Abstracts

Rationale:
Traumatic brain injury can lead to post-traumatic epilepsy (PTE) in a proportion of patients, yet the pathophysiology and epileptogenesis of PTE remains unclear and is primarily studied in the lissencephalic brain. Here, we aim to determine the rate and time course of epileptogenesis in a large animal, gyrencephalic model. Validating a swine model of PTE will enable future studies investigating the pathophysiology of PTE and testing of potential therapeutics.
Method:
To date, a series of three male, Yucatan swine aged 4.5 ± 0.6 months received bilateral cortical impacts (right: rostral gyrus, left: prefrontal cortex/frontal lobe) using our previously characterized scaled cortical impact model (PMID: 19469691). A wireless EEG transmitter allowing free ambulation was implanted in the neck with six biopotential leads connected to intra-cranial screws placed epidurally creating a 3-channel bipolar montage spanning hemispheres. EEG and synchronized video were recorded. After development of PTE or after 10 months, brains were collected for analysis via ex vivo MRI and histopathology. NeuroScoreTM (DSI) with synchronized video and LabChart Reader were used to analyze overnight EEG via manual detection of simple spikes, complex spikes, spike trains, and convulsions using previously published seizure criteria. Two spontaneous seizures after two weeks post-TBI was considered the initiation of PTE.
Results:
Of the 3 subjects, two developed PTE at 3-5 months post-injury. The third subject is nearing the end of the study and no complex spikes nor convulsions have been observed. In the two that developed PTE, an increase in simple and complex spike frequency was observed starting two months post-injury. In one subject, complex spikes occurred in repetitive bursts that eventually coalesced into spike trains lasting over 10 seconds and were accompanied by convulsions. In the second subject, simple and complex spike frequency increased and was accompanied by an array of seizure activity including convulsions. Both subjects that developed PTE appeared to have disturbed sleep patterns frequently waking from sleep after complex spikes. Both brains of the epileptic pigs had focal lesions at the impact sites with remodeling of the gray and white matter detected via MRI. One brain was markedly atrophic.
Conclusion:
In this interim analysis, two of three gyrencephalic porcine subjects developed PTE. Ongoing analysis of an additional 9 subjects including shams will determine the rate of PTE in this model. This large animal model of PTE may be useful for studying the pathophysiology and potential therapeutic approaches to this form of acquired epilepsy.
Funding:
:This work was supported by CURE based on a grant CURE received from the United States Army Medical Research and Materiel Command, Department of Defense (DoD), through the Psychological Health and Traumatic Brain Injury Research Program under Award No. W81XWH-15-2-0069.