Neurons Recorded from Pediatric Epilepsy Surgery Patients with Cortical Dysplasia

Abstract

Summary: Purpose: Cortical dysplasia (CD) is a common pathological substrate in patients with early‐onset childhood epilepsy. In CD tissue, little is known about the mechanisms responsible for cellular hyperexcitability. In this study, we report initial electrophysiological and morphological observations from normal and dysmorphic cells in pediatric CD patients. Methods: Neocortical “most” and “least” epileptogenic areas were sampled based on neuroimaging and electrocorticography from 15 CD patients (ages 0.3 to 14 years). Whole‐cell voltage clamp recordings combined with infrared videomicroscopy sampled abnormal cells (cytomegalic neurons, cells with bifurcated dendrites, disoriented pyramidal cells, etc.) compared with normal‐appearing neurons from the same patient. Cells were filled with biocytin, and adjacent tissue blocks were stained for neuronal and glial markers. Results: About 15% of the 161 recorded cells were abnormal in appearance. Abnormal cells showed electrophysiological irregularities ranging from intrinsic cellular hyperexcitability to hyposensitivity after application of ionotropic receptor agonists. Other findings included increased excitatory postsynaptic currents and alterations in γ‐aminobutyric acid reversal potentials. Conclusions: In pediatric CD tissue, these preliminary results indicate that abnormal‐appearing cells showed abnormalities in electrophysiological measures compared with normal‐appearing neurons. The abnormalities varied from hyperexcitability to hypoexcitability. More detailed results and conclusions will be forthcoming as additional patient material is analyzed.