Increased sighing during sleep as a marker of multiple system atrophy.

Parkinson's disease (PD) and multiple system atrophy (MSA) can be preceded by isolated REM sleep behavior disorder (iRBD). As excessive sighing during wakefulness is a red flag for MSA in individuals with parkinsonism, we measured sighing during slow wave sleep (N3) and REM sleep as potential biomarkers in 73 participants with MSA, 111 with iRBD, 257 with PD, and 115 controls. The number of sighs/hour of N3 (index) was higher in the MSA group than in the other groups. Sighs were rarer in REM sleep than in N3 sleep. A sigh index greater than 3.4/h of N3 was 95% sensitive in discriminating participants with MSA from controls, and a sigh index greater than 0.8 sigh/h of REM sleep was 87% specific in discriminating participants with MSA from controls. MSA participants with (vs. without) sigh were younger, had a lower apnea-hypopnea index (but no more stridor), and had no other difference in motor, autonomic, cognitive, and sensory symptoms. The sigh index could be used for screening for MSA in the millions of middle-aged persons who receive polysomnography for other purposes. Whether sighing in iRBD predicts preferential conversion towards MSA should be measured in a longitudinal study.

"I know when to stop": Sentinels and counter-strategies against drowsy driving in narcolepsy and idiopathic hypersomnia.

STUDY OBJECTIVES: To collect prodromal symptoms experienced by participants with narcolepsy and idiopathic hypersomnia (considered "hypersomnolence experts") prior to drowsy driving and counter-strategies used to maintain alertness. METHODS: Systematic, face-to-face interview (using a semi-structured questionnaire), including clinical measures, frequency of car accidents/near misses, and symptoms experienced before impending drowsy driving episodes and counter-strategies. RESULTS: Among 61 participants (32 with narcolepsy, 29 with idiopathic hypersomnia; 56 drivers), 61% of drivers had at least one lifetime accident/near miss. They had a higher sleepiness score (14 ± 4 vs. 11 ± 5, P<0.04) than those without an accident/near miss, but no other differences in demographics, driving experience, medical conditions, symptoms, sleep tests, and treatment. All but three participants experienced prodromal symptoms of drowsy driving, which included postural and motor changes (86.9%: axial hypotonia - e.g., eyelid droop, stereotyped movements), cognitive impairment (53.3%: automatic steering, difficulty concentrating/shifting, dissociation, mind wandering, dreaming), sensory (65%: paresthesia, pain, stiffness, heaviness, blunted perceptions such as a flat dashboard with loss of 3D, illusions and hallucinations), and autonomic symptoms (10%, altered heart/breath rate, penile erection). Counterstrategies included self-stimulation from external sources (pain, cold air, music, drinks, driving with bare feet), motor changes (upright posture, movements), and surprise (sudden braking). CONCLUSIONS: Drowsy driving symptoms can result from "local" NREM, entry in N1 sleep, and hybrid wake/REM sleep states. These rich qualitative insights from participants with narcolepsy and idiopathic hypersomnia, as well as sophisticated counter-strategies, can be gathered to reduce the crash risk in this population, but also in inexperienced healthy drivers.

Circadian Motor Improvement in MS and Core Body Temperature Dipping.

This case report describes a man with multiple sclerosis and insomnia who noticed improved motor function during nocturnal awakenings compared with daytime.

Isolated REM Sleep without Atonia Is Not Equivalent to REM Sleep Behavior Disorder in Early-Stage Parkinson's Disease.

