Multiday epileptic seizure cycles may occur in many individuals with epilepsy, according to a retrospective cohort study published online ahead of print September 12 in Lancet Neurology.
About 80% of patients in the study showed circadian modulation of their seizure rates, and more than 20% had strong circaseptan (ie, seven-day) rhythms, said Mark J. Cook, MD, a neurologist at St. Vincent’s Hospital in Melbourne, and colleagues.
The high prevalence of multiday seizure cycles could present an opportunity to improve treatment through the development of patient-specific chronotherapy (ie, the administration of medication when seizures are most likely). “Even without fully understanding the mechanisms of seizure cycles, temporal patterns can be incorporated into patient management plans,” said Dr. Cook.
The investigators based their study on two seizure datasets. One was a US cohort of 1,118 patients who reported at least 100 seizures through the SeizureTracker website or mobile app. The other was an Australian cohort of 12 patients with focal epilepsy who had at least 30 seizures recorded by an implanted electrocorticography device during follow-up that ranged between six months and three years.
In the US cohort, 86% of participants had at least one significant cycle in their seizure times, and 64% had more than one cycle. Most of the cycles (80%) were circadian, while 21% of people had significant circaseptan cycles in one analysis using the Hodges-Ajne test, a statistical method used to test for circular uniformity. “Many patients also showed some evidence of cycles lasting up to a month,” said the authors.
A confirmatory analysis using Monte Carlo simulation found that 7% of people, or 77 individuals, had significant circaseptan cycles. “The probability that 77 patients would randomly share a specific cycle is infinitesimal,” said the authors.
In the Australian study, 11 of 12 patients had strong rhythms at 24 hours, one had a significant cycle of exactly one week, and two others had cycles of approximately one week.
“Some people had stronger rhythms at time scales longer than 24 hours, which suggests that circadian regulation was not necessarily the strongest modulating factor of epileptic activity,” said the investigators. The cause of longer seizure cycles remains unclear, though peak seizure times might be linked to varying stress levels, seasonal changes in sleep quality, or biologic cycles such as menstruation.
—Andrew D. Bowser
Karoly PJ, Goldenholz DM, Freestone DR, et al. Circadian and circaseptan rhythms in human epilepsy: a retrospective cohort study. Lancet Neurol. 2018 Sep 12 [Epub ahead of print].