Diagnosis Of REM Sleep Behavior Disorder Research Articles

Functional neuroimaging and clinical features of drug naive patients with de novo Parkinson’s disease and probable RBD

IntroductionThe association between Parkinson Disease (PD) and REM sleep behavior disorder (RBD) has been related to a specific, malignant clinical phenotype. Definite RBD diagnosis requires video-polysomnography that is often unfeasible. A malignant clinical PD-RBD phenotype could be expected also in PD patients with probable RBD. Aim of this cross-sectional study was to evaluate whether a more severe neuropsychological and functional neuroimaging phenotype can be identified in PD patients with probable RBD. MethodsThirty-eight de novo, drug naïve PD patients underwent a first-line clinical assessment and a second-line multimodal assessment, including neuropsychological evaluation, 123I-FP-CIT-SPECT and 18F-FDG-PET, which were compared between PD patients with (PD + RBD+) and without (PD + RBD-) probable RBD. ResultsOn first-line assessment, PD + RBD + patients had significantly more constipation (p = 0.02) and showed worse olfaction (p = 0.01) compared with PD + RBD-while the two groups were similar as for age, presence of orthostatic hypotension, UPDRS-III and MMSE scores. On second-line assessment, PD + RBD + patients showed a worse neuropsychological test profile, more severe nigro-striatal dopaminergic impairment, mainly at caudate level in the less affected hemisphere (p = 0.004) and impaired brain glucose metabolism, with relative hypometabolism in posterior cortical regions and relative hypermetabolism mainly in anterior regions of the more affected hemisphere (p = 0.015). ConclusionsPD patients with probable RBD are likely to have a more severe neuropsychological and functional brain-imaging phenotype already at the time of diagnosis.

REM sleep behavior disorder (RBD): Update on diagnosis and treatment.

BackgroundREM sleep behavior disorder (RBD) is parasomnia characterized by dream enactment and enabled by disruption of physiological muscle atonia during REM sleep. Over the past few years, diagnostic criteria and the methods used to confirm diagnosis have been updated.ObjectiveIn this review article, the current knowledge regarding RBD diagnosis and treatment is presented.MethodsA selective literature search was carried out.Results and discussionAlthough several RBD screening questionnaires have been developed, diagnosis can only be definitely confirmed on the basis of polysomnography. New methods for scoring electromyography (EMG) activity during REM sleep have been proposed during recent years and cutoff values have been established. The latest cutoff values for scoring EMG activity during REM sleep are included in the International Classification of Sleep Disorders (ICSD). The cutoff of 27 % muscle activity during REM sleep suggested by the Sleep Innsbruck Barcelona (SINBAR) group was also included in the third edition of the ICSD. The best-researched treatments for RBD are clonazepam and melatonin.

The Prevalence and Characteristics of REM Sleep without Atonia (RSWA) in Patients Taking Antidepressants.

The association of REM sleep without atonia (RSWA) as well as REM sleep behavior disorder (RBD) with the intake of selective serotonin reuptake inhibitors (SSRI) and selective norepinephrine reuptake inhibitors (SNRI) is well established. Our study objective was to determine the prevalence of RSWA and RBD among a group of sleep center patients taking SSRI and SNRI. A retrospective chart review was done at our tertiary sleep center, and 10,746 consecutive records from October 1, 2007, through October 31, 2013, were searched for SSRI and SNRI names using the Sleep Cataloguer Software. The search resulted in 1,444 records, which were then reviewed for keywords of RSWA and RBD. The AASM scoring criteria were used to determine RSWA. Reports of 41 patients with known narcolepsy or α-synucleinopathies were excluded. The remaining records were mined for age, sex, presence of obstructive sleep apnea (OSA), type of antidepressant (SSRI or SNRI), and diagnosis for which antidepressant was prescribed. We used logistic regression analysis to adjust for age, OSA, and sex. Of the 1,444 participants on antidepressants, 176 (12.2%) had RSWA (all confirmed by the investigators) compared to 226 of the entire sleep lab population of 10,746 (2.1%), risk ratio (95% CI) 9.978 (8.149, 12.22). Seven of the 176 patients on antidepressants had RBD (0.48%) compared to 108 of 10,746 (1%), p = 0.005. SSRI and SNRI are associated with a higher prevalence of RSWA but not of RBD. This is independent of medication type.

