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.     

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.     

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.     

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.     

Obstructive sleep apnea in Parkinson's disease: a study in 239 Chinese patients

ObjectiveOur objective was to explore the clinical characteristics of Parkinson's disease (PD) comorbidity with obstructive sleep apnea (OSA), explore the correlation between OSA and PD features and identify factors that are independent predictors of OSA in PD patients.MethodsIn sum, 239 PD patients were divided into two groups according to the presence of OSA (apnea–hypopnea index (AHI) score ≥5) (PD-OSA vs PD-non-OSA). Blinded to sleep apnea status, participants underwent an extensive assessment to determine demographic features, concomitant disease, disease severity, polysomnography (PSG) characteristics and non-motor symptoms (NMSs).ResultsOf the 239 patients, 66 (27.62%) had an AHI score ≥5, including 14.2% (34/239) with mild, 6.7% (16/239) with moderate, and 6.7% (16/239) with severe sleep apnea. The binary logistic regression analyses indicated that age and male gender were risk factors for OSA, while rapid eye movement (REM) sleep disorder (RBD) and higher Levodopa equivalent dose (LED) were protective factors for OSA. PD-OSA patients had higher Epworth Sleepiness Scale (ESS) scores than those of PD-non-OSA patients. No differences were found for other NMSs between groups.ConclusionOur data suggest that OSA in PD was lower in patients with RBD and higher LED. RBD and higher LDEs were significant protective factors for OSA in PD. OSA in PD was increased with age and male gender. Age and male gender were risk factors for OSA in PD. OSA can aggravate excessive daytime somnolence in PD patients but is not associated with other NMSs.     

Total durations of respiratory events are modulated within REM and NREM sleep by sleeping position and obesity in OSA patients

BackgroundSupine sleeping position and obesity are well-known risk factors for obstructive sleep apnea (OSA) and modulate the risk for OSA-related daytime symptoms. Although respiratory event durations are associated with OSA-related severe health consequences, it is unclear how sleeping position, obesity, and daytime sleepiness are associated with respiratory event durations during REM and NREM sleep. We hypothesize that irrespective of the apnea-hypopnea index (AHI), respiratory event durations differ significantly between various OSA subgroups during REM and NREM sleep.MethodsOne night in-lab polysomnographic recordings were retrospectively analyzed from 1910 untreated suspected OSA patients. 599 patients (AHI ≥ 5) were included in study and divided into subgroups based on positional dependency, BMI, and daytime sleepiness (Epworth Sleepiness Scale and Multiple Sleep Latency Test). Differences in total hypopnea time (THT), total apnea time (TAT), and total apnea-hypopnea time (TAHT) within REM and NREM sleep between the subgroups were evaluated.ResultsDuring REM sleep, positional OSA patients had lower THT (OR = 0.952, p < 0.001) and TAHT (OR = 0.943, p < 0.001) than their non-positional counterparts. Compared to normal-weight patients (BMI < 25 kg/m²), obese patients (BMI ≥ 30 kg/m²) had lower THT, TAT, and TAHT (ORs = 0.942–0.971, p ≤ 0.009) during NREM sleep but higher THT (OR = 1.057, p = 0.001) and TAHT (OR = 1.052, p = 0.001) during REM sleep. No significant differences were observed in THT, TAT, and TAHT between patients with and without daytime sleepiness.ConclusionRegardless of the AHI, respiratory event durations vary significantly between OSA sub-groups during REM and NREM sleep. Therefore, to personalize OSA severity estimation the diagnosis should be tailored based on patient's demographics, clinical phenotype, and PSG characteristics.     

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.     

