Clinical REM Sleep Behavior Disorder Research Articles

Continued Validation of the RBD Symptom Severity Scale (RBDSSS) in Participants of the North American Prodromal Synucleinopathy (NAPS) Consortium (P6-13.004)

Continued Validation of the RBD Symptom Severity Scale (RBDSSS) in Participants of the North American Prodromal Synucleinopathy (NAPS) Consortium (P6-13.004)

Treatment with the novel TAAR1 agonist ulotaront is associated with reductions in quantitative polysomnographic REM sleep without atonia in healthy human subjects: Results of a post-hoc analysis

BackgroundIsolated REM sleep behavior disorder (RBD) is a potentially injurious parasomnia lacking an established treatment. Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist with 5-HT1A receptor agonist activity that has demonstrated efficacy in patients with schizophrenia. In a single dose challenge study in humans, ulotaront 50 mg demonstrated significant REM suppressant effects. We now report post-hoc exploratory analyses designed to evaluate the effect of ulotaront on quantitative REM sleep without atonia (RSWA). MethodsYoung healthy adult men (ages 19–35) were randomized to double-blind, cross-over treatment (after 7-day wash-out) with single doses of ulotaront (50 mg or 10 mg) versus placebo followed by polysomnography (PSG) on each of the nights following treatment. Quantitative RSWA was analyzed in a blinded fashion using established visual and automated methods. ResultsSubjects received 50 mg (n = 11) or 10 mg (n = 9) of ulotaront. Treatment with ulotaront 50 mg was associated with lower RSWA (p < 0.05), with greatest RSWA reduction (vs. placebo) observed in subjects with RSWA levels above the mean on the baseline night. RSWA levels were similar between treatment with ulotaront 10 mg and placebo. ConclusionTreatment with ulotaront 50 mg (but not 10 mg) was associated with reductions in RSWA levels in healthy subjects, especially in subjects with higher baseline RSWA levels, providing proof-of-concept for ulotaront efficacy in reducing RSWA levels. However, whether ulotaront might have efficacy as a treatment for human RBD awaits double-blind trials with ulotaront in clinical RBD populations.

Caracterização Clínica e Polissonográfica do Distúrbio Comportamental do Sono REM: Casuística de um Centro de Medicina do Sono Português

Introduction: REM sleep behavior disorder (RBD) is diagnosed by clinical history of abnormal and complex movements during sleep and by polysomnographic findings. Accordingly, RBD may occur isolated (iRBD) or, frequently, in association with neurodegenerative diseases, namely synucleinopathies generally preceding its onset. Thereby, our aim was to characterize the clinical and video-polysomnography (vPSG) features of patients diagnosed with iRBD and RBD plus Parkinson disease (RBDPD); analyze the symptoms and signs (motor and non-motor) that RBDPD patients presented before the diagnosis of PD, to realize if there is any predictive factor for phenoconversion. Methods: Retrospective, observational and unicentric study. The study included all patients with a clinical diagnosis of RBD (isolated and associated with PD), according to the diagnostic criteria of DSM-5 and ICSD-3 and who underwent polysomnographic recording at the Sleep Medicine Center of a hospital. level III, between January 2008 and May 2021. Results: A total of 48 patients were included and divided in iRBD (27 patients) and RBDPD (21 patients) groups. We proceeded to a clinical, demographic and vPSG characterization and comparison. In both groups, the majority of patients were male and the average age of RBD diagnosis was 64-65 years. In iRBD group, the most reported manifestation was violent sleep movements. In this group, we found five patients with subtle motor signs. In the RBDPD group, the majority had a previous diagnosis of RBD, on average, about six years before. The most common clinical feature was the presence of vivid dreams with violent content. In the iRBD group, the percentage of RSWA was higher in the subgroup of patients with subtle motor signs and other premotor symptoms, namely depression (34.2%), than in patients without any of those features (31.6%). Conclusion: As we found, in the most of RBDDP group, RBD preceded the diagnosis of PD. Although it was not possible to obtain a correlation, as with clinical RBD, the percentage of RSWA should be considered a potential biomarker of phenoconversion in neurodegenerative disease. Early diagnosis of REM sleep anomalies, in a phase of subtil motor symptoms is essential and should be used as a biomarker to an earlier investigation, as DATscan, and therapeutic action.

