Are cytomegalic neurons and balloon cells generators of epileptic activity in pediatric cortical dysplasia?
OBJECTIVE
Severe cortical dysplasia (CD) is characterized by the presence of cytomegalic neurons and balloon cells. These aberrant cells could participate in the generation of epileptic activity. The aim of this study was to morphologically and electrophysiologically characterize cells in pediatric CD tissue.


METHODS
We used infrared video-microscopy to visualize normal and abnormal-appearing cells. To characterize electrophysiological properties, we used whole-cell patch clamp recordings in tissue slices obtained from 42 cases of pediatric CD (ages 0.2-14 years). The pipette contained biocytin for determination of morphological features.


RESULTS
Approximately 25% of recorded cells displayed morphologic differences compared with normal-appearing pyramidal neurons, and were divided as follows: immature, misoriented, dysmorphic, cytomegalic, and balloon cells. Immature cells displayed electrophysiological membrane properties typical of developing neurons. Misoriented pyramidal neurons and pyramidal neurons with dysmorphic processes displayed properties similar to normal-appearing pyramidal neurons. In contrast, cytomegalic neurons and balloon cells displayed abnormal membrane properties. Balloon cells had a very high input resistance and lacked voltage-gated Na+ and Ca2+ currents. Cytomegalic neurons had a very high membrane capacitance, very low input resistance, and showed signs of hyperexcitability, as exemplified by the occurrence of repetitive, slowly inactivating Ca2+ spikes when depolarized.


CONCLUSIONS
We suggest that cytomegalic neurons but not balloon cells have the potential to be epileptic generators, although probably not instigators, in severe CD tissue.
Cepeda
Carlos
C
Mental Retardation Research Center, David Geffen School of Medicine, University of California Los Angeles, California 90024, USA. ccepeda@mednet.ucla.edu
André
Véronique M
VM
Vinters
Harry V
HV
Levine
Michael S
MS
Mathern
Gary W
GW
D000200:Action Potentials / Q000502:physiology; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D004594:Electrophysiology; D004827:Epilepsy / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008239:Lysine / Q000031:analogs & derivatives*; D018715:Microscopy, Video; D009421:Nervous System Malformations / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000473:pathology*; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000002:abnormalities* / Q000473:pathology
C013411:biocytin; D008239:Lysine