REM sleep behavior disorder and REM sleep without atonia in Parkinson's disease

OBJECTIVE: To determine the frequency of REM sleep behavior disorder (RBD) among patients with PD using both history and polysomnography (PSG) recordings and to further study REM sleep muscle atonia in PD. BACKGROUND: The reported occurrence of RBD in PD varies from 15 to 47%. However, no study has estimated the frequency of RBD using PSG recordings or analyzed in detail the characteristics of REM sleep muscle atonia in a large group of unselected patients with PD. METHODS: Consecutive patients with PD (n = 33) and healthy control subjects (n = 16) were studied. Each subject underwent a structured clinical interview and PSG recording. REM sleep was scored using a method that allows the scoring of REM sleep without atonia. RESULTS: One third of patients with PD met the diagnostic criteria of RBD based on PSG recordings. Only one half of these cases would have been detected by history. Nineteen (58%) of 33 patients with PD but only 1 of 16 control subjects had REM sleep without atonia. Of these 19 patients with PD, 8 (42%) did not present with behavioral manifestations of RBD, and their cases may represent preclinical forms of RBD associated with PD. Moreover, the percentage of time spent with muscle atonia during REM sleep was lower among patients with PD than among healthy control subjects (60.1% vs 93.2%; p = 0.003). CONCLUSIONS: RBD and REM sleep without atonia are frequent in PD as shown by PSG recordings.     

Loss of REM sleep features across nighttime in REM sleep behavior disorder

ObjectivesMelatonin is a chronobiotic treatment which also alleviates rapid eye movement (REM) sleep behavior disorder (RBD). Because the mechanisms of this benefit are unclear, we evaluated the clock-dependent REM sleep characteristics in patients with RBD, whether idiopathic (iRBD) or associated with Parkinson's Disease (PD), and we compared findings with PD patients without RBD and with healthy subjects.MethodsAn overnight videopolysomnography was performed in ten iRBD patients, ten PD patients with RBD (PD + RBD+), ten PD patients without RBD (PD + RBD−), and ten controls. The rapid eye movement frequency per minute (REMs index), the tonic and phasic electromyographic (EMG) activity of the levator menti muscle, and the duration of each REM sleep episode were evaluated. A generalized linear model was applied in each group, with the REM sleep cycle (four ordinal levels) as the dependent variable, as a function of REMs index, REM sleep duration, and tonic and phasic EMG activity.ResultsFrom the first to the fourth sleep cycle, REM sleep duration progressively increased in controls only, REMs index increased in subjects without RBD but not in patients with RBD, whether idiopathic or associated with PD, whereas tonic and phasic EMG activity did not change.ConclusionsPatients with PD or iRBD lost the physiologic nocturnal increase in REM sleep duration, and patients with RBD (either with or without PD) lost the increase of REMs frequency across the night, suggesting an alteration in the circadian system in RBD. This supports the hypothesis of a direct effect of melatonin on RBD symptoms by its chronobiotic activity.     

Pathophysiologic mechanisms in REM sleep behavior disorder

REM sleep behavior disorder (RBD) is a fascinating experiment in nature predicted by animal studies in 1964. A defining feature of REM sleep is active paralysis of all somatic musculature (sparing the diaphragm to permit respiration). RBD is characterized by the absence of REM atonia, permitting the appearance of dream-enacting behaviors. These oneiric behaviors may be violent or injurious. RBD typically affects men over the age of 50 years. Longitudinal follow-up has shown that the majority of individuals with RBD will eventually develop additional signs and symptoms of a number of neurodegenerative disorders, most notably one of the synucleinopathies (Parkinson’s disease, dementia with Lewy body disease, multiple system atrophy, or pure autonomic failure), often after a prolonged interval lasting more than 10 years. RBD is also a common manifestation of narcolepsy. RBD may be induced by medications, especially the tricyclic antidepressants and serotonin-specific reuptake inhibitors. In most cases, clonazepam is a highly effective treatment.     