0555 Isolated REM Sleep Without Atonia Following COVID-19 Infection: A Case-Control Study

IntroductionREM sleep without atonia (RSWA) is the neurophysiological substrate of REM sleep behavior disorder (RBD), a form of prodromal parkinsonism in most older adults. Isolated RSWA (without clinical RBD) elevation was demonstrated recently in older adults following SARS-CoV2 (COVID-19) infection, but comparison to controls was not reported. We aimed to comparatively analyze RSWA between patients with previous COVID-19 infection and COVID-19 negative controls.Methods25 patients with previous COVID-19 infection were compared to 25 age-sex matched controls who tested negative for COVID-19 prior to polysomnography. Patients receiving medications known to increase RSWA were excluded. We reviewed medical records to determine clinical features and quantitatively analyzed RSWA in the submentalis (SM) and anterior tibialis (AT) muscles for phasic, tonic, and “any” muscle activity, phasic burst duration, and the automated REM atonia index. Non-parametric analyses compared clinical and polysomnographic features between groups, with combined SM and AT RSWA as the defined primary outcome. The comparative frequency of COVID-19 positive cases and COVID-19 negative controls who met or exceeded proposed isolated RSWA thresholds was also determined.ResultsCOVID-19 patients had significantly greater RSWA than COVID-19 negative controls in the combined SM and AT muscles (p = 0.00076). Most other RSWA metrics were also higher in COVID-19 patients than controls (p<0.03), except tonic muscle activity, phasic burst durations, and RAI. Isolated RSWA occurred more frequently in COVID-19 (9 patients, 36%) than controls (3, 12%; p>0.05). No patients had a clinical history or polysomnographic evidence for parasomnia behavior or a primary neurological condition.ConclusionQuantitative RSWA amounts were comparatively greater in COVID-19 patients than in COVID-19 tested-negative controls, suggesting association of previous COVID-19 infection with central nervous system brainstem dysfunction in the region of the dorsal pons and/or ventromedial medulla. Further prospective studies are needed to determine whether RSWA is a predisposing influence to, or consequence of, COVID-19 infection in these patients, and whether COVID-19 survivors might harbor neurodegenerative risk or disease markers.Support (If Any)

REM sleep behavior disorder as a complex condition with heterogeneous underlying disorders: clinical management and prognostic implications [Commentary

To review how REM sleep behavior disorder (RBD) is a complex condition with heterogeneous underlying disorders; and to review clinical management issues and prognostic implications. PubMed literature search and contents from the first textbook of RBD (2018). RBD, with its core objective diagnostic feature of REM-without-atonia (RWA) documented by video-polysomnography, can emerge during the entire lifespan, and can initially present as an idiopathic (isolated) condition (iRBD), or can be associated with a broad spectrum of disorders including narcolepsy, alpha-synuclein neurodegenerative disorders (esp. Parkinson's disease [PD] and dementia with Lewy bodies [DLB]), paraneoplastic neurological syndromes and autoimmune disorders, CNS lesions (e.g., tumors, stroke), other neurological disorders, psychiatric disorders (PTSD, mood disorders), can be triggered by antidepressant/other medications, and can emerge acutely with drug withdrawal states, toxic-metabolic states, etc. Important clinical issues include the evolution of iRBD to PD/DLB in most middle-aged and older patients over a period of years to several decades, with compelling prognostic implications, along with the hope of enrolling these patients in future clinical trials to test promising disease-modifying therapies. Also, the strong link of RBD with narcolepsy needs further investigation. Parasomnia overlap disorder involves RBD and NREM parasomnias that can be idiopathic or linked with a broad range of clinical disorders. RBD usually responds to therapy consisting mainly of melatonin and/or clonazepam at bedtime. The complex associations of RBD with OSA are being increasingly investigated. RBD mimics with dream-enactment need to be recognized for diagnostic and management purposes, including severe OSA, NREM parasomnias, PLMD, nocturnal seizures, and other conditions. The clinical and research RBD fields span across the disciplines of neurology, pulmonary, psychiatry, psychology, and pediatric sleep medicine, along with physical medicine and rehabilitation medicine, other allied disciplines, and the basic and clinical neurosciences.

