The interaction between circadian rhythm and epilepsy

Abstract

Evidence about the interaction between circadian rhythms (CR) and epilepsy has been expanded with the application of advanced detection technology. An adequate understanding of how circadian system and epilepsy interact with each other could contribute to more accurate seizure prediction as well as rapid development of potential treatment timed to specific phases of CR. In this review, we present the reciprocal relationship between CR and epileptic activities from aspects of sleep effect, genetic modulation and brain biochemistry. It has been found that sleep-wake patterns, circadian timing systems and multidien rhythms have essential roles in seizure activities and interictal epileptiform discharge (IED). For instance, specific distribution patterns of seizures and IED have been reported, i.e., lighter non-rapid eye movement (NREM) sleep stage (stage 2) induces seizures while deeper NREM sleep stage (stage 3) activates IEDs. Furthermore, the epilepsy type, seizure type and seizure onset zone can significantly affect the rhythms of seizure occurrence. Apart from the common seizure types, several specific epilepsy syndromes also have a close correlation with sleep-wakefulness patterns. Sleep influences the epilepsy rhythm, and conversely, epilepsy alters the sleep rhythm through multiple pathways. Clock genes accompanied by two feedback loops of regulation have an important role in cortical excitability and seizure occurrence, which may be involved in the mTORopathy. The suprachiasmatic nuclei (SCN) has a rhythm of melatonin and cortisol secretion under the circadian pattern, and then these hormones can feed back into a central oscillator to affect the SCN-dependent rhythms, leading to variable but prominent influence on epilepsy. Furthermore, we discuss the precise predictive algorithms and chronotherapy strategies based on different temporal patterns of seizure occurrence for patients with epilepsy, which may offer a valuable indication for non-invasive closed-loop treatment system. Optimization of the time and dose of antiseizure medications, and resynchronization of disturbed CR (by hormone therapy, light exposure, ketogenic diet, novel small molecules) would be beneficial for epileptic patients in the future. Before formal clinical practice, future large-scale studies are urgently needed to assist prediction and treatment of circadian seizure activities and address unsolved restrictions.