Magnetic resonance findings in REM sleep behavior disorder

Rapid eye movement (REM) sleep behavior disorder is characterized by bizarre acts during nocturnal sleep that may lead to physical injuries. Dream content suggests that motor overactivity is an attempted dream enactment and polygraphic studies reveal REM stage without atonia, an alteration of REM sleep generation that facilitates excessive motor activity. In 6 patients with REM sleep behavior disorder. MRI of the brain showed multifocal signal intensity lesions suggestive of lacunar infarcts in periventricular regions (5 patients) and in dorsal pontomesencephalic areas (3 patients). REM sleep behavior disorder may be the result of injury to the midrostral tegmentum nuclei, the tegmentoreticular tracts, or both. This condition is easily controlled with clonazepam.     

Midbrain hyperechogenicity in idiopathic REM sleep behavior disorder

Recent studies have reported an increased risk to develop Parkinson's disease (PD) in patients with idiopathic RBD (iRBD). Midbrain hyperechogenicity is a common transcranial sonography (TCS) finding in PD and has been suggested as a PD risk‐marker in nonparkinsonian subjects. The objective of this study is to assess midbrain echogenicity by TCS in patients with iRBD and compare the findings with the healthy controls. TCS was performed in 55 iRBD patients and in 165 age and sex‐matched controls. The area of echogenicity in the SN region in the iRBD group was significantly increased compared with the control group (P < 0.001). About 19 (37.3%) of patients with iRBD were found to have SN hyperechogenicity when compared with 16 (10.7%) of the controls (P < 0.001). This is the first case‐control study assessing midbrain echogenicity in a large iRBD cohort compared to age‐ and sex‐matched healthy individuals. The finding of an increased prevalence of hyperechogenicity in a subgroup of individuals with a priori increased risk for PD supports the potential role of hyperechogenicity as a risk marker for PD. The prospective follow‐up of this iRBD cohort is needed to establish if those with midbrain hyperechogenicity will go on to develop clinically defined PD or not. © 2009 Movement Disorder Society     

Impaired decision-making in idiopathic REM sleep behavior disorder

BackgroundPatients with REM sleep behavior disorder (RBD) frequently develop Parkinson’s disease (PD), which can impair decision-making ability. This study was undertaken to investigate decision-making ability and its relation to olfactory function in patients with idiopathic RBD.MethodsThis study used the Iowa Gambling Task (IGT) and the Sniffin’ Stick Test for examination of 38 patients with idiopathic RBD (iRBD) and 34 age-matched healthy control subjects (HC). Associations between these test results and other clinical RBD variables were also assessed.ResultsTotal IGT score and Sniffin’ Stick Test scores were significantly lower in the iRBD group than in the HC group. The iRBD group IGT scores in the first, third, and final blocks were significantly lower than those of the HC group. In the iRBD group, no association was found between the total IGT score and the Sniffin’ Stick Test score or any clinical RBD variable.ConclusionsImpaired decision-making associated with iRBD can herald PD. However, decision-making disability is thought to appear irrespective of olfactory dysfunction and progression of RBD pathology.     

Olfactory dysfunction in idiopathic REM sleep behavior disorder

BackgroundOlfactory dysfunction is frequently observed in patients with idiopathic REM sleep behavior disorder (iRBD) such as Parkinson’s disease or dementia with Lewy bodies.MethodsOlfactory function tests using Sniffin’ Sticks and Odor Stick Identification Test for Japanese (OSIT-J) were performed in 73 consecutive middle-aged (range, 50–69 years) patients with iRBD, 33 consecutive older-aged (71–82 years) patients with iRBD, and 28 control subjects (55–70 years).ResultsOdor identification was more frequently impaired than odor threshold or discrimination among the iRBD group and allowed better discrimination between the middle-aged iRBD group and age-adjusted control subjects. The area under the curve for threshold, discrimination, identification, TDI score and OSIT-J score determined from receiver operating characteristic curves were 0.831 (0.753–0.909), 0.761 (0.666–0.855), 0.938 (0.894–0.982), 0.939 (0.897–0.981), and 0.965 (0.931–0.999), respectively. Discrimination and identification scores were significantly lower in the older-aged iRBD group than in the middle-aged iRBD group. A significant correlation was observed between the identification score on Sniffin’ Sticks and OSIT-J score (r = 0.5910, P < 0.0001, n = 106, Spearman’s rank).ConclusionAnosmia/hyposmia may be a feature of iRBD. Olfactory dysfunction in iRBD is a consistent, widespread central nervous abnormality of different olfactory modalities with different cognitive complexity.     

