Validation of semiautomatic scoring of REM sleep without atonia in patients with RBD

Objective/BackgroundTo evaluate REM sleep without atonia (RSWA) in REM sleep behavior disorder (RBD) several automatic algorithms have been developed. We aimed to validate our algorithm (Mayer et al., 2008) in order to assess the following: (1). capability of the algorithm to differentiate between RBD, night terror (NT), somnambulism (SW), Restless legs syndrome (RLS), and obstructive sleep apnea (OSA), (2). the cut-off values for short (SMI) and long muscle activity (LMI), (3). which muscles qualify best for differential diagnosis, and (4). the comparability of RSWA and registered movements between automatic and visual analysis of videometry.Patients/MethodsRSWA was automatically scored according to Mayer et al., 2008 in polysomnographies of 20 RBD, 10 SW/NT, 10 RLS and 10 OSA patients. Receiver operating characteristic (ROC) curves were used to determine the sensitivity and specificity of SMI and LMI. Independent samples were calculated with t-tests. Boxplots were used for group comparison. The comparison between motor events by manual scoring and automatic analysis were performed with “Visual Basic for Applications” (VBA) for every hundredth second.ResultsOur method discriminates RBD from SW/NT, OSA and RLS with a sensitivity of 72.5% and a specificity of 86.7%. Automatic scoring identifies more movements than visual video scoring. Mentalis muscle discriminates the sleep disorders best, followed by FDS, which was only recorded in SW/NT. Cut-off values for RSWA are comparable to those found by other groups.ConclusionThe semi-automatic RSWA scoring method is capable to confirm RBD and to discriminate it with moderate sensitivity from other sleep disorders.     

REM sleep without atonia and nocturnal body position in prediagnostic Parkinson's disease

BackgroundSleep disturbances are features of Parkinson's disease (PD), that can already occur before PD diagnosis. The most investigated prodromal PD sleep disorder is REM sleep behavior disorder (RBD). The relation between other polysomnographic (PSG) alterations and the prediagnostic stages of PD, however, is less clear.MethodsWe performed a retrospective case–control study to characterize polysomnographic alterations in PD and prediagnostic PD. We included 63 PD subjects (33 subjects that underwent a video-PSG before PD diagnosis [13 with and 20 without RBD] and 30 subjects that underwent a PSG after PD diagnosis) and 30 controls. PSGs were analyzed for sleep stages, different RSWA variables, body position, arousals, periodic limb movements, and REM density.ResultsHigher subscores of all RSWA variables were observed in subjects with PD and prediagnostic PD (with and without RBD). Total RSWA, tonic RSWA and chin RSWA severity were significant predictors for all PD and prediagnostic PD groups. Our study also shows a higher percentage of nocturnal supine body position in all PD and prediagnostic PD groups. Supine body position percentage is the highest in the PD group and has a positive correlation with time since diagnosis.ConclusionsThese findings suggest that increased total, tonic and chin RSWA as well as nocturnal supine body position are already present in prediagnostic PD, independently of RBD status. Prospective longitudinal studies are necessary to confirm the additional value of these PSG abnormalities as prodromal PD biomarkers.     

Frequency and characteristic features of REM sleep without atonia

ObjectivesIsolated REM sleep without atonia (iRSWA) is regarded as prodromal phase of REM sleep behavior disorder (RBD) and synucleinopathies. Other factors, however, have also been described to cause RSWA, including sleep apnea, antidepressants use and narcolepsy. We investigated the frequency of RSWA and its different etiologies.MethodsWe investigated RSWA in patients that underwent a clinical video polysomnography. In iRSWA subjects, we examined polysomnography indication and two markers of prodromal Parkinson’s disease: excessive daytime sleepiness and depressive symptoms, with a case-control design.ResultsOf the 864 included polysomnographies, 188 were positive for RSWA (21.8%), 17 for RBD (2.0%) and 48 for iRSWA (5.6%). Mean Epworth Sleepiness Scale scores were 9.8 ± 4.8 (iRSWA subjects) and 7.5 ± 4.9 (controls), p = 0.014. Mean Beck Depression Inventory-II scores were 11.3 ± 7.9 (iRSWA subjects) and 9.5 ± 8.4 (controls), p = 0.229. Excessive daytime sleepiness was more often the polysomnography indication in the iRSWA group (p = 0.006).ConclusionsRSWA is a frequent finding in the context of antidepressant use or synucleinopathies. iRSWA subjects reported increased excessive daytime sleepiness and more often had excessive daytime sleepiness as polysomnography indication.SignificanceOur study provides evidence for high frequency of RSWA, underscoring the need for longitudinal studies in iRSWA patients, with interest for conversion to synucleinopathies.     

