Abstracts

Tuberous sclerosis complex (TSC) is often associated with intractable focal epilepsy secondary to cortical tubers. We aimed to assess the role of excitatory pathways in resected tuber tissues and its immediately adjacent cortex through the study of the cytoarchitecture and expression of various NMDA receptor subunits. Sixteen samples from 4 patients who underwent surgery for treatment of drug-resistant epilepsy were included in the study. The samples were fixed in 4% paraformaldehyde, cryoprotected and cut in 30 micrometers thick slices. Adjacent slices were used for cresyl-violet staining and immunocytochemistry to NMDA receptor subunits types 1 (NR1), 2A (NR2A) and 2B (NR2B). Two blinded investigators (CQT and IN) analyzed the protein expression patterns under light microscopy. Disruption of normal organization of cortex with gliosis and the presence of dysmorphic neurons (DN) and balloon cells (BC) were observed in all 4 patients. Giant neurons (GN) were seen in one sample, and were rare in the other 3 patients. Calcifications intermixed with multiple fibers and giant astrocytes (GA) were observed in 3 patients. Heterotopic cells in layer I of cortex (HC) were also observed in all patients. NR1 expression was increased in abnormal cells (DN, GA, HC and BC) of TSC. These cells also showed high expression of NR2A, and to a lesser extent NR2B subtypes of NMDA receptor (see table). No significant expression of NR2A or B subtypes was seen in normal-appearing neurons. Our results indicate a differential expression of NMDA receptor subunits in abnormal cell types from TSC. These results suggest a possible role of GA, HC and BC in the expression of epileptogenesis in human tuberous sclerosis.[table1] (Supported by NIH grants K08 NS02046 and R21 NS42354 to IN.)