Comorbid parasomnias in narcolepsy and idiopathic hypersomnia: more REM than NREM parasomnias.

To assess the frequency, determinants, and clinical impact of clinical rapid eye movement (REM) and non-REM (NREM) parasomnias in adult patients with narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia compared with healthy controls. Familial and past and current personal parasomnias were assessed by questionnaire and medical interviews in 710 patients (220 NT1, 199 NT2, and 221 idiopathic hypersomnia) and 595 healthy controls. Except for sleep-related eating disorder, current NREM parasomnias were rare in all patient groups and controls. Sleep-related eating disorder was more frequent in NT1 patients (7.9% vs 1.8% in NT2 patients, 2.1% in patients with idiopathic hypersomnia, and 1% in controls) and associated with disrupted nighttime sleep (odds ratio = 3.9) and nocturnal eating in full awareness (odds ratio = 6.9) but not with sex. Clinical REM sleep behavior disorder was more frequent in NT1 patients (41.4%, half being violent) than in NT2 patients (13.2%) and affected men more often than women (odds ratio = 2.4). It was associated with disrupted nighttime sleep, depressive symptoms, and antidepressant use. Frequent (> 1/week) nightmares were reported by 39% of patients with NT1, 29% with NT2, and 27.8% with idiopathic hypersomnia (vs 8.3% in controls) and were associated with depressive symptoms in narcolepsy. No parasomnia (except sleep-related hallucinations) worsened daytime sleepiness. In patients with central disorders of hypersomnolence, comorbid NREM parasomnias (except for sleep-related eating disorder) are rare and do not worsen sleepiness. In contrast, REM parasomnias are prevalent (especially in NT1) and are associated with male sex, disrupted nighttime sleep, depressive symptoms, and antidepressant use. Leu-Semenescu S, Maranci J-B, Lopez R, etal. Comorbid parasomnias in narcolepsy and idiopathic hypersomnia: more REM than NREM parasomnias. J Clin Sleep Med. 2022;18(5):1355-1364.

Global Brain Consortium Open Science Platform

Rapid eye movement (REM) sleep without atonia (RWA) is observed in some patients without a clinical history of REM sleep behavior disorder (RBD). It remains unknown whether these patients meet the refined quantitative electromyographic (EMG) criteria supporting a clinical RBD diagnosis. We quantitatively evaluated EMG activity and investigated its overnight distribution in patients with isolated qualitative RWA.Fifty participants with an incidental polysomnographic finding of RWA (isolated qualitative RWA) were included. Tonic, phasic, and ‘any’ EMG activity during REM sleep on PSG were quantified retrospectively.Referring to the quantitative cut-off values for a polysomnographic diagnosis of RBD, 7/50 (14%) and 6/50 (12%) of the patients showed phasic and ‘any’ EMG activity in the mentalis muscle above the respective cut-off values. No patient was above the cut-off value for tonic EMG activity or phasic EMG activity in the anterior tibialis muscles. Patients with RWA above the cut-off value showed higher amounts of RWA during later REM sleep periods.This is the first study showing that some subjects with incidental RWA meet the refined quantitative EMG criteria for a diagnosis of RBD. Future longitudinal studies must investigate whether this subgroup with isolated qualitative RWA is at an increased risk of developing fully expressed RBD and/or neurodegenerative disease.

A Questionnaire-Based Study on Clinical REM Sleep Behavior Disorder and Subtypes in Multiple System Atrophy

