Dead in the night. The nocturnality of SUDEP

Benton S. Purnell, Roland D. Thijsand Gordon F. Buchanan.  Dead in the Night: Sleep-Wake and Time-Of-Day Influences on Sudden Unexpected Death in Epilepsy.  Front. Neurol., 11 December 2018 | https://doi.org/10.3389/fneur.2018.01079

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death in patients with refractory epilepsy. Convergent lines of evidence suggest that SUDEP occurs due to seizure induced perturbation of respiratory, cardiac, and electrocerebral function as well as potential predisposing factors. It is consistently observed that SUDEP happens more during the night and the early hours of the morning. The aim of this review is to discuss evidence from patient cases, clinical studies, and animal research which is pertinent to the nocturnality of SUDEP. There are a number of factors which might contribute to the nighttime predilection of SUDEP. These factors fall into four categories: influences of (1) being unwitnessed, (2) lying prone in bed, (3) sleep-wake state, and (4) circadian rhythms. During the night, seizures are more likely to be unwitnessed; therefore, it is less likely that another person would be able to administer a lifesaving intervention. Patients are more likely to be prone on a bed following a nocturnal seizure. Being prone in the accouterments of a bed during the postictal period might impair breathing and increase SUDEP risk. Sleep typically happens at night and seizures which emerge from sleep might be more dangerous. Lastly, there are circadian changes to physiology during the night which might facilitate SUDEP. These possible explanations for the nocturnality of SUDEP are not mutually exclusive. The increased rate of SUDEP during the night is likely multifactorial involving both situational factors, such as being without a witness and prone, and physiological changes due to the influence of sleep and circadian rhythms. Understanding the causal elements in the nocturnality of SUDEP may be critical to the development of effective preventive countermeasures….

The reason that SUDEP happens more during the night is likely multifactorial involving both situational factors, such as being unattended, and physiological changes due to the influence of sleep and circadian rhythms. Human studies suggest that being without a witness and prone following a seizure, which is more likely during the night, might increase risk for nocturnal SUDEP. At the same time, experimentation in animal models and observation of human seizures indicate that both sleep and circadian phase may adversely affect postictal cardiovascular recovery. Sleep and circadian phase have additive effects on breathing which may compound in some way to produce a hazardous postictal state. Similarly, it may be that sleep, and circadian phase have additive effects on vulnerability to seizure induced respiratory arrest. When the factors associated with being without a witness and prone are added to the mix along with the potential effects of sleep and circadian phase SUDEP might be more likely.

Altering the circumstances in which a seizure occurs is currently the best way for reducing the probability of nocturnal SUDEP, but it is not enough. Patients who do not sleep alone or are being monitored by the use of a device seem to be somewhat protected against SUDEP; however, numerous SUDEP cases have occurred in the direct presence of medical professionals and none of their interventions were sufficient to prevent death. Families and caregivers should be educated about SUDEP and given instruction in basic seizure first aid; however, it should be made abundantly clear that such interventions might be sufficient to prevent death, but it might not and those who have lost someone due to SUDEP are in no way at fault. The risk of SUDEP, nocturnal and otherwise, should be taken into account by patients considering any choice which might alter their likelihood of having a seizure such as adherence, titrating off their medications, switching medication, or pursuing surgical interventions or other non-pharmacological measures.