Abstracts

Rationale: Current clinical practice in focal epilepsy involves brain source imaging (BSI) to localize brain areas wherefrom interictal epileptogenic discharges (IEDs) emerge. These areas, named irritative zones, are useful to evaluate candidate seizures-onset zones during presurgical workup. Since human histological data are only available from final resected zones, there are no previous systematic studies characterizing pathophysiological mechanisms and abnormal molecular/cellular substrates in irritative zones. Combining BSI and histological analysis from all these zones, independent of them being epileptogenic, is necessary to address this issue, which is only possible through the use of preclinical animal models. Methods: Improvements in the strategies to create focal chronic epilepsy in rats and the recent development in high-density scalp electroencephalogram (EEG) on small animals made this specie very attractive for such a study. Here, we recorded 32-channel spontaneous EEG data from rats that have focal cortical dysplasia and chronic seizures. BSI for different IED subtypes was performed using the methodology presented in Bae et al. (2015). Post-mortem brain sections were stained for anatomical, functional, and inflammatory biomarkers on IED-generating brain regions. Target and control areas were defined by co-registering IED-based BSI and a rat T2-MRI probabilistic atlas. Results: We found abnormal anatomical structures in the irritative zones (i.e. larger neuronal processes, glioreactivity, and vascular cuffing) and larger expressions for neurotransmission (NR2B) and inflammation (i.e., IL߱, TNF? and HMGB1). We conclude that irritative zones comprise abnormal tissues highly prospective for epileptogenesis disregarding whether they are actually involved in icto-genesis or not at the time of recording. Conclusions: Defining abnormal tissues with BSI before they could become seizure-onset zones will help develop preventive strategies for populations at risk. Seizure perpetuation happens gradually; hence, our results could support the use of IED-based BSI for the early diagnosis and treatment of potential epileptic foci. Funding: FIU Startup funding