Suppression of interictal spikes during phasic rapid eye movement sleep: a quantitative stereo‐electroencephalography study

Abstract

Tonic and phasic rapid eye movement (REM) sleep seem to represent two different brain states exerting different effects on epileptic activity. In particular, interictal spikes are suppressed strongly during phasic REM sleep. The reason for this effect is not understood completely. A different level of synchronization in phasic and tonic REM sleep has been postulated, yet never measured directly. Here we assessed the interictal spike rate across non-REM (NREM) sleep, phasic and tonic REM sleep in nine patients affected by drug resistant focal epilepsy: five with type II focal cortical dysplasia and four with hippocampal sclerosis. Moreover, we applied different quantitative measures to evaluate the level of synchronization at the local and global scale during phasic and tonic REM sleep. We found a lower spike rate in phasic REM sleep, both within and outside the seizure onset zone. This effect seems to be independent from the histopathological substrate and from the brain region, where epileptic activity is produced (temporal versus extra-temporal). A higher level of synchronization was observed during tonic REM sleep both on a large (global) and small (local) spatial scale. Phasic REM sleep appears to be an interesting model for understanding the mechanisms of suppression of epileptic activity.

The microstructure of REM sleep: Why phasic and tonic?

“…Such an inhibitory effect of epileptic activity has been interpreted as the result of the depolarization of the thalamocortical neurons leading to a blockage of the thalamocortical oscillations [112]. However, more recently it has been shown that this inhibitory effect on epileptic activity is mostly exerted by phasic REM sleep, which markedly suppresses the occurrence and propagation of both interictal spikes and pathological high frequency oscillations (HFO) [113,114]. On the other end, the effect of tonic REM sleep is not significantly different from that of NREM sleep.…”

NREM sleep is the state of vigilance that best identifies the epileptogenic zone in the interictal electroencephalogram

“…In contrast, our findings do not support a role for the REM sleep-suppressive effects on interictal features to contribute to a better prediction of the EZ. 23,24,28,29,45,46 Lower AUCs during REM sleep as compared to NREM sleep are rather pointing to a suboptimal trade-off between sensitivity and specificity for REM sleep.…”

Interictal epileptiform discharges in sleep and the role of the thalamus in Encephalopathy related to Status Epilepticus during slow Sleep

“…Scalp EEG studies have shown that NREM sleep increases the number of IEDs and favours seizure occurrence both in focal and generalized epilepsies while REM sleep does not (Ferrillo et al, 2000;Herman et al, 2001;Campana et al, 2017). NREM sleep can also facilitate the spread of IEDs, both ipsilaterally and contralaterally from the primary focus in focal epilepsy (Malow et al, 1998;Sammaritano et al, 1991), especially during arousal fluctuations, namely phase A of the cyclic alternating pattern (CAP) (Halász et al, 2004;Parrino et al, 2006).…”

“…NREM sleep can also facilitate the spread of IEDs, both ipsilaterally and contralaterally from the primary focus in focal epilepsy (Malow et al, 1998;Sammaritano et al, 1991), especially during arousal fluctuations, namely phase A of the cyclic alternating pattern (CAP) (Halász et al, 2004;Parrino et al, 2006). Conversely, this phenomenon is not observed in REM sleep, where a reduced spatial and temporal summation of electrical signals is observed, thereby limiting the propagation and scalp EEG expression of the IEDs (Sammaritano et al, 1991;Frauscher et al, 2016;Campana et al, 2017). The mechanisms by which NREM sleep activates IEDs have been extensively studied since the original publication by Gibbs and Gibbs on the usefulness of sleep to record IEDs (Gibbs and Gibbs, 1947).…”