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.     

REM sleep without atonia is associated with increased rigidity in patients with mild to moderate Parkinson’s disease

ObjectiveIncreased muscle activity during rapid eye movement (REM) sleep (i.e. REM sleep without atonia) is common in people with Parkinson’s disease (PD). This study tested the hypotheses that people with PD and REM sleep without atonia (RSWA) would present with more severe and symmetric rigidity compared to individuals with PD without RSWA and age-matched controls.MethodsSixty-one individuals participated in this study (41 PD, 20 controls). An overnight sleep study was used to classify participants with PD as having either elevated (PD-RSWA+) or normal muscle activity (PD-RSWA−) during REM sleep. Quantitative measures of rigidity were obtained using a robotic manipulandum that passively pronated and supinated the forearm.ResultsQuantitative measures of forearm rigidity were significantly higher in the PD-RSWA+ group compared to the control group. Rigidity was significantly more asymmetric between limbs in the PD-RSWA− group compared with controls, while there was no significant difference in symmetry between the control and PD-RSWA+ groups.ConclusionIn people with mild to moderate PD, RSWA is associated with an increased and more symmetric presentation of upper limb rigidity.SignificanceDysfunction of brainstem systems that control muscle tone during REM sleep may contribute to increased rigidity during wakefulness in people with PD.     

Sensorimotor gating deficits in multiple system atrophy: Comparison with Parkinson's disease and idiopathic REM sleep behavior disorder

BackgroundPrepulse inhibition (PPI) of the auditory blink reflex is a measure of sensorimotor gating, which reflects an organism's ability to filter out irrelevant sensory information. PPI has never been studied in patients with multiple system atrophy (MSA), although sensorimotor deficits are frequently associated with synucleinopathies. We investigated whether alterations in PPI were more pronounced in MSA compared with Parkinson's disease (PD), idiopathic rapid eye movement sleep behavior disorder (iRBD) and healthy controls.Methods10 patients with MSA, 12 patients with iRBD, 40 patients with PD, and 20 healthy controls completed the study. A passive acoustic prepulse inhibition paradigm was applied with prepulses 5 dB and 15 dB above background noise at 30-, 60-, 120- and 300-ms intervals.ResultsNon-parametric analyses showed that MSA patients had significantly lower prepulse inhibition, as measured with max-amplitude, than PD patients and iRBD patients on the 60 ms–85 dB and 120 ms–85 dB inter-stimulus intervals. The same relation was found when using area under the curve. No differences were found between groups for the 30 ms–85 dB and 300 ms–85 dB. Furthermore, blink reflex characteristics such as habituation did not differ between patients and controls.ConclusionsThe present study showed that sensorimotor gating, as measured with PPI, is markedly reduced in MSA. This may be due to the pronounced severity of striatal and brainstem dysfunction, as well as the degeneration of other structures related to the PPI modulating pathways in MSA. PPI may be a non-invasive neurophysiological measure that can aid in the differential diagnosis between PD and MSA.     

Does REM sleep behavior disorder change in the progression of Parkinson’s disease?

Objectives/backgroundRapid eye movement (REM) Sleep Behavior Disorder (RBD) in Parkinson's disease (PD) may be associated with a malignant phenotype. Despite its prognostic value, little is known about the time course of RBD in PD. In this study, we aimed to ascertain whether or not RBD is a stable feature in PD. In this study, we prospectively evaluated clinical and neurophysiological features of RBD, including REM Sleep Without Atonia (RSWA), in PD patients with RBD at baseline and after three years then assessed whether the changes in measures of RSWA parallel the progression of PD.Patients/methodsIn sum, 22 (17M, mean age 64.0 ± 6.9 years) moderate-to-advanced PD patients (mean PD duration at baseline:7.6±4.8 years) with RBD, underwent a video-polysomnography (vPSG) recording and clinical and neuropsychological assessment at baseline and after three years.ResultsAt follow-up, the self-assessed frequency of RBD symptoms increased in six patients, decreased in six and remained stable in 10, while RSWA measures significantly increased in all subjects. At follow-up, patients showed worse H&Y stage (p = 0.02), higher dopaminergic doses (p = 0.05) and they performed significantly worse in phonetic and semantic fluency tests (p = 0.02; p = 0.04). Changes in RSWA correlated significantly with the severity in levodopa-induced dyskinesia (r = 0.61,p = 0.05) and motor fluctuation (r = 0.54,p = 0.03) scores, and with the worsening of executive functions (r = 0.78,p = 0.001) and visuo-spatial perception (r = −0.57,p = 0.04).ConclusionDespite the subjective improvement of RBD symptoms in one-fourth of PD patients, all RSWA measures increased significantly at follow-up, and their changes correlated with the clinical evolution of motor and non-motor symptoms. RBD is a long-lasting feature in PD and RSWA is a marker of the disease's progression.     

