Sleep‐related hypermotor epilepsy and non‐rapid eye movement parasomnias: Differences in the periodic and aperiodic component of the electroencephalographic power spectra

Over the last two decades, our understanding of clinical and pathophysiological aspects of sleep-related epileptic and non-epileptic paroxysmal behaviours has improved considerably, although it is far from complete. Indeed, even if many core characteristics of sleep-related hypermotor epilepsy and non-rapid eye movement parasomnias have been clarified, some crucial points remain controversial, and the overlap of the behavioural patterns between these disorders represents a diagnostic challenge. In this work, we focused on segments of multichannel sleep electroencephalogram free from clinical episodes, from two groups of subjects affected by sleep-related hypermotor epilepsy (N = 15) and non-rapid eye movement parasomnias (N = 16), respectively. We examined sleep stages N2 and N3 of the first part of the night (cycles 1 and 2), and assessed the existence of differences in the periodic and aperiodic components of the electroencephalogram power spectra between the two groups, using the Fitting Oscillations & One Over f (FOOOF) toolbox. A significant difference in the gamma frequency band was found, with an increased relative power in sleep-related hypermotor epilepsy subjects, during both N2 (p < .001) and N3 (p < .001), and a significant higher slope of the aperiodic component in non-rapid eye movement parasomnias, compared with sleep-related hypermotor epilepsy, during N3 (p = .012). We suggest that the relative power of the gamma band and the slope extracted from the aperiodic component of the electroencephalogram signal may be helpful to characterize differences between subjects affected by non-rapid eye movement parasomnias and those affected by sleep-related hypermotor epilepsy

Preliminary finding of a randomized, double-blind, placebo-controlled, crossover study to evaluate the safety and efficacy of 5-hydroxytryptophan on REM sleep behavior disorder in Parkinson's disease

Altered serotonergic neurotransmission may contribute to the non-motor features commonly associated with Parkinson's disease (PD) such as sleep disorders. The 5-hydroxytryptophan (5-HTP) is the intermediate metabolite of L-tryptophan in the production of serotonin and melatonin. The purpose of this study was to compare the effects of 5-HTP to placebo on REM sleep behavior disorder (RBD) status in patients with PD

Sleep, Sleep Structure and Sleep Disorders in a Cohort of Patients Affected by ALS

Amyotrophic Lateral Sclerosis is a neurodegenerative disease, mostly due to progressive loss of motor neurons, with poor prognosis. Although motor involvement is predominant, other systems may be altered, and, among these, also sleep. The aim of this study is to evaluate sleep in a cohort of patients affected by ALS. We consecutively enrolled 48 patients, whom underwent to clinical and instrumental evaluation, including a full night video-PSG. They were compared to 15 control subjects. Respect to controls, patients had fragmented sleep, with poor sleep efficiency, higher amount of WASO and N1 sleep stage, and lower percentage of N2 and REM sleep stages, despite they perceived a sleep of good quality. Moreover, 33% of patients underwent video-PSG was diagnosed with OSAS, and 14, 28% with nocturnal respiratory insufficiency. Start NIV early is known to raise QOL, prolong life expectancy, and improve compliance to subsequent 24h NIV and tracheal ventilation. Furthermore, sleep of bad quality is a cardiovascular risk factor. In conclusion, in patients with ALS, instrumental assessment of sleep in early stages of the disease should be mandatory

Quantification of REM sleep without atonia: A review of study methods and meta-analysis of their performance for the diagnosis of RBD

: The present review focuses on REM sleep without atonia (RSWA) scoring methods. In consideration of the numerous papers published in the last decade, that used different methods for the quantification of RSWA, their systematic revision is an emerging need. We made a search using the PubMed, Embase, Scopus and Web of Science Databases, from 2010 until December 2021, combining the search term "RSWA" with "scoring methods", "IRBD", "alfasyn disease", and "neurodegenerative disease", and with each of the specific sleep disorders, diagnosed according to current criteria, with the identification of the references of interest for the topic. Furthermore, a Meta-analysis of the diagnostic performance of RSWA scoring methods, in terms of sensitivity and specificity, was carried out. The comparison of the hierarchical summary receiver-operating characteristic curves obtained for visual methods and that obtained for the automated REM sleep atonia index (RAI), shows substantially similar prediction areas indicating a comparable performance. This systematic review and meta-analysis support the validity of a series of visual methods and of the automated RAI in the quantification of RSWA with the purpose to guide clinicians in the interpretation of their results and their correct and efficient use within the diagnostic work-up for REM sleep behavior disorder

Neuropsychological and Behavioral Profile in Sleep-Related Hypermotor Epilepsy (SHE) and Disorders of Arousal (DOA): A Multimodal Analysis

