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

Abstract Large-animal models of traumatic brain injury may yield translatable data on epileptogenesis, given their similarities in anatomy, brain size, and immune systems to humans. Adult male and female swine received bilateral cortical impact (N=16) or sham surgery (N=6) and were screened for convulsions via video-EEG for up to one year. Post-traumatic epilepsy (PTE) was defined as 2 seizures after 1-week post-injury. Nine out of sixteen pigs (56%) receiving bilateral cortical impact developed PTE, with an average 4.6 months (±3.4,SD) latent period. Seizures (N = 199) began focally, sometimes with motor onset including automatisms, before becoming generalized, with tonic-clonic or tonic convulsions. We defined a library differentiating peri-ictal behaviors (N = 31) from rhythmic/odd behaviors typical in healthy pigs (N = 12). Seizures had an average of 7.3 behaviors per seizure (max 26) lasting an average of 1.8 minutes (max 7.9). For seizures comprised of multiple convulsive episodes, the first convulsion had a greater number of peri-ictal behaviors than subsequent convulsions (P < 0.001). The array of peri-ictal behaviors displayed was pig-specific, with many behaviors consistently observed across seizures. The seizure frequency detected was 0.38/day. This large-brain model of PTE exhibits a variable 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, enabling the identification and testing of therapeutics that translate into human patients. Highlights The average time from bilateral cortical impact to post-traumatic epilepsy in swine is 6 months, and is highly variable, ranging from 2 to 47 weeks post-TBI. Swine with post-traumatic epilepsy display an array of specific behaviors around convulsions, distinct from pigs without post-traumatic epilepsy. Though the duration of convulsion was typically a few seconds, the entire seizure, with the associated peri-ictal behaviors, lasts up to 7.9 minutes. The complexity of behaviors around convulsions tended to increase from early traumatic seizures to post-traumatic seizures. Peri-ictal behaviors observed around convulsions in an individual were often displayed prior to the first convulsion. Competing Interest Statement The authors have declared no competing interest. Footnotes We reanalyzed one pig, revised Table 1, added a figure, revised the EEG figure (now Figure 6), and the videos to be consistent with Table 1. This is the version we just submitted for publication.