Search tips
Search criteria

Results 1-25 (1071212)

Clipboard (0)

Related Articles

1.  Probable rapid eye movement sleep behavior disorder, nocturnal disturbances and quality of life in patients with Parkinson’s disease: a case-controlled study using the rapid eye movement sleep behavior disorder screening questionnaire 
BMC Neurology  2013;13:18.
Increasing evidence provides a clear association between rapid eye movement sleep behavior disorders (RBD) and Parkinson’s disease (PD), but the clinical features that determine the co-morbidity of RBD and PD are not yet fully understood.
We evaluated the characteristics of nocturnal disturbances and other motor and non-motor features related to RBD in patients with PD and the impact of RBD on their quality of life. Probable RBD (pRBD) was evaluated using the Japanese version of the RBD screening questionnaire (RBDSQ-J).
A significantly higher frequency of pRBD was observed in PD patients than in the controls (RBDSQ-J ≥ 5 or ≥ 6: 29.0% vs. 8.6%; 17.2% vs. 2.2%, respectively). After excluding restless legs syndrome and snorers in the PD patients, the pRBD group (RBDSQ-J≥5) showed higher scores compared with the non-pRBD group on the Parkinson’s disease sleep scale-2 (PDSS-2) total and three-domain scores. Early morning dystonia was more frequent in the pRBD group. The Parkinson’s Disease Questionnaire (PDQ-39) domain scores for cognition and emotional well-being were higher in the patients with pRBD than in the patients without pRBD. There were no differences between these two groups with respect to the clinical subtype, disease severity or motor function. When using a cut-off of RBDSQ-J = 6, a similar trend was observed for the PDSS-2 and PDQ-39 scores. Patients with PD and pRBD had frequent sleep onset insomnia, distressing dreams and hallucinations. The stepwise linear regression analysis showed that the PDSS-2 domain “motor symptoms at night”, particularly the PDSS sub-item 6 “distressing dreams”, was the only predictor of RBDSQ-J in PD.
Our results indicate a significant impact of RBD co-morbidity on night-time disturbances and quality of life in PD, particularly on cognition and emotional well-being. RBDSQ may be a useful tool for not only screening RBD in PD patients but also predicting diffuse and complex clinical PD phenotypes associated with RBD, cognitive impairment and hallucinations.
PMCID: PMC3575252  PMID: 23394437
Parkinson’s disease; Rapid eye movement sleep behavior disorder; Cognition; Quality of life; Nocturnal problems
2.  REM sleep behaviour disorder is associated with worse quality of life and other non-motor features in early Parkinson's disease 
Concomitant REM sleep behaviour disorder (RBD) is commonly observed in patients with Parkinson's disease (PD). Although the brainstem structures responsible for the symptoms of RBD correspond to the premotor stages of PD, the association of RBD with motor and non-motor features in early PD remains unclear.
The study evaluated 475 patients with PD within 3.5 years of diagnosis for the presence of probable RBD (pRBD) using the REM Sleep Behaviour Disorder Screening Questionnaire (RBDSQ). A neurologist and a trained research nurse carried out evaluation of each participant blinded to the results of the RBDSQ. Standardised rating scales for motor and non-motor features of PD, as well as health-related quality of life measures, were assessed. Multiple linear and logistic regression analyses were used to determine the relationship between pRBD and a variety of outcomes, controlling for confounding factors.
The overall frequency of pRBD was 47.2% (95% CI 42.7% to 51.9%). None of the patients had a previous diagnosis of RBD. Patients with PD and concomitant pRBD did not differ on motor phenotype and scored comparably on the objective motor scales, but reported problems with motor aspects of daily living more frequently. Adjusted for age, sex, disease duration and smoking history, pRBD was associated with greater sleepiness (p=0.001), depression (p=0.001) and cognitive impairment (p=0.006).
pRBD is common and under-recognised in early PD. It is associated with increased severity and frequency of non-motor features, poorer subjective motor performance and a greater impact on health-related quality of life.
PMCID: PMC3995329  PMID: 24187013
3.  Probable REM Sleep Behavior Disorder Increases Risk for Mild Cognitive Impairment and Parkinson’s Disease: A Population-Based Study 
Annals of Neurology  2012;71(1):49-56.
REM sleep behavior disorder (RBD) is associated with neurodegenerative disease and particularly with the synucleinopathies. Convenience samples involving subjects with idiopathic RBD have suggested an increased risk of incident mild cognitive impairment (MCI), dementia (usually dementia with Lewy bodies) or Parkinson’s disease (PD). There is no data on such risk in a population-based sample.
Cognitively normal subjects aged 70–89 in a population-based study of aging who screened positive for probable RBD using the Mayo Sleep Questionnaire were followed at 15 month intervals. In a Cox Proportional Hazards Model, we measured the risk of developing MCI, dementia, PD among the exposed (pRBD+) and unexposed (pRBD−) cohorts.
Forty-four subjects with pRBD+ at enrollment (median duration of pRBD features was 7.5 years), and 607 pRBD− subjects, were followed prospectively for a median of 3.8 years. Fourteen of the pRBD+ subjects developed MCI and one developed PD (15/44=34% developed MCI / PD); none developed dementia. After adjustment for age, sex, education, and medical comorbidity, pRBD+ subjects were at increased risk of MCI / PD [Hazard Ratio (HR) 2.2, 95% Confidence Interval (95%CI) 1.3 – 3.9; p=0.005]. Inclusion of subjects who withdrew from the study produced similar results, as did exclusion of subjects with medication-associated RBD. Duration of pRBD symptoms did not predict the development of MCI / PD (HR 1.05 per 10 years, 95%CI 0.84 – 1.3; p=0.68).
In this population-based cohort study, we observed that pRBD confers a 2.2-fold increased risk of developing MCI / PD over four years.
