Introduction from Dr Markus Reuber, editor-in-chief of Seizure
Probably like the majority of readers of Seizure, I am more of a clinician than a scientist. This does not mean that I do not care about the scientific underpinnings of the disorders I deal with or the therapeutic interventions at my disposal, but in my daily working practice, it is more important to me that the treatments I use work than to understand why they work. Having said that, my clinical work raises many questions – why does a particular drug work for one patient but not for another with very similar seizures? Why does a particular treatment work well on one occasion but does not work at all on another in the same patient? Why do treatments sometimes work well at first but then loose their effectiveness?
My editor’s choice in this issue of Seizure does not answer these questions comprehensively - they are much too big to be answered adequately in a single paper - however, it masterfully picks out one key location relevant to the aetiology of some and the treatment of many epilepsies: the GABA-A receptor (1). In his fascinating account, Lazar John Greenfield explains how this single receptor can change in chronic epilepsy and acute epileptic emergencies, how it can be affected by chemical or physiological changes in its vicinity, and how its functioning is enhanced or reduced by a wide range of antiepileptic and other drugs demonstrates simultaneously how much we understand about the brain and how much more there is to learn.
Even though this paper only concentrates on one particular (albeit important) receptor, it implicitly, communicates how far we have got with the understanding of epilepsy and its treatment at the molecular level. In some cases, this molecular understanding seems to explain well, what clinicians see when they treat patients - for instance why phenobarbitone may disrupt status epilepticus when benzodiazepines have failed (although both drugs act on the GABA-A receptor). In other respects, the clinical reader will realize how difficult it is likely to understand the complex practical treatment questions they have to deal with when treating individual patients at cellular or receptor level.
I thoroughly recommend this paper to clinicians who want to learn more about epilepsy and scientists who want to learn more about epilepsy.
 Greenfield J. L.. Molecular Mechanisms of Antiseizure Drug Activity at GABA-A Receptors. Seizure 2013:22:589-600.