Objectives: Studies documenting the association between rapid eye movement sleep behavior disorder (RBD) and subtypes of multiple system atrophy (MSA) are rare. In this study, we investigated the presence of clinical RBD in MSA patients and compared the prevalence and severity of RBD in patients with MSA-P and MSA-C subtypes. Methods: We evaluated 54 consecutive patients presenting with MSA and hospitalized in the neurology ward of Beijing Hospital from February 2012 to June 2020. The healthy control (HC) group consisted of 100 healthy individuals who came to our hospital for physical examination. The clinical diagnosis of RBD was based on the minimal diagnostic criteria of International Classification of Sleep Disorders, revised. The severity of clinical RBD was rated on a digital scale from 0 to 3. The patients were divided into 2 subgroups: MSA-P and MSA-C. The MSA and HC groups were compared in terms of frequency of clinical RBD. The MSA-P and MSA-C subgroups were compared with each other for age, sex, onset age, disease duration, and features of clinical RBD. The correlation between severity of clinical RBD and clinical characteristics of MSA was analyzed in the patient groups. Results: The frequency of clinical RBD in MSA and HC groups was 70.4% (38/54) and 5% (5/100), respectively. The difference between 2 groups was significant (χ² = 74.453, p = 0.000). Among the patients, 57.4% (31/54) had the MSA-P subtype. There were no significant differences between MSA-P and MSA-C subtypes in the prevalence (χ² = 1.734, p = 0.188) and severity (χ² = 1.776, p = 0.412) of clinical RBD. The onset of clinical RBD during the premotor period was not different between the subtypes of MSA, either in patients’ number of preceding the onset of motor symptoms (χ² = 0.581, p = 0.446) or the preceding time (Z = −0.550, p = 0.582). For the MSA-C patients, there was a negative correlation between the score of severity of the RBD scale and RBD preceding motor symptoms (r = −0.482, p = 0.020). Conclusion: In our study, the prevalence of clinical RBD is unrelated to the subtypes of MSA. The onset of clinical RBD during the premotor period was not different between subtypes of MSA. However, we found that the severity of RBD occurring before the motor symptoms was more than that occurring after the motor symptoms in MSA-C patients. Our results showed that MSA-P and MSA-C patients may have a probable indicator for the similar pathologic mechanism of the disease and its sleep problems.

Olfactory function deteriorates in patients with Parkinson's disease complicated with REM sleep behavior disorder.

IntroductionIt is not concluded whether the association between olfactory dysfunction and REM sleep behavior disorder (RBD) were worsen cognitive function in patients with Parkinson's disease (PD). We sought to evaluate the impact of these symptoms in PD.MethodsWe examined 62 patients with PD using an olfactory test (Odor Stick Identification Test for Japanese: OSIT-J) and polysomnography (PSG). We divided the patients into 3 groups: PD with clinical RBD (n = 32), PD with subclinical RBD (n = 11), and PD with normal REM sleep (n = 19). We compared their clinical backgrounds, results of OSIT-J, autonomic functions, and cognitive functions such as Montreal cognitive assessment Japanese version (MoCA-J). Some factors associated with RBD were analyzed by multiple regression.ResultsThere were significant differences in the results of OSIT-J, and autonomic and cognitive functions between the 3 groups. There were significant differences in the total OSIT-J score between the 3 groups (PD with clinical RBD: 3.3 ± 2.2, PD with subclinical RBD: 4.0 ± 2.6, PD with normal REM sleep: 6.7 ± 3.0, p < 0.001). Patients in the group with PD with clinical RBD had a significantly lower score than those with normal REM sleep (p < 0.001). Logistic regression analysis showed that OSIT-J score was significantly associated with RBD. The PD group with clinical RBD had more patients with mild cognitive impairment than the group with normal REM sleep. Multiple regression analysis revealed that olfactory dysfunction was correlated with MoCA-J.ConclusionsOlfactory dysfunction is associated with RBD. Especially, it is important to screen olfactory function in RBD complicated patients with PD in view of cognitive impairment.

Gender differences in clinical findings and α-synucleiopathy-related markers in patients with idiopathic REM sleep behavior disorder

