Cortical dysplasia

Abstract

Human cortical dysplastic lesions are frequently associated with severe partial epilepsies. We report an immunocytochemical investigation on cortical tissue from three surgically treated patients, 20, 38, and 14 years old, with intractable epilepsy due to cortical dysplasia. The studies were performed using antibodies recognizing cytoskeletal proteins, calcium-binding proteins, and some subunits of glutamate receptors. The specimens from the three patients displayed common features: (1) focal cytoarchitectural abnormalities with an increased number of giant pyramidal neurons through all cortical layers except layer I; (2) large, round-shaped balloon cells mainly concentrated in the deepest part of the cortex and in the white matter; (3) a decrease of calcium binding protein immunopositive gamma-aminobutyric acid (GABA)ergic neurons; and (4) abnormal baskets of parvalbumin-positive terminals around the excitatory (pyramidal and large, round-shaped) neurons. These data provide evidence that the epileptogenicity in these types of cortical dysplasia is due to an increase in excitatory neurons coupled with a decrease in GABAergic interneurons.

Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

“…Downregulation of several GABA A R subunits, as well as a reduction in the number of inhibitory cells, has been shown in FCD, supporting the impairment of GABAergic inhibition [107,[156][157][158][159]. In addition, electrophysiological studies performed in brain slices from FCD tissue show immature GABA receptor-mediated responses, and GABA receptormediated synchronization appears to be involved in the mechanism leading to in vitro ictal activity in FCD [147,148,160].…”

Consequences of Cortical Dysplasia During Development in Rats

“…In a study of human cortical dysplastic lesions, Spreafico et al (26) reported a decrease of GABAergic interneurons as well as abnormal baskets of parvalbumin-positive terminals around excitatory neurons. These studies suggest that the dysplasia may also have impaired inhibition.…”

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

“…For instance, a synchronous GABA A receptormediated event appears to be able to initiate ictal discharges in post-surgical neocortical tissue removed from patients with Taylor type focal cortical dysplasia (Avoli et al, 1999;D'Antuono et al, 2004); it was shown in these experiments that, as reported in rodent limbic structures, this synchronous GABAergic potential is accompanied by a transient increase in [K + ] o as well as that the ictal activity is abolished by GABA A receptor antagonists or μ-opioid receptor agonism. Interestingly, it has been reported that the dysplastic tissue resected from these patients presents with decreased number of presumptive interneurons that, however, provide increased GABAergic innervation to principal cells (Spreafico et al, 1998;Tassi et al, 2002). In addition, Alonso-Nanclares et al (2005) have reported that giant ectopic neurons in the white matter are surrounded by hypertrophic basket formations.…”