Chapter

GABA<sub>B</sub> Receptor and Absence Epilepsy

Hua A. Han, Miguel A. Cortez and O. Carter Snead

in Jasper's Basic Mechanisms of the Epilepsies

Fourth edition

Published on behalf of ©Jeffrey L. Noebels, Massimo Avoli, Michael A. Rogawski, Richard W. Olsen, and Antonio V. Delgado-Escueta

Published in print July 2012 | ISBN: 9780199746545
Published online April 2013 | e-ISBN: 9780199322817 | DOI: http://dx.doi.org/10.1093/med/9780199746545.003.0019

Series: Contemporary Neurology Series

GABAB Receptor and Absence Epilepsy

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GABABR-mediated mechanisms have been known for many years to be involved in the genesis and propagation of both TASs126–129 and AASs,78,84 as well as in the associated cognitive impairments.54,79 Moreover, the data reviewed in this chapter indicate that TAS and AAS share the same pharmacological profile, because they share common thalamic circuitry perturbations, notably nRT involvement. However, TAS and AAS phenotypes differ in seizure severity, SWD characteristics, and impairment in learning abilities, mainly because they differ in the other parts of the circuitry involved. In TAS, cognition is not affected because the SWD is constrained within thalamocortical circuits and does not involve limbic circuits. In AAS, on the other hand, cognition is impaired because of the SWD involvement of limbic circuitry that is recruited through cortico-thalamo-hippocampal pathways,130 hence the difference in seizure semiology and cognitive involvement. Because of the demonstrated efficacy of GABABR antagonists in preventing SWDs, the potential of GABABR antagonists as powerful antiabsence drugs has been long proposed,61 yet clinical trials of GABABR are lacking both in TAS and AAS. Frequent refractory seizures and severe impairment in cognition represent the most disabling aspects of pediatric epilepsy and are the major contributors to the burden of illness in children affected by epilepsy.131 Because of data suggesting that atypical absence seizures are independent of their comorbid cognitive deficits, yet both are GABABR dependent,79 there is a clinical imperative to initiate clinical trials of a GABABR antagonist in the AASs observed in Lennox-Gastaut syndrome.119,120

Chapter.  8804 words.  Illustrated.

Subjects: Neurology

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