Khan S, Nobili L, Khatami R, Loddenkemper T, Cajochen C, Dijk DJ, Eriksson SH. Circadian rhythm and epilepsy. Lancet Neurol. 2018 Dec;17(12):1098-1108. doi:10.1016/S1474-4422(18)30335-1. Epub 2018 Oct 23. Review. Erratum in: Lancet Neurol. 2018 Nov 19.
Advances in diagnostic technology, including chronic intracranial EEG recordings, have confirmed the clinical observation of different temporal patterns of epileptic activity and seizure occurrence over a 24-h period. The rhythmic patterns in epileptic activity and seizure occurrence are probably related to vigilance states and circadian variation in excitatory and inhibitory balance. Core circadian genes BMAL1 and CLOCK, which code for transcription factors, have been shown to influence excitability and seizure threshold. Despite uncertainties about the relative contribution of vigilance states versus circadian rhythmicity, including circadian factors such as seizure timing improves sensitivity of seizure prediction algorithms in individual patients. Improved prediction of seizure occurrence opens the possibility for personalised antiepileptic drug-dosing regimens timed to particular phases of the circadian cycle to improve seizure control and to reduce side-effects and risks associated with seizures. Further studies are needed to clarify the pathways through which rhythmic patterns of epileptic activity are generated, because this might also inform future treatment options.