NEUROCHEMICAL PROFILE OF GLIONEURONAL LESIONS FROM PATIENTS WITH PHARMACORESISTANT FOCAL EPILEPSIES

Gangliogliomas, dysembryoplastic neuroepithelial tumors (DNT) and glio neuronal malformations are frequently encountered in patients with pha rmacoresistant focal epilepsies. In order to characterize the neuroche mical profile of these neoplastic and malformative glioneuronal lesion s, we have examined the presence of the alpha(1) subunit of the GABA(A ) receptor, the N-methyl-D-aspartate receptor subunit 1 (NR1), glutama te decarboxylase, tyrosine hydroxylase, somatostatin, parvalbumin, and calretinin in 60 gangliogliomas, 11 DNT, 10 tuberous sclerosis-like l esions and 17 non-tuberous sclerosis-like glioneuronal malformations. All DNT and tuberous sclerosis-like lesions, 59 gangliogliomas (98%), and 13 non-tuberous sclerosis-like hamartias (76%) were positive for a t least one of the markers. Despite a great variation between and with in the different entities, the neurochemical profile was generally rem iniscent of normal neocortex: glutamate decarboxylase, GABA(A) recepto r and NR1 which are common in neocortical neurons were present in the great majority of the lesions and often showed high labeling indices. There were three tuberous sclerosis-like lesions (30%) that contained both NR1 and glutamate decarboxylase immunoreactive giant cells in add ition to well-differentiated ganglion cells. This supports the idea th at at least some of these giant cells are of neuronal origin. The olig odendroglia-like cells of DNT and glioneuronal hamartias did not show immunoreactivity for any of the markers. The very high incidence of ga nglioglial lesions in patients with chronic focal epilepsies and the p resence of neurotransmitter-producing enzymes, neurotransmitter recept ors, neuropeptides, and calcium-binding proteins in many of these lesi ons suggests that they may play an active role in the pathogenesis of epileptic seizures.