An Ex vivo Model to Study Fast Ripple High-frequency Oscillations Detected by SEEG Using Dedicated Surgical Specimens from Pediatric Focal Epilepsy Patients
Abstract number :
1.331
Submission category :
9. Surgery / 9B. Pediatrics
Year :
2022
Submission ID :
2204111
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:23 AM
Authors :
Adriano Cattani, MD, PhD – Montreal Children Hospital, McGill University, 1001 Decarie Blvd, Montreal, QC, Canada, H4A 3J1; Siyan Wang, PhD – Montreal Neurological Hospital-Institute, Department of Neurology and Neurosurgery; Maxime Levesque, PhD – Montreal Neurological Hospital-Institute, Department of Neurology and Neurosurgery; Nicolás von Ellenrieder, PhD – Montreal Neurological Hospital-Institute, Department of Neurology and Neurosurgery; Jeffrey Atkinson, MD, PhD – Montreal Children Hospital, McGill University; Jean-Pierre Farmer, MD, PhD – Neurosurgery Chief – Montreal Children Hospital, McGill University; Massimo Avoli, PhD – Montreal Neurological Hospital-Institute, Department of Neurology and Neurosurgery; Roy Dudley, MD, PhD – Montreal Children Hospital, McGill University
Rationale: High-frequency oscillations (HFOs, 80-500 Hz), specifically fast ripples (FRs, >250 Hz), are recorded from ictogenic brain areas and are commonly observed in pediatric patients with drug-resistant epilepsy during stereoelectroencephalography (SEEG) evaluation. Detection of FRs helps to delineate the seizure onset zone for surgical resection increasing seizure freedom rates. Here, we investigate single neuron activity from dedicated pediatric epilepsy surgery specimens containing FRs during pre-surgical evaluation in order to establish an ex vivo model to study these important electrophyiological biomarkers toward a better understand of their epileptogenesis and potential pharmacological treatment.
Methods: Electrophysiological recordings were performed in acute slices from pediatric epilepsy surgery specimens containing high FRs rates (> 6 per minute), as detected by pre-surgical SEEG evaluation. Cell attached and whole-cell patch clamp recordings in voltage and/or- current-clamp modes were obtained from neurons located in cortical layers II to V. Spontaneous excitatory post-synaptic currents (sEPSCs) and ictal seizures-like events (SLEs) were analyzed.
Results: Twenty-five cells were recorded from 62 slices obtained from 6 patients. Thirteen spontaneous SLEs were recorded and high frequency of sEPSCs were identified in 8 neurons within the FRs resection areas. Pharmacology showed strong AMPA and Kainate component in cells recorded within FRs areas since most of EPSCs were blocked by NBQX. Field potential recordings were not able to improve localization of FRs in the slice.
Conclusions: Surgical specimens taken from areas of SEEG-detected FRs can be used as an ex vivo model to study FRs and to assess the impact of pharmacological interventions on these epileptogenic pertubations. This may allow for new insights aiming glutamate in the treatment of pharmaco-resistant epilepsy in pediatric patients.
Funding: McGill University
Surgery