Non-rapid eye movement (NREM) sleep parasomnias (or NREM parasomnias) are fascinating disorders with mysterious neurobiological substrates. These conditions are common and often severe, with social, personal and forensic implications. The NREM parasomnias include sleepwalking, sleep terrors and confusional arousals — collectively termed disorders of arousal (DOAs) — as well as less well-known entities such as sleep-related sexual behaviours and eating disorders. Affected patients can exhibit waking behaviours arising abruptly out of NREM sleep. Although the individual remains largely unresponsive to the external environment, their EEG shows both typical sleep-like and wake-like features, and they occasionally report dreaming afterwards. Therefore, these disorders offer a unique natural model to explore the abnormal coexistence of local sleep and wake brain activity and the dissociation between behaviour and various aspects of consciousness. In this article, we critically review major findings and updates on DOAs, focusing on neurophysiological studies, and offer an overview of new clinical frontiers and promising future research areas. We advocate a joint effort to inform clinicians and the general public about the management and follow-up of these conditions. We also strongly encourage collaborative multicentre studies to add more objective polysomnographic criteria to the current official diagnostic definitions and to develop clinical practice guidelines, multidisciplinary research approaches and evidence-based medical care.
The non-rapid eye movement (NREM) sleep parasomnias (or NREM parasomnias) encompass disorders of arousal (DOAs) — namely, sleepwalking, sleep terrors and confusional arousals — and lesser-known entities such as sleep-related sexual behaviours and eating disorders.
NREM parasomnias are common during both childhood and adulthood and can have adverse and frequently overlooked consequences, including unintentional self-harm, harm to others (with potential legal implications), daytime sleepiness and psychological distress.
A key feature of NREM parasomnias is the dissociation between self-awareness and behaviour, as well as between wakefulness and sleep in different brain regions, as demonstrated by single-photon emission CT and stereo-EEG case reports.
Neurophysiological and neuroimaging studies in people with DOAs have provided evidence of abnormal brain function not only during slow-wave sleep but also during REM sleep and wakefulness.
Research in the field is currently hindered by the commonly held view of DOAs as benign conditions and by a lack of animal models, strong neurobiological hypotheses and clear pharmacological target symptoms.
Collaborative networks need to be established to promote the development of objective diagnostic criteria and evidence-based clinical practice guidelines and to facilitate controlled pharmacological studies and multidisciplinary research.
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Articles discussed in this Review were identified by PubMed searches using the search terms “parasomnias”, “disorders of arousal”, “sleepwalking”, “somnambulism”, “sleep terrors”, “confusional arousals”, “sleep-related eating disorder” and “sexsomnia”, among others. The reference lists of identified papers were searched for further relevant articles, and related citations for identified papers as listed on the PubMed site were evaluated. The final selection of references was based on the relevance to the scope of this Review.
Nature Reviews Neurology thanks C. Schenck and F. Provini for their contribution to the peer review of this work.
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- Non-rapid eye movement (NREM) sleep
Non-rapid eye movement sleep encompasses stages 1–3 of sleep and is characterized by distinct electrophysiological features from rapid eye movement sleep, such as the absence of phasic rapid eye movements and of muscle atonia.
Sleep disorders defined as undesirable behavioural and physiological, autonomic or experiential events that accompany sleep.
- Slow-wave sleep
(SWS). The deepest stage of non-rapid eye movement sleep, characterized by synchronized EEG activity producing high-amplitude slow waves with a frequency range of 0.5–4.0 Hz.
- Local sleep
Refers to evidence that sleep can occur locally and asynchronously across brain regions, and that local sleep-like and wake-like activities can coexist in different brain areas at the same time.
- Cyclic alternating pattern
(CAP). An EEG marker of arousal fluctuations of non-rapid eye movement sleep.
- Slow-wave activity
(SWA). A quantitative measure of non-rapid eye movement sleep intensity and dynamics that is based on spectral analysis of the slow waves.
- Sleep spindles
Short bursts of neural oscillatory activity that are generated by thalamic nuclei during stage 2 non-rapid eye movement sleep.
The practice of recording EEG signals via invasive electrodes surgically implanted into the brain tissue in presurgical, treatment-resistant patients with epilepsy.
- LOD score
The LOD score is a statistical test often used for genetic linkage analyses. It compares the likelihood of two loci actually being linked against the likelihood of observing this result purely by chance.
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Castelnovo, A., Lopez, R., Proserpio, P. et al. NREM sleep parasomnias as disorders of sleep-state dissociation. Nat Rev Neurol 14, 470–481 (2018). https://doi.org/10.1038/s41582-018-0030-y
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