Commonalities and Differences in NREM Parasomnias and Sleep-Related Epilepsy: Is There a Continuum Between the Two Conditions?

Abstract

Introduction: Differential diagnosis between disorders of arousal (DoA) and sleep-related hypermotor epilepsy (SHE) often represents a clinical challenge. The two conditions may be indistinguishable from a semiological point of view and the scalp video-polysomnography is often uninformative. Both disorders are associated with variable hypermotor manifestations ranging from major events to fragments of a hierarchical continuum of increasing intensity, complexity, and duration. Given their semiological overlap we decided to explore the sleep texture of DoA and SHE seeking for similarities and differences.Methods: We analyzed sleep macrostructure and CAP (cyclic alternating pattern) parameters in a cohort of 35 adult DoA patients, 40 SHE patients and 24 healthy sleepers, all recorded and scored in the same sleep laboratory. Nocturnal behavioral manifestations included minor motor events, paroxysmal arousals and major attacks in SHE, and simple, rising, or complex arousal movements in DoA.Results: Compared to healthy controls, DoA and SHE showed similar amounts of sleep efficiency, light sleep, deep sleep, REM sleep, CAP subtypes. Both groups also showed slow wave sleep fragmentation and an increased representation of stage N3 in the second part of the night. The only discriminating elements between the two conditions regarded sleep length (more reduced in DoA) and sleep instability (more elevated in SHE). In DoA recordings, all motor episodes arose from NREM sleep: 37% during light NREM stages and 63% during stage N3 (simple arousal movements: 94%). In SHE recordings, 57% of major attacks occurred during stage N3.Conclusions: So far, emphasis has been placed on the differentiation of sleep-related epilepsy and NREM arousal disorders. However, the impressive analogies between DoA and SHE suggest the existence of an underestimated continuum across the conditions, linked by increased levels of sleep instability, higher amounts of slow wave sleep and NREM/REM sleep imbalance. Sleep texture is extremely similar in the two conditions, although CAP metrics disclose quantitative differences. In particular, SHE patients show a higher arousal instability compared to DoA subjects. Given their clinical and epidemiological overlap, a common genetic background is also hypothesized. In such a perspective, we suggest that the consolidated dichotomy DoA vs. SHE should be reappraised.

Sleep medicine: Practice, challenges and new frontiers

“…The relationship between OSA and epilepsy is a complex and bidirectional one: epileptic patients with untreated OSA experienced more nocturnal seizures and, in drug-resistant epilepsy the prevalence of OSA is estimated around 33% (121,122). The two conditions share the reduction of REM sleep that had been proposed as a biomarker for epilepsy severity/drugrefractiveness (120,123). Accordingly, the restoration of REM sleep should be included as one of the main goals of OSA and epilepsy therapies (124).…”

“…Routine clinical practice is often complicated by the overlap of sleep apnea with other sleep disorders (PLMD, NREM sleep parasomnia, epilepsy, RBD, narcolepsy). Coexistent sleep pathologies may lower patients' compliance to OSA treatment, and untreated sleep apneas may trigger abnormal arousals leading to NREM sleep parasomnias or nocturnal seizures (120). The relationship between OSA and epilepsy is a complex and bidirectional one: epileptic patients with untreated OSA experienced more nocturnal seizures and, in drug-resistant epilepsy the prevalence of OSA is estimated around 33% (121,122).…”

“…strongly to sleep, while other forms are less sleep-related (178). Thus, a doubt has persisted on the uniformity of the SHE groups (120,176,179). Also, the definition of "sleep relatedness" needs an extension.…”

“…The relationship between arousals and sleep in DOA and SHE is still a matter of debate: two recent studies (120,159) highlighted the role of the fascinating clash between sleep and arousal forces in triggering seizures/events.…”

Sleep and epilepsy: A snapshot of knowledge and future research lines

“…Moreover, analysing specific semiological features captured on video-PSG such as duration, sleep stage at onset, limb involvement, movement progression and behaviours can be useful to differentiate seizure fragment in SHE from SAMs in DOA (Loddo et al, 2020). However, other studies suggest the existence of a possible continuum between the two conditions, mitigating the sharp dichotomy DOA versus SHE (Halász, Kelemen, & Szűcs, 2012;Mutti et al, 2020).…”