Rapid eye movement sleep disturbance in patients with refractory epilepsy: A polysomnographic study

Objective/BackgroundPatients with epilepsy have disrupted sleep architecture and a higher prevalence of sleep disturbance. Moreover, obstructive sleep apnea (OSA) is more common among patients with refractory epilepsy. Few studies have compared subjective sleep quality, sleep architecture, and prevalence of OSA between patients with refractory epilepsy and those with medically controlled epilepsy. Therefore, this study aimed to evaluate the differences in sleep quality, sleep architecture, and prevalence of OSA between patients with refractory epilepsy and patients with medically controlled epilepsy.PatientsThis retrospective case–control study included 38 patients with refractory epilepsy and 96 patients with medically controlled epilepsy. Sleep parameters and indices of sleep-related breathing disorders were recorded by standard in-laboratory polysomnography. The scores from sleep questionnaires on sleep quality and daytime sleepiness were compared between the two groups.ResultsPatients with refractory epilepsy versus medically controlled epilepsy had statistically significantly decreased rapid eye movement (REM) sleep (13.5 ± 6.1% vs. 16.2 ± 6.1%) and longer REM latency (152.2 ± 84.1 min vs. 117.2 ± 61.9 min). Further, no differences were found in the prevalence of sleep-related breathing disorders, subjective sleep quality, prevalence of daytime sleepiness, and quality of life. Although not statistically significant, patients with refractory epilepsy have a lower rate of OSA compared with those with medically controlled epilepsy (21.1% vs. 30.2%).ConclusionsPatients with refractory epilepsy had more disrupted REM sleep regulation than those with medically controlled epilepsy. Although patients with epilepsy have a higher risk of OSA, in this study patients with refractory epilepsy were not susceptible to OSA.     

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.     

Idiopathic REM sleep behavior disorder in the elderly Spanish community: a primary care center study with a two-stage design using video-polysomnography

ObjectiveTo examine the presence and characteristics of idiopathic REM sleep behavior disorder (IRBD) in a representative Caucasian sample from the elderly community of Lleida, Spain, attending primary care centers.MethodsParticipants were individuals aged 60 years or older who underwent routine visits in two primary care centers. They underwent a two-stage study; a validated screening single question for IRBD diagnosis (RBD1Q) followed by, in those who endorsed positive answer, clinical assessment by a neurologist plus video-polysomnography (V-PSG).ResultsOf 539 individuals (56.4% women, mean age 72.86 ± 8.20 years), 28 (5.2%) endorsed positively the RBD1Q. Four of these 28 refused further assessments. Four of the 24 remaining subjects underwent clinical assessment but refused V-PSG. Of the 20 who underwent clinical assessment plus V-PSG, REM sleep was not recorded in four (20%, all four taking antidepressants). V-PSG ruled out RBD in 12 subjects who had obstructive sleep apnea (n = 9), periodic limb movement disorder in sleep (n = 2) and normal sleep (n = 1). IRBD was diagnosed in four individuals giving an estimated prevalence of 0.74% (95% CI = 0.29–1.89). They were three men and one woman between 74 and 82 years of age who never reported dream-enacting behaviors to their doctors because they thought they represented a normal phenomenon despite suffering sleep-related injuries. These patients had history of violent sleep behaviors with an interval between estimated RBD onset and V-PSG of 4.5 ± 4.2 years.ConclusionsIRBD is not uncommon in the elderly community and its demographic and clinical profile is similar to those diagnosed in sleep centers.     

Effects of an individualized exercise training program on severity markers of obstructive sleep apnea syndrome: a randomised controlled trial