PMCID: PMC3270692  PMID: 22275251
sleep disorders; parasomnias; dementia; Alzheimer’s disease; dementia with Lewy bodies; parkinsonism; synuclein
4.  Family history of idiopathic REM behavior disorder 
Neurology  2013;80(24):2233-2235.
To compare the frequency of proxy-reported REM sleep behavior disorder (RBD) among relatives of patients with polysomnogram-diagnosed idiopathic RBD (iRBD) in comparison to controls using a large multicenter clinic-based cohort.
A total of 316 patients with polysomnography-confirmed iRBD were recruited from 12 RBD study group centers, along with 316 controls matched on sex and age group. All subjects completed a self-administered questionnaire that collected proxy-reported information on family history of tremor, gait trouble, balance trouble, Parkinson disease, memory loss, and Alzheimer disease. The questionnaire also included a single question that asked about possible symptoms of RBD among first-degree relatives (siblings, parents, and children).
A positive family history of dream enactment was reported in 13.8% of iRBD cases compared to 4.8% of controls (odds ratio [OR] = 3.9, 95% confidence interval [CI] 2.0–7.7). ORs were increased for both siblings (OR = 6.1, 95% CI 2.1–18.1) and parents (OR = 3.2, 95% CI 1.4–7.8). We found no significant difference in sex, current age (65.3 ± 10.2 vs 66.9 ± 10.2 years), or age at self-reported RBD onset (55.2 ± 11.7 vs 56.6 ± 15.1 years) in possible familial vs sporadic iRBD. No differences were found in family history of tremor, walking and balance troubles, Parkinson disease, memory loss, or Alzheimer disease.
We found increased odds of proxy-reported family history of presumed RBD among individuals with confirmed iRBD. This suggests the possibility of a genetic contribution to RBD.
PMCID: PMC3721098  PMID: 23658378
5.  Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder 
Sleep medicine  2013;14(8):754-762.
To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder.
The clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria.
172 cases were identified, of whom 143 (83%) were men. The mean ± SD age of onset in years for the core features were as follows – RBD, 62 ± 14 (range, 20–93), cognitive impairment (n = 147); 69 ± 10 (range, 22–90), parkinsonism (n = 151); 68 ± 9 (range, 20–92), and autonomic dysfunction (n = 42); 62 ± 12 (range, 23–81). Death age was 75 ± 9 years (range, 24–96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10 ± 12 (range, 1–61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n = 97), Parkinson’s disease with or without mild cognitive impairment or dementia (n = 32), multiple system atrophy (MSA) (n = 19), Alzheimer’s disease (AD)(n = 9) and other various disorders including secondary narcolepsy (n = 2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n = 1). The neuropathologic diagnoses were Lewy body disease (LBD)(n = 77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n = 59), MSA (n = 19), AD (n = 6), progressive supranulear palsy (PSP) (n = 2), other mixed neurodegenerative pathologies (n = 6), NBIA-1/LBD/tauopathy (n = 1), and hypothalamic structural lesions (n = 2). Among the neurodegenerative disorders associated with RBD (n = 170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features.
In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.
PMCID: PMC3745815  PMID: 23474058
REM sleep behavior disorder; Parasomnia; Lewy body disease; Dementia with Lewy bodies; Parkinson’s disease; Multiple system atrophy; Synuclein; Synucleinopathy
6.  Restless legs syndrome and daytime sleepiness are prominent in myotonic dystrophy type 2 
Neurology  2013;81(2):157-164.
Although sleep disturbances are common in myotonic dystrophy type 1 (DM1), sleep disturbances in myotonic dystrophy type 2 (DM2) have not been well-characterized. We aimed to determine the frequency of sleep disturbances in DM2.
We conducted a case-control study of 54 genetically confirmed DM2 subjects and 104 medical controls without DM1 or DM2, and surveyed common sleep disturbances, including symptoms of probable restless legs syndrome (RLS), excessive daytime sleepiness (EDS), sleep quality, fatigue, obstructive sleep apnea (OSA), probable REM sleep behavior disorder (pRBD), and pain. Thirty patients with DM2 and 43 controls responded to the survey. Group comparisons with parametric statistical tests and multiple linear and logistic regression analyses were conducted for the dependent variables of EDS and poor sleep quality.
The mean ages of patients with DM2 and controls were 63.8 and 64.5 years, respectively. Significant sleep disturbances in patients with DM2 compared to controls included probable RLS (60.0% vs 14.0%, p < 0.0001), EDS (p < 0.001), sleep quality (p = 0.02), and fatigue (p < 0.0001). EDS and fatigue symptoms were independently associated with DM2 diagnosis (p < 0.01) after controlling for age, sex, RLS, and pain scores. There were no group differences in OSA (p = 0.87) or pRBD (p = 0.12) scores.
RLS, EDS, and fatigue are frequent sleep disturbances in patients with DM2, while OSA and pRBD symptoms are not. EDS was independently associated with DM2 diagnosis, suggesting possible primary CNS hypersomnia mechanisms. Further studies utilizing objective sleep measures are needed to better characterize sleep comorbidities in DM2.
