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

OBJECTIVE: Rapid 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. METHODS: A 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. RESULTS: Among 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). CONCLUSION: Our 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.

Impact of sleep-related symptoms on clinical motor subtypes and disability in Parkinson's disease: a multicentre cross-sectional study.

OBJECTIVES: To investigate the impact of sleep disturbances on Parkinson's disease (PD) clinical motor subtypes and disease-related disability in a multicentre setting. METHODS: We report a cross-sectional relationship between sleep-related symptoms and clinical motor subtypes (tremor dominant (TD); intermediate; postural instability and gait disturbances (PIGDs)) identified in a multicentre study, including 436 patients with PD and 401 age-matched controls. PD-related sleep problems (PD-SP), excessive daytime sleepiness (EDS) and probable REM sleep behaviour disorder (pRBD) were evaluated using the PD sleep scale (PDSS)-2, Epworth Sleepiness Scale (ESS) and RBD screening questionnaire-Japanese version (RBDSQ-J), respectively. RESULTS: PD-SP (PDSS-2 ≥18; 35.1% vs 7.0%), EDS (ESS ≥10; 37.8% vs 15.5%) and pRBD (RBDSQ-J ≥5; 35.1% vs 7.7%) were more common in patients with PD than in controls. The prevalence of restless legs syndrome did not differ between patients with PD and controls (3.4% vs 2.7%). After adjusting for age, sex, disease duration and Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) part III score, the PIGD group had higher PDSS-2 and ESS scores than the TD group. The RBDSQ-J scores did not differ among the TD, intermediate and PIGD groups. A stepwise regression model predicting the MDS-UPDRS part II score identified the Hoehn and Yahr stage, followed by the number of sleep-related symptoms (PD-SP, EDS and pRBD), disease duration, MDS-UPDRS part III score, PIGD subtype, depression and MDS-UPDRS part IV score as significant predictors. CONCLUSION: Our study found a significant relationship between sleep disturbances and clinical motor subtypes. An increased number of sleep-related symptoms had an impact on disease-related disability.

Classification of iRBD and Parkinson's disease patients based on eye movements during sleep.

Patients suffering from the sleep disorder idiopathic rapid-eye-movement sleep behavior disorder (iRBD) have been observed to be in high risk of developing Parkinson's disease (PD). This makes it essential to analyze them in the search for PD biomarkers. This study aims at classifying patients suffering from iRBD or PD based on features reflecting eye movements (EMs) during sleep. A Latent Dirichlet Allocation (LDA) topic model was developed based on features extracted from two electrooculographic (EOG) signals measured as parts in full night polysomnographic (PSG) recordings from ten control subjects. The trained model was tested on ten other control subjects, ten iRBD patients and ten PD patients, obtaining a EM topic mixture diagram for each subject in the test dataset. Three features were extracted from the topic mixture diagrams, reflecting "certainty", "fragmentation" and "stability" in the timely distribution of the EM topics. Using a Naive Bayes (NB) classifier and the features "certainty" and "stability" yielded the best classification result and the subjects were classified with a sensitivity of 95 %, a specificity of 80% and an accuracy of 90 %. This study demonstrates in a data-driven approach, that iRBD and PD patients may exhibit abnorm form and/or timely distribution of EMs during sleep.

Parasomnia overlap disorder: a distinct pathophysiologic entity or a variant of rapid eye movement sleep behavior disorder? A case series.

BACKGROUND: Parasomnia overlap disorder (POD) currently is classified by the International Classification of Sleep Disorders, Second Edition (ICSD-2) as a variant of rapid eye movement (REM) sleep behavior disorder (RBD), and therefore its diagnosis also implies counseling the patients on the increased risk for developing neurodegenerative disorders. POD pathophysiology is not clear to date. METHODS: The authors report 5 cases of POD, review the literature, and analyze previously published cases of POD. RESULTS: In all 5 reported cases sleep-related activity was clearly demonstrated, though the RBD component was mild or incidentally discovered. None of the patients had Parkinsonian clinical features. Based on ICSD-2 criteria, there are 139 more POD cases reported in the literature and 69. 2% are idiopathic. The POD patients had an earlier age of onset than the patients with RBD. The RBD component was milder than the disorder of arousal (DOA) in most cases. Recently an updated classification was published, which included new categories of POD. The features mentioned above and the revised classification suggests that POD is not just a subtype of RBD. CONCLUSIONS: We propose that POD is a distinct pathophysiologic parasomnia. Further research to identify the underlying mechanism is needed. Proper counseling is necessary for patients presenting with POD at a young age of onset.

