We describe clinical studies and studies using experimental animals showing that alteration of genes mediating function of the mammalian biological clock can influence the expression of seizures, and conversely that seizures can alter the expression of clock genes and activity in related gene pathways. In the present paper, we review circadian influences relevant to nervous system dysfunction associated with epilepsy. In addition to influencing the sleep/wake cycle, protein products of the primary oscillating mechanism have broad impact on homeostatic processes at the cellular (e.g., cell cycle regulation, energy metabolism) and systems (e.g., endocrine, immune, cardiovascular, pulmonary, gastrointestinal, and nervous) levels. Cycles of activity and rest occur in essentially all cells of the body (peripheral oscillations), but they are largely governed by a primary oscillating mechanism (sometimes referred to as a “master clock”) that occurs in neurons of the suprachiasmatic nucleus (SCN) of the hypothalamus ( 1, 2). We conclude that better understanding of the relationship between circadian rhythms, neuronal excitability, and seizures will allow both the identification of new therapeutic targets for treating epilepsy as well as more effective treatment regimens using currently available pharmacological and non-pharmacological strategies.Īcross evolution, nearly all eukaryotic organisms, including humans, have relied on predictable cycles of sustained activity and rest for survival. Finally, we review the concept of chronotherapy and provide a perspective regarding its application to patients with epilepsy based on their individual characteristics (i.e., being a “morning person” or a “night owl”). We focus on the overlap between mechanisms of circadian-associated changes in SCN neuronal excitability and mechanisms of epileptogenesis as a means of identifying key pathways and molecules that could represent new targets or strategies for epilepsy therapy. We review studies investigating how seizures and epilepsy disrupt expression of core clock genes, and how disruption of clock mechanisms impacts seizures and the development of epilepsy. We present basic information on circadian biology, but focus on research studying the influence of both the time of day and the sleep/wake cycle as independent but related factors on the expression of seizures in epilepsy. This review addresses key topics in the relationship between circadian rhythms and seizures in epilepsy. Seizure patterns observed in patients with epilepsy suggest that circadian rhythms and sleep/wake mechanisms play some role in the disease. Floyd College of Medicine, Washington State University, Spokane, WA, United States
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