Seizure Cycles May Follow Circadian Rhythms

Megan Brooks

September 18, 2018

The timing of epileptic seizures may be linked to natural circadian rhythms, which may help to guide future treatment options, new research suggests.

In what is believed to be the largest study of individual patients' seizure cycles, researchers found that most seizures followed a circadian rhythm. Some patients experienced weekly and 3-weekly seizure cycles, and some had a combination of daily, weekly, or longer cycles associated with their seizures.

"I think clinicians could use this information now to help recognize that there are very individual patterns of seizure occurrence, and understanding this may allow them to more accurately judge the variations in seizure frequency they are seeing clinically," Mark Cook, MD, University of Melbourne, Victoria, Australia, told Medscape Medical News.

"This will help guide therapy, and may ultimately allow more tailored therapies to be provided," Cook said.

The study was published online September 12 in Lancet Neurology.

Suspicions Confirmed

It has long been suspected that patterns of epileptic seizures exist, but these patterns have been poorly defined, chiefly because no accurate databases of seizure activity over sufficiently long time frames were available, Cook and colleagues note.

"Our results suggest that seizure cycles are robust, patient specific, and more widespread than previously understood," they write.

For the study, the investigators used data from two unique databases of seizure activity. The NeuroVista study captured continuous EEG recordings from intracranial electrodes for up to 3 years in 12 patients. The SeizureTracker study, which included 1118 patients with epilepsy, recorded and tracked seizures for up to 8 years using a seizure tracking mobile phone app and website (seizuretracker.com; Seizure Tracker, LLC).

Seizure cycles occurred in more than 80% of all patients; for 891 of 1118 people using SeizureTracker (80%) and for 11 of 12 of those with EEG recordings (92%), seizures followed a circadian rhythm.

In the SeizureTracker cohort, between 77 (7%) and 233 (21%) of the 1118 patients experienced seizures that followed strong weekly rhythms, with a clear 7-day period. Between 151 (14%) and 247 (22%) patients experienced significant seizure cycles that were longer than 3 weeks.

Seizure cycles were equally common in men and women, and peak seizure rates were evenly distributed across all days of the week.

In addition, for about two thirds (64%) of the SeizureTracker study cohort, seizures were associated with more than one type of cycle.

For those whose seizures followed a circadian cycle, peak time of seizures varied as per time of day, but more seizures occurred in the morning (8:00 AM) and evening (8:00 PM).

Weekly cycles did not favor any day of the week, but for slightly more patients, seizure rates were higher on Tuesdays and Wednesdays.

"The fact that seizure occurrence did not favor a particular day of the week provides some support that cycles were not purely due to environmental causes or reporting biases (in the case of SeizureTracker data)," the researchers write.

Ready for Prime Time?

Detecting and tracking seizure cycles on an individual basis "should be standard in epilepsy management practices," write the investigators.

"Seizure tracking can be implemented now with systems like SeizureTracker," Cook said. "And although we know that patients may often be unaware of events and not record them accurately, it is still possible to find these patterns using diaries like this, as we have shown in this study. New wearable and implantable devices are available or being developed that will make this even more accurate in the future."

In an accompanying editorial, Andreas Schulze-Bonhage, MD, PhD, from the Epilepsy Center at the University Medical Center, Freiburg, Germany, notes that "ultraslow oscillations in brain excitability are so far barely understood.

"There is evidence emerging that such slow cycles below well-known circadian rhythms influence both physiological functioning and disease states. It is remarkable that the group of Mark Cook found such long-lasting cycling alterations in seizure propensity over several weeks, which have also been reported in chronic psychiatric diseases," he writes.

Seizure rhythms can vary between individuals, and "identification of this can be a step towards individualized adaptations of treatment," Schulze-Bonhage told Medscape Medical News.

"As present-day state-of-the-art documentation of seizures suffers from problems of correct memorizing by patients, objective means of seizure documentation are presently an object of research. Some but not all seizure types can already be detected by devices during the night, but major effort is yet needed to provide a complete and reliable seizure documentation. This certainly would have major implications for the steering of treatment," said Schulze-Bonhage.

This study was funded by the Australian National Health and the Medical Research Council. Dr Cook and Dr Schulze-Bonhage have reported no relevant financial relationships. One of the study authors is cofounder of SeizureTracker.com.

Lancet Neurol. Published online September 12, 2018. Abstract, Editorial

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