Non-rapid eye movement sleep characteristics in idiopathic REM sleep behavior disorder

This study investigated slow waves (SW; >75μV and <4Hz) characteristics in patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). Thirty patients with iRBD and 30 age- and sex-matched healthy subjects underwent one polysomnographic (PSG) nocturnal sleep recording. SW automatic detection was performed on F3, C3, P3, and O1 leads and SW characteristics were derived (SW density, amplitude, frequency, slope, and duration of negative and positive phases). We also compared iRBD patients and control subjects on PSG variables and delta (0.25-4.0Hz) spectral power. No between-group differences were found on PSG variables, delta spectral power, or SW characteristics. Results show no SW abnormalities in iRBD patients compared to healthy participants, which suggests similar level of synchronization of thalamo-cortical neurons during N-REM sleep.     

The influence of sleep disordered breathing in REM sleep behavior disorder

Objectives/backgroundBecause both REM sleep behavior disorder (RBD) and Obstructive Sleep Apnea (OSA) can present with similar symptoms, it is important to understand the influence of OSA in the clinical manifestations of RBD and whether RBD modulates OSA severity. Our objectives were to compare: 1. the intensity of non-motor symptoms between RBD patients with (RBD-OSA) and without OSA (RBD-non-OSA), and 2. polysomnographic features between RBD-OSA and OSA without RBD (OSA-non-RBD) patients.Methods32 RBD cases were divided in two groups according to the presence of moderate to severe OSA [Apnea Hypopnea Index (AIH) > 14] (RBD-OSA vs. RBD-non-OSA). Non-motor symptoms were assessed with Montreal Cognitive Assessment Scale, SCOPA-Sleep and the Non-Motor Symptom Scale (NMSS) for Parkinson's disease. RBD-OSA patients were compared to 20 OSA-non-RBD patients matched for age, AHI and gender.ResultsCompared to RBD-non-OSA (n = 22) patients, RBD-OSA patients (n = 10) showed significantly higher scores in SCOPA-Sleep Daytime and NMSS Attention/Memory, Gastrointestinal and Urinary domains, as well as higher sleep fragmentation, more oxygen desaturation and higher AIH in NREM sleep. RBD-OSA patients presented with less O₂ desaturation, snoring, and BMI when compared to OSA-non-RBD patients.DiscussionOur data suggests that OSA contributes to hypersomnolence, gastro-intestinal, memory, and urinary complaints in RBD patients. RBD patients seem to have a milder OSA phenotype (possible reflecting a protective role conferred by the maintenance of muscle tone during REM sleep) and to be less prone to obesity and snoring than non-RBD patients.     

REM sleep behavior disorder: relevance to epileptologists

Clinical Epileptology - Rapid eye movement (REM) sleep behavior disorder (RBD) is a&nbsp;parasomnia that features loss of the generalized skeletal muscle atonia of mammalian REM sleep, with...     

Pareidolias and cognition in isolated REM sleep behavior disorder

BackgroundThough visual illusions and hallucinations are common in dementia with Lewy bodies (DLB) and Parkinson's disease (PD), they are not typically observed clinically in prodromal stages, including isolated REM sleep behavior disorder (iRBD). False-noise errors on the pareidolia test (seeing faces when none are present) may be an effective measure of susceptibility to future hallucinations in iRBD.MethodsOne hundred patients with iRBD underwent the 20-image pareidolia test. Clinical markers were assessed and a neuropsychological battery was administered. An exploratory analysis on the impact of pareidolic errors on phenoconversion was also performed.ResultsIn our cohort, 17 patients (17%) made false-noise pareidolic errors. These patients had significantly lower total Montreal Cognitive Assesment (MoCA) scores (26.7 ± 2.3 vs. 24.4 ± 2.6, B = −1.88, 95% CI: [-3.17, −0.59]), with lower subcomponent MoCA scores on memory and visuospatial-executive sections. Pareidolic errors were also associated with lower visuospatial, attention/executive, and memory scores on the neuropsychological tests. Furthermore, after 1.6 years follow-up, 3/16 (19%) patients making pareidolic errors had phenoconverted at time of publication compared to 6/71 (8%) patients who did not make errors.ConclusionPareidolic errors in patients with iRBD are associated with poorer overall cognition and may indicate higher risk of DLB.     