BACKGROUND: In early-stage Parkinson's disease (PD), rapid eye movement (REM) sleep behavior disorder (RBD) predicts poor cognitive and motor outcome. However, the baseline significance and disease evolution associated with isolated REM sleep without atonia (iRWA, ie, enhanced muscle tone during 8.7% of REM sleep, but no violent behavior) are not well understood. OBJECTIVES: The objective is to determine whether iRWA was a mild form of RBD and progressed similarly over time. METHODS: Participants with early PD (<4 years from medical diagnosis) were included from 2014 to 2021 in a longitudinal study. They underwent interviews and examinations in the motor, cognitive, autonomous, psychiatric, sensory, and sleep domains every year for 4 years along with a video polysomnography and magnetic resonance imaging examination of the locus coeruleus/subcoeruleus complex (LC/LsC) at baseline. The clinical characteristics were compared between groups with normal REM sleep, with iRWA and with RBD, at baseline and for 4 years. RESULTS: Among 159 PD participants, 25% had RBD, 25% had iRWA, and 50% had normal REM sleep. At baseline, the non-motor symptoms were less prevalent and the LC/LsC signal intensity was more intense in participants with iRWA than with RBD. Over 4 years, participants with normal REM sleep and with iRWA had a similar cognitive and motor trajectory, whereas participants with RBD had greater cognitive and motor decline. CONCLUSIONS: We demonstrated that iRWA is frequent in early PD, but is not a milder form of RBD. Both groups have distinct baseline characteristics and clinical trajectories. They should be distinguished in clinical routine and research protocols. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Long sleep time and excessive need for sleep: State of the art and perspectives.

The mechanisms underlying the individual need for sleep are unclear. Sleep duration is indeed influenced by multiple factors, such as genetic background, circadian and homeostatic processes, environmental factors, and sometimes transient disturbances such as infections. In some cases, the need for sleep dramatically and chronically increases, inducing a daily-life disability. This "excessive need for sleep" (ENS) was recently proposed and defined in a European Position Paper as a dimension of the hypersomnolence spectrum, "hypersomnia" being the objectified complaint of ENS. The most severe form of ENS has been described in Idiopathic Hypersomnia, a rare neurological disorder, but this disabling symptom can be also found in other hypersomnolence conditions. Because ENS has been defined recently, it remains a symptom poorly investigated and understood. However, protocols of long-term polysomnography recordings have been reported by expert centers in the last decades and open the way to a better understanding of ENS through a neurophysiological approach. In this narrative review, we will 1) present data related to the physiological and pathological variability of sleep duration and their mechanisms, 2) describe the published long-term polysomnography recording protocols, and 3) describe current neurophysiological tools to study sleep microstructure and discuss perspectives for a better understanding of ENS.

Sleep disorders in Parkinson's disease, an early and multiple problem.

In Parkinson's disease (PD), it remains unclear whether sleep disorders including insomnia, REM sleep behavior disorder (RBD), excessive daytime sleepiness (EDS), restless legs syndrome (RLS) and sleep-disordered breathing (SDB), are isolated or combined, interact with each other and are associated with clinical factors. We sought to determine the prevalence and combinations of the main sleep disorders, and their clinical and polysomnographic associations in early stage PD. Sleep disorders were systematically diagnosed after medical interview and video-polysomnography in 162 participants with early stage PD and 58 healthy controls from the baseline of the longitudinal ICEBERG cohort. Demographic, clinical (motor, cognitive, autonomic, psychological and sensory tests), therapeutic and polysomnographic associations of sleep disorders were investigated. Sleep disorders were frequent (71%) and combined in half of the patients. The number of sleep disorders increased with disease duration and dysautonomia. Insomnia was the most common (41%), followed by definite RBD (25%), EDS (25%), and RLS (16%). These disorders were more frequent than in controls whereas SDB was rare, moderate and similar in both groups. In patients, insomnia (mainly difficulties maintaining sleep) was associated with female gender, shorter sleep time and RLS, but not with motor or psychological symptoms. RBD was associated with dysautonomia and advanced age, but not with motor and cognitive measures. EDS was associated with psychiatric and motor symptoms as well as the sedative effects of dopamine agonists but not with other sleep disturbances. Sleep disturbances are frequent and combined in early patients with PD. Their determinants and markers are more organic than psychological.

