Timing Mechanisms for Circadian Seizures

Abstract

For centuries, epileptic seizures have been noticed to recur with temporal regularity, suggesting that an underlying biological rhythm may play a crucial role in their timing. In this review, we propose to adopt the framework of chronobiology to study the circadian timing of seizures. We first review observations made on seizure timing in patients with epilepsy and animal models of the disorder. We then present the existing chronobiology paradigm to disentangle intertwined circadian and sleep-wake timing mechanisms. In the light of this framework, we review the existing evidence for specific timing mechanisms in specific epilepsy syndromes and highlight that current knowledge is far from sufficient. We propose that individual seizure chronotypes may result from an interplay between independent timing mechanisms. We conclude with a research agenda to help solve the urgency of ticking seizures.

Keywords: circadian; epileptic seizures; sleep.

Figure 1

Two-process model of seizure timing. (A) Hypothetical patient with seizures linked to increases in sleep homeostasis (Process S, cyan curve), who has two additional seizures (dotted empty dots) after a 32 h sleep deprivation (dotted cyan line). (B) Hypothetical patient with seizures during wakefulness or during sleep linked to increases in sleep homeostasis. A circadian phase shift is followed by an entrainment of the sleep–wake cycle on a different schedule, and seizures as well as sleep are decoupled from Process C (black curve) for a few days. (C) Two hypothetical subjects undergoing forced desynchrony on a 10-h light/10-h dark schedule. In the subject with seizures linked to Process S (full dots), seizures occur with peaks in sleep pressure at the end of the scheduled active period (light). In the subject with seizures linked to Process C (empty dots), seizures occur at the circadian peaks, independently of the light-dark schedule. (D) Subject with polyphasic sleep (e.g., mouse model, sleep bout as grey boxes on top), in which Process S shows more variations at different circadian phases. As a result, seizures linked to Process S may occur at more than one circadian phase.