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Mechanisms of epileptogenesis in tuberous sclerosis complex and related malformations of cortical development with abnormal glioneuronal proliferation Wong MEpilepsia 2008[Jan]; 49 (1): 8-21Malformations of cortical development (MCDs) are increasingly recognized as causes of medically intractable epilepsy. In order to develop more effective, rational therapies for refractory epilepsy related to MCDs, it is important to achieve a better understanding of the underlying mechanisms of epileptogenesis, but this is complicated by the wide variety of different radiographic, histopathological, and molecular features of these disorders. A subset of MCDs share a number of characteristic cellular and molecular abnormalities due to early defects in neuronal and glial proliferation and differentiation and have a particularly high incidence of epilepsy, suggesting that this category of MCDs with abnormal glioneuronal proliferation may also share a common set of primary mechanisms of epileptogenesis. This review critically analyzes both clinical and basic science evidence for overlapping mechanisms of epileptogenesis in this group of disorders, focusing on tuberous sclerosis complex, focal cortical dysplasia with balloon cells, and gangliogliomas. Specifically, the role of lesional versus perilesional regions, circuit versus cellular/molecular defects, and nonneuronal factors, such as astrocytes, in contributing to epileptogenesis in these MCDs is examined. An improved understanding of these various factors involved in epileptogenesis has direct clinical implications for optimizing current treatments or developing novel therapeutic approaches for epilepsy in these disorders.|Animals[MESH]|Astrocytes/pathology/physiology[MESH]|Brain Neoplasms/physiopathology[MESH]|Brain/pathology/*physiopathology[MESH]|Cell Differentiation/physiology[MESH]|Cell Division/physiology[MESH]|Disease Models, Animal[MESH]|Epilepsy/pathology/*physiopathology[MESH]|Ganglioglioma/pathology/*physiopathology[MESH]|Humans[MESH]|Malformations of Cortical Development/pathology/*physiopathology[MESH]|Models, Neurological[MESH]|Neuroglia/pathology/physiology[MESH]|Tuberous Sclerosis/pathology/*physiopathology[MESH] |
