"There is growing awareness in the field of epilepsy that, contrary to a canonical view, seizures are not entirely random events and that their occurrence relates to cyclical patterns of brain activity," Dr. Vikram Rao of the UCSF Epilepsy Center, in San Francisco, and corresponding co-author of the paper in JAMA Neurology, told Reuters Health by email.
The researchers studied 222 adults with medically refractory focal epilepsy who had previously been implanted with an approved therapeutic device that provides long-term recordings of brain activity.
"Using these recordings, we found cycles of brain activity of various durations - daily, multi-day, and annual - and we characterized their strength and prevalence. We found that these cycles are surprisingly robust, that they are likely more common than previously recognized, and that they help explain the timing of seizures experienced by these individuals," Dr. Rao said.
The prevalence of circadian (approximately 24 hours) seizure cycles was 89%; the prevalence of multi-day (approximately weekly to approximately monthly) seizure cycles was 60% and the prevalence of circannual (approximately one year) seizure cycles was 12%.
"Circadian (24-hour) cycles are well-known in biology and medicine, but we were surprised to find that multi-day cycles of brain activity are equally strong and highly prevalent," Dr. Rao commented.
The strengths of circadian and multi-day seizure cycles were comparable, whereas circannual seizure cycles were weaker. Across individuals, circadian seizure cycles displayed five peaks: morning, mid-afternoon, evening, early night, and late night. Multi-day cycles of seizure activity showed peak periods centered around 7, 15, 20 and 30 days.
"So, for example, one person might have a 30-day cycle of brain activity that helps determine days when seizure risk is highest and a cyclical tendency for seizures to occur around 6 pm on those days," Dr. Rao explained. "Another person might have a 20-day cycle determining high-risk days and an early morning peak for seizures on those days."
"Interestingly, we also did not find statistical evidence that environmental cues such as phases of the moon, or societal conventions, such as calendar days of the week or month played any major role in the timing of seizures," co-corresponding author Dr. Maxime Baud of the Sleep-Wake-Epilepsy Center, University of Bern, in Switzerland, told Reuters Health by email.
"With the former, we hope to settle a century-long debate about celestial influences on seizures and brain disorders more broadly. The latter is more surprising, because for most individuals, activities are paced by the rhythm of weekdays and weekends. Yet, more potent endogenous rhythms that do not synchronize among individuals seem to be at play in epilepsy, maybe related to hormonal cycles," Dr. Baud said.
The researchers say their observations have potential clinical implications.
"Patients frequently make observations about patterns of their seizures. By revealing the high prevalence of cyclical patterns of seizures, our findings validate many of these observations and may inform the dialogue between patients and providers regarding fluctuations in seizures over time," Dr. Rao told Reuters Health.
"The natural cyclical variability of seizures also has implications for diagnostic tests that rely on capturing seizures and for the design of clinical trials that aim to determine the effect of an intervention on seizure frequency. With additional study, it may be possible to leverage knowledge of seizure cycles to adjust medications and other treatments based on times when seizures are most likely," Dr. Rao said.
Dr. Baud added, "Beyond immediate clinical practice, these now well-characterized clinical phenomena call for a search for the underlying mechanisms. Indeed, we may one day fully understand why seizures recur in cycles. This may open new therapeutic possibilities in the more distant future."
The research had no commercial funding. Dr. Rao reported receiving grants and personal fees from NeuroPace Inc during the conduct of the study. Dr. Baud has a patent for a brain-monitoring device pending.
SOURCE: https://bit.ly/3tyJtpT JAMA Neurology, online February 8, 2021.
By Megan Brooks
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