Sleep architecture in drug‐naïve adult patients with epilepsy: Comparison between focal and generalized epilepsy

Abstract

Objective: Sleep impairment is one of the most common comorbidities affecting people with epilepsy (PWE). The bidirectional relation between epilepsy and sleep has been widely established. Several studies investigated subjective sleep quality and daytime vigilance in PWE, highlighting frequent complaints of sleep fragmentation, difficulties in falling asleep, and daytime sleepiness. The present study aimed to evaluate sleep structure in drug-naive PWE, distributed on the basis of epilepsy type, and compared with controls. Methods: This observational study included adult patients newly diagnosed with epilepsy and drug-naive as well as a control group of healthy subjects. All PWE and controls underwent a dynamic 24-h EEG with signals for sleep recording to evaluate sleep architecture, structure, continuity, and fragmentation.Results: Twenty-four PWE were included and distributed in two groups based on epilepsy type. Eleven patients were included in the generalized epilepsy group (63.6% male; 34.91 ± 9.80 years) and 13 patients in the focal epilepsy group (53.8% male; 38.69 ± 12.74 years). The control group included 16 subjects (56.3% male; 32.75 ± 12.19 years). Patients with generalized or focal epilepsy had a significantly lower sleep efficiency than controls. Moreover, both patient groups presented the alteration of markers of sleep fragmentation and loss of continuity, with higher indices of sleep stage transitions and arousal. Finally, the two patient groups presented less REM sleep than controls.

Role of the orexin system in the bidirectional relation between sleep and epilepsy: New chances for patients with epilepsy by the antagonism to orexin receptors?

“…11,16,107 Recent data also include the increased frequency of sleep stage shifts in PWE, coupled with more frequent wake bouts, producing sleep instability, lack of sleep continuity, and REM sleep impairment. 21 Sleep fragmentation has been previously associated with changes in orexin neurotransmission in animal models and human studies 40,[108][109][110][111] and, although in a purely hypothetical model, it is conceivable that sleep impairment in PWE may be associated with increased orexin expression and function and that this neurotransmission overactivity can, in turn, impair sleep and possibly trigger IEDs and seizures (Figure 3). Therefore, antagonisms to orexin receptors may represent a strategy for improving sleep and thus seizures in PWE.…”

“…21 In this research, patients with focal epilepsy presented an increase in stage 2 of non-REM (NREM) sleep (N2) and wake after sleep onset and a decrease in REM, with consequent fragmentation of the sleep structure, compared to controls. 21 Previous studies showed that REM sleep presents an antiepileptic effect due to the reduction of ictal and interictal epileptic discharges (IEDs) in this sleep stage. It was consequently hypothesized that there is an important role of REM sleep in regulating the epileptic spiking threshold and hampering the risk of seizures.…”

“…To date, the scientific literature has clearly highlighted the impairment of sleep architecture in patients with focal and generalized epilepsy; nevertheless, as shown in a recent review, 20 few studies have compared the sleep structure of PWE with controls and there is no general agreement about objective sleep impairment in PWE, because of the heterogeneity of patients included (considering type of epilepsy, type of seizure, etiology of epilepsy) and the different methods for sleep recording and analysis. To increase the knowledge about sleep macrostructure in PWE, a very recent study documented the alteration of sleep stability and continuity in both focal and generalized epilepsy 21 . In this research, patients with focal epilepsy presented an increase in stage 2 of non‐REM (NREM) sleep (N2) and wake after sleep onset and a decrease in REM, with consequent fragmentation of the sleep structure, compared to controls 21 .…”

“…28 Epileptic manifestations during sleep can be therefore mainly triggered by the frequent sleep stage shifting. 21 Hence, the microstructural assessment (cyclic alternating pattern rate), identifying the sleep stability, is needed to add details on the intrinsic dynamics of the different NREM and REM stages in PWE and their relation to IEDs and seizures. Therefore, to better define the effect of REM sleep on seizures, IEDs, and high-frequency oscillations (HFOs), and to understand the increase in seizure propensity due to insufficient sleep, sleep deprivation, instability, or fragmentation, 29,30 the investigation of further neurotransmitting systems involved in sleep regulation, namely orexin, can be useful in epilepsy research.…”

“…To increase the knowledge about sleep macrostructure in PWE, a very recent study documented the alteration of sleep stability and continuity in both focal and generalized epilepsy 21 . In this research, patients with focal epilepsy presented an increase in stage 2 of non‐REM (NREM) sleep (N2) and wake after sleep onset and a decrease in REM, with consequent fragmentation of the sleep structure, compared to controls 21 . Previous studies showed that REM sleep presents an antiepileptic effect due to the reduction of ictal and interictal epileptic discharges (IEDs) in this sleep stage.…”