Neurophysiological assessment of REM sleep behaviour disorder

REM sleep behaviour disorder (RBD) is characterized by violent dream-enacting behaviours associated with nightmares and increased EMG activity during REM sleep. RBD may be secondary to neurological diseases, particularly Parkinson’s disease, dementia with Lewy bodies, or multiple system atrophy. The majority of patients with idiopathic RBD will develop one of these synucleinopathies, indicating that this parasomnia represents in most instances the prodromal state of a neurodegenerative disease. RBD is also a treatable condition associated with injury potential. Thus, a correct diagnosis of RBD has relevant prognostic and treatment implications. Video-polysomnography (video-PSG) is mandatory for a definite RBD diagnosis. Video-polysomnography will rule out other conditions that can mimic RBD, such as obstructive sleep apnoea or periodic limb movement disorder. Video-polysomnography is also essential to record REM sleep-related behaviours or demonstrate REM sleep without atonia (RWA). RWA is defined as either excessive tonic or phasic EMG activity during REM sleep. However, excessive EMG activity is usually based on the scorer’s subjective impression and objective quantification is not routinely performed. Several manual and computer-assisted scoring methods of EMG activity in the chin and limb muscles have been developed, and recently quantitative EMG cut-off values for RBD diagnosis have been proposed.

The Role of the Serotonergic System in REM Sleep Behavior Disorder.

REM sleep behavior disorder (RBD) can be induced by antidepressants, especially serotonin reuptake inhibitors (SSRI), thus a role of the serotonergic system in the pathogenesis of RBD has been proposed. However, the serotonergic system integrity in idiopathic RBD (iRBD) is still unknown. We aimed to study brain stem serotonergic system integrity, by means of (123)I-FP-CIT-SPECT, in a group of iRBD patients as compared to normal subjects. Single-center, prospective observational study. University hospital. Twenty iRBD outpatients and 23 age-matched normal controls. The diagnosis of RBD was determined clinically and confirmed by means of overnight, laboratory-based video-polysomnography. Both iRBD patients and normal subjects underwent (123)I-FP-CIT-SPECT as a marker of dopamine transporter (DAT) at basal ganglia level and of serotonin transporter (SERT) at brainstem and thalamus levels. (123)I-FP-CIT-SPECT images were analyzed and compared between iRBD patients and controls by means of both region of interest analysis at basal ganglia, midbrain, pons and thalamus levels, and voxel-based analysis, taking into account age and the use of SSRI as confounding factors. No difference in (123)I-FP-CIT-SPECT specific to nondisplaceable binding ratios (SBR) values was found between iRBD and normal subjects at brainstem and thalamus levels while iRBD patients showed lower SBR values in all basal ganglia nuclei (P < 0.0001) compared to controls. These results suggest that the serotonergic system is not directly involved in RBD pathogenesis while confirming nigro-striatal dopaminergic deafferentation in iRBD.

Rapid eye movement sleep behavior disorder: a window on the emotional world of Parkinson disease.

REM sleep behavior disorder (RBD) is a parasomnia characterized by motor activity during sleep with dream mentation. Aggressiveness has been considered a peculiar feature of dreams associated with RBD, despite normal score in aggressiveness scales during wakefulness. We aimed to measure daytime aggressiveness and analyze dream contents in a population of patients with Parkinson disease (PD) with and without RBD. This is a single-center prospective observational study; it concerns the description of the clinical features of a medical disorder in a case series. The study was performed in the Department of Neurosciences of the Catholic University in Rome, Italy. Three groups of subjects were enrolled: patients with PD plus RBD, patients with PD without RBD, and healthy controls. The diagnosis of RBD was determined clinically and confirmed by means of overnight, laboratory-based video-polysomnography. For the evaluation of diurnal aggressiveness, the Buss-Perry Aggression Questionnaire (BPAQ) was used. The content of dreams was evaluated by means of the methods of Hall and Van De Castle. Patients with PD without RBD displayed higher levels of anger, and verbal and physical aggressiveness than patients with PD and RBD and controls. Patients with PD and RBD and controls did not differ in hostility. It can be hypothesized that a noradrenergic impairment at the level of the locus coeruleus could, at the same time, explain the presence of RBD, as well as the reduction of diurnal aggressiveness. This finding also suggests a role for REM sleep in regulating homeostasis of emotional brain function.