PMCID: PMC3770170  PMID: 23749798
7.  Increased Corticomuscular Coherence in Idiopathic REM Sleep Behavior Disorder 
The authors hypothesized that if locomotor drive increases along with rapid eye movement (REM) sleep without atonia in idiopathic REM sleep behavior disorder (RBD), then RBD patients would have greater corticomuscular coherence (CMC) values during REM sleep than at other sleep stages and than in healthy control subjects during REM sleep. To explore this hypothesis, we analyzed beta frequency range CMC between sensorimotor cortex electroencephalography (EEG) and chin/limb muscle EMG in idiopathic RBD patients. Eleven drug naive idiopathic RBD patients and 11 age-matched healthy control subjects were included in the present study. All participants completed subjective sleep questionnaires and underwent polysomnography for one night. The CMC value between EEGs recorded at central electrodes and EMGs acquired at leg and chin muscles were computed and compared by repeated measures analysis of variance (ANOVA). Sleep stages and muscle (i.e., chin vs. leg) served as within-subject factors, and group served as the between-subject factor. Repeated measures ANOVA revealed no significant main effect of group (F1,20 = 0.571, p = 0.458) or muscle (F1,20 = 1.283, p = 0.271). However, sleep stage was found to have a significant main effect (F2.067,41.332 = 20.912, p < 0.001). The interaction between group and sleep stage was significant (F2.067,41.332 = 3.438, p = 0.040). RBD patients had a significantly higher CMC value than controls during REM sleep (0.047 ± 0.00 vs. 0.052 ± 0.00, respectively, p = 0.007). This study reveals increased CMC during REM sleep in patients with RBD, which indicates increased cortical locomotor drive. Furthermore, this study supports the hypothesis that sufficient locomotor drive plays a role in the pathophysiology of RBD in addition to REM sleep without atonia.
PMCID: PMC3332227  PMID: 22536195
REM sleep behavior disorder; pathophysiology; corticomuscular coherence; REM sleep without atonia
8.  Daytime Sleepiness in Parkinson’s Disease: A Reappraisal 
PLoS ONE  2014;9(9):e107278.
Excessive daytime sleepiness is a frequent complaint in Parkinson’s disease (PD); however the frequency and risk factors for objective sleepiness remain mostly unknown. We investigated both the frequency and determinants of self-reported and objective daytime sleepiness in patients with Parkinson’s disease (PD) using a wide range of potential predictors.
One hundred and thirty four consecutive patients with PD, without selection bias for sleep complaint, underwent a semi-structured clinical interview and a one night polysomnography followed by a multiple sleep latency test (MSLT). Demographic characteristics, medical history, PD course and severity, daytime sleepiness, depressive and insomnia symptoms, treatment intake, pain, restless legs syndrome, REM sleep behaviour disorder, and nighttime sleep measures were collected. Self-reported daytime sleepiness was defined by an Epworth Sleepiness Scale (ESS) score above 10. A mean sleep latency on MSLT below 8 minutes defined objective daytime sleepiness.
Of 134 patients with PD, 46.3% had subjective and only 13.4% had objective sleepiness with a weak negative correlation between ESS and MSLT latency. A high body mass index (BMI) was associated with both ESS and MSLT, a pain complaint with ESS, and a higher apnea/hypopnea index with MSLT. However, no associations were found between both objective and subjective sleepiness, and measures of motor disability, disease onset, medication (type and dose), depression, insomnia, restless legs syndrome, REM sleep behaviour disorder and nighttime sleep evaluation.
We found a high frequency of self-reported EDS in PD, a finding which is however not confirmed by the gold standard neurophysiological evaluation. Current treatment options for EDS in PD are very limited; it thus remains to be determined whether decreasing pain and BMI in association with the treatment of sleep apnea syndrome would decrease significantly daytime sleepiness in PD.
PMCID: PMC4157859  PMID: 25198548
9.  Validation of the Mayo Sleep Questionnaire to Screen for REM Sleep Behavior Disorder in an Aging and Dementia Cohort 
Sleep medicine  2011;12(5):445-453.
To validate a questionnaire focused on REM sleep behavior disorder (RBD) among participants in an aging and dementia cohort.
RBD is a parasomnia that can develop in otherwise neurologically-normal adults as well as in those with a neurodegenerative disease. Confirmation of RBD requires polysomnography (PSG). A simple screening measure for RBD would be desirable for clinical and research purposes.
We had previously developed the Mayo Sleep Questionnaire (MSQ), a 16 item measure, to screen for the presence of RBD and other sleep disorders. We assessed the validity of the MSQ by comparing the responses of patients’ bed partners with the findings on PSG. All subjects recruited in the Mayo Alzheimer’s Disease Research Center at Mayo Clinic Rochester and Mayo Clinic Jacksonville from 1/00 to 7/08 who had also undergone a PSG were the focus of this analysis.
The study sample was comprised of 176 subjects [150 male; median age 71 years (range 39–90)], with the following clinical diagnoses: normal (n=8), mild cognitive impairment (n=44), Alzheimer’s disease (n=23), dementia with Lewy bodies (n=74), as well as other dementia and/or parkinsonian syndromes (n=27). The core question on recurrent dream enactment behavior yielded a sensitivity (SN) of 98% and specificity (SP) of 74% for the diagnosis of RBD. The profile of responses on four additional subquestions on RBD and one on obstructive sleep apnea improved specificity.
These data suggest that among aged subjects with cognitive impairment and/or parkinsonism, the MSQ has adequate SN and SP for the diagnosis of RBD. The utility of this scale in other patient populations will require further study.
PMCID: PMC3083495  PMID: 21349763
sleep disorders; parasomnias; dementia; Alzheimer’s disease; dementia with Lewy bodies; parkinsonism
10.  Abnormal metabolic network activity in REM sleep behavior disorder 
Neurology  2014;82(7):620-627.
To determine whether the Parkinson disease–related covariance pattern (PDRP) expression is abnormally increased in idiopathic REM sleep behavior disorder (RBD) and whether increased baseline activity is associated with greater individual risk of subsequent phenoconversion.
For this cohort study, we recruited 2 groups of RBD and control subjects. Cohort 1 comprised 10 subjects with RBD (63.5 ± 9.4 years old) and 10 healthy volunteers (62.7 ± 8.6 years old) who underwent resting-state metabolic brain imaging with 18F-fluorodeoxyglucose PET. Cohort 2 comprised 17 subjects with RBD (68.9 ± 4.8 years old) and 17 healthy volunteers (66.6 ± 6.0 years old) who underwent resting brain perfusion imaging with ethylcysteinate dimer SPECT. The latter group was followed clinically for 4.6 ± 2.5 years by investigators blinded to the imaging results. PDRP expression was measured in both RBD groups and compared with corresponding control values.
