Objective

Pre-surgical evaluation from refractory pediatric epileptic patients is crucial in order to identify epileptogenic zone (EZ) and increases the chances of post operative seizures free. However the complexity of an epileptic circuitry remains unclear. High frequency oscillations (HFOs) expressed during sEEG recordings are commonly used as biomarkers to identify EZ. In this study, we performed electrophysiological recordings on acute slices from pediatric patients to better understand the physiopathology of EZ.

Methods

Electrophysiological recordings were performed in acute slices from surgical resections containing maximal HFOs recorded in sEEG evaluation from pediatric patients with refractory epilepsy. Spontaneous excitatory post-synaptic currents (sEPSCs) and spontaneous seizures like events (sSLEs) were analyzed. Immersion chamber bath application of in vitro pro-convulsivants (e.g. 4-aminopyridine (4AP) and bicuculline methobromide (BMO)) was performed to investigate pharmacological properties from induced interictal epileptiform discharges (IEDs).

Results

Abnormal trends of sEPSCs were recorded in 10 neurons and 10 sSLEs were identified in 9 other cells. Both sEPSCs and sSLEs were completely abolished by application of NBQX (5 µM). Application of 4AP (150 µM) and BMO (100 µM) induced transient recurrence of GABAB outward currents (GABOCs; n = 55) before neuronal network synchronization and the generation of IEDs. GABOCs were completely blocked by the GABAB receptors antagonist CGP-55845 (10-20 µM; n = 11). Levetiracetam (300-1200 µM) reduced amplitude and frequency (n = 14) but failed to block IEDs and Lacosamide (200-800 µM) strongly reduced (n = 4) and completely abolished (n = 16) IEDs.

Conclusion

Using sEEG for exact localization of EZ and target resection increases identification of sEPSCs and sSLEs electrophysiological ex vivo recordings, thus providing unique scenario for better epileptogenesis comprehension in pediatric epilepsy. GABOCs play a major role in neuronal network synchronization and cadence of IEDs. Lacosamide shows better effect in blocking IEDs compared to Levetiracetam.