Circadian rhythms and epilepsy:A suitable case for absence epilepsy

Many physiological processes such as sleep, hormonal secretion, or thermoregulation, are expressed as daily rhythms orchestrated by the circadian timing system. A powerful internal clock mechanism ensures proper synchronization of vital functions within an organism on the one hand, and between the organism and the external environment on the other. Some of the pathological processes developing in the brain and body are subjected to circadian modulation as well. Epilepsy is one of the conditions which symptoms often worsen at a very specific time of a day. Variation in peak occurrence depends on the syndrome and localization of the epileptic focus. Moreover, the timing of some types of seizures is closely related to the sleep-wake cycle, one of the most prominent circadian rhythms. This review focuses on childhood absence epilepsy (CAE), a genetic generalized epilepsy syndrome, in which both, the circadian and sleep influences play a significant role in manifestation of symptoms. Human and animal studies report rhythmical occurrence of spike-wave discharges (SWDs), an EEG hallmark of CAE. The endogenous nature of the SWDs rhythm has been confirmed experimentally in a genetic animal model of the disease, rats of the WAG/Rij strain. Well-known detrimental effects of circadian misalignment were demonstrated to impact the severity of ongoing epileptic activity. SWDs are vigilance-dependent in both humans and animal models, occurring most frequently during passive behavioral states and light slow-wave sleep. The relationship with the sleep-wake cycle seems to be bidirectional, while sleep shapes the rhythm of seizures, epileptic phenotype changes sleep architecture. Circadian factors and the sleep-wake states dependency have a potential as add-ons in seizures' forecasting. Stability of the rhythm of recurrent seizures in individual patients has been already used as a variable which refines existing algorithms for seizures' prediction. On the other hand, apart from successful pharmacological approach, circadian hygiene including sufficient sleep and avoidance of internal desynchronization or sleep loss, may be beneficial for patients with epilepsy in everyday management of seizures.