PDRP expression was elevated in both groups of subjects with RBD (cohort 1: p < 0.04; cohort 2: p < 0.005). Of the 17 subjects with long-term follow-up, 8 were diagnosed with Parkinson disease or dementia with Lewy bodies; the others did not phenoconvert. For individual subjects with RBD, final phenoconversion status was predicted using a logistical regression model based on PDRP expression and subject age at the time of imaging (r2 = 0.64, p < 0.0001).
Latent network abnormalities in subjects with idiopathic RBD are associated with a greater likelihood of subsequent phenoconversion to a progressive neurodegenerative syndrome.
PMCID: PMC3963420  PMID: 24453082
11.  Sleep Disorders in Parkinsonian and Nonparkinsonian LRRK2 Mutation Carriers 
PLoS ONE  2015;10(7):e0132368.
In idiopathic Parkinson disease (IPD) sleep disorders are common and may antedate the onset of parkinsonism. Based on the clinical similarities between IPD and Parkinson disease associated with LRRK2 gene mutations (LRRK2-PD), we aimed to characterize sleep in parkinsonian and nonmanifesting LRRK2 mutation carriers (NMC).
A comprehensive interview conducted by sleep specialists, validated sleep scales and questionnaires, and video-polysomnography followed by multiple sleep latency test (MSLT) assessed sleep in 18 LRRK2-PD (17 carrying G2019S and one R1441G mutations), 17 NMC (11 G2019S, three R1441G, three R1441C), 14 non-manifesting non-carriers (NMNC) and 19 unrelated IPD.
Sleep complaints were frequent in LRRK2-PD patients; 78% reported poor sleep quality, 33% sleep onset insomnia, 56% sleep fragmentation and 39% early awakening. Sleep onset insomnia correlated with depressive symptoms and poor sleep quality. In LRRK2-PD, excessive daytime sleepiness (EDS) was a complaint in 33% patients and short sleep latencies on the MSLT, which are indicative of objective EDS, were found in 71%. Sleep attacks occurred in three LRRK2-PD patients and a narcoleptic phenotype was not observed. REM sleep behavior disorder (RBD) was diagnosed in three LRRK2-PD. EDS and RBD were always reported to start after the onset of parkinsonism in LRRK2-PD. In NMC, EDS was rarely reported and RBD was absent. When compared to IPD, sleep onset insomnia was more significantly frequent, EDS was similar, and RBD was less significantly frequent and less severe in LRRK2-PD. In NMC, RBD was not detected and sleep complaints were much less frequent than in LRRK2-PD. No differences were observed in sleep between NMC and NMNC.
Sleep complaints are frequent in LRRK2-PDand show a pattern that when compared to IPD is characterized by more frequent sleep onset insomnia, similar EDS and less prominent RBD. Unlike in IPD, RBD and EDS seem to be not markers of the prodromal stage of LRRK2-PD.
PMCID: PMC4503402  PMID: 26177462
12.  Treatment Outcomes in REM Sleep Behavior Disorder 
Sleep medicine  2013;14(3):237-242.
REM sleep behavior disorder (RBD) is usually characterized by potentially injurious dream enactment behaviors (DEB). RBD treatment aims to reduce DEBs and prevent injury, but outcomes require further elucidation. We surveyed RBD patients to describe longitudinal treatment outcomes with melatonin and clonazepam.
We surveyed and reviewed records of consecutive RBD patients seen at Mayo Clinic between 2008–2010 to describe RBD-related injury frequency/severity as well as RBD Visual Analog Scale (VAS) ratings, medication dosage, and side effects. Statistical analyses were performed with appropriate non-parametric matched pairs tests before and after treatment, and with comparative group analyses for continuous and categorical variables between treatment groups. The primary outcome variables were RBD VAS ratings and injury frequency.
Forty-five (84.9%) of 53 respondent surveys were analyzed. Mean age was 65.8 years and 35 (77.8%) patients were men. Neurodegenerative disorders were seen in 24 (53%) patients, and 25 (56%) received antidepressants. Twenty-five patients received melatonin, 18 received clonazepam, and 2 received both as initial treatment. Before treatment, 27 patients (60%) reported an RBD associated injury. Median dosages were melatonin 6 mg and clonazepam 0.5 mg. RBD VAS ratings were significantly improved following both treatments (pm=.0001, pc=.0005). Melatonin-treated patients reported significantly reduced injuries (pm=.001, pc=.06) and fewer adverse effects (p=0.07). Mean durations of treatment were no different between groups (for clonazepam 53.9 +/− 29.5 months, and for melatonin 27.4 +/− 24 months, p=0.13) and there were no differences in treatment retention, with 28% of melatonin and 22% of clonazepam-treated patients discontinuing treatment (p=0.43).
Melatonin and clonazepam were each reported to reduce RBD behaviors and injuries and appeared comparably effective in our naturalistic practice experience. Melatonin-treated patients reported less frequent adverse effects than those treated with clonazepam. More effective treatments that would eliminate injury potential and evidence-based treatment outcomes from prospective clinical trials for RBD are needed.
PMCID: PMC3617579  PMID: 23352028
REM sleep behavior disorder; parasomnia; melatonin; clonazepam; treatment; side effects; tolerability; retention; injury; falls; synucleinopathy
13.  Prevalence of REM sleep behavior disorder in multiple system atrophy: a multicenter study and meta-analysis 
Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia frequently affecting patients with synucleinopathies but its exact prevalence in multiple system atrophy (MSA) is unclear. Whether questionnaires alone are sufficient to diagnose RBD is also unknown.
Cross-sectional study of patients with probable MSA from six academic centers in the US and Europe. RBD was ascertained clinically and with polysomnography; and meta-analysis according to PRISMA guidelines for studies published before September 2014 that reported the prevalence of RBD in MSA. A random-effects model was constructed using weighted prevalence proportions. Only articles in English were included. Studies were classified into those that ascertained the presence of RBD in MSA clinically and with polysomnography. Case reports or case series (≤5 patients) were not included.
