Pediatric Cortical Dysplasia: Correlations between Neuroimaging, Electrophysiology and Location of Cytomegalic Neurons and Balloon Cells and Glutamate/GABA Synaptic Circuits

Abstract

Seizures in cortical dysplasia (CD) could be from cytomegalic neurons and balloon cells acting as epileptic ‘pacemakers’, or abnormal neurotransmission. This study examined these hypotheses using in vitro electrophysiological techniques to determine intrinsic membrane properties and spontaneous glutamatergic and GABAergic synaptic activity for normal-pyramidal neurons, cytomegalic neurons and balloon cells from 67 neocortical sites originating from 43 CD patients (ages 0.2–14 years). Magnetic resonance imaging (MRI), ¹⁸fluoro-2-deoxyglucose positron emission tomography (FDG-PET) and electrocorticography graded cortical sample sites from least to worst CD abnormality. Results found that cytomegalic neurons and balloon cells were observed more frequently in areas of severe CD compared with mild or normal CD regions as assessed by FDG-PET/MRI. Cytomegalic neurons (but not balloon cells) correlated with the worst electrocorticography scores. Electrophysiological recordings demonstrated that cytomegalic and normal-pyramidal neurons displayed similar firing properties without intrinsic bursting. By contrast, balloon cells were electrically silent. Normal-pyramidal and cytomegalic neurons displayed decreased spontaneous glutamatergic synaptic activity in areas of severe FDG-PET/MRI abnormalities compared with normal regions, while GABAergic activity was unaltered. In CD, these findings indicate that cytomegalic neurons (but not balloon cells) might contribute to epileptogenesis, but are not likely to be ‘pacemaker’ cells capable of spontaneous paroxysmal depolarizations. Furthermore, there was more GABA relative to glutamate synaptic neurotransmission in areas of severe CD. Thus, in CD tissue alternate mechanisms of epileptogenesis should be considered, and we suggest that GABAergic synaptic circuits interacting with cytomegalic and normal-pyramidal neurons with immature receptor properties might contribute to seizure generation.

Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

“…The intrinsic and high epileptogenicity of FCD is clearly supported by different clinical and electrographic features [140][141][142][143][144][145]. Particular attention has been focused on the contribution of the population of dysplastic neurons to the epiloptogenesis of FCD.…”

Removing interictal fast ripples on electrocorticography linked with seizure freedom in children

“…Intraoperative ECoG was performed using a standard surgical and anesthesia protocol whereby sevoflurane was reduced to 0.1% or less recorded end-tidal either at, or achieved shortly after, the start of the ECoG recording, so as to minimize potential interference from anesthesia. 21,22 Patients were kept on nitrous oxide and narcotics with muscle paralysis during the ECoG, and incision and Mayfield pin sites were injected with local anesthesia (0.25% Marcaine with epinephrine). In addition, the patient's core body temperature was maintained above 35.5°C.…”

Epilepsy Surgery in Patients With Tuberous Sclerosis

“…Вероятнее всего, это наблюдение объясняется тем, что транскор-тикальные очаги при ТС, несмотря на их визуализа-ционную схожесть, несколько отличаются от транс-кортикальных очагов при ФКД по клеточному составу: при ТС баллоновидные клетки превосходят количест-венно дисморфные нейроны, тогда как при ФКД типа IIb с транскортикальным признаком -наоборот [11]. Несколькими авторами было продемонстрировано, что эпилептические приступы в большей степени коррелируют с наличием дисморфных нейронов и менее -с наличием баллоновидных клеток [2,7,9,10]. Тем не менее представляется, что два других ти-па туберов (кальцинированные и кистоподобные) чаще сопряжены с генерацией эпилептических при-ступов [14].…”