Sleep Disruption in Epilepsy: Ictal and Interictal Epileptic Activity Matter

Abstract

Objective: Disturbed sleep is common in epilepsy. The direct influence of nocturnal epileptic activity on sleep fragmentation remains poorly understood. Stereo-electroencephalography paired with polysomnography is the ideal tool to study this relationship. We investigated whether sleep-related epileptic activity is associated with sleep disruption. Methods: We visually marked sleep stages, arousals, seizures, and epileptic bursts in 36 patients with focal drugresistant epilepsy who underwent combined stereo-electroencephalography/polysomnography during presurgical evaluation. Epileptic spikes were detected automatically. Spike and burst indices (n/sec/channel) were computed across four 3-second time windows (baseline sleep, pre-arousal, arousal, and post-arousal). Sleep stage and anatomic localization were tested as modulating factors. We assessed the intra-arousal dynamics of spikes and their relationship with the slow wave component of non-rapid eye-movement sleep (NR) arousals. Results: The vast majority of sleep-related seizures (82.4%; 76.5% asymptomatic) were followed by awakenings or arousals. The epileptic burst index increased significantly before arousals as compared to baseline and postarousal, irrespective of sleep stage or brain area. A similar pre-arousal increase was observed for the spike index in NR stage 2 and rapid eye-movement sleep. In addition, the spike index increased during the arousal itself in neocortical channels, and was strongly correlated with the slow wave component of NR arousals (r = 0.99, p < 0.0001). Interpretation: Sleep fragmentation in focal drug-resistant epilepsy is associated with ictal and interictal epileptic activity. The increase in interictal epileptic activity before arousals suggests its participation in sleep disruption. An additional increase in the spike rate during arousals may result from a sleep-wake boundary instability, suggesting a bidirectional relationship.

Invasive Electrophysiology for Circuit Discovery and Study of Comorbid Psychiatric Disorders in Patients With Epilepsy: Challenges, Opportunities, and Novel Technologies

“…Sleep difficulties and disorders are common in epilepsy and are likely multifactorial (Grigg-Damberger and Foldvary-Schaefer, 2015 ; Freeman et al, 2020 ; Winkelman and Lecea, 2020 ). In focal, drug-resistant epilepsy, sleep fragmentation is associated with seizures as well as bursts of inter-ictal epileptiform activity (Peter-Derex et al, 2020 ). Although objective sleep alterations can be attributable to seizures, the relationship between subjective sleep quality and factors such as quality of life and psychiatric comorbidities is more complicated.…”

Relationship Between Epilepsy and Dreaming: Current Knowledge, Hypotheses, and Perspectives

“…Conversely, REM sleep (particularly the phasic REM sleep microstate) has an inhibitory influence on epileptic activity potentially linked to neuronal desynchronization mediated by cholinergic neurotransmission ( Ng and Pavlova, 2013 ; Frauscher et al, 2016 ). Although very rare, epileptic seizures can nonetheless be observed during REM sleep ( Minecan et al, 2002 ; Peter-Derex et al, 2020 ). Chronobiological factors also influence the occurrence of seizures ( Karoly et al, 2021 ).…”

“…On the other hand, epilepsy has a disrupting effect on sleep macro- and micro-architecture. It is associated with an increase in wake after sleep onset ( Sudbrack-Oliveira et al, 2019 ; Peter-Derex et al, 2020 ) but also with a micro-structural fragmentation of sleep, linked to both ictal and inter-ictal epileptic activity ( Malow et al, 2000 ; Peter-Derex et al, 2020 ). Recently, it has been proposed that epileptic activity might disrupt NREM sleep oscillations (slow waves, spindles, ripples) underlying sleep-related memory consolidation processes, which may have a deleterious effect on patients’ cognition ( Gelinas et al, 2016 ; Lambert et al, 2020 ; Lambert et al, 2021 ).…”

“…Epilepsy is not only characterized by seizures, but it is further complicated by significant comorbidities such as cognitive impairment and psychiatric disorders ( Fisher et al, 2005 ; Keezer et al, 2016 ). The interactions between epilepsy and sleep are numerous, including the comorbidity between epilepsy and sleep disorders, the activating effect of sleep on seizures and interictal epileptic activity, and the disturbance of sleep macro- and microstructure by these abnormalities ( Bazil, 2000 ; Van Golde et al, 2011 ; Peter-Derex et al, 2020 ; Bergmann et al, 2021 ). Thus, epilepsy is likely to have an impact on sleep-related cognitive activity (e.g., memory consolidation, stimuli perception/integration, dreaming).…”

Deep-Seated Interictal Epileptiform Activity: Another Reason to Lose Sleep

“…A recent study of side-specific hippocampal memory function of patients with focal epilepsy, evaluated with SEEG, has reported that retention of verbal memory over 1 week was negatively correlated with hippocampal spike frequency during sleep, whereas no significant correlation was found with hippocampal interictal EA occurring when awake. 7 As highlighted by Laure Peter-Derex et al, 6 not only ictal but also interictal EA occurring in the hippocampus during sleep may impair sleep quality and possibly impact memory consolidation.…”