Forty-two patients completed questionnaires and underwent polysomnography. Of those, 32 (76.1%) had clinically-suspected RBD and 34 (81%) had polysomnography-confirmed RBD. Two patients reported no symptoms of RBD but had polysomnography-confirmed RBD.
The primary search strategy yielded 374 articles of which 12 met the inclusion criteria The summary prevalence of clinically suspected RBD was 73% (95% CI, 62%-84%) in a combined sample of 324 MSA patients. The summary prevalence of polysomnography-confirmed RBD was 88% (95% CI, 79%-94%) in a combined sample of 217 MSA patients.
Polysomnography-confirmed RBD is present in up to 88% of patients with MSA. RBD was present in some patients that reported no symptoms. More than half of MSA patients report symptoms of RBD before the onset of motor deficits.
PMCID: PMC4406814  PMID: 25739474
α-synuclein; sleep disorders; parasomnias; polysomnography; parkinsonism
14.  MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies 
Neurology  2013;81(19):1681-1689.
To determine structural MRI and digital microscopic characteristics of REM sleep behavior disorder in individuals with low-, intermediate-, and high-likelihood dementia with Lewy bodies (DLB) at autopsy.
Patients with autopsy-confirmed low-, intermediate-, and high-likelihood DLB, according to the probability statement recommended by the third report of the DLB Consortium, and antemortem MRI, were identified (n = 75). The clinical history was assessed for presence (n = 35) and absence (n = 40) of probable REM sleep behavior disorder (pRBD), and patients' antemortem MRIs were compared using voxel-based morphometry. Pathologic burdens of phospho-tau, β-amyloid, and α-synuclein were measured in regions associated with early neuropathologic involvement, the hippocampus and amygdala.
pRBD was present in 21 patients (60%) with high-likelihood, 12 patients (34%) with intermediate-likelihood, and 2 patients (6%) with low-likelihood DLB. Patients with pRBD were younger, more likely to be male (p ≤ 0.001), and had a more frequent neuropathologic diagnosis of diffuse (neocortical) Lewy body disease. In the hippocampus and amygdala, phospho-tau and β-amyloid burden were lower in patients with pRBD compared with those without pRBD (p < 0.01). α-Synuclein burden did not differ in the hippocampus, but trended in the amygdala. Patients without pRBD had greater atrophy of temporoparietal cortices, hippocampus, and amygdala (p < 0.001) than those with pRBD; atrophy of the hippocampus (p = 0.005) and amygdala (p = 0.02) were associated with greater phospho-tau burdens in these regions.
Presence of pRBD is associated with a higher likelihood of DLB and less severe Alzheimer-related pathology in the medial temporal lobes, whereas absence of pRBD is characterized by Alzheimer-like atrophy patterns on MRI and increased phospho-tau burden.
PMCID: PMC3812105  PMID: 24107861
15.  Surface EMG activity during REM sleep in Parkinson’s disease correlates with disease severity 
Parkinsonism & related disorders  2014;20(7):766-771.
Over 40% of individuals with Parkinson’s disease (PD) have rapid eye movement sleep behavior disorder (RBD). This is associated with excessive sustained (tonic) or intermittent (phasic) muscle activity instead of the muscle atonia normally seen during REM sleep. We examined characteristics of manually-quantitated surface EMG activity in PD to ascertain whether the extent of muscle activity during REM sleep is associated with specific clinical features and measures of disease severity.
In a convenience sample of outpatients with idiopathic PD, REM sleep behavior disorder was diagnosed based on clinical history and polysomnogram, and severity was measured using the RBD sleep questionnaire. Surface EMG activity in the mentalis, extensor muscle group of the forearms, and anterior tibialis was manually quantitated. Percentage of REM time with excessive tonic or phasic muscle activity was calculated and compared across PD and RBD characteristics.
Among 65 patients, 31 had confirmed RBD. In univariate analyses, higher amounts of surface EMG activity were associated with longer PD disease duration (srho = 0.34; p = 0.006) and greater disease severity (p < 0.001). In a multivariate regression model, surface EMG activity was significantly associated with RBD severity (p < 0.001) after adjustment for age, PD disease duration, PD severity and co-morbid sleep abnormalities.
Surface EMG activity during REM sleep was associated with severity of both PD and RBD. This measure may be useful as a PD biomarker and, if confirmed, may aid in determining which PD patients warrant treatment for their dream enactment to reduce risk of injury.
PMCID: PMC4407824  PMID: 24787758
Parkinson’s disease; REM sleep behavior disorder; REM sleep without atonia; Surface EMG activity
16.  REM Sleep Behavior Disorder and REM Sleep Without Atonia as an Early Manifestation of Degenerative Neurological Disease 
Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by repeated episodes of dream enactment behavior and REM sleep without atonia (RSWA) during polysomnography recording. RSWA is characterized by increased phasic or tonic muscle activity seen on polysomnographic electromyogram channels. RSWA is a requisite diagnostic feature of RBD, but may also be seen in patients without clinical symptoms or signs of dream enactment as an incidental finding in neurologically normal individuals, especially in patients receiving antidepressant therapy. RBD may be idiopathic or symptomatic. Patients with idiopathic RBD often later develop other neurological features including parkinsonism, orthostatic hypotension, anosmia, or cognitive impairment. RSWA without clinical symptoms as well as clinically overt RBD also often occurs concomitantly with the α-synucleinopathy family of neurodegenerative disorders, which includes idiopathic Parkinson disease, Lewy body dementia, and multiple system atrophy. This review article considers the epidemiology of RBD, clinical and polysomnographic diagnostic standards for both RBD and RSWA, previously reported associations of RSWA and RBD with neurodegenerative disorders and other potential causes, the pathophysiology of which brain structures and networks mediate dysregulation of REM sleep muscle atonia, and considerations for the effective and safe management of RBD.