REM sleep behavior disorder in Parkinson disease: Association with abnormal ocular motor findings

BackgroundThe anatomical substrates associated with generalized muscle atonia during REM sleep are located on the pontine tegmentum and medial medulla oblongata. We examined whether patients with REM sleep behavior disorder (RBD) have abnormal ocular movements suggesting brainstem or cerebellar dysfunction in Parkinson's disease (PD).MethodsCross-sectional survey for the existence of RBD and abnormal ocular movements. Ocular movements were examined by video-oculography (VOG).ResultsA total of 202 patients were included in this study. One hundred and sixteen (57.4%) of the 202 patients have clinically probable RBD, and 28 (24.1%) of the 116 with clinically probable RBD patients had abnormal VOG findings suggesting brainstem or cerebellar dysfunction; whereas 86 of the 202 patients did not have clinically probable RBD, and only 7 (8.1%) of the 86 patients had abnormal VOG findings suggesting brainstem or cerebellar dysfunction (P = 0.001).ConclusionThis study suggests that the presence of RBD is associated with more severe or extensive brainstem pathology or different distribution of pathology in PD.     

Surface EMG activity during REM sleep in Parkinson's disease correlates with disease severity

ObjectivesOver 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.MethodsIn 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.ResultsAmong 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.ConclusionSurface 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.     

Revisiting the impact of REM sleep behavior disorder on motor progression in Parkinson's disease

BackgroundEstimation of progression in Parkinson's disease (PD) is useful to guide clinical decisions and to enable patients to plan and manage their life with PD. Rapid eye movement (REM) sleep behavior disorder (RBD) and REM sleep without atonia (RWA) are recognized as early harbingers of neurodegeneration and may precede motor symptoms by years. However, their impact on motor progression remains elusive.MethodsWe retrospectively analyzed polysomnographic and clinical data of 59 PD patients, grouping them into patients with RBD (n = 15), RWA (n = 22) and those with normal muscle atonia (n = 22). We compared the three groups with regard to motor progression, defined as changes in Unified Parkinson's Disease Rating Scale (UPDRS) III values per year, and selected PD specific characteristics.ResultsMotor disability at first visit and time interval between first and last visits were similar between groups. We observed a significantly faster motor progression in PD patients with RBD and RWA than in those with preserved REM sleep atonia.ConclusionOur findings suggest that impaired muscle atonia during REM sleep might represent a marker of faster motor progression in PD.     

Neuroimaging-evident lesional pathology associated with REM sleep behavior disorder

Background/RationaleRapid eye movement (REM) sleep behavior disorder (RBD) is a potentially injurious parasomnia characterized by dream enactment behavior and polysomnographic REM sleep without atonia (RSWA). Recently, RBD not only has been shown to be strongly associated with synucleinopathy neurodegeneration but has also been rarely reported to be associated with structural lesions involving the brainstem or limbic system. The aim of this study was to describe the clinical, neuroimaging, and outcome characteristics in a case series of patients with lesional RBD.MethodsThis is a retrospective case series from a tertiary care referral center.ResultsA total of 10 patients with lesional RBD were identified. Seven (70%) were men, with an average age of sleep symptom onset of 53.7 ± 17.0 years. Structural pathology evident on neuroimaging included four extraaxial (three meningiomas and one basilar fusiform aneurysm with brainstem compression) and six intraaxial (encephalomalacia, multiple sclerosis, vasculitis, autoimmune limbic encephalitis, and leukodystrophy) lesions. No patient developed parkinsonian features or cognitive impairment suggestive of synucleinopathy over an average of 45.4 ± 35.2 months of follow-up.ConclusionsRBD is rarely associated with non-synuclein structural lesions affecting the pons, medulla, or limbic system. The spectrum of lesional RBD comprises tumors, aneurysms, leukodystrophy, and autoimmune/inflammatory/demyelinating brain lesions.     