Latency to N3 interruption in arousal disorders.

STUDY OBJECTIVES: To help expert witnesses in criminal cases using the "sleepwalking defense," we studied the time of first and last interruptions from stage N3 in patients with arousal disorders, including sexsomnia, as well as their determinants. METHODS: The epochs of lights off, sleep onset, first N3 interruption (with and without behaviors), and last N3 interruption were determined by videopolysomnography on two consecutive nights in 163 adults with disorders of arousal, including 46 with and 117 without sexsomnia. RESULTS: The first N3 interruption (independently of concomitant behavior) occurred as early as 8 minutes after sleep onset and within 100 minutes of falling asleep in 95% of cases. The first motor arousal from N3 occurred as early as 25 minutes after lights off time, a timing more variable between participants (between 30 and 60 minutes after lights off time in 25% of participants and within 60 minutes of falling asleep in 50%). These latencies did not differ between the groups with and without sexsomnia. No correlation was found between these latencies and the young age, sex, or clinical severity. The latency of motor arousals was shorter when they were associated with a fast-wave EEG profile and were not preceded by another type of N3 arousal. CONCLUSIONS: The first motor arousal may occur early in the night in patients with arousal disorders, with or without sexsomnia, suggesting that abnormal behaviors occurring as early as 25 minutes after lights off time in clinical and criminal cases can be a parasomnia manifestation.

Charting Disease Trajectories from Isolated REM Sleep Behavior Disorder to Parkinson's Disease.

BACKGROUND: Clinical presentation and progression dynamics are variable in patients with Parkinson's disease (PD). Disease course mapping is an innovative disease modelling technique that summarizes the range of possible disease trajectories and estimates dimensions related to onset, sequence, and speed of progression of disease markers. OBJECTIVE: To propose a disease course map for PD and investigate progression profiles in patients with or without rapid eye movement sleep behavioral disorders (RBD). METHODS: Data of 919 PD patients and 88 isolated RBD patients from three independent longitudinal cohorts were analyzed (follow-up duration = 5.1; 95% confidence interval, 1.1-8.1] years). Disease course map was estimated by using eight clinical markers (motor and non-motor symptoms) and four imaging markers (dopaminergic denervation). RESULTS: PD course map showed that the first changes occurred in the contralateral putamen 13 years before diagnosis, followed by changes in motor symptoms, dysautonomia, sleep-all before diagnosis-and finally cognitive decline at the time of diagnosis. The model showed earlier disease onset, earlier non-motor and later motor symptoms, more rapid progression of cognitive decline in PD patients with RBD than PD patients without RBD. This pattern was even more pronounced in patients with isolated RBD with early changes in sleep, followed by cognition and non-motor symptoms and later changes in motor symptoms. CONCLUSIONS: Our findings are consistent with the presence of distinct patterns of progression between patients with and without RBD. Understanding heterogeneity of PD progression is key to decipher the underlying pathophysiology and select homogeneous subgroups of patients for precision medicine. © 2023 International Parkinson and Movement Disorder Society.

Night-Time Apomorphine Infusion: Who Are the Best Candidates?

Background: We recently demonstrated in a randomized controlled trial (APOMORPHEE, NCT02940912) that night-time only subcutaneous apomorphine infusion improves sleep disturbances and insomnia in patients with advanced Parkinson's disease and moderate to severe insomnia. Objectives: To identify the best candidates for receiving night-time only subcutaneous apomorphine infusion in routine care. Methods: In this post-hoc analysis of APOMORPHEE, we compared the characteristics of patients according to whether they chose to continue night-time only subcutaneous apomorphine infusion at the end of the study period or not. Results: Half of the patients (22/42) chose to continue the treatment. Off duration (day or night), painful Off dystonia, and insomnia severity at baseline were associated with night-time only apomorphine continuation. Multivariate analysis retained only Off duration as an independent predictor of continuation. Conclusions: The best candidates for night-time only apomorphine are patients with severe and prolonged Off periods (day or night) and severe insomnia.