PMCID: PMC3656587  PMID: 22328094
REM sleep behavior disorder; REM sleep without atonia; Parasomnia; α-synucleinopathy; Parkinsonism; Neurodegeneration; Braak staging; Melatonin; Clonazepam; Treatment; Neuropsychological testing; Neurological disease
17.  REM sleep behavior disorder preceding other aspects of synucleinopathies by up to half a century(e–Pub ahead of print)(CME) 
Neurology  2010;75(6):494-499.
Idiopathic REM sleep behavior disorder (RBD) may be the initial manifestation of synucleinopathies (Parkinson disease [PD], multiple system atrophy [MSA], or dementia with Lewy bodies [DLB]).
We used the Mayo medical records linkage system to identify cases presenting from 2002 to 2006 meeting the criteria of idiopathic RBD at onset, plus at least 15 years between RBD and development of other neurodegenerative symptoms. All patients underwent evaluations by specialists in sleep medicine to confirm RBD, and behavioral neurology or movement disorders to confirm the subsequent neurodegenerative syndrome.
Clinical criteria were met by 27 patients who experienced isolated RBD for at least 15 years before evolving into PD, PD dementia (PDD), DLB, or MSA. The interval between RBD and subsequent neurologic syndrome ranged up to 50 years, with the median interval 25 years. At initial presentation, primary motor symptoms occurred in 13 patients: 9 with PD, 3 with PD and mild cognitive impairment (MCI), and 1 with PDD. Primary cognitive symptoms occurred in 13 patients: 10 with probable DLB and 3 with MCI. One patient presented with primary autonomic symptoms, diagnosed as MSA. At most recent follow-up, 63% of patients progressed to develop dementia (PDD or DLB). Concomitant autonomic dysfunction was confirmed in 74% of all patients.
These cases illustrate that the α-synuclein pathogenic process may start decades before the first symptoms of PD, DLB, or MSA. A long-duration preclinical phase has important implications for epidemiologic studies and future interventions designed to slow or halt the neurodegenerative process.
= dementia with Lewy bodies;
= mild cognitive impairment;
= multiple system atrophy;
= Parkinson disease;
= PD with associated mild cognitive impairment;
= Parkinson disease dementia;
= polysomnogram;
= REM sleep behavior disorder.
PMCID: PMC2918473  PMID: 20668263
18.  Increased REM sleep without atonia in Parkinson disease with freezing of gait 
Neurology  2013;81(12):1030-1035.
The objective of this cross-sectional study was to test the hypothesis that patients with Parkinson disease (PD) and freezing of gait (PD+FOG) would demonstrate sleep disturbances comparable to those seen in patients with REM sleep behavior disorder (RBD) and these changes would be significantly different from those in PD patients without FOG (PD-FOG) and age-matched controls.
We conducted overnight polysomnography studies in 4 groups of subjects: RBD, PD-FOG, PD+FOG, and controls. Tonic and phasic muscle activity during REM sleep were quantified using EMG recordings from the chin, compared among study groups, and correlated with disease metrics.
There were no significant differences in measures of disease severity, duration, or dopaminergic medications between the PD+FOG and PD-FOG groups. Tonic muscle activity was increased significantly (p < 0.007) in the RBD and PD+FOG groups compared to the PD-FOG and control groups. There was no significant difference in tonic EMG between the PD+FOG and RBD group (p = 0.364), or in tonic or phasic EMG between the PD-FOG and control group (p = 0.107). Phasic muscle activity was significantly increased in the RBD group compared to all other groups (p = 0.029) and between the PD+FOG and control group (p = 0.001), but not between the PD+FOG and PD-FOG groups (p = 0.059).
These findings provide evidence that increased muscle activity during REM sleep is a comorbid feature of patients with PD who exhibit FOG as a motor manifestation of their disease.
PMCID: PMC3795590  PMID: 23946301
19.  Parasomnias: An Updated Review 
Neurotherapeutics  2012;9(4):753-775.
Parasomnias are abnormal behaviors emanating from or associated with sleep. Sleepwalking and related disorders result from an incomplete dissociation of wakefulness from nonrapid eye movement (NREM) sleep. Conditions that provoke repeated cortical arousals, or promote sleep inertia lead to NREM parasomnias by impairing normal arousal mechanisms. Changes in the cyclic alternating pattern, a biomarker of arousal instability in NREM sleep, are noted in sleepwalking disorders. Sleep-related eating disorder (SRED) is characterized by a disruption of the nocturnal fast with episodes of feeding after an arousal from sleep. SRED is often associated with the use of sedative-hypnotic medications; in particular, the widely prescribed benzodiazepine receptor agonists. Recently, compelling evidence suggests that nocturnal eating may in some cases be a nonmotor manifestation of Restless Legs Syndrome (RLS). rapid eye movement (REM) Sleep Behavior Disorder (RBD) is characterized by a loss of REM paralysis leading to potentially injurious dream enactment. The loss of atonia in RBD often predates the development of Parkinson’s disease and other disorders of synuclein pathology. Parasomnia behaviors are related to an activation (in NREM parasomnias) or a disinhibition (in RBD) of central pattern generators (CPGs). Initial management should focus on decreasing the potential for sleep-related injury followed by treating comorbid sleep disorders. Clonazepam and melatonin appear to be effective therapies in RBD, whereas paroxetine has been reported effective in some cases of sleep terrors. At this point, pharmacotherapy for other parasomnias is less certain, and further investigations are necessary.
Electronic supplementary material
The online version of this article (doi:10.1007/s13311-012-0143-8) contains supplementary material, which is available to authorized users.
PMCID: PMC3480572  PMID: 22965264
Parasomnia; Sleepwalking; Sleep terrors; REM sleep behavior disorder; Restless legs syndrome
20.  Brainstem infarcts predict REM sleep behavior disorder in acute ischemic stroke 
BMC Neurology  2014;14:88.
