This chapter summarizes many of the cellular alterations that give rise to an imbalance between excitation and inhibition, and to a hypersynchronous neuronal discharge. Contributing intrinsic neuronal properties include aberrant channel function and/or location that may cause excessive discharge and/or inadequate hyperpolarization of excitatory (projection) cells or loss of inhibition resulting from changes (damage to) inhibitory interneurons. Altered/abnormal synaptic function may also be critical, such as activity-dependent changes in receptor properties and/or plasticity of synaptic connectivity; such changes may affect both excitatory (e.g., mediated by glutamatergic synapses) and inhibitory (e.g., local GABA circuits) function. Finally, dysfunction of extracellular influences, such as those mediated by glial activities, changes in extracellular spaces, effects of hormonal modulators, and dependent on an intact vascular system, can result in hyperexcitability and seizures discharge. These cellular changes can result from genetic disorders, from aberrant developmental programs, or from trauma-induced brain injury. The net effect of these changes - often multiple and complex - can lead to a focal epilepsy such as temporal lobe epilepsy (if the abnormalities are restricted to temporal lobe structures) or to a more generalized phenotype (e.g., generalized epilepsy with febrile seizures plus, GEFS. +). Insight into underlying cellular and molecular abnormalities of a given epilepsy phenotype will, we hope, lead to better and earlier treatments.
|Original language||English (US)|
|Number of pages||21|
|Journal||Handbook of Clinical Neurology|
|State||Published - 2012|
ASJC Scopus subject areas
- Clinical Neurology