Chronobiology of epilepsy and sudden unexpected death in epilepsy

Abstract

Epilepsy is a neurological disease characterized by spontaneous, unprovoked seizures. Various insults render the brain hyperexcitable and susceptible to seizure. Despite there being dozens of preventative anti-seizure medications available, these drugs fail to control seizures in nearly 1 in 3 patients with epilepsy. Over the last century, a large body of evidence has demonstrated that internal and external rhythms can modify seizure phenotypes. Physiologically relevant rhythms with shorter periodic rhythms, such as endogenous circadian rhythms and sleep-state, as well as rhythms with longer periodicity, including multidien rhythms and menses, influence the timing of seizures through poorly understood mechanisms. The purpose of this review is to discuss the findings from both human and animal studies that consider the effect of such biologically relevant rhythms on epilepsy and seizure-associated death. Patients with medically refractory epilepsy are at increased risk of sudden unexpected death in epilepsy (SUDEP). The role that some of these rhythms play in the nocturnal susceptibility to SUDEP will also be discussed. While the involvement of some of these rhythms in epilepsy has been known for over a century, applying the rhythmic nature of such phenomenon to epilepsy management, particularly in mitigating the risk of SUDEP, has been underutilized. As our understanding of the physiological influence on such rhythmic phenomenon improves, and as technology for chronic intracranial epileptiform monitoring becomes more widespread, smaller and less invasive, novel seizure-prediction technologies and time-dependent chronotherapeutic seizure management strategies can be realized.

Neural signal data collection and analysis of Percept™ PC BrainSense recordings for thalamic stimulation in epilepsy

“…In addition to the in-clinic recording capabilities, Percept™ PC can record a 10 min average LFP measurement within a 5 Hz band, determined by the clinician, and store it in a 60 d running memory with a first-in first out buffer. This signal allows for the detection of biorhythmic cycles [27][28][29][30][31] with periods of hours, days, weeks, and months; these cycles have been observed in both males and females, and in some patients, they are correlated with seizure frequency [29,32]. The raw LFP average measurements of alpha band activity (8.79 Hz ± 2.5 Hz) over 28 d are shown in figure 6(A).…”

Sudden unexpected death in epilepsy

“…It is somewhat surprising that the preponderance of death from seizures occurs during the night in both diurnal humans and nocturnal rodents. This suggests a conserved mechanism, one of which could be the circadian oscillation in 5-HT, which is similar in some brain loci between species [133,134,141]. The relative importance of sleep state versus time or day/circadian pattern is yet to be determined.…”

“…There is a strong bidirectional interaction between sleep and epilepsy [132]. There is also a well described influence of circadian rhythms and time of day on epilepsy and seizures [133]. A large proportion, if not most, SUDEP occurs during the night [134].…”

Cyclical underreporting of seizures in patient‐based seizure documentation

“…Moreover, the cyclical structure of the manifestation of epileptic seizures is relevant in several regards. The distribution of seizures over time may provide data to model endogenous 2 , 3 , 4 or exogenous 5 , 6 factors modulating brain excitability. Cyclical seizure distributions may be relevant for SUDEP risk assessment.…”