Rapid eye movement (REM) sleep behavior disorder (RBD) is a sleep disturbance in which patients enact their dreams while in REM sleep. The behavior is typically violent in association with violent dream content, so serious harm can be done to the patient or the bed partner. The prevalence of RBD is well-known in Parkinson’s disease, Lewy body dementia, and multiple systems atrophy. However, its prevalence and causes in stroke remained unclear. The aim of this study was to determine factors influencing the appearance of RBD in a prospective cohort of patients with acute ischemic stroke.
A total of 2,024 patients with first-ever or recurrent acute ischemic stroke were admitted to the Acute Stroke Unit at the Prince of Wales Hospital between January 2010 and November 2011; 775 of them received an MRI scan. Within 2 days of admission, a research nurse collected demographic and clinical data and assessed the severity of each stroke using the National Institute of Health Stroke Scale (NIHSS). One hundred and nineteen of the 775 patients meeting study entry criteria formed the study sample. All eligible participants were invited to attend a research clinic 3 months after the onset of the index stroke. In the attendance, a research assistant administered the MMSE and the 13-item RBD questionnaire (RBDQ).
Among 119 stroke patients, 10.9% were exhibited RBD, defined as an REM sleep behavior disorder questionnaire score of 19 or above. The proportion of patients with acute brainstem infarct was significantly higher in RBD patients than those without RBD. Compared with patients without RBD, RBD patients were more likely to have brainstem infarcts and had smaller infarct volumes. In a multivariate analysis, in which stroke location and infarct volume were inserted, brainstem infarcts were an independent predictor of RBD (odds ratio = 3.686; P = 0.032).
The results support the notion of a predominant role of brainstem injury in the development of RBD and suggest that patients with brainstem infarcts RBD should be evaluated by a clinical neurologist.
PMCID: PMC4004510  PMID: 24758223
Sleep; Acute ischemic stroke; Ischemia; Brainstem; Infarcts
21.  Symptoms of Rapid Eye Movement Sleep Behavior Disorder are Associated with Cholinergic Denervation in Parkinson Disease 
Annals of neurology  2012;71(4):560-568.
Rapid eye movement sleep behavior disorder (RBD) is common in Parkinson disease (PD), but its relationship to the varied neurotransmitter deficits of PD and prognostic significance remain incompletely understood. RBD and cholinergic system degeneration are identified independently as risk factors for cognitive impairment in PD. We aimed to assess the association between cholinergic denervation and symptoms of RBD in PD patients without dementia.
Eighty subjects with PD without dementia (age, 64.6 ± 7.0 years; range, 50–82 years; 60 males, 20 females; mean Montreal Cognitive Assessment Test [MoCA] score, 26.2 ± 2.1; range 21–30) underwent clinical assessment, neuropsychological testing, and [11C]methylpiperidyl propionate acetylcholinesterase and [11C]dihydrotetrabenazine (DTBZ) vesicular monoamine transporter type 2 positron emission tomography (PET) imaging. 11C3-Amino-4-(2-dimethylaminomethyl-phenylsulfaryl)-benzonitrile (DASB) serotonin transporter PET imaging was performed in a subset of 35 subjects. The presence of RBD symptoms was determined using the Mayo Sleep Questionnaire.
Twenty-seven of 80 subjects (33.8%) indicated a history of RBD symptoms. Subjects with and without RBD symptoms showed no significant differences in age, motor disease duration, MoCA, Unified Parkinson Disease Rating Scale motor scores, or striatal DTBZ binding. Subjects with RBD symptoms, in comparison to those without, exhibited decreased neocortical, limbic cortical, and thalamic cholinergic innervation (0.0213 ± 0.0018 vs 0.0236 ± 0.0022, t = 4.55, p < 0.0001; 0.0388 ± 0.0029 vs 0.0423 ± 0.0058, t = 2.85, p = 0.0056; 0.0388 ± 0.0025 vs 0.0427 ± 0.0042, t = 4.49, p < 0.0001, respectively). Brainstem and striatal DASB binding showed no significant differences between groups.
The presence of RBD symptoms in PD is associated with relative neocortical, limbic cortical, and thalamic cholinergic denervation although not with differential serotoninergic or nigrostriatal dopaminergic denervation. The presence of RBD symptoms may signal cholinergic system degeneration.
PMCID: PMC3727906  PMID: 22522445
22.  Dysautonomia in Narcolepsy: Evidence by Questionnaire Assessment 
Background and Purpose
Excessive daytime sleepiness and sudden sleep attacks are the main features of narcolepsy, but rapid-eye-movement sleep behavior disorder (RBD), hyposmia, and depression can also occur. The latter symptoms are nonmotor features in idiopathic Parkinson's disease (IPD). In the present study, IPD-proven diagnostic tools were tested to determine whether they are also applicable in the assessment of narcolepsy.
This was a case-control study comparing 15 patients with narcolepsy (PN) and 15 control subjects (CS) using the Scales for Outcomes in Parkinson's Autonomic Test (SCOPA-AUT), Parkinson's Disease Nonmotor Symptoms (PDNMS), University of Pennsylvania Smell Test, Farnsworth-Munsell 100 Hue test, Beck Depression Inventory, and the RBD screening questionnaire.
Both the PN and CS exhibited mild hyposmia and no deficits in visual tests. Frequent dysautonomia in all domains except sexuality was found for the PN. The total SCOPA-AUT score was higher for the PN (18.47±10.08, mean±SD) than for the CS (4.40±3.09), as was the PDNMS score (10.53±4.78 and 1.80±2.31, respectively). RBD was present in 87% of the PN and 0% of the CS. The PN were more depressed than the CS. The differences between the PN and CS for all of these variables were statistically significant (all p<0.05).