BackgroundRapid eye movement (REM) sleep behavior disorder (RBD) is a male-predominant parasomnia. Earlier clinical RBD patient studies showed gender differences of clinical symptoms and polysomnographic (PSG) findings. However, no previous investigated this issue by means of validated severity scales or by neuropsychological examination related to alpha-synucleinopathy. This study elucidates gender differences in clinical, physiological, and neuropsychological findings in Japanese idiopathic RBD (iRBD) patients. MethodsFrom 220 patients with complaint of sleep-related vocalization or behaviors who visited Yoyogi Sleep Disorder Center from June 2003 through December 2016, 43 female (68.7 ± 7.3 yr) and 141 male patients (66.7 ± 6.7 yr) diagnosed as having iRBD by video-polysomnography (v-PSG) were selected. All subjects answered the RBD questionnaire (RBDQ-JP) and underwent olfactory function test (Sniffin' Sticks test) and cognitive function test (MoCA-J). ResultsFemale iRBD patients had later first symptom-witnessed age (sleep-talking 63.2 ± 10.5 yr, behaviors 60.9 ± 8.6 yr) than male patients (sleep-talking 59.1 ± 8.8 yr, behaviors 64.7 ± 8.9 yr). No gender difference was found in age at diagnosis, clinical severity (RBDQ-JP), or olfactory or cognitive function. Regarding electromyogram (EMG) findings during REM sleep, phasic EMG activity was higher in female patients (22.3 ± 17.8% vs. 16.5 ± 16.1%), although no difference was found in tonic EMG activity. ConclusionsAlthough female iRBD patient symptoms were first recognized later than those of male patients, they showed elevated EMG activity during REM sleep and showed deteriorated olfactory and cognitive function similarly to male patients at the first medical consultation. Results suggest that disease progression in female RBD patients is equivalent to that in male patients.

Prodromal Parkinson's and RBD: Clinical signs and polysomnographical changes

The current diagnosis of Parkinson’s disease (PD) includes only motor symptoms: two of the three cardinal motor features, hypokinesia, tremor and rigidity, have to be present according to UK Parkinson’s Disease Society Brain Bank Criteria (Gibb and Lees, JNNP 1988). “Prodromal Parkinson” includes signs in the gastrointestinal system, in sleep-wake regulation, and in the autonomic nervous system, changes in pain perception and psychopathological alterations. When motor symptoms start, more than 50% of dopaminergic neurons are already degenerated, and long before the affection of these midbrain areas α-synuclein positive pathology occurs in the lower brainstem and olfactory bulb. REM sleep behavior disorder (RBD) is currently the most specific prodromal feature of α-synuclein pathology, which may manifest even a decade before motor symptoms. In an 18-year follow-up study more than 80% of the subjects of a cohort with idiopathic RBD have developed a neurodegenerative disease (Schenck et al Sleep Med 2013). Idiopathic RBD is defined by the International Classification of Sleep Disorders in its current 2014 version (ICSD-3, (Sleep 2014)). Clinical RBD is characterized by vocalizations, jerky movements of the extremities or the whole body, bed falls or complex movements and are shown in videos taken from patients with idiopathic RBD or RBD in PD. RBD includes a pathologically increased muscle tone of the chin (REM without atonia, RWA) recorded during REM sleep in polysomnography. For measurement of RWA surface electromyography (EMG) activity of the mentalis muscle is commonly quantified according to the method published by the SINBAR group (Frauscher et al Sleep 2012), with an amplitude exceeding twice the background EMG activity and a cut-off value of >18.2%. The prevalence of RBD in newly diagnosed PD patients is about 25%, with an increasing percentage during the course of the disease, such as a marker of progression of PD (Sixel-Doering et al, MDJ abstr 2019). RBD occurs in synucleinopathies such as PD and even more frequently in dementia with Lewy Bodies (DLB) and in multiple system atrophy (MSA). Unfortunately none of these non-motor parameters and RBD can be shown in each single PD patient, some PD patients even miss many of these non-motor features or develop them later in the disease. Therefore the term “Prodromal Parkinson” has still to be elucidated by larger studies to delineate the most specific pattern of premotor signs.

REM-Sleep Behavior Disorder in Patients With Essential Tremor: What Is Its Clinical Significance?

Objective: REM sleep behavior disorder (RBD) is an important risk factor for the dementia development and for the deterioration of autonomic functions in patients with Parkinson's Disease. RBD has also been reported in patients with Essential Tremor (ET). However, its clinical significance in ET remains still unknown. We aimed to investigate clinical, neuropsychological and cardiac autonomic scintigraphic differences between ET patients with and without RBD.Methods: To assess RBD symptoms, RBD Single-Question has been administered in a cohort of 55 patients with a clinical diagnosis of ET. Patients with clinical RBD underwent polysomnography (PSG) confirmation. All patients completed a battery of neuropsychological assessment of memory, executive function, attention, language, and visuospatial function. Cardiac MIBG scintigraphy was performed in order to measure the cardiac autonomic innervation.Results: Ten ET patients (18%) had a PSG-confirmed RBD (ETRBD+). Compared to ET patients without RBD (ETRBD−), significantly reduced scores on memory domain tests such as Rey auditory verbal learning test immediate recall (p = 0.015) and Rey auditory verbal learning test delayed recall (p = 0.004) and phonemic fluency test (p = 0.028) were present in ETRBD+. By contrast, no other significant clinical difference has emerged from the comparison between two ET groups. Similarly, ETRBD+ patients have cardiac MIBG tracer uptake in the normal value range as occurred in those with ETRBD−.Conclusions: This study improves the knowledge on clinical significance of RBD symptoms in ET patients. Our preliminary findings demonstrate that presence of RBD in ET is associated with neurocognitive impairment, but not with cardiac autonomic dysfunction. Further longitudinal studies are needed to investigate whether ET patients with RBD will develop a frank dementia over the time.

