IS FOCAL CORTICAL DYSPLASIA TYPE IIB THE FOCAL FORM OF TUBEROUS SCLEROSIS COMPLEX?

Objectives: Focal Cortical Dysplasia (FCD) type IIB is a malformation of cortical development characterized by presence of balloon cells. These cells share phenotypic features of giant cells found in Tuberous Sclerosis Complex (TSC), but the relationship between FCD type IIB and TSC is not established.

Methods: The panel of antigens, including hamartin, tuberin, mTOR, pS6K, pAkt, pErk, NSE, GFAP and nestin was studied under the confocal microscope in two FCD IIB and two FCD I cases. The specimens were obtained from patients operated on for intractable epilepsy, who did not manifest clinical symptoms of TSC. Normal brain tissue was used as control group.

Results: We found loss of tuberin and hamartin expression as well as strong immunoreactivity for mTOR, pS6K, pAkt, and pErk in both FCD type IIB lesions. Cortical balloon cells in these samples were NSE-positive, whereas most subcortical giant cells were labeled with GFAP. In FCD type I and normal brain tissue, tuberin and hamartin were detected, and immunoreactivity for mTOR, pS6K, pAkt, and pErk was subtle. Nestin expression in all samples was weak or absent.

Conclusion: Loss of TSC1 and TSC2 products expression as well as enhanced mTOR pathway immunoreactivity suggest that FCD type IIB may represent focal form of TSC.