Quantification of REM Sleep without Atonia in Korean REM Sleep Behavior Disorder Patients: Comparison of Manual and Computer-Assisted Scoring Methods

Address for correspondence Won Chul Shin, MD, PhD Department of Neurology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, 892 Dongnam-ro, Gangdong-gu, Seoul 134-727, Korea Tel: +82-2-440-6166 Fax: +82-2-440-7262 E-mail: shinwc@khu.ac.kr Objectives: The polysomnographic hallmark of rapid eye movement (REM) sleep behavior disorder (RBD) is loss of muscle atonia during REM sleep; REM sleep without atonia (RSWA). However, the International Classification of Sleep Disorders (ICSD) criteria did not suggest optimized diagnostic value of RSWA and how to score muscle activity during REM sleep. Many previous studies have been tried to figure out the objective quantitative cut-off values of RSWA. We investigated RSWA in Korean RBD patients compared with normal control, to quantify the cut-off value in diagnosis of RBD, using both manual and computer-assisted scoring methods (REM atonia index, RAI). Methods: We retrospectively analyzed polysomnography and clinical data of 40 patients, 10 age-matched controls by ICSD-3 criteria. The quantitative analysis of chin electromyography density during REM sleep was done by both manual and computerized method. The RSWA and RAI were compared within two groups. Results: In computerized method, the mean RAI of RBD patient was 0.66±0.20, and 0.93±0.38 in control group (p<0.001). Also, in manual method, RSWA were also significantly increased within RBD patient compared with normal controls (tonic activity: 9.1±10.3 vs. 0.1±0.2, phasic activity: 7.5±6.4 vs. 1.6±1.2, p<0.002). Conclusions: We quantify the characteristics of RSWA in Korean RBD patients and suggest that we may diagnose RBD who present RSWA with 4.1% or more increase in total REM sleep duration and RAI more than 0.84. J Korean Sleep Res Soc 2014;11(2):50-56

A Patient with Obstructive Sleep Apnea Syndrome Presenting with REM Sleep Behavior Disorder Mimicking Symptoms

Received December 7, 2014 Revised December 15, 2014 Accepted December 23, 2014 Address for correspondence Jae-Wook Cho, MD Department of Neurology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan 626-770, Korea Tel: +82-55-360-3014 Fax: +82-55-360-2152 E-mail: sleep.cho@gmail.com Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream-enacting behaviors during REM sleep. However, many sleep disorders can produce RBD mimicking symptoms, also known as ‘pseudo-RBD’. We report a patient with severe obstructive sleep apnea with ‘pseudo-RBD’ symptoms that were eliminated by continuous positive airway pressure treatment. Polysomnography is mandatory to establish the proper diagnosis of RBD. J Korean Sleep Res Soc 2014;11(2):72-75

Validation of an integrated software for the detection of rapid eye movement sleep behavior disorder.