The results of this study provide evidence for the presence of dysautonomia and confirm the comorbidities of depression and RBD in narcolepsy patients. The spectrum, which is comparable to the nonmotor complex in IPD, suggests wide-ranging, clinically detectable dysfunction beyond the narcoleptic core syndrome.
PMCID: PMC4198712  PMID: 25324880
autonomic failure; multisystem disorder; narcolepsy; Parkinson's disease
23.  Prostatic hyperplasia is highly associated with nocturia and excessive sleepiness: a cross-sectional study 
BMJ Open  2012;2(3):e000505.
The objective of this study is to assess the impact of nocturia on sleep in patients with lower urinary tract symptoms (LUTS)/benign prostatic enlargement (BPE) (nocturia≥2).
Cross-sectional survey.
798 urologists and general practitioners randomly selected from the overall population of urologists and general practitioners of every French region.
A total of 2179 LUTS/BPE men (aged 67.5±7.5 years old) were recruited.
Primary and secondary outcome measures
Validated patients' self-administered questionnaires were used to assess the severity of LUTS/BPE (the International Prostate Symptom Score), sleep characteristics (sleep log) and sleep disorders (the International Classification of Sleep Disorders (ICSD-2) and the DSM-IV). Sleepiness was assessed with the Epworth Sleepiness Scale (ESS). The volume of 24 h diuresis (1500 ml) was measured.
Participants had on average 2.9±0.9 nocturia episodes (three or more episodes in 67%) and the International Prostate Symptom Score of 15.8±5.7; 60.9% complained of insomnia according to the ICSD-2, 7.9% of restless leg syndrome and 6.4% of obstructive sleep apnoea. 32.3% had excessive sleepiness (ESS >10) and 3.1% severe excessive sleepiness (ESS >16). Insomnia was mainly nocturnal awakenings with an average wake after sleep onset of 89±47 min. The number of episodes of nocturia per night correlated significantly with wake after sleep onset and ESS but not with total sleep time and sleep latency.
Nocturia is significantly associated with sleep maintenance insomnia and sleepiness in men with BPE.
Article summary
Article focus
Complaint of nocturia and its links with excessive sleepiness.
Assessment of the impact of nocturia on sleep.
Key messages
By being disruptive to sleep, the nocturia episodes affected sleep efficiency and quality.
The number of nocturia episodes was associated with an increased sleepiness in men with benign prostatic hyperplasia.
Strengths and limitations of this study
This is a cross-sectional study. It would have been more convincing to compare our subjects to a similar group of older people with no benign prostatic hyperplasia. However, our study focused on the frequency of insomnia and on the correlates between benign prostatic hyperplasia and insomnia.
PMCID: PMC3367152  PMID: 22649170
24.  Rapid eye movement sleep behavior disorder 
Current opinion in neurobiology  2013;23(5):793-798.
Rapid eye movement (REM) sleep behavior disorder (RBD) is a failure of the circuitry regulating motor atonia during REM sleep. In REM sleep, neurons of the sublaterodorsal tegmental nucleus (SLD) project to interneurons in the ventromedial medulla (VMM) and spinal cord that in turn inhibit spinal motoneurons. In RBD, degeneration of this circuitry disinhibits phasic motor commands originating from motor generators. The resulting behavior ranges from simple twitches or jerks to complex behavior. Simple behaviors in RBD may originate from cortical, brainstem and spinal cord motor generators, while complex behavior may originate from cortical motor generators, possibly related to dream content in REM sleep. While RBD can occur idiopathically, it is usually comorbid with or a precursor to a synucleinopathy such as Parkinson’s disease (PD). RBD can precede the onset of PD by decades, suggesting a an underlying pathology that can progressively afflict REM atonia and midbrain dopaminergic centers. The relative recovery of motor function during REM sleep in some cases of PD with RBD emphasizes the complexity of motor pathway control during wakefulness and REM sleep.
PMCID: PMC3750096  PMID: 23518139
25.  Neurotoxic lesions at the ventral mesopontine junction change sleep time and muscle activity during sleep: An animal model of motor disorders in sleep 
Neuroscience  2008;154(2):431-443.
There is no adequate animal model of restless legs syndrome (RLS) and periodic leg movements disorder (PLMD), disorders affecting 10% of the population. Similarly, there is no model of rapid eye movement (REM) sleep behavior disorder (RBD) that explains its symptoms and its link to Parkinsonism. We previously reported that the motor inhibitory system in the brainstem extends from the medulla to the ventral mesopontine junction (VMPJ). We now examine the effects of damage to the VMPJ in the cat. Based on the lesion sites and the changes in sleep pattern and behavior, we saw three distinct syndromes resulting from such lesions; the rostrolateral, rostromedial and caudal VMPJ syndromes. The change in sleep pattern was dependent on the lesion site, but was not significantly correlated with the number of dopaminergic neurons lost. An increase in wakefulness and a decrease in slow wave sleep (SWS) and REM sleep were seen in the rostrolateral VMPJ lesioned animals. In contrast, the sleep pattern was not significant changed after lesion in rostromedial and caudal VMPJ lesioned animals. All 3 groups of animals showed a significant increase in periodic and isolated leg movements in SWS and increased tonic muscle activity in REM sleep. Beyond these common symptoms, an increase in phasic motor activity in REM sleep, resembling that seen in human RBD, was found in the caudal VMPJ lesioned animals. In contrast, the increase in motor activity in SWS in rostral VMPJ lesioned animals is similar to that seen in human RLS/PLMD patients. The proximity of the VMPJ region to the substantia nigra suggests that the link between RLS/PLMD and Parkinsonism, as well as the progression from RBD to Parkinsonism may be mediated by the spread of damage from the regions identified here into the substantia nigra.
PMCID: PMC4283489  PMID: 18487021
periodic leg movements; REM sleep behavior disorder; Parkinsonism; pons; retrorubral nucleus; substantia nigra

Results 1-25 (1071212)