A Particular Medullary-Spinal Inhibitory Pathway is Recruited for the Expression of Muscle Atonia During REM Sleep.

Muscle atonia is a major pathognomonic sign of paradoxical sleep (PS; coined REM Sleep), during which dreams mainly occur. In the 1980s, an idiopathic syndrome called REM sleep behavior disorder (RBD) was described in patients endowed with loss of PS paralysis concomitant to abnormal movements, suggesting a dysfunction of PS networks. Another major clinical RBD feature is its prevalent phenoconversion into synucleinopathies as Parkinson’s disease in a delay of 10-15 years after diagnosis. Thus, we undertook experiments in rats to disentangle brainstem networks involved in PS, including atonia. We first identified a contingent of pontine glutamate neurons recruited during PS with inputs to the ventromedial medulla (vmM) where they contact γ-aminobutyric acid (GABA)/glycine inhibitory neurons also activated during PS. Here, we further show that these vmM inhibitory neurons send efferents to somatic spinal motoneurons until lumbar levels. As reported for the pontine generator, the genetic inactivation of the vmM inhibitory neurons abolishes atonia during PS without effects on waking locomotion and is sufficient to recapitulate major RBD symptoms. These original data suggest that RBD may reflect a severe dysfunction and/or degeneration linked to a developing synucleinopathic attack targeting specifically neurons that generate PS-specific atonia.

Melatonin Effects in REM Sleep Behavior Disorder Associated with Obstructive Sleep Apnea Syndrome: A Case Series.

REM sleep behavior disorder (RBD), with its main clinical symptoms of nightmares with dream-enacting behavior, is considered as a possible precursor of neurodegenerative disease. Obstructive Sleep Apnea Syndrome (OSAS) is known to be capable of provoking RBD-like symptoms by apneic event related arousals. The two sleep related pathologies must coincide in a relevant number of individuals because of overlapping prevalence in similar age groups. Until now RBD symptoms coexisting with OSAS are rarely described in scientific literature and in fact considered as OSAS mimicking RBD. We report four cases with a severe clinical RBD syndrome which were polysomnographically also diagnosed with concomitant OSAS (AHI range: 10.1 -53.2/h). Treatment with 2 mg prolonged release melatonin led to a relevant clinical improvement of RBD symptoms in all patients, so far untreated for the sleep related breathing disorder. Measure of REM sleep without atonia (RSWA) in polysomnography showed values ranging from 5.1 to 20.4% determined with the Montplaisir method. Surprisingly, RSWA values in PSG with melatonin were high, probably because of the still untreated OSAS. We presume that in patients with RBD and OSAS both pathologies contribute in varying degrees to the emergence of RBD symptoms by a destabilization of REM sleep. We suggest by consequence to consider a therapeutic strategy including the treatment of both disorders for an optimal therapeutic response.