Polysomnographic predictors of sleep,motor and cognitive dysfunction progression in Parkinson's disease: a longitudinal study

ObjectiveTo assess the predictive value of polysomnographic (PSG) data in the prospective assessment of cognitive, motor, daytime and nighttime sleep dysfunction in Parkinson's Disease (PD) patients.MethodsPD patients were assessed at baseline with video-PSG and with cognitive (MoCA), Sleep (SCOPA-Sleep Nighttime and Daytime scores) and Motor (UPDRSIII) function scales at both baseline and four years later. Linear regression analysis was used to assess the relation between PSG variables at baseline and change in symptoms scores.ResultsWe included a total of 25 patients, 12 with rapid eye movement (REM) sleep behavior disorder (RBD) (in 8 PSG was inconclusive, due to lack of REM sleep). MoCA scores decreased significantly at follow-up, while SCOPA-Sleep Daytime and SCOPA-Sleep Nighttime and UPDRSIII did not vary. Lower N3 percentage at baseline was significantly associated with MoCA decrease. Higher Periodic Limb Movements in Sleep index (PLMS) and the presence of RBD were significantly associated with SCOPA daytime score increase. Higher global severity of RBD, tonic RSWA and total number of motor events during REM sleep were associated with SCOPA Nighttime score increase.ConclusionsThe present work suggests that PSG data could be useful for predicting PD cognitive and sleep dysfunction progression. Reduced SWS could predict deterioration of cognitive function, while baseline PLMS could be useful to predict worsening of daytime sleep dysfunction. Severity of RBD could be used for estimating nighttime sleep symptoms progression.     

Polysomnographic phenotype of isolated REM sleep without atonia

ObjectiveIsolated REM sleep without atonia (iRSWA) is regarded as a prodromal phase of REM sleep behavior disorder and synucleinopathies. In iRSWA patients, we investigated the polysomnographic characteristics that are known to be altered in (prodromal) Parkinson’s disease (PD): periodic limb movements of sleep [PLMS] (increased), REM density (reduced), and heart rate variability ([HRV] (reduced).MethodsWe compared video-polysomnographic studies of 49 iRSWA subjects with 41 controls. RSWA and PLMS were scored visually. REM density (REM/hour) and HRV were calculated automatically.ResultsWe found a higher median total (15.90 vs 7.20; p = 0.001), REM (21.80 vs 11.0; p < 0.001) and non-REM (11.75 vs 5.72; p = 0.027) PLMS index, and a higher mean REM density (342.45 vs 275.96; p = 0.010) in the iRSWA group, with a significant positive correlation between RSWA severity and these variables (r = 0.39; p < 0.00, r = 0.48; p < 0.001, r = 0.24; p = 0.021, r = 0.28; p = 0.012). We found no significant difference in HRV between groups.ConclusionsOur results suggest an association between RWSA and REM density and PLMS, but not HRV. The positive correlation between these variabilities may imply overlapping pathophysiological processes.SignificanceThe evidence of higher REM density and normal HRV weakens the hypothesis that iRWSA is a prodromal PD stage. An alternative interpretation is, however, that REM density and HRV change during caudal-rostral neurodegeneration.     

Difference in severity of sleep apnea in patients with rapid eye movement sleep behavior disorder with or without parkinsonism

ObjectiveRapid eye movement sleep behavior disorder (RBD) is a common sleep disturbance in patients with neurodegenerative disorders. We aimed to compare sleep parameters among the different types of RBD patients.MethodsA total of 122 patients with dream enactment behavior were screened. Of these, 92 patients who were diagnosed with RBD by polysomnography were included in this study. Enrolled patients with RBD were classified into four groups based on the following diagnoses: idiopathic RBD (iRBD); RBD with Parkinson disease (PD-RBD); multiple system atrophy (MSA) with RBD (MSA-RBD); and dementia with Lewy bodies (DLB) with RBD (DLB-RBD). Various clinical and polysomnographic parameters were compared.ResultsAmong the 92 patients with RBD, 35 had iRBD, 25 had PD-RBD, 17 had MSA-RBD, and 15 had DLB-RBD. The mean apnea−hypopnea index of atypical parkinsonism with RBD (AP-RBD) group was 16.2 ± 17.7 events/h (MSA-RBD, 14.0 ± 16.6; DLB-RBD, 18.8 ± 19.1), which was significantly higher than the other groups (p < 0.05). The proportion of patients with 100% supine sleep in the AP-RBD group (44%) was higher than that in the iRBD group (14%; p = 0.030). The proportion of OSA with 100% supine sleep position was significantly higher in the MSA-RBD and DLB-RBD groups than in the iRBD group (p = 0.042 and p = 0.029, respectively).ConclusionOur study demonstrated that patients in the MSA-RBD and DLB-RBD groups had a tendency to sleeping in the supine position and a higher vulnerability to OSA compared to other RBD groups. Further cohort studies are needed to evaluate the influence of these factors on the development of parkinsonism.     

