Individualized and stereotypical seizure semiology in a porcine model of post-traumatic epilepsy.

ObjectiveMany patients develop post-traumatic epilepsy (PTE). Post-traumatic epileptogenesis has been carefully studied in rodents, but the time course of epileptogenesis is correlated to brain size, raising the possibility that large animal models will provide more translatable data regarding epileptogenesis. Here, we use our large-brained model to describe the development, rate, and seizure semiology of PTE. MethodsAdult male and female swine received bilateral cortical impact (N=16) or sham surgery (N=9) and were screened for convulsions via video EEG for up to one year. PTE was defined as 2 seizures after 1 week post-injury. ResultsNine out of sixteen pig (56%) receiving bilateral cortical impact developed PTE, with an average latent period of 6.6 months ({+/-} 3.9, SD). Seizure began focally, sometimes with motor onset including automatisms (lip smacking, yawning) and sometimes nonmotor (freezing) before becoming generalized, with tonic-clonic or tonic convulsions. Most pigs had a period of post-ictal stillness (nonmotor) after the convulsions. Temporary incoordination occurred both pre- and post-ictal. We defined a library differentiating peri-ictal behaviors (N = 27) from rhythmic/odd behaviors typical in healthy pigs (N = 11). Pigs with PTE had an average of 5.6 behaviors per seizure, with a max of 22 behaviors in a seizure. The longest seizure was 7.9 minutes. For seizures comprised of multiple convulsive episodes, the first convulsion had a greater number of peri-ictal behaviors than subsequent convulsions (P < 0.02). The array of peri-ictal behaviors displayed was pig-specific, with many behaviors consistently observed across seizures. The overall seizure frequency was 0.43/day. SignificanceThis large-brain model of PTE exhibits a prolonged period of epileptogenesis, a substantial rate of PTE, and an expansive repertoire of ictal behaviors. This first description of semiology in this species will serve as a guide for other porcine epilepsy models. Biofidelic models of PTE are expected to increase our understanding of the pathophysiology of post-traumatic epileptogenesis and to identify and test therapeutics that translate into human patients. Key PointsO_LIThe average time from bilateral cortical impact to post-traumatic epilepsy is 6 months. C_LIO_LISwine with post-traumatic epilepsy display an array of specific behaviors distinct from pigs without post-traumatic epilepsy. C_LIO_LIPigs have individualized stereotypical behaviors around convulsions and can have many convulsions within a seizure. C_LIO_LIThough convulsions last a few seconds, the entire seizure, with the associated peri-ictal behaviors, lasts up to 7.9 minutes. C_LI