title: An integrative view of mechanisms underlying generalized spike-and-wave epileptic seizures and its implication on optimal therapeutic treatments.
abstract: Many types of epileptic seizures are characterized by generalized spike-and-wave discharges. In the past, notable effort has been devoted to understanding seizure dynamics and various hypotheses have been proposed to explain the underlying mechanisms. In this paper, by taking an integrative view of the underlying mechanisms, we demonstrate that epileptic seizures can be generated by many different combinations of synaptic strengths and intrinsic membrane properties. This integrative view has important medical implications: the specific state of a patient characterized by a set of biophysical characteristics ultimately determines the optimal therapeutic treatment. Through the same view, we further demonstrate the potentiation effect of rational polypharmacy in the treatment of epilepsy and provide a new angle to resolve the debate on polypharmacy. Our results underscore the need for personalized medicine and demonstrate that computer modeling and simulation may play an important role in assisting the clinicians in selecting the optimal treatment on an individual basis.
authors.affiliation: Department of Electrical and Computer Engineering, Texas A&M University, College Station, Texas, United States of America. byan@tamu.edu
authors.forename: Boyuan
authors.initials: B
authors.lastname: Yan
authors.forename: Peng
authors.initials: P
authors.lastname: Li
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008959:Models, Neurological; D057285:Precision Medicine; D018079:Receptors, GABA / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013788:Thalamus / Q000187:drug effects / Q000503:physiopathology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D012964:Sodium