Rapid eye movement sleep without atonia (RWA) is the polysomnographic hallmark of REM sleep behavior disorder (RBD). To partially overcome the disadvantages of manual RWA scoring, which is time consuming but essential for the accurate diagnosis of RBD, we aimed to validate software specifically developed and integrated with polysomnography for RWA detection against the gold standard of manual RWA quantification. Academic referral center sleep laboratory. Polysomnographic recordings of 20 patients with RBD and 60 healthy volunteers were analyzed. N/A. Motor activity during REM sleep was quantified manually and computer assisted (with and without artifact detection) according to Sleep Innsbruck Barcelona (SINBAR) criteria for the mentalis ("any," phasic, tonic electromyographic [EMG] activity) and the flexor digitorum superficialis (FDS) muscle (phasic EMG activity). Computer-derived indices (with and without artifact correction) for "any," phasic, tonic mentalis EMG activity, phasic FDS EMG activity, and the SINBAR index ("any" mentalis + phasic FDS) correlated well with the manually derived indices (all Spearman rhos 0.66-0.98). In contrast with computerized scoring alone, computerized scoring plus manual artifact correction (median duration 5.4 min) led to a significant reduction of false positives for "any" mentalis (40%), phasic mentalis (40.6%), and the SINBAR index (41.2%). Quantification of tonic mentalis and phasic FDS EMG activity was not influenced by artifact correction. The computer algorithm used here appears to be a promising tool for REM sleep behavior disorder detection in both research and clinical routine. A short check for plausibility of automatic detection should be a basic prerequisite for this and all other available computer algorithms.

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.

Actigraphy as a diagnostic aid for REM sleep behavior disorder in Parkinson’s disease

BackgroundRapid eye movement (REM) sleep behavior disorder (RBD) is a common parasomnia in Parkinson’s disease (PD) patients. The current International Classification of Sleep Disorders (ICSD-II) requires a clinical interview combined with video polysomnography (video-PSG) to diagnose. The latter is time consuming and expensive and not always feasible in clinical practice. Here we studied the use of actigraphy as a diagnostic tool for RBD in PD patients.MethodsWe studied 45 consecutive PD patients (66.7% men) with and without complaints of RBD. All patients underwent one night of video-PSG and eight consecutive nights of actigraphy. Based on previous studies, the main outcome measure was the total number of bouts classified as “wake”, compared between patients with (PD + RBD) and without RBD (PD- RBD).Results23 (51.1%) patients had RBD according to the ICSD-II criteria. The total number of wake bouts was significantly higher in RBD patients (PD + RBD 73.2 ± 40.2 vs. PD-RBD 48.4 ± 23.3, p = .016). A cut off of 95 wake bouts per night resulted in a specificity of 95.5%, a sensitivity of 20.1% and a positive predictive value of 85.7%. Seven patients were suspected of RBD based on the interview alone, but not confirmed on PSG; six of whom scored below 95 wake bouts per night on actigraphy.ConclusionPD patients with RBD showed a significantly higher number of bouts scored as “wake” using actigraphy, compared to patients without RBD. In clinical practice, actigraphy has a high specificity, but low sensitivity in the diagnosis of RBD. The combination of actigraphy and previously reported RBD questionnaires may be a promising method to diagnose RBD in patients with PD.

Pilot quantitative analyses of rem sleep without atonia in children and adolescents with rem sleep behavior disorder

Introduction Growing evidence suggests that idiopathic REM sleep behavior disorder (RBD) may be a forme fruste of synucleinopathy neurodegeneration in older adults. The clinical significance of REM sleep without atonia (RSWA) and overt RBD in children and adolescents remains unclear. Furthermore, the lower age bound for occurrence of RSWA, the neurophysiologic substrate for RBD, is not well established. This pilot quantitative analysis of RSWA in pediatric patients with clinical RBD or RSWA – to our knowledge the first such data available in children – aims to determine the relationship between age, RBD symptoms, and RSWA. Materials and methods We analyzed phasic and tonic RSWA according to established methods in 12 RBD/RSWA patients and 12 age-gender matched controls with primary snoring who underwent polysomnography (PSG) at Mayo Clinic between 2008 and 2013, and reviewed medical records to determine RSWA or RBD diagnosis. We then measured phasic muscle activity durations and made group comparisons of phasic, tonic, and “any” muscle activity percentage densities as well as phasic muscle activity burst durations with non-parametric statistical tests. Multiple regression models were fit to explore potential associations between clinical and muscle activity dependent variables. Results Among the 12 RSWA/RBD cases, 7 were male, with a mean (range) age of 8.6 (1–17) years when PSG was performed. One RBD patient received clomipramine; no others were on medications associated with RSWA. Phasic and tonic densities were no different between cases and controls, although there appeared to be a subgroup of RSWA/RBD cases with higher phasic densities. Univariate regression analyses demonstrated that higher phasic density was associated with increasing age (p = 0.009 for chin and p = .004 for “any” muscle activity). Anterior tibialis phasic burst duration was significantly longer in the RSWA/RBD group compared to controls (p = 0.02), prolonged to a degree similar to that of adult RBD subjects. Multivariate regression demonstrated an independent association of anterior tibialis phasic burst duration with RBD/RSWA diagnosis, controlling for age. Conclusion In our pilot study, the earliest detectable manifestation of RSWA appears to be increased phasic burst duration in anterior tibialis. We also found that phasic muscle activity density increases with age in pediatric patients. We plan continued analysis in an expanded group of pediatric subjects to better elucidate the influences of age and RBD symptoms on quantitative RSWA metrics. Acknowledgements The project described was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health , through Grant No. 1 UL1 RR024150-01 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Sleep bruxism and masseter muscle activity during rem sleep of rem sleep behavior disorder patients: a case control study