Do the EEG and behavioral criteria of NREM arousal disorders apply to sexsomnia?

STUDY OBJECTIVES: To establish whether the recent EEG and behavioral criteria of arousal disorders apply to sexsomnia. METHODS: EEG and behavioral markers upon N3 sleep interruptions in videopolysomnography were retrospectively compared in 24 participants with sexsomnia, 41 participants with arousals disorders, and 40 healthy controls. The specificity and sensitivity of previously suggested EEG and behavioral cutoffs for supporting arousal disorders diagnosis were measured in the sexsomnia vs. control groups. RESULTS: Participants with sexsomnia and arousals disorders showed a higher N3 fragmentation index, slow/mixed N3 arousal index, and number of eye openings during N3 interruptions than healthy controls. Ten (41.7%) participants with sexsomnia (vs. one sleepwalker and no control) displayed an apparently sexual behavior (masturbation, sexual vocalization, pelvic thrusting, and hand within the pajama) during N3 arousal. An N3 sleep fragmentation index ≥6.8/h of N3 sleep and two or more N3 arousals associated with eye opening was 95% specific but poorly (46% and 42%) sensitive for diagnosing sexsomnia. An index of slow/mixed N3 arousals ≥2.5/h of N3 sleep was 73% specific and 67% sensitive. An N3 arousal with trunk raising, sitting, speaking, showing an expression of fear/surprise, shouting, or exhibiting sexual behavior was 100% specific for a diagnosis of sexsomnia. CONCLUSIONS: In patients with sexsomnia, videopolysomnography based markers of arousal disorders are intermediate between healthy individuals and patients with other arousal disorders, supporting the concept of sexsomnia as a specialized, but less neurophysiologically severe, NREM parasomnia. Previously validated criteria for arousal disorders partially fit in patients with sexsomnia.

Hypersomnia and narcolepsy in 42 adult patients with craniopharyngioma.

STUDY OBJECTIVES: To evaluate sleep, sleepiness, and excessive need for sleep in patients with craniopharyngioma (a suprasellar tumor which can affect sleep-wake systems). METHODS: A retrospective study of all adult patients living with craniopharyngioma referred to the sleep clinic, who received a sleep interview, nocturnal polysomnography, multiple sleep latency tests (MSLT), and 18-h bed rest polysomnography. Their sleep measurements were compared with those of age- and sex-matched healthy controls. RESULTS: Of 54 patients screened with craniopharyngioma, 42 were analyzed, 80% of whom complained of excessive daytime sleepiness. Sleep testing revealed that 6 (14.3%) of them had secondary narcolepsy (including one with cataplexy), and 11 (26.2%) had central hypersomnia associated with a medical disorder. Compared with controls, patients were more frequently obese, had a shorter mean sleep latency on MSLT, and slept longer on the first night. There was a nonsignificant trend for patients with (vs. without) narcolepsy and hypersomnia to be younger, to have a higher body mass index, to be more likely to have received radiation therapy, and to have more severe damage to the hypothalamus after surgery. Treatment with stimulants (modafinil, pitolisant, and methylphenidate) was beneficial in 9/10 patients. CONCLUSIONS: Nearly half of the patients with craniopharyngioma and sleep disorders have a central disorder of hypersomnolence (narcolepsy and hypersomnia), which should be investigated and lead to considerations beyond sleep apnea syndrome in these obese patients.

Neuromelanin-Sensitive Magnetic Resonance Imaging Changes in the Locus Coeruleus/Subcoeruleus Complex in Patients with Typical and Atypical Parkinsonism.