ObjectiveObstructive sleep apnea (OSA) is a high prevalent disorder with severe consequences including sleepiness, metabolic, and cardiovascular disorders. The aim of this study was to assess the effect of an individualized exercise-training (IET) program with educational sessions vs educational sessions alone on severity markers of OSA over an eight-week duration.MethodsThis was a randomised, controlled, parallel-design study. In sum, 64 patients with moderate-to-severe OSA (apnea-hypopnea index AHI 15–45/hour), low physical activity level (Voorrips<9), body-mass index (BMI) <40 kg/m² were included in intervention group (IG) or control group (CG), and 54 patients finished the study. All underwent polysomnography (PSG), multiple sleep latency test (MSLT), constant workload exercise test, blood samples and fulfilled questionnaires twice. The primary endpoint was the change in apnea-hypopnea (AHI) at eight weeks from baseline. Main secondary endpoints were daytime sleepiness assessed by questionnaire and objective tests.ResultsNo significant between-group differences were found for changes in AHI. A reduction in AHI was found in IG only (p = 0.005). Compared to CG, exercise training leads to a greater decrease in AHI during REM sleep (p = 0.0004), with a significant increase in mean daytime sleep latency (p = 0.02). Between-group differences were significant for weight reduction, severity of fatigue, insomnia and depressive symptoms with trend for sleepiness symptoms.ConclusionsIn adult patients with moderate-to-severe OSA, IET did not decrease AHI compared to the control group but improved markers of severity of OSA, in particular AHI in rapid eye movement (REM) sleep and objective daytime sleepiness. Adding personalized exercise training to the management of patients with OSA should be considered.ClinicalTrials.gov identifierNCT01256307.     

Is snoring during pregnancy a predictor of later life obstructive sleep apnoea? A case–control study

BackgroundObstructive sleep apnoea (OSA) appears common in pregnancy. Complications of pregnancy such as gestational diabetes and hypertension predispose women to cardiometabolic disease in later life. It is unknown if snoring during pregnancy is a risk marker for later-life OSA.MethodsWe analysed data from N = 897 women in the Sleep Apnea Global Interdisciplinary Consortium (SAGIC), which recruited patients attending sleep clinics at 11 sites. There were 577 cases with current OSA and 320 controls. Cases were further categorised into mild, moderate, and severe OSA based on apnoea-hypopnoea index. Retrospective self-report of snoring during pregnancy was the exposure of interest and was reported by 2.9% of cases and 3.4% of controls.ResultsMultinomial regression demonstrated that snoring during a previous pregnancy was not significantly associated with mild (OR 0.34, 95% CI 0.09–1.25, p = 0.10), moderate (OR 0.69, 95% CI 0.21–2.19, p = 0.52), or severe OSA (OR 1.86, 95% CI 0.77–4.48, p = 0.17) compared to no snoring during pregnancy. Results were unchanged after adjustment for age, body mass index, and ethnicity. 79% of women reported current snoring but all who snored during pregnancy reported current snoring.ConclusionsWomen who snore during pregnancy continue snoring in later-life but do not appear more likely to develop OSA. These findings are limited by self-reported data, recall bias, and small numbers of women who reported snoring during pregnancy. A prospective study with objective measurement of sleep and snoring during pregnancy is needed to examine the links between sleep disorders in pregnancy with health in later life.     

REM sleep behavior disorder and motor dysfunction in Parkinson's disease – A longitudinal study

ObjectivesLongitudinal assessment of a Parkinson's disease (PD) cohort, to investigate the evolution or REM sleep behavior symptoms (RBD) over time and to test the relation between RBD at onset and motor dysfunction progression.MethodsAn early stage PD cohort (n = 61) was assessed at two time points, separated by a two years interval. Diagnostic criteria for RBD were: violent behavior during sleep and body movements or vocalization indicative of dream enacting and at least six affirmative answers in the REM sleep behavior disorder screening questionnaire. Motor function assessment was performed with the Unified Parkinson's Disease Scale part II and III (total and partial scores for tremor, bradykinesia, rigidity, gait/postural instability and dysarthria).Results25 Patients had RBD at baseline, vs. 35 at follow-up. Three RBD changed to non-RBD at follow-up, while 10 non-RBD patients developed RBD at follow-up (annual incidence of 12.5%). RBD and non-RBD patients did not differ significantly at baseline or follow-up. The presence of RBD at baseline was significantly related to an increase in UPDRS total and bradykinesia scores over time.DiscussionRBD symptoms can vary over time and have a tendency to increase during the early stages of disease. The presence of RBD symptoms could be a risk factor for motor function deterioration and particularly for bradykinesia worsening.     

