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Alteration of motor control during rapid eye movements (REM) sleep has been extensively described in sleep disorders, in particular in isolated REM sleep behavior disorder (iRBD) and narcolepsy type 1 (NT1). NT1 is caused by the loss of orexin/hypocretin (ORX) neurons. Unlike in iRBD, the RBD comorbid symptoms of NT1 are not associated with alpha-synucleinopathies. To determine whether the chronic absence of ORX neuropeptides is sufficient to induce RBD symptoms, we analyzed during REM sleep the EMG signal of the prepro-hypocretin knockout mice (ORX-/-), a recognized mouse model of NT1. Then, we evaluated the severity of motor alterations by comparing the EMG data of ORX-/- mice to those of mice with a targeted suppression of the sublaterodorsal glutamatergic neurotransmission, a recognized rodent model of iRBD. We found a significant alteration of tonic and phasic components of EMG during REM sleep in ORX-/- mice, with more phasic events and more REM sleep episodes without atonia compared to the control wild-type mice. However, these phasic events were fewer, shorter, and less complex in ORX-/- mice compared to the RBD-like ORX-/- mice. We thus show that ORX deficiency, as seen in NT1, is sufficient to impair muscle atonia during REM sleep with a moderate severity of alteration as compared to isolated RBD mice. As described in NT1 patients, we report a major interindividual variability in the severity and frequency of RBD symptoms in ORX-deficient mice., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Disrupted nighttime sleep is one of the pentad of symptoms defining Narcolepsy. REM sleep behavior disorder (RBD) largely contributes to night sleep disruption and narcolepsy is the most common cause of secondary RBD. However, RBD linked to narcolepsy (N-RBD) has been insufficiently characterized, leaving unsolved a number of issues. Indeed, it is still debated whether N-RBD is an intrinsic feature of narcolepsy, as indubitable for cataplexy, and therefore strictly linked to the cerebrospinal fluid hypocretin-1 (CSF hcrt-1) deficiency, or an associated feature, with a still unclear pathophysiology. The current review aims at rendering a comprehensive state-of-the-art of N-RBD, highlighting the open and unsettled topics. RBD reportedly affects 30-60% of patients with Narcolepsy type 1 (NT1), but it may be seen also in Narcolepsy type 2 (NT2). When compared to idiopathic/isolated RBD (iRBD), N-RBD has been reported to be characterized by less energetic and quieter episode, which however occur with the same probability in the first and the second part of the night and sometime even subcontinuously. N-RBD patients are generally younger than those with iRBD. N-RBD has been putatively linked to wake-sleep instability due to CSF hcrt-1 deficiency, but this latter by itself cannot explain completely the phenomenon as N-RBD has not been universally linked to low CSF hcrt-1 levels and it may be observed also in NT2. Therefore, other factors may probably play a role and further studies are needed to clarify this issue. In addition, therapeutic options have been poorly investigated. [ABSTRACT FROM AUTHOR]

In recent years, the diagnostic approach to rapid eye movement (REM) sleep behavior disorder (RBD) has become more objective and accurate. This was achieved mainly by introduction of methods to exactly quantify electromyographic (EMG) activity in various muscles during REM sleep. The most established muscle combination for RBD diagnosis is the mentalis and upper extremity EMG. Computer-assisted systems for this analysis have been described, and an increasing number of studies looked into analysis of video events. Recently, prodromal phases of isolated RBD have been recognized., (Copyright © 2019 Elsevier Inc. All rights reserved.)