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.     

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.     

Sleep bruxism and oromandibular myoclonus in rapid eye movement sleep behavior disorder: a preliminary report

Objective

We aimed to compare rhythmic masticatory muscle activity typical of sleep bruxism and oromandibular myoclonus (OMM) during rapid eye movement (REM) sleep in patients with idiopathic REM sleep behavior disorder (iRBD) and in Parkinson disease (PD) patients with RBD (PD-RBD).

Methods

Sleep polygraphic data were collected from 9 age-matched controls and 28 patients (mean ± standard error of the mean, 66.0 ± 1.7 y) with a clinical and sleep laboratory diagnosis of RBD. Patients were divided into two groups: 13 patients with iRBD and 15 patients with PD-RBD. Rhythmic masticatory muscle activity, a marker of sleep bruxism, and OMM were scored blind to subject’s diagnosis from jaw electromyographic recordings during sleep.

Results

The rhythmic masticatory muscle activity index was significantly higher during REM sleep in iRBD subjects compared to controls (P < .01) and was significantly higher during non-REM (NREM) sleep in both subject groups compared to controls (P ? .03). A positive sleep laboratory diagnosis of sleep bruxism was made in 25% of all patients. In iRBD, patients had more OMM during REM sleep than controls (2.4 times higher; P = .01).

Conclusion

In the presence of a high frequency of rhythmic masticatory muscle activity during REM sleep, RBD may be suspected and further neurologic assessment is recommended.     

A case series and systematic review of rapid eye movement sleep behavior disorder outcome after deep brain stimulation in Parkinson's disease

REM-sleep behavior disorder (RBD) is a parasomnia and a common sleep disorder in Parkinson's disease (PD). While deep brain stimulation (DBS) is an established treatment for advanced PD with beneficial effects on cardinal PD motor symptoms, the data on the impact of DBS on RBD are limited and often controversial.We reviewed published articles that reported on RBD in the context of DBS surgery via systematic PubMed search. We identified 75 studies and included 12 studies, involving a total of 320 subjects, in our review. Results in respect to EMG activity outcome after subthalamic stimulation are inconsistent. We found no study that reported on RBD outcome after pallidal DBS and no DBS study quantified complex behavior during REM sleep.We also added data on RBD outcome after subthalamic (N = 4 patients) or pallidal (N = 3 patients) DBS from patients with PD with RBD, obtained as part of a prospective DBS study in our centre. Our case series showed an increase of complex behavior during REM (CB-REM) after surgery, independent of DBS target. Conversely, we found a trend towards increasing REM sleep without atonia (RSWA) in subthalamic-stimulated patients and a trend towards decreased RSWA in pallidal stimulated patients.We conclude that CB-REM and RSWA might represent two distinct elements in RBD and should be assessed separately, especially in studies that report on RBD outcome after treatment interventions. Further, larger, prospective, controlled studies in different DBS targets, reporting separately on the different RBD modalities, are needed.     

Cerebrospinal fluid hypocretin levels are normal in idiopathic REM sleep behaviour disorder

Background: Rapid eye movement (REM) sleep behaviour disorder (RBD) is a common sleep disorder that can be associated with a number of neurodegenerative conditions as well as with narcolepsy. Current diagnostic criteria require overnight polysomnography, and there are no other biomarkers available. The control of REM sleep is complex with a putative on/off switch within the brainstem activated, amongst other things, by hypocretinergic pathways from the lateral hypothalamus. Methods: Cerebrospinal fluid hypocretin levels were measured in five patients with idiopathic RBD. Results: Hypocretin levels were between 254 and 450 pg/ml and therefore within the normal range of >100 pg/ml. Conclusion: Hypocretin levels in patients with idiopathic RBD are normal.     

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

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