Authors: Eleonora Aronica, Peter B. Crino

Neurotherapeutics. 2014 Apr;11(2):251-68. doi: 10.1007/s13311-013-0251-0.


Structural abnormalities of the brain are increasing-ly recognized in patients with neurodevelopmental delay andintractable focal epilepsies. The access to clinically well-characterized neurosurgical material has provided a uniqueopportunity to better define the neuropathological, neuro-chemical, and molecular features of epilepsy-associated focaldevelopmental lesions. These studies help to further under-stand the epileptogenic mechanisms of these lesions.Neuropathological evaluation of surgical specimens from pa-tients with epilepsy-associated developmental lesions revealstwo major pathologies: focal cortical dysplasia and low-gradedevelopmental tumors (glioneuronal tumors). In the last fewyears there have been major advances in the recognition of awide spectrum of developmental lesions associated with aintractable epilepsy, including cortical tubers in patients withtuberous sclerosis complex and hemimegalencephaly. As anincreasing number of entities are identified, the developmentof a unified and comprehensive classification represents agreat challenge and requires continuous updates. The presentarticle reviews current knowledge of molecular pathogenesisand the pathophysiological mechanisms of epileptogenesis inthis group of developmental disorders. Both emerging neuro-pathological and basic science evidence will be analyzed,highlighting the involvement of different, but often converg-ing, pathogenetic and epileptogenic mechanisms, which maycreate the basis for new therapeutic strategies in thesedisorders.