Introduction Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by abnormal and excessive motor activity in electromyographic (EMG) during REM sleep. Presence of sleep bBruxism (SB)/tooth grinding and oromandibular myoclonus (OMM) were investigated in RBD patients not taking medications in comparison to age matched control subjects (CTRL). Materials and methods Polygraphy sleep and oromotor activity data from 9 RBD patients (68.22 ± 3.63 y.o.) and 9 healthy CTRL (65.11 ± 3.95 y.o.) were analyzed. RBD patients were diagnosed by a neurologist and confirmed by sleep laboratory recording. Rhythmic masticatory muscle activity (RMMA), a marker of sleep bruxism, and oromandibular myoclonus were scored from jaw electromyographic recordings during sleep using published criteria (Lavigne 1996; Kato 1999). Results RBD patients had significantly higher index of RMMA/SB than CTRL during sleep (p 0.01). During REM sleep, RBD patients had significantly higher index of RMMA/SB episodes and bursts than CTRL subjects (p 0.001). During non-REM sleep, no significantly difference between RBD and CTRL was observed (p = 0.12). Compared to controls, the OMM episode and burst indexes were significantly higher in RBD patients (p = 0.04 and 0.03, respectively). Conclusion RBD patient’s not taking medication had significantly higher RMMA activity, a proxy of sleep bruxism diagnosis, than CTRL subjects over night and during REM sleep. The higher index of RMMA/SB during REM sleep of RBD patients suggest that activity in jaw closing muscles can be scored during sleep of suspected RBD patients. Furthermore, sleep bruxism occurring during REM may be a concomitant finding influencing the diagnosis and management of both SB and RBD. Acknowledgements (Supported by the Canadian Institutes of Health Research. grant from CIHR).

Diagnostic thresholds for quantitative REM sleep muscle densities, phasic burst duration, and REM atonia index in REM sleep behavior disorder with co-morbid obstructive sleep apnea

Introduction Previous REM sleep without atonia (RSWA) studies have excluded patients with sleep apnea, potentially limiting application to clinical REM sleep behavior disorder (RBD) populations. We determined whether phasic burst duration and conventional RSWA methods could accurately diagnose RBD patients with co-morbid OSA. Materials and methods We analyzed RSWA phasic burst durations, phasic, “any” and tonic densities, and automated REM atonia index (RAI) in RBD and matched controls with OSA. Group RSWA metrics were then analyzed and regression models fit to explore associations with clinical variables, with receiver operator characteristic (ROC) curves determining the best diagnostic cut-off thresholds for RBD diagnosis. Results All mean RSWA phasic durations and densities were higher in RBD patients than controls ( p p Conclusion This study provides evidence for RSWA diagnostic thresholds applicable in clinical RBD patient populations with co-morbid OSA using conventional EMG lead placements during split-night polysomnograms, with suggested cut-offs for combined SM/AT muscles of 43.4%, RAI of 0.88, and phasic muscle burst durations of 0.65 and 0.79 s in the SM and AT muscles, respectively. Future studies with similar methods in idiopathic RBD patients with co-morbid OSA are planned. Acknowledgements The project described was supported by a Mayo Clinic Alzheimer’s Disease Research Center Grant Award from the National Institute on Aging (P50 AG016574), and the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant No. 1 UL1 RR024150-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Predictors of injury in REM sleep behavior disorder

