Original Paper Dev Neurosci 2005;27:59–76 DOI: 10.1159/000084533 Pediatric Cortical Dysplasia: Correlations between Neuroimaging, Electrophysiology and Location of Cytomegalic Neurons and Balloon Cells and Glutamate/GABA Synaptic Circuits C. Cepeda f V.M. André a,f J. Flores-Herna ´ ndez f,g O.K. Nguyen f N. Wu f G.J. Klapstein f S. Nguyen a S. Koh b H.V. Vinters c–f M.S. Levine e, f G.W. Mathern a,e,f Divisions of a Neurosurgery, b Pediatric Neurology and c Neuropathology, d Department of Neurology, e The Brain Research Institute, and f The Mental Retardation Research Center, David Geffen School of Medicine, University of California, Los Angeles, Calif., USA; g Institute of Physiology, Benemérita Universidad Auto ´ noma de Puebla, Puebla City, Mexico Received: October 29, 2004 Accepted: November 8, 2004 Gary W. Mathern, MD Reed Neurological Research Center 710 Westwood Plaza, Room 2123 Los Angeles, CA 90095-1769 (USA) Tel. +1 310 206 8777, Fax +1 310 206 8461, E-Mail gmathern@ucla.edu ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2005 S. Karger AG, Basel Accessible online at: www.karger.com/dne Key Words Cortical dysplasia W Electrophysiology W Cytomegalic neurons W Balloon cells Abstract Seizures in cortical dysplasia (CD) could be from cytome- galic neurons and balloon cells acting as epileptic ‘pace- makers’, or abnormal neurotransmission. This study ex- amined these hypotheses using in vitro electrophysio- logical techniques to determine intrinsic membrane properties and spontaneous glutamatergic and GABAer- gic synaptic activity for normal-pyramidal neurons, cy- tomegalic neurons and balloon cells from 67 neocortical sites originating from 43 CD patients (ages 0.2–14 years). Magnetic resonance imaging (MRI), 18 fluoro-2-deoxyglu- cose positron emission tomography (FDG-PET) and elec- trocorticography graded cortical sample sites from least to worst CD abnormality. Results found that cytomegalic neurons and balloon cells were observed more frequent- ly 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 re- cordings 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 glutamater- gic 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 paroxys- mal depolarizations. Furthermore, there was more GABA relative to glutamate synaptic neurotransmission in ar- eas of severe CD. Thus, in CD tissue alternate mecha- nisms of epileptogenesis should be considered, and we suggest that GABAergic synaptic circuits interacting with cytomegalic and normal-pyramidal neurons with imma- ture receptor properties might contribute to seizure gen- eration. Copyright © 2005 S. Karger AG, Basel