BACKGROUND: The locus coeruleus/subcoeruleus complex (LC/LsC) is a structure comprising melanized noradrenergic neurons. OBJECTIVE: To study the LC/LsC damage across Parkinson's disease (PD) and atypical parkinsonism in a large group of subjects. METHODS: We studied 98 healthy control subjects, 47 patients with isolated rapid eye movement sleep behavior disorder (RBD), 75 patients with PD plus RBD, 142 patients with PD without RBD, 19 patients with progressive supranuclear palsy (PSP), and 19 patients with multiple system atrophy (MSA). Twelve patients with MSA had proven RBD. LC/LsC signal intensity was derived from neuromelanin magnetic resonance imaging using automated software. RESULTS: The signal intensity was reduced in all parkinsonian syndromes compared with healthy control subjects, except in PD without RBD. The signal intensity decreased as age increased. Moreover, the signal intensity was lower in MSA than in isolated RBD and PD without RBD groups. In PD, the signal intensity correlated negatively with the percentage of REM sleep without atonia. There were no differences in signal intensity between PD plus RBD, PSP, and MSA. CONCLUSIONS: Neuromelanin signal intensity was reduced in all parkinsonian disorders, except in PD without RBD. The presence of RBD in parkinsonian disorders appears to be associated with lower neuromelanin signal intensity. Furthermore, lower LC/LsC signal changes in PSP could be partly caused by the effect of age. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The dynamics of emotional behaviors in rapid eye movement sleep.

Dream's emotions could exert a major role in desensitizing negative emotions. Studying emotional dynamics (how emotions fluctuate across time) during rapid eye movement (REM) sleep could provide some insight into this function. However, studies so far have been limited to dream reports. To bypass this limit, REM sleep behavior disorder (RBD), in which participants enact their dreams, enables direct access to overt emotional dream behaviors (such as facial expressions and speeches). In total, 17 participants with RBD, and 39.7 h of REM sleep video were analyzed. The frequency of emotional behaviors did not differ between REM sleep episodes of early and late night. Within individual REM sleep episodes, emotional behaviors exhibited a biphasic temporal course, including an increased frequency for the first 10 min, followed by a progressive decrease. The negative emotional behaviors occurred earlier (mean time: 11.3 ± 10 min) than positive (14.4 ± 10.7 min) and neutral behaviors (16.4 ± 11.8 min). Emotional behaviors of opposing (negative and positive) valences were observed in 31% (N = 14) of episodes containing at least one emotional behavior, and were separated by a median time of 4.2 [1.1-10.9] min. The biphasic temporal course of behaviors in REM sleep could include the generation reactivation of emotional content during the ascending phase, followed by processing and extinction during the descending phase. The earlier occurrence time of negative emotional behavior suggests that negative emotions may need to be processed first. The rapid succession of emotions of opposite valence could prevent prolonged periods of negative emotions and eventually nightmares.

Precision Medicine for Idiopathic Hypersomnia.

Idiopathic hypersomnia (IH) includes a clinical phenotype resembling narcolepsy (with repeated, short restorative naps), and a phenotype with an excess of sleep, sleep drunkenness, drowsiness, and infrequent long, nonrestorative naps. Sleep tests reflect this heterogeneity. MSLTs are greater than 8 min in 2/3 of the cases and poorly repeatable. Sleep excess is better captured by extended monitoring identifying 11 to 16h of sleep/24 h. Patients with IH are young and more often female. Possible mechanisms of IH include deficiencies in arousal systems, inappropriate stimulation of sleep-inducing systems, and long biological night. Treatments now include robust studies of modafinil, clarithromycin, and sodium oxybate.

Proteomic biomarkers of Kleine-Levin syndrome.

