3 weeks.