Prolonged-release melatonin in Parkinson's disease patients with a poor sleep quality: A randomized trial

BackgroundThe present study was a randomized, double-blind, placebo-controlled, multi-center trial to evaluate the efficacy and safety of prolonged-release melatonin (PRM) in Parkinson's disease (PD) patients with poor sleep quality.MethodsPD patients with a global Pittsburgh Sleep Quality Index (PSQI) score > 5 were included. Patients were assessed using the PSQI, a rapid eye movement sleep behavior disorder screening questionnaire, the Epworth Sleepiness Scale, Non-Motor Symptoms Scale (NMSS), Parkinson's Disease Quality of Life-39 (PDQ-39), and Unified Parkinson's Disease Rating Scale (UPDRS)-III at the beginning of the study and after 4 weeks of treatment with 2 mg of PRM. Partial correlation analysis was performed to investigate the relationship between PSQI score and the other scales.ResultsThirty-four PD patients with poor sleep quality were enrolled and divided into 2 groups based on medication; PRM (n = 16) and placebo (n = 18). Regarding efficacy, PSQI was significantly improved in the PRM group compared to the control group. Improvement in the NMSS and PDQ-39 summary index were observed in the PRM but not in the placebo group; UPDRS-III score was not significantly changed in either group. PSQI improvement correlated with improvement in NMSS score and PDQ-39 summary index. Regarding safety, all enrolled subjects did not complain of side effects due to PRM.ConclusionPRM is an effective and safe treatment option for subjective sleep quality in PD patients and beneficial effects on sleep quality are associated with improved non-motor symptoms and quality of life in PD patients.     

Severity of idiopathic rapid eye movement sleep behavior disorder correlates with depression and alexithymia

BackgroundDepression and alexithymia often accompany early stages of Parkinson's disease (PD). However, these symptoms in idiopathic rapid eye movement sleep behavior disorder (iRBD) remain incompletely understood. The aim of this study was to compare depression and alexithymia between iRBD patients and healthy controls, and to evaluate the association between clinical RBD severity and severity of depression and alexithymia.MethodsPolysomnography-confirmed iRBD patients (n = 86) and healthy controls (n = 74) were enrolled. Clinical RBD severity was assessed using the RBD questionnaire-Hong Kong (RBDQ-HK). Depression and alexithymia were evaluated by the Beck Depression Inventory (BDI) and the 20-item Toronto Alexithymia Scale (TAS-20), respectively. Multivariate linear regression analysis was performed with adjustments for several covariates to determine the correlations between RBD severity and severity of depression and alexithymia.ResultsBDI scores were significantly higher in the iRBD group (10.6 ± 7.3) than in healthy controls (8.2 ± 6.0, p = 0.024). Higher total RBDQ-HK scores were associated with more severe depression in iRBD patients, even after controlling for confounding variables. iRBD patients exhibited significantly higher TAS-20 scores (45.7 ± 10.4) than healthy controls (42.1 ± 9.8, p = 0.026). Total RBDQ-HK scores were positively correlated with TAS-20 scores independent of BDI scores.ConclusionsPatients with iRBD were more depressed and had more severe alexithymia than healthy controls. Notably, as the clinical severity of RBD increased, both depression and alexithymia worsened.     

QT interval variability index and QT interval duration during different sleep stages in patients with obstructive sleep apnea