STUDY OBJECTIVES: Kleine-Levin syndrome (KLS) is characterized by relapsing-remitting episodes of hypersomnia, cognitive impairment, and behavioral disturbances. We quantified cerebrospinal fluid (CSF) and serum proteins in KLS cases and controls. METHODS: SomaScan was used to profile 1133 CSF proteins in 30 KLS cases and 134 controls, while 1109 serum proteins were profiled in serum from 26 cases and 65 controls. CSF and serum proteins were both measured in seven cases. Univariate and multivariate analyses were used to find differentially expressed proteins (DEPs). Pathway and tissue enrichment analyses (TEAs) were performed on DEPs. RESULTS: Univariate analyses found 28 and 141 proteins differentially expressed in CSF and serum, respectively (false discovery rate <0.1%). Upregulated CSF proteins included IL-34, IL-27, TGF-b, IGF-1, and osteonectin, while DKK4 and vWF were downregulated. Pathway analyses revealed microglial alterations and disrupted blood-brain barrier permeability. Serum profiles show upregulation of Src-family kinases (SFKs), proteins implicated in cellular growth, motility, and activation. TEA analysis of up- and downregulated proteins revealed changes in brain proteins (p < 6 × 10-5), notably from the pons, medulla, and midbrain. A multivariate machine-learning classifier performed robustly, achieving a receiver operating curve area under the curve of 0.90 (95% confidence interval [CI] = 0.78-1.0, p = 0.0006) in CSF and 1.0 (95% CI = 1.0-1.0, p = 0.0002) in serum in validation cohorts, with some commonality across tissues, as the model trained on serum sample also discriminated CSF samples of controls versus KLS cases. CONCLUSIONS: Our study identifies proteomic KLS biomarkers with diagnostic potential and provides insight into biological mechanisms that will guide future research in KLS.

Sleep Disorders in Adults with Prader-Willi Syndrome: Review of the Literature and Clinical Recommendations Based on the Experience of the French Reference Centre.

Prader-Willi syndrome (PWS) is a rare, genetic, multisymptomatic, neurodevelopmental disease commonly associated with sleep alterations, including sleep-disordered breathing and central disorders of hypersomnolence. Excessive daytime sleepiness represents the main manifestation that should be addressed by eliciting the detrimental effects on quality of life and neurocognitive function from the patients' caregivers. Patients with PWS have impaired ventilatory control and altered pulmonary mechanics caused by hypotonia, respiratory muscle weakness, scoliosis and obesity. Consequently, respiratory abnormalities are frequent and, in most cases, severe, particularly during sleep. Adults with PWS frequently suffer from sleep apnoea syndrome, sleep hypoxemia and sleep hypoventilation. When excessive daytime sleepiness persists after adequate control of sleep-disordered breathing, a sleep study on ventilatory treatment, followed by an objective measurement of excessive daytime sleepiness, is recommended. These tests frequently identify central disorders of hypersomnolence, including narcolepsy, central hypersomnia or a borderline hypersomnolent phenotype. The use of wake-enhancing drugs (modafinil, pitolisant) is discussed in multidisciplinary expert centres for these kinds of cases to ensure the right balance between the benefits on quality of life and the risk of psychological and cardiovascular side effects.

Safety and efficacy of subcutaneous night-time only apomorphine infusion to treat insomnia in patients with Parkinson's disease (APOMORPHEE): a multicentre, randomised, controlled, double-blind crossover study.

