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Multiday seizure cycles may be very common

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Remarkable data generate provocative hypotheses

It is “remarkable” that there were such long-lasting cycling alterations in seizure propensity over the course of several weeks in this study, Andreas Schulze-Bonhage, PhD, wrote in a published commentary.

“Ultraslow oscillations in brain excitability are scarcely understood,” he wrote in The Lancet Neurology, adding that emerging evidence suggests slow cycles below well-known circadian rhythms influence both physiological functioning and disease states.

Of note, the study showed that longer cycle durations of several weeks were not limited to women, in whom such cycles might reflect monthly hormonal changes, Dr. Schulze-Bonhage wrote.

The authors of the study acknowledged the inherent limitations of analyzing patient-reported seizure information and long-term assessment of electrocorticography recordings. Some of those limitations might be overcome with technical advances, including seizure trackers that can be worn by large cohorts of patients, according to Dr. Schulze-Bonhage.

“The approach of generating hypotheses in small patient cohorts assessed with high-quality methods and testing them in much larger patient samples from whom only behavioral data can be obtained can be considered seminal for future investigations on big data,” he wrote.

Dr. Schulze-Bonhage is with the Epilepsy Center at University Medical Center, University of Freiburg (Germany). He reported no competing interests related to his editorial (Lancet Neurol. 2018 Sep 12. doi: 10.1016/S1474-4422(18)30337-5 ).



Multiday epileptic seizure cycles may occur in a substantial number of individuals with epilepsy, results of a retrospective cohort study suggest.

Dr. Mark J. Cook

Dr. Mark J. Cook

While about 80% of patients in the study showed circadian modulation of their seizure rates, a substantial portion showed strong circaseptan (7 day) rhythms, according to the study’s senior author, Mark J. Cook, MD, of the department of medicine at St. Vincent’s Hospital, Melbourne.

Significant circaseptan cycles were seen in more than 20% of patients in one analysis from the study, which Dr. Cook and his colleagues reported in the Lancet Neurology.

The high prevalence of multiday seizure cycles could present an opportunity to improve treatment through development of patient-specific chronotherapy or the timing of medication to match when seizures would be most likely. “Even without fully understanding the mechanisms of seizure cycles, temporal patterns can be incorporated into patient management plans,” Dr. Cook said in a news release.

The study by Dr. Cook and his colleagues was based on two seizure datasets. One was a U.S. cohort of 1,118 patients who self-reported at least 100 episodes through the SeizureTracker website or mobile app. The other was an Australian cohort of 12 patients with focal epilepsy who had at least 30 recorded seizures in a study of an implanted electrocorticography device that tracked them between 6 months and 3 years.

In the SeizureTracker data, 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 7-day cycles in one analysis using the Hodges-Ajne test, a statistical method used to assess circular data.

“Many patients also showed some evidence of cycles lasting up to a month,” wrote Dr. Cook and his coauthors.

A confirmatory analysis using Monte Carlo simulation found that 7% of people, or 77 individuals, had significant 7-day cycles. “The probability that 77 patients would randomly share a specific cycle [such as a 7-day cycle] is infinitesimal,” the authors wrote.

In the implantable device study, 11 out of 12 patients had strong rhythms at 24 hours, according to the investigators, while 1 had a significant cycle of exactly 1 week, and 2 others had cycles of approximately 1 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,” the investigators wrote.

The cause of longer seizure cycles remains unclear, according to the investigators, though peak seizure times might be linked to behavioral changes such as varying stress levels over the course of the week, seasonal changes in sleep quality, or biologic drivers such as menstruation.

“A better understanding of seizure cycles might provide new targets for treatment,” they wrote.

Funding for the study came from the Australian National Health and Medical Research Council. Dr. Cook declared no competing interests, while his coauthors reported support from sources outside of this study. One study author is a cofounder of

SOURCE: Cook MJ et al. Lancet Neurol. 2018 Sep 12. doi: 10.1016/S1474-4422(18)30274-6.

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