Neurons recorded from pediatric epilepsy surgery patients with cortical dysplasia

Purpose: Cortical dysplasia (CD) is a common pathological substrate in pati ents with early-onset childhood epilepsy. In CD tissue, little is known abo ut the mechanisms responsible for cellular hyperexcitability. In this study , we report initial electrophysiological and morphological observations fro m normal and dysmorphic cells in pediatric CD patients. Methods: Neocortical "most" and "least" epileptogenic areas were sampled ba sed on neuroimaging and electrocorticography from 15 CD patients (ages 0.3 to 14 years). Whole-cell voltage clamp recordings combined with infrared vi deomicroscopy sampled abnormal cells (cytomegalic neurons, cells with bifur cated dendrites, disoriented pyramidal cells, etc.) compared with normal-ap pearing 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 al,normal in appearance. Abnormal cells showed electrophysiological irregularities ranging from intr insic cellular hyperexcitability to hyposensitivity after application of io notropic receptor agonists. Other findings included increased excitatory po stsynaptic currents and alterations in gamma-aminobutyric acid reversal pot entials. Conclusions: In pediatric CD tissue, these preliminary results indicate tha t abnormal-appearing cells showed abnormalities in electrophysiological mea sures compared with normal appearing neurons. The abnormalities varied from hyperexcitability to hypoexcitability. More detailed results and conclusio ns will be forthcoming as additional patient material is analyzed.