BACKGROUND: Insomnia is a frequent complaint of patients with Parkinson's disease, and it negatively affects quality of life. Drugs that improve both sleep and parkinsonism would be of major benefit to patients with Parkinson's disease-related insomnia. We aimed to test the safety and efficacy of subcutaneous night-time only apomorphine infusion in patients with Parkinson's disease and insomnia. METHODS: We did a randomised, multicentre, double-blind, placebo-controlled, crossover trial in 11 expert centres in Parkinson's disease and sleep centres in France. Participants aged 35-90 years with fluctuating Parkinson's disease and moderate to severe insomnia (Insomnia Severity Index score ≥15) were randomly assigned to either first receive night-time subcutaneous apomorphine (up to 5 mg/h) or matching placebo. Randomisation was done using a computer-generated plan in blocks of four, stratified by centre. This first intervention was followed by a 14-night washout period, then crossover to the other intervention. The treatment periods consisted of a 10-night titration phase followed by a 7-night fixed-dose phase. The dose was adjusted during the titration phase on the basis of a daily telephone call assessing sleep quality and treatment tolerability. The primary efficacy endpoint was the difference in Parkinson's disease sleep scale (PDSS) scores from the beginning to the end of each treatment period. Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT02940912. FINDINGS: Between Jan 31, 2017, and Jan 29, 2021, 46 participants were enrolled. 25 (54%) patients were randomly assigned to receive apomorphine first and 21 (46%) patients to receive placebo first. Mean change in PDSS score was significantly greater with night-time apomorphine infusion (15·18 [SD 24·34]) compared with placebo (5·23 [21·52]; treatment effect 9·95 [95% CI 0·88-19·03]; p=0·041). Adverse events were reported in 25 (54%) participants during the apomorphine period and in 17 (37%) participants during the placebo period (p=0·16). Apomorphine was associated with more frequent dizziness than was placebo (seven [15%] vs 0; p=0·041). INTERPRETATION: Subcutaneous night-time only apomorphine infusion improved sleep disturbances according to difference on PDSS score, with an overall safety profile consistent with previous studies in Parkinson's disease. This treatment might be useful to manage sleep disturbances in patients with advanced Parkinson's disease and moderate to severe insomnia. FUNDING: Orkyn and Aguettant Pharma. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Eye movement patterns correlate with overt emotional behaviours in rapid eye movement sleep.

Growing evidence suggests that sleep plays a key role in regulating emotions. Rapid eye movements (REMs) in REM sleep could be associated with dreams emotions, but supporting evidence is indirect. To highlight this association, we studied the REM sleep during video-polysomnography of 20 subjects with REM sleep behaviour disorder (RBD), a model of enacted dreams offering direct access to the emotional content of the sleeper (face expression, speeches, behaviour). Video and the electro-oculography recordings were divided into 3 s time intervals and classified as non-behavioural, or behavioural (neutral, positive or negative emotions), and as containing no eye movements (EMs), slow eye movements (SEMs) or REMs (isolated or bursts). Compared to the absence of EMs, neutral behaviours successively increased in the presence of SEMs (odd ratio, OR = 1.4), then isolated REMs (OR = 2.8) and then REM bursts (OR = 4.6). Positive behaviours increased with SEMs (OR = 2.8) but did not increase further with isolated REMs (OR = 2.8) and REM bursts (OR = 3). Negative behaviours were absent with SEMs, increased with isolated REMs (OR = 2.6) and further with REM bursts (OR = 10.1). These results support an association between REMs and SEMs, and dream emotions.

Deep Learning-Based Neuromelanin MRI Changes of Isolated REM Sleep Behavior Disorder.

BACKGROUND: Isolated REM sleep behavior disorder (iRBD) is considered a prodromal stage of parkinsonism. Neurodegenerative changes in the substantia nigra pars compacta (SNc) in parkinsonism can be detected using neuromelanin-sensitive MRI. OBJECTIVE: To investigate SNc neuromelanin changes in iRBD patients using fully automatic segmentation. METHODS: We included 47 iRBD patients, 134 early Parkinson's disease (PD) patients and 55 healthy volunteers (HVs) scanned at 3 Tesla. SNc regions-of-interest were delineated automatically using convolutional neural network. SNc volumes, volumes corrected by total intracranial volume, signal-to-noise ratio (SNR) and contrast-to-noise ratio were computed. One-way general linear models (GLM) analysis of covariance (ANCOVA) was conducted while adjusting for age and sex. RESULTS: All SNc measurements differed significantly between the three groups (except SNR in iRBD). Changes in iRBD were intermediate between those in PD and HVs. CONCLUSIONS: Using fully automated SNc segmentation method and neuromelanin-sensitive imaging, iRBD patients showed neurodegenerative changes in the SNc at a lower level than in PD patients. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.