Inhibitory circuits in human dysplastic tissue

Purpose: Different types of epilepsies and seizures depend on the nature an d location of the primary disturbance and are presumably mediated by differ ent physiopathological mechanisms. We immunocytochemically investigated pos sible changes in the inhibitory -aminobutyric acid (GABA)ergic system in sp ecimens taken from four patients who underwent surgery for intractable epil epsy and presented two different types uf focal cortical dysplasia in the t emporal lobe. Methods: The patients were selected on the basis of electroclinical, imagin g, and routine neuropathological data: two had Taylor focal dysplasia, and two had non-Taylor dysplasia (microdysgenesia). The study was performed usi ng antibodies against parvalbumin (PV), glutamic acid decarboxylase (GAD), and GABA-transporter 1 (GAT1). Results: In the patients with Taylor dysplasia, laminar disorganization of the cortex was associated with the presence of giant neurons and ballooned cells; there was a reduced number of PV-positive neurons and terminals, the giant neurons were surrounded by clusters of PV- and GAD-positive terminal s, and then was an overall reduction in GAT1. Despite the presence of corti cal laminar disorganization, no giant or ballooned cells were found in the patients with non-Taylor microdysgenesia; there was a marked decrease in PV and GAD immunoreactive elements, with a patchy distribution of GAD and GAT 1 immunoreactivity but no clustering: of PV and GAD terminals. Conclusions: These results suggest that the two forms of cortical dysplasia are characterized by different and selective morphofunctional alterations in the GABAergic system.