Rapid eye movement sleep behavior disorder and subtypes in autopsy-confirmed dementia with Lewy bodies.

The purpose of this study was to determine whether dementia with Lewy bodies with and without probable rapid eye movement sleep behavior disorder differ clinically or pathologically. Patients with dementia with Lewy bodies (DLB) with probable rapid eye movement sleep behavior sleep disorder (n = 71) were compared with those without it (n = 19) on demographics, clinical variables (core features of dementia with Lewy bodies, dementia duration, rate of cognitive/motor changes), and pathologic indices (Lewy body distribution, neuritic plaque score, Braak neurofibrillary tangle stage). Individuals with probable rapid eye movement sleep behavior disorder were predominantly male (82% vs 47%) and had a shorter duration of dementia (mean, 8 vs 10 years), earlier onset of parkinsonism (mean, 2 vs 5 years), and earlier onset of visual hallucinations (mean, 3 vs 6 years). These patients also had a lower Braak neurofibrillary tangle stage (stage IV vs stage VI) and lower neuritic plaque scores (18% vs 85% frequency), but no difference in Lewy body distribution. When probable rapid eye movement sleep behavior disorder developed early (at or before dementia onset), the onset of parkinsonism and hallucinations was earlier and Braak neurofibrillary tangle stage was lower compared with those who developed the sleep disorder after dementia onset. Women with autopsy-confirmed DLB without a history of dream enactment behavior during sleep had a later onset of hallucinations and parkinsonism and a higher Braak NFT stage. Probable rapid eye movement sleep behavior disorder is associated with distinct clinical and pathologic characteristics of dementia with Lewy bodies.

Validation of a new REM sleep behavior disorder questionnaire (RBDQ-HK).

OBJECTIVES: There are limited screening instruments for diagnosis of REM sleep behavior disorder (RBD) and none for quantifying the severity of disease. We aimed to validate a 13-item self-reported RBD questionnaire (RBDQ-HK) for diagnostic and monitoring purposes. METHODS: Based on ICSD-II and our previous clinical and empirical work, the RBDQ-HK questionnaire was designed and administered in patients attending university-affiliated sleep clinic and psychiatric out-patient clinic, and subjects from the general population. ROC curve and exploratory factor analysis were employed to evaluate the scale, which had a score ranging from 0 to 100. RESULTS: One hundred and seven RBD patients [mean age 62.6 (15.5) years; male 70.1%] and 107 control subjects [mean age 55.3 (9.0) years, male 57.9%] completed the questionnaire. The diagnoses of all the study subjects were independently ascertained by clinical interview and PSG. RBD patients had a significantly higher total RBDQ-HK score [mean (s.d.): 32.1 (16.1), range 3-71] than the control group [9.5 (10.2), range 0-55] (p<0.005). The RBDQ-HK demonstrated robust psychometric properties with moderate sensitivity (82.2%), specificity (86.9%), positive predictive value (PPV; 86.3%), and negative predictive value (NPV; 83.0%), high internal consistency and test-retest reliability. Exploratory factor analysis revealed two components (dream-related and behavioral factors) that corresponded to the essential clinical features of RBD. The best cut-off for total score (range 0-100) was at 18/19 and the best cut-off for factor 2 (behavioral factors including sleep talking, shouting, limb movements and sleep-related injuries, range 0-70) was at 7/8. CONCLUSIONS: The RBDQ-HK has satisfactory validity and reliability as a measure of clinical RBD symptoms and severity. It may serve as an effective tool for diagnosis and evaluation of the disease course to facilitate future clinical and research studies.

Classical Parkinson disease versus Parkinson complex--reflections against staging and in favour of heterogeneity.

Pathological studies have prompted the idea that Parkinson disease (PD) is a multisystem disorder, which starts far away from the nigrostriatal dopamine system and it goes through a long pre-clinical period. Evidence from epidemiological research, functional imaging, olfaction and sleep studies provides support to this hypothesis. Accordingly, PD is seen as an homogeneous disease which sequentially affects different neural structures leading to a well-defined clinical picture. This concept, recently named PD complex, has deep theoretical and practical implications which raise some concerns. This report shows the concept of classical PD as opposed to PD complex. Although the relevance of the central argument concerning the PD complex concept is admitted, it needs to be fully proved before premature conclusions are drawn. In contrast, the notion of classical and clinically significant PD can explain many of the well-characterized pathological and clinical features of the disease and it gives support to the idea that the magic word in PD is variability.