Cardiac autonomic dysfunction in idiopathic REM sleep behavior disorder

More than 50% of persons with idiopathic REM sleep behavior disorder (RBD) will develop Parkinson's disease or Lewy body dementia. Symptom screens and metaiodobenzylguanine (MIBG)‐scintigraphy suggest autonomic abnormalities in idiopathic RBD, but it is unclear whether autonomic abnormalities can predict neurodegenerative disease. From a cohort of 99 patients with idiopathic RBD, we selected those who developed parkinsonism or dementia. These were matched by age, sex, and follow‐up duration to patients with RBD who remained disease free and to matched controls. From the polysomnographic trace performed at baseline evaluation, measures of beat‐to‐beat RR variability including time domains (mean RR‐interval and RR‐standard deviation) and frequency domains (low and high frequency components) were retrospectively assessed. Twenty‐one patients with idiopathic RBD who developed neurodegenerative disease were included (Parkinson's disease‐11, multiple system atrophy‐1, and dementia‐9). Age at PSG was 66 years, and 86% were male. PSG was performed on average 6.7 years before defined neurodegenerative disease. Comparing all patients with idiopathic RBD to controls, there were significant reductions in RR‐standard deviation (24.6 ± 2.2 ms vs. 35.2 ± 3.5 ms, P = 0.006), very low frequency components (238.6 ± 99.6 ms² vs. 840.1 ± 188.3 ms², P < 0.001), and low frequency components (127.8 ± 26.3 ms² vs. 288.7 ± 66.2 ms², P = 0.032). However, despite clear differences between patients with idiopathic RBD and controls, there were no differences in any measure between those who did or did not develop disease. RR‐variability analysis demonstrates substantial autonomic dysfunction in idiopathic RBD. However, this dysfunction is identical in patients who will or will not develop defined neurodegenerative disease. This suggests that autonomic dysfunction is linked with RBD independent of associated Parkinson's disease or Lewy body dementia. © 2010 Movement Disorder Society     

The effects of pramipexole in REM sleep behavior disorder

The authors evaluated the effects of pramipexole, a dopaminergic D2-D3 receptor agonist, on eight patients with idiopathic REM sleep behavior disorder. Five patients reported a sustained reduction in the frequency or intensity of sleep motor behaviors, which was confirmed by video recording, although no change was observed for the percentage of phasic EMG activity during REM sleep. Surprisingly, a decrease in the percentage of time spent with REM sleep muscle atonia was observed with treatment. The treatment did not modify the indexes of periodic leg movements.     

Factors associated with injury in REM sleep behavior disorder

ObjectiveAs factors associated with injury in rapid eye movement (REM) sleep behavior disorder (RBD) remain largely unknown, we aimed to identify such factors.MethodsWe surveyed consecutive idiopathic (iRBD) or symptomatic RBD patients seen between 2008 and 2010 regarding RBD-related injuries. Associations between injuries and clinical variables were determined with odds ratios (OR) and multiple logistic regression analyses. The primary outcome variables were injury and injury severity.ResultsFifty-three patients (40%) responded. Median age was 69 years, and 35 (73.5%) were men. Twenty-eight (55%) had iRBD. Twenty-nine (55%) reported injury, with 37.8% to self and 16.7% to the bed partner. 11.3% had marked injuries requiring medical intervention or hospitalization, including two (4%) subdural hematomas. iRBD diagnosis (OR = 6.8, p = 0.016) and dream recall (OR = 7.5, p = 0.03) were associated with injury; and iRBD diagnosis was independently associated with injury and injury severity adjusting for age, gender, DEB frequency, and duration. Falls (p = 0.03) were also associated with injury severity. DEB frequency was not associated with injury, injury severity, or falls.ConclusionsInjuries appear to be a frequent complication of RBD, although the relatively low response rate in our survey could have biased results. iRBD patients are more likely to suffer injury – and more severe injuries – than symptomatic RBD patients. In addition, recall of dreams was also associated with injury, and dream enactment behavior (DEB)-related falls were associated with more severe injuries. One in nine patients suffered injury requiring medical intervention. The frequency of DEB did not predict RBD-related injuries, highlighting the importance of timely initiation of treatment for RBD in patients having even rare DEB episodes. Future prospective studies will be necessary to define predictors of injury in RBD.