Two polysomnographic features of REM sleep behavior disorder: Clinical variations insight for Parkinson's disease

IntroductionLoss of REM sleep muscle atonia (RWA) and dream-enactment behavior (DEB) are two associated features of REM sleep behavior disorder (RBD), which is frequently associated with Parkinson's disease (PD). Few studies have examined both DEB and RWA simultaneously in patients with PD. This study aimed to evaluate relationships between RWA, DEB and clinical characteristics of PD. MethodsWe conducted overnight polysomnography in 145 patients with PD. DEB (motor behaviors and/or vocalizations during REM) and increased RWA (IRWA; tonic and phasic chin EMG density ≥ 30% and ≥15%, respectively) were identified. Patients were categorized as clinical RBD (DEB and IRWA), sub-DEB positive (DEB only), subclinical RBD (IRWA only), or normal REM sleep. ResultsPatients with DEB had higher Hoehn and Yahr (H&Y) stage, Unified Parkinson's Disease Rating Scale (UPDRS) III score, levodopa equivalent dose(LEDs), and worse cognition. RWA was associated with H&Y stage, LEDs, cognition, and sleep structure in all patients. PD duration was associated with RWA, but not DEB. The PD patients who exhibited clinical or subclinical RBD, compared to sub-DEB positive, had higher H&Y stage, UPDRS III score and LEDs, lower cognitive score, worse sleep structure than the PD + cREM group. ConclusionBoth DEB and RWA were associated with severity of PD illness. Subclinical RBD might have different disease progression from sub-DEB positive. DEB symptoms may fluctuate or disappear whereas RWA may continue to develop as PD progresses. Differences in the course of DEB and RWA may reflect the difference in the degeneration process of neurodegenerative disorders.

Wilson's disease with and without rapid eye movement sleep behavior disorder compared to healthy matched controls

ObjectiveQuantitative data are reported on rapid eye movement (REM) sleep behavior disorder (RBD) in a cohort of predominantly neurological Wilson's disease (WD). MethodsA total of 41 patients with WD and 41 healthy, age- and gender-matched controls were studied by conducting face-to-face interviews, neurological and clinical examinations, laboratory tests, and WD- and RBD-specific scales. Video-polysomnography and quantification of REM sleep without atonia (RWA) were conducted in 35 patients and 41 controls. ResultsPatients with WD showed significantly worse sleep quality, less sleep efficiency, increased wakefulness after sleep onset, and more arousals compared to healthy controls. Five patients with WD (four women) fulfilled the diagnostic criteria for RBD with significantly higher values in RWA, RBD Questionnaire-Hong Kong, and RBD Screening Questionnaire compared to patients with WD without RBD. In three patients with WD, RBD had manifested before any other symptom that could be attributed to WD. Percentage of RWA was significantly lower in WD without RBD than in WD with RBD, but still significantly increased compared to controls. ConclusionsRBD can be comorbid with WD. RWA is commonly present in WD, both in the presence or absence of clinical RBD. A causal connection is possible, though retrospective determination of RBD onset and the low number of patients do not allow a definitive conclusion at this point. However, screening for WD in idiopathic RBD is available at low cost and is recommended. Early-stage copper chelation therapy provides a highly effective treatment to prevent further WD manifestations and might also control the comorbid RBD.

Impulse control disorder and rapid eye movement sleep behavior disorder in Parkinson's disease

The relationship between ICD and RBD is still not yet understood and the results from the current literature are contradictory in PD. We aimed to explore the association between rapid eye movement (REM) sleep behavior disorder (RBD) and impulse control disorder in Parkinson's disease. Ninety-eight non-demented patients with Parkinson's disease underwent one night of video-polysomnography recording. The diagnosis of RBD was established according to clinical and polysomnographic criteria. Impulse control disorders were determined by a gold standard, semi-structured diagnostic interview. Half of the patients (n=49) reported clinical history of RBD while polysomnographic diagnosis of RBD was confirmed in 31.6% of the patients (n=31). At least one impulse control disorder was identified in 21.4% of patients, 22.6% with RBD and 20.9% without. Logistic regression controlling for potential confounders indicated that both clinical RBD (OR=0.34, 95% CI=0.07-1.48, P=0.15) and polysomnographic confirmed RBD diagnoses (OR=0.1.28, 95% CI=0.31-5.33, P=0.34) were not associated with impulse control disorder. In Parkinson's disease, REM Sleep Behavior Disorder is not associated with impulse control disorder. The results of our study do not support the notion that PSG-confirmed RBD and ICD share a common pathophysiology.