Introduction REM sleep behavior disorder (RBD) is widely recognized to involve potentially injurious dream enactment behaviors (DEB), but which clinical factors are associated with RBD-related injuries remain largely unknown. We aimed to identify injury predictors in RBD. Materials and methods We surveyed consecutive RBD patients seen at Mayo Clinic between 2008 and 2010 regarding RBD-related injuries and reviewed medical records to determine idiopathic (iRBD) or symptomatic RBD diagnosis. Associations between injuries prior to treatment and demographic, clinical, and medication variables were then determined with odd’s ratios and multiple logistic regression analyses. The primary outcome variables were injury and injury severity. Results Fifty-three patients (40%) responded. Median age was 69 years and 35 (75%) were men. Twenty-five (47%) had symptomatic RBD. Twenty-nine (55%) reported injury, including self (37.8%) and bed partner (16.7%) injury. 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 during DEB ( p = 0.03) were also associated with more severe injury, while DEB frequency was not associated with injury, injury severity, or falls. Conclusion Injuries are a frequent complication of RBD. 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 DEB-related falls were associated with more severe injuries. 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. Acknowledgements The project described was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant No. 1 UL1 RR024150-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

REM sleep behaviour disorder is associated with worse quality of life and other non-motor features in early Parkinson's disease

BackgroundConcomitant 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...

Subtle gait changes in patients with REM sleep behavior disorder

Many people with rapid eye movement (REM) sleep behavior disorder (RBD) have an underlying synucleinopathy, the most common of which is Lewy body disease. Identifying additional abnormal clinical features may help in identifying those at greater risk of evolving to a more severe syndrome. Because gait disorders are common in the synucleinopathies, early abnormalities in gait in those with RBD could help in identifying those at increased risk of developing overt parkinsonism and/or cognitive impairment. We identified 42 probable RBD subjects and 492 controls using the Mayo Sleep Questionnaire and assessed gait velocity, cadence, and stride dynamics with an automated gait analysis system. Cases and controls were similar in age (79.9 ± 4.7 and 80.1 ± 4.7, P = 0.74), Unified Parkinson's Disease Rating Scale Part III (UPDRS) score (3.3 ± 5.5 and 1.9 ± 4.1, P = 0.21) and Mini-Mental State Examination scores (27.2 ± 1.9 and 27.7 ± 1.6, P = 0.10). A diagnosis of probable RBD was associated with decreased velocity (-7.9 cm/s; 95% confidence interval [CI], -13.8 to -2.0; P < 0.01), cadence (-4.4 steps/min; 95% CI, -7.6 to -1.3; P < 0.01), significantly increased double limb support variability (30%; 95% CI, 6-60; P = 0.01), and greater stride time variability (29%; 95% CI, 2-63; P = 0.03) and swing time variability (46%; 95% CI, 15-84; P < 0.01). Probable RBD is associated with subtle gait changes prior to overt clinical parkinsonism. Diagnosis of probable RBD supplemented by gait analysis may help as a screening tool for disorders of α-synuclein.