ObjectivesThe aim of the study was to investigate the impact of obstructive sleep apnea (OSA) on the QT interval variability and duration in patients during different sleep stages.MethodsPolysomnographic recordings of 28 (13 male, 15 female) patients with OSA and 30 (15 male, 15 female) patients without OSA were analyzed. The QT interval variability index (QTVI) and the corrected QT interval (QTc) analyses were performed using two awake, 3–4 non-rapid eye movement (NREM) and three rapid eye movement (REM) sleep episodes (each 300 s). The Bazett formula, linear, and parabolic heart rate correction formulas with two separate α values were used.ResultsQTVI was statistically higher in OSA than in non-OSA patients for males while awake (awake −0.7 ± 0.3 vs −1.2 ± 0.2, p = 0.001; NREM ‒0.9 ± 0.4 vs −1.1 ± 0.3, p = 0.110; REM ‒1.1 ± 0.3 vs −1.3 ± 0.2, p = 0.667) and for females in all wake–sleep stages (awake −0.3 ± 0.7 vs −0.9 ± 0.5, p = 0.001; NREM ‒0.3 ± 0.5 vs −0.8 ± 0.4, p = 0.002; REM −0.3 ± 0.5 vs −1.0 ± 0.4, p < 0.001). QTVI was significantly higher during awake compared to sleep stages in OSA males (p < 0.05); no difference between wake–sleep stages was found in females (p > 0.05). Significant gender differences in QTVI existed in OSA patients during sleep (p < 0.05) but not while awake. No significant differences in QTc between patients groups were observed.ConclusionsOSA is associated with increased QT variability. REM sleep per se does not increase QTVI. In OSA patients, QTVI might be a more useful measure to detect ventricular repolarization abnormality than measures of QTc.     

Sex differences within symptom subtypes of mild obstructive sleep apnea

ObjectivesPrior studies have identified symptom subtypes of moderate to severe (AHI >15) obstructive sleep apnea (OSA). They have not yet been consistently examined in those with mild OSA (AHI 5–15 events/hour). This is important as women are more likely than men to present with mild OSA and may present with different OSA symptoms. The objectives of this study were to determine 1) symptom subtypes in mild OSA and 2) if there are sex differences in the distribution of subtypes.MethodsThe sample included men (n = 921) and women (n = 797) with mild OSA, aged 39–90 years, evaluated with a single night of in–home polysomnography as part of the Sleep Heart Health Study. Latent class analysis determined symptom subtypes. Testing for sex differences relative to OSA severity and symptom subtype used chi-squared test for independence. Bonferroni corrected z-tests compared column proportions.ResultsSymptom subtypes of mild OSA were not significantly different than those identified in prior studies of moderate-severe OSA (p > 0.05): minimally symptomatic (36.4%), disturbed sleep (11.6%), moderately sleepy (37%), and excessively sleepy (15%), p > 0.05. Sex differences within the symptom subtypes were significant [χ²(df = 3) = 30.04, p < 0.001, Cramer's V = 0.132]. Relative to men, women were more likely to be in the disturbed sleep subtype (p < 0.05), and the excessively sleepy subtype (p < 0.05) while less likely to be in the moderately sleep (<0.05) subtype. Women and men were equally represented in the minimal symptoms subtype (p > 0.05).ConclusionsResults suggest symptom reporting among individuals with mild OSA differs as a function of sex. These data have important clinical implications for screening men and women for OSA.     

Circadian rhythms of melatonin and peripheral clock gene expression in idiopathic REM sleep behavior disorder

ObjectiveTo evaluate changes in the expression of clock genes and melatonin levels in patients with idiopathic REM sleep behavior disorder (RBD) as a potential early stage of synucleinopathies.MethodsWe assessed the rhythmicity of circadian clock genes using real time-quantitative polymerase chain reaction and 24-h blood melatonin profiles using radio-immunoassay in 10 RBD patients and nine age-matched controls.ResultsThe RBD patients did not show circadian rhythmicity for clock genes Per2, Bmal1, and Nr1d1 but the rhythmicity of Per 1 remained, and the amplitude of Per3 was diminished. The 24-h melatonin rhythm did not differ between RBD patients and healthy control subjects. Melatonin profile in RBD patients was delayed by 2 h compared to controls, the habitual sleep phases were phase delayed by about 1 h, however no phase shift occurred in any of the clock genes studied. The control group had stable acrophases of melatonin rhythms of approximately 5 h whereas the RBD patients had a more dispersed range over 11 h.ConclusionsOur results suggest that RBD could be associated with altered expression of clock genes and delayed melatonin secretion. Thus, we argue that circadian system dysregulation could play a role in RBD.     

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.     

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.