Quantitative assessment of isolated rapid eye movement (REM) sleep without atonia without clinical REM sleep behavior disorder: clinical and research implications

BackgroundRapid eye movement (REM) sleep without atonia (RWA) is observed in some patients without a clinical history of REM sleep behavior disorder (RBD). It remains unknown whether these patients meet the refined quantitative electromyographic (EMG) criteria supporting a clinical RBD diagnosis. We quantitatively evaluated EMG activity and investigated its overnight distribution in patients with isolated qualitative RWA. MethodsFifty participants with an incidental polysomnographic finding of RWA (isolated qualitative RWA) were included. Tonic, phasic, and ‘any’ EMG activity during REM sleep on PSG were quantified retrospectively. ResultsReferring to the quantitative cut-off values for a polysomnographic diagnosis of RBD, 7/50 (14%) and 6/50 (12%) of the patients showed phasic and ‘any’ EMG activity in the mentalis muscle above the respective cut-off values. No patient was above the cut-off value for tonic EMG activity or phasic EMG activity in the anterior tibialis muscles. Patients with RWA above the cut-off value showed higher amounts of RWA during later REM sleep periods. ConclusionsThis is the first study showing that some subjects with incidental RWA meet the refined quantitative EMG criteria for a diagnosis of RBD. Future longitudinal studies must investigate whether this subgroup with isolated qualitative RWA is at an increased risk of developing fully expressed RBD and/or neurodegenerative disease.

REM sleep behavior disorder: association with motor complications and impulse control disorders in Parkinson's disease.

Clinical phenotypes such as old age, longer disease duration, motor disability, akineto-rigid type, dementia and hallucinations are known to be associated with REM sleep behavior disorder (RBD) in Parkinson's disease (PD). However, the relationship between motor fluctuations/impulse control and related behaviors (ICRB) and RBD is not clear. We designed this study to elucidate the clinical manifestations associated with RBD to determine the implications of RBD in PD. In a cross-sectional study, a total of 994 patients with PD were interviewed to determine the presence of RBD and their associated clinical features including motor complications and ICRB. Of the 944 patients, 578 (61.2%) had clinical RBD. When comparing the clinical features between patients with RBD (RBD group) and without RBD (non-RBD group), older age, longer disease duration, higher Hoehn and Yahr stage (H&Y stage), higher levodopa equivalent daily dose (LEDD), and the existence of wearing off, dyskinesia, freezing, and ICRB, especially punding, were associated with the RBD group compared to the non-RBD group (P<.05 in all). Multivariate analysis showed that motor complications including wearing off, peak dose dyskinesia, and diphasic dyskinesia were the only relevant factors for RBD after adjusting for age and disease duration. Motor complications and ICRB are more frequent in patients with RBD than in patients without RBD. In addition, motor complications are related to RBD even after adjusting for age and disease duration.

Clinical REM sleep behavior disorder and motor subtypes in Parkinson’s disease: A questionnaire-based study

ObjectivesStudies documenting the association between rapid eye movement sleep behavior disorder (RBD) and motor subtypes in Parkinson’s disease (PD) are rare. Our hypothesis is that RBD may be more severe in non-tremor dominant (NTD) patients with RBD than those tremor dominant (TD) with RBD. In this study, we investigated the association between motor subtypes and clinical RBD in PD. Patients and methodsWe evaluated 104 consecutive patients older than 18 years presenting with PD to the Neurology Clinic of the University Hospital for one year in this study. The clinical diagnosis of RBD was based on the minimal diagnostic criteria of International Classification of Sleep Disorders, revised. The Stavanger Sleepiness Questionnaire was used to rate the severity of clinical RBD. The patients were divided into two subgroups as TD and NTD. The patient and control groups were compared with each other for severity and frequency of clinical RBD, and the Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn–Yahr stage scores. The correlation between severity of clinical RBD and clinical severity of PD was analyzed in the patient groups. ResultsOf the patients, 45.2% (n=47) had the NTD subtype of PD and 54.8% (n=57) had the TD subtype of PD. There was no significant difference among the groups in terms of frequency and severity of clinical RBD. For the NTD patients, there was a weak positive correlation between severity of clinical RBD and clinical severity of PD. However, there was no correlation in the TD subgroup. ConclusionIn our study, frequency of clinical RBD was unrelated to motor subtypes of PD. However, in the present study, we found a weak correlation between clinical severity (UPDRS and the Hoehn–Yahr) of PD and severity of clinical RBD in the NTD subtype but not in the TD subtype.