Cycles in epilepsy

• Published in: Nature reviews. Neurology Vol. 17; no. 5; pp. 267 - 284
• Main Authors: Karoly, Philippa J., Rao, Vikram R., Gregg, Nicholas M., Worrell, Gregory A., Bernard, Christophe, Cook, Mark J., Baud, Maxime O.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2021; Nature Publishing Group
• Subjects: 631/378/1689/178; 692/617/375/178; Animals; Brain - physiopathology; Brain research; Causes of; Chronobiology Phenomena - physiology; Circadian Rhythm - physiology; Cognitive science; Convulsions & seizures; Electroencephalography - trends; Epilepsy; Epilepsy - diagnosis; Epilepsy - physiopathology; Humans; Medicine; Medicine & Public Health; Neural circuitry; Neurology; Neuroscience; Periodicity; Review Article; Seizures (Medicine); Sleep Stages - physiology; France
• ISSN: 1759-4758; 1759-4766; 1759-4766
• DOI: 10.1038/s41582-021-00464-1

Epilepsy is among the most dynamic disorders in neurology. A canonical view holds that seizures, the characteristic sign of epilepsy, occur at random, but, for centuries, humans have looked for patterns of temporal organization in seizure occurrence. Observations that seizures are cyclical date back to antiquity, but recent technological advances have, for the first time, enabled cycles of seizure occurrence to be quantitatively characterized with direct brain recordings. Chronic recordings of brain activity in humans and in animals have yielded converging evidence for the existence of cycles of epileptic brain activity that operate over diverse timescales: daily (circadian), multi-day (multidien) and yearly (circannual). Here, we review this evidence, synthesizing data from historical observational studies, modern implanted devices, electronic seizure diaries and laboratory-based animal neurophysiology. We discuss advances in our understanding of the mechanistic underpinnings of these cycles and highlight the knowledge gaps that remain. The potential clinical applications of a knowledge of cycles in epilepsy, including seizure forecasting and chronotherapy, are discussed in the context of the emerging concept of seizure risk. In essence, this Review addresses the broad question of why seizures occur when they occur. In this Review, the authors provide an overview of the evidence for daily, multi-day and yearly cycles in epileptic brain activity. They also discuss advances in our understanding of the mechanisms underlying these cycles and the potential clinical applications of this knowledge. Key points Cyclical phenomena have long been described in epilepsy, but tools to quantify them in humans have only recently become available. Chronic recordings of brain activity in rodents, canines and humans have yielded converging evidence that robust cycles in epilepsy exist across species. Cycles of epileptic brain activity exist over multiple timescales, including circadian, multidien and circannual. Critical phases of these cycles help determine periods of highest seizure risk, opening the possibility of forecasting seizures over long horizons. Unanswered questions involve the mechanistic basis of cycles in epilepsy and how to leverage these cycles for clinical applications such as chronotherapy.