REM Sleep Problems Predict Parkinson's, Lewy Body Dementia

SAN DIEGO – Rapid eye movement (REM) sleep behavior disorder (RBD) is the earliest indication that elderly patients are destined to develop Parkinson's disease, Lewy body dementia, or another synucleinopathy, and it precedes the onset of motor and cognitive problems by years, according to a growing body of research. Its presence also distinguishes synucleinopathies from Alzheimer's disease and other problems that can have similar early presentations. RBD “equals synucleinopathy,” said Dr. Ronald Postuma of the department of neurology at McGill University in Montreal. “The way I explain RBD to patients is that normally, when most people dream, they are paralyzed, but you are not. Therefore, you are capable of acting out the content of your dreams.” Dr. Postuma made his comments at the annual meeting of the American Academy of Neurology. Also there, researchers from the Mayo Clinic in Rochester, Minn., presented an autopsy study, now published in Sleep Medicine. The Mayo team analyzed neuropathologic findings from 172 patients diagnosed with RBD before death. They found that 160 (94%) were synucleinopathies. Among them were 136 patients with Lewy bodies and 19 with multiple-system atrophy. The remaining few had findings consistent with Alzheimer's disease or other nonsynucleinopathies. RBD was diagnosed at a mean age of 62 years. It preceded the diagnosis of Parkinsonism in 151 patients by a mean of 6 years. The diagnosis of RBD preceded death by a mean of 13 years. “Lewy body disease was by far the most common underlying neurologic disorder. … We've been looking for [cases of] Alzheimer's associated with RBD for well over 10 years, and they are just hard to find,” said lead investigator Dr. Bradley Boeve, chair of the division of behavioral neurology at Mayo. The findings “argue that the selective vulnerability involves … REM sleep circuitry.” At autopsy, 98% of polysomnography (PSG)-confirmed cases had a synucleinopathy, Dr. Boeve noted. The take-home message is that “if you have a pretty good history of RBD but don't have a PSG to confirm it, there's a 94% chance that you have a synucleinopathy. If you do have PSG, there's a 98% chance of having a synucleinopathy,” Dr. Postuma said. “Asking about REM sleep behavior disorder in your clinics tomorrow will help you diagnose disease.” Investigators from Barcelona, Spain, came to similar conclusions in a paper published recently in Lancet Neurology (Lancet Neurol. 2013;12[5]:443-53). For most, RBD “represents the prodromal phase of a Lewy body disorder … such as Parkinson's disease (PD) or dementia with Lewy bodies. … [RBD] is a candidate for the study of early events and progression of this prodromal phase, and to test disease-modifying strategies to slow or stop the neurodegenerative process,” they concluded. The Spanish team followed 44 RBD cases diagnosed between 1991 and 2003. By 2012, 82% had developed a synucleinopathy: 16 with Parkinson's disease, 14 with Lewy body dementia, and 1 with multiple system atrophy. “The rates of neurological-disease-free survival from time of [RBD] diagnosis were 65.2% at 5 years, 26.6% at 10 years, and 7.5% at 14 years,” they reported. Most RBD patients “developed a Lewy body disorder with time. Patients who remained disease-free at follow-up showed markers of increased short-term risk for developing PD,” including lesions “in the brainstem nuclei that regulate REM sleep atonia,” the Spanish researchers found. Asked to comment on the Spanish study, Dr. Postuma said that the findings “emphatically confirm the incredible risk that patients with RBD have for developing neurodegenerative disease.” The ability to identify a neurodegenerative disease 10 years before it can be diagnosed “provides profound opportunities to study early stages of disease.” Dr. Boeve's research has been supported by Cephalon, Allon Therapeutics, and GE Healthcare. Dr. Postuma disclosed personal support from Teva and Novartis.

Towards a more objective diagnosis of REM Sleep Behavior Disorder

The prevalence of REM sleep behavior disorder (RBD) has been estimated to be around 0.5 % in the general population, while in patients with Parkinson’s disease the frequency ranges between 40 and 46 %. Current criteria for the diagnosis of RBD do not specify a clear quantitative cut-off for muscle activity, that is, how much EMG activity during REM sleep is normal, and at what point does it become abnormal? It is important that RBD be correctly diagnosed as (1) RBD can be the first manifestation of a neurodegenerative disease, (2) it can involve serious injury to the patient and/or bed partner, and (3) because it is a treatable disorder. In this review we seek to improve this situation and to move toward a more objective diagnosis of RBD. The time has come to move from a qualitative diagnosis of RBD to a quantitative diagnosis. Increased tonic and phasic muscle activity can and should be quantified. Cut-offs have now been established: the combination of “any” EMG activity in the mentalis muscle with both phasic flexor digitorum superficialis muscles yielded a cut-off of 32 % (AUC 0.998) for patients with idiopathic RBD and with Parkinson RBD. Such cut-offs help make the diagnosis of RBD more objective and avoid false positive diagnosis.