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New Insights in the Circadian Rhythm and Epilepsy

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Through many centuries, epilepsy has remained a prevalent and disabling neurological disorder given the unpredictable nature of epileptic seizures. Current accumulating evidence, however, suggests the occurrence of seizures are not truly “random”. In a significant proportion of patients, the occurrence of ...

Through many centuries, epilepsy has remained a prevalent and disabling neurological disorder given the unpredictable nature of epileptic seizures. Current accumulating evidence, however, suggests the occurrence of seizures are not truly “random”. In a significant proportion of patients, the occurrence of seizures has been associated with the sleep/wake cycle. From the Babylonian era, a day-and-night temporal pattern of epileptic seizures was documented. The specific circadian rhythm of epileptic seizures has strong therapeutic implications, as clinicians can tailor the timing and dosage of drug administration to each patient.

Currently, literature indicates a more complex and bidirectional interplay between epilepsy and the circadian rhythm; the endogenous 24-hour cycle that determines the various physiological processes of our body. For example, circadian rhythms also influence seizure occurrence. The circadian timing system may modulate seizure susceptibility through the temporal variation of neuronal excitability. In patients with sleep-related epilepsy, sleep rhythms contribute to the recruitment and spreading of epileptic discharges. In addition, sleep-deprivation is a very common seizure trigger. Therefore, the effect of circadian rhythms on epilepsy may be underestimated in the clinic. However, the circadian rhythm is usually not a sole modulator of seizure susceptibility in most patients, since seizure occurrence can be influenced by multiple factors. On the other hand, epileptic seizures themselves cause sleep disorders, including sleep architecture impairment, parasomnia and insomnia. Looking forward, elucidating the relationship between epilepsy and the circadian rhythm may potentially lead to novel treatment approaches (e.g. chronotherapy) and shed new light on ictogenesis.

The specific localization of seizure origin, certain types of epileptic syndrome, and the pathology of the epileptogenic lesion (i.e. focal cortical dysplasia precipitates sleep-related epilepsy) all seem to constitute an epileptogenic network interacting with the circadian rhythm. It may be related to (but not limited to) varying body temperature, hormone secretion as well as thalamocortical oscillation, however the underlying mechanism of this interaction requires further investigation. Furthermore, novel chronotype-based treatments are still under exploration. The regulation of mTOR pathways and core clock genes are emerging as promising treatment options, as suggested by basic neuroscience research. Yet the clinical application remains unknown.

We call upon this Research Topic, hoping to improve our understanding of the temporal pattern of epilepsy and pave new ways to novel treatment strategies. Manuscripts with the following themes are especially welcome:
- circadian rhythmicity of seizure occurrence,
- sleep disorders in epileptic patients,
- the role of electrophysiological studies in seizure detection and prediction,
- mechanism of the circadian rhythm in epilepsy, and
- the potential application of chronotherapy in epileptic patients.

The editors would like to receive clinical or translational research, in the form of original research, commentaries or reviews.


Keywords: Epilepsy, Seizures, Parasomnias, Sleep-Related Hypermotor Epilepsy, Nocturnal Frontal Lobe Epilepsy, REM Sleep, Pathophysiology


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