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Sleep and Cortisol Offer Insight into Epileptic Seizures

Sleeping patterns and stress hormones could be the key to understanding how and when people with epilepsy are likely to experience seizures, according to a study published in PLoS Computational Biology.

Epilepsy is one of the most common serious neurological conditions in the world, and affects around 630,000 people in the UK – equating to around 1 in 100 people. Epilepsy Action highlighted that around 80 people are diagnosed with epilepsy in the UK every day.

Epileptiform discharge frequency increases during the night, early in the morning, and in stressful situations in many people with epilepsy, the authors of the new study said. 

"Some 65 million people have epilepsy worldwide, many of whom report specific triggers that make their seizures more likely - the most common of which include stress, sleep deprivation and fatigue," commented study first author Dr Isabella Marinelli from the Centre for Systems Modelling and Quantitative Biomedicine at the University of Birmingham.

Epilepsy is characterised by a tendency to have recurrent, spontaneous seizures, which had been assumed to occur at random. However, the study authors noted that recent research had uncovered "underlying rhythms both in seizures and in key signatures of epilepsy — so-called interictal epileptiform activity" — with timescales that varied from hours and days through to months. 

However, understanding the physiological mechanisms that determined these rhythmic patterns of epileptiform discharges "remained an open question", they emphasised.

Sleep and Stress Offer Clues About Epileptic Seizures

Along with colleagues from the University of Exeter, University of Bristol, University of Melbourne, Australia, and Monash University, Australia, they set out to provide a computational framework for assessing how the likelihood of epileptiform discharge was impacted by different physiological mechanisms and processes, such as sleep and changes in concentration of the stress-hormone cortisol. 

To do so, the researchers analysed 24-hour EEG recordings from 107 people with idiopathic generalised epilepsy in order to quantify the impact of physiological factors. They used mathematical modelling to understand the impact of different physiological processes, such as sleep and changes in concentration of the stress-hormone cortisol, on epileptiform discharges observed across the day. 

They found that the median number of epileptiform discharges over 24 hours was approximately 29, although several individuals had more than 200 events.

The researchers discovered two subgroups with distinct distributions of epileptiform discharges, one with highest incidence during sleep and the other during daytime. Also, that sleep accounted for 90% of variation in one subgroup and cortisol around 60% in the other subgroup.

The authors explained that "either the dynamics of cortisol or sleep stage transition, or a combination of both, explained most of the observed distributions of epileptiform discharges".

Better Understanding of Potential Seizure Triggers

Dr Marinelli said: "Our findings provide conceptual evidence that sleep patterns and changes in concentration of cortisol are underlying physiological drivers of rhythms of epileptiform discharges." 

The mathematical approach provided a framework for better understanding which factors facilitated the occurrence of epileptiform discharge activity and potentially triggered seizures, she highlighted.

"Sleep alone cannot account for the changes in epileptiform discharge likelihood during wakefulness observed in our first subgroup," explained Dr Marinelli. "There is a reduction in epileptiform discharge likelihood during the sleep time after an initial sharp increase during the first hours. This can be explained by the fact that deep sleep, which is linked to an increase of epileptiform discharges, is predominant during the first third of the sleep period. We found an increase in epileptiform discharge occurrence before waking, which, given that the level of cortisol is known to increase around waking, suggests a combined effect of sleep and cortisol."

The authors concluded that they had provided quantitative evidence that "underlying physiological modulators for epileptiform discharge events exist", had identified sleep and cortisol as such modulators that "influence how likely it is for epileptiform activity to occur", and that these "can explain most of the daily variability".

Asked to comment for Medscape News UK, Tom Shillito, health improvement and research manager at Epilepsy Action said, "We know that lack of sleep and stress are two of the seizure triggers most commonly reported by people with epilepsy and so it is promising that this research has identified the role that these factors can have on the frequency of seizures."

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