Study Objectives: Disorder of arousal (DOA) and sleep-related hypermotor epilepsy (SHE) are complex, often bizarre, involuntary sleep behaviors, whose differential diagnosis may be challenging because they share some clinical features, such as sleep fragmentation. Mounting evidence highlights the critical role of sleep in cognitive functions. Controversial findings are raised about the cognitive profile in SHE; however, no studies have investigated the cognitive profile in DOA. This study aimed to assess whether sleep instability affects cognitive functions in patients with SHE or DOA. Methods: This study analyzed 11 patients with DOA, 11 patients with SHE, and 22 healthy controls (HC). They underwent full-night video polysomnography (vPSG) and comprehensive neuropsychological and behavioral evaluation. Differences in the variables of interest among the SHE group, DOA group, and their respective control groups were evaluated. The auto-contractive map (auto-CM) system was used to evaluate the strength of association across the collected data. Results: The SHE group had reduced sleep efficiency and increased wake after sleep onset (WASO); both the SHE and DOA groups showed increased % of N2 and REM sleep compared to the HC group. Neuropsychological and behavioral evaluations showed a different cognitive profile in the SHE group with respect to the HC group. The auto-CM showed that Pittsburgh Sleep Quality Index (PSQI), Beck depression inventory (BDI), MWCST_PE, Epworth sleepiness scale (ESS), WASO, N1, and % REM were strictly correlated with SHE, whereas the SE and arousal index (AI) were strictly related to DOA. Conclusions: Patients with SHE and DOA present different cognitive and psychiatric profiles, with subtle and selective cognitive impairments only in those with SHE, supporting the discriminative power of cognitive and psychiatric assessment in these two conditions

REM Sleep without atonia correlates with abnormal vestibular-evoked myogenic potentials in isolated REM sleep behavior disorder

The neurophysiological hallmark of REM sleep behavior disorder (RBD) is loss of atonia during REM sleep. Indeed, signs and symptoms of neurodegeneration can occur after years, even decades, from its beginning. This study aimed to measure neurophysiological alterations of the brainstem that potentially correlate with the severity of atonia loss, and determining whether a prodromal neurodegenerative disorder underlines this condition when it occurs as an isolated condition (iRBD). Methods: Subjects with iRBD and matched healthy controls were recruited. The study included the recording of one-night polysomnography, vestibular-evoked myogenic potentials (VEMPs), and a [123I]-FP-CIT dopamine transporter (DAT) scan. The quantification of REM sleep without atonia (RSWA) was made according to two previously published manual methods and one automated method. Results: The rate of alteration of VEMPs and VEMP score were significantly higher in iRBD patients than controls. Moreover, VEMP score was negatively correlated with the automated REM atonia index; a marginal statistical significance was also reached for the positive correlation with the visual tonic electromyographic parameter, while the other correlations, including that with DAT-scan score were not statistically significant. Conclusions: Brainstem neurophysiology in iRBD can be assessed by VEMPs and their alterations may possibly indicate an early expression of the neurodegenerative process underlying this disorder at the brainstem level, which awaits future longitudinal confirmation. The correlation between RSWA and VEMP alteration might also represent a prodromal aspect anticipating the possible evolution from iRBD to neurodegeneration, whereas DAT-scan abnormalities might represent a later step in this evolution

Severity of REM sleep without atonia correlates with measures of cognitive impairment and depressive symptoms in REM sleep behaviour disorder

This study aimed to correlate REM sleep without atonia (RSWA) and neuropsychological data in patients with idiopathic/isolated REM sleep behaviour disorder (iRBD) and those with RBD associated with Parkinson's disease (PDRBD), in order to assess whether higher degrees of RSWA are related to poorer cognitive performance. A total of 142 subjects were enrolled: 48 with iRBD, 55 with PDRBD, and 39 PD without RBD (PDnoRBD). All participants underwent video-polysomnographic recording, clinical and neuropsychological assessment. RSWA was quantified according to two manual scoring methods (Montreal, SINBAR) and one automated (REM atonia index, RAI). Mild cognitive impairment (MCI) was diagnosed according to diagnostic criteria for MCI in Parkinson's disease. The relationship between neuropsychological scores and RSWA metrics was explored by multiple linear regression analysis and logistic regression models. Patients with iRBD showed significantly lower visuospatial functions and working memory, compared with the others. More severe RSWA was associated with a higher risk of reduced visuospatial abilities (OR 0.15), working memory (OR 2.48), attention (OR 2.53), and semantic fluency (OR 0.15) in the iRBD. In the whole group, a greater RSWA was associated with an increased risk for depressive symptoms (OR 3.6). A total of 57(40%) MCI subjects were found (17 iRBD, 26 PDRBD, and 14 PDnoRBD). Preserved REM-atonia was associated with a reduced odds of multi-domain MCI in the whole study population (OR 0.54). In conclusion, a greater severity of RSWA was associated with an increased risk for poor cognitive performance and depressive mood in patients with RBD. Moreover, higher RAI was associated with a lower risk of multi-domain MCI