Searching for a marker of REM sleep behavior disorder: submentalis muscle EMG amplitude analysis during sleep in patients with narcolepsy/cataplexy

STUDY OBJECTIVES: To evaluate the amplitude of submentalis muscle EMG activity during sleep in patients with narcolepsy/cataplexy with or without REM sleep behavior disorder (RBD). DESIGN: Observational study with consecutive recruitment. SETTINGS: Sleep laboratory. PATIENTS: Thirty-four patients with narcolepsy/cataplexy and 35 age-matched normal controls. MEASUREMENTS AND RESULTS: Half the patients (17 subjects) had a clinical and video polysomnographic diagnosis of RBD. The average amplitude of the rectified submentalis muscle EMG signal was used to assess muscle atonia, and the new REM sleep Atonia Index was computed. Chin muscle activations were detected and their duration and interval analyzed. REM sleep Atonia Index was lower in both patient groups (with narcolepsy patients with RBD showing the lowest values) with respect to controls, and it did not correlate with age as it did in controls. The total number of chin EMG activations was significantly higher in both patient groups than controls. No significant differences were found between the two groups of patients, although more chin EMG activations were noted in narcolepsy patients with RBD than those without. CONCLUSIONS: Elevated muscle activity during REM sleep is the only polysomnographic marker of RBD. This study shows that polysomnographically evident RBD is present in many patients with narcolepsy/ cataplexy. This condition might be specific to narcolepsy/cataplexy, reflecting a peculiar form of REM sleep related motor dyscontrol (i.e., status dissociatus), paving the way to enacting dream behaviors, and correlated with the specific neurochemical and neuropathological substrate of narcolepsy/cataplexy.     

A quantitative analysis of the submentalis muscle electromyographic amplitude during rapid eye movement sleep across the lifespan

The current definition of rapid eye movement (REM) sleep without atonia has no quantitative character, and cut-off values above which the level of electromyographic tone can be considered to be 'excessive' are unclear. The aim of this study was to analyse the characteristics of chin electromyographic amplitude by means of an automatic approach in a large group of normal controls, subdivided into different age groups. Eighty-eight normal controls were included, subdivided into six age groups: preschoolers (≤6 years); schoolers (6-10 years); preadolescents (10-13 years); young adults (24-40 years); middle-aged (58-65 years); and old (>65 years). The average amplitude of the rectified submentalis muscle electromyographic signal was used for the computation of the REM sleep Atonia Index. Chin muscle activations were detected, and their amplitude, duration and interval analysed. REM sleep Atonia Index showed a progressive and rapid increase from the preschool age to school and preadolescent age, reaching the maximum in the young adult group; after this age a small decline was observed in the middle-aged and old subjects. Conversely, the number of movements per hour in REM sleep showed a 'U'-shaped distribution across these age groups, with the minimum in the preadolescent group and the two extremes (preschool age and old) showing similar average levels of activity. Our results show that REM sleep atonia develops continuously during the lifespan, and undergoes complex changes with different developmental trajectories for REM atonia and electromyographic activations during REM sleep. Different mechanisms might subserve these two phenomena and their differential developmental dynamics.     

REM sleep characteristics in narcolepsy and REM sleep behavior disorder

STUDY OBJECTIVES: To assess the presence of polysomnographic characteristics of REM sleep behavior disorder (RBD) in narcolepsy; and to quantify REM sleep parameters in patients with narcolepsy, in patients with "idiopathic" RBD, and in normal controls. DESIGN: Sleep laboratory study PARTICIPANTS: Sixteen patients with narcolepsy and cataplexy matched for age and sex with 16 patients with "idiopathic" RBD and with 16 normal controls were studied. MEASUREMENTS AND RESULTS: Higher percentages of REM sleep without atonia, phasic electromyographic (EMG) activity, and REM density were found in patients with narcolepsy than normal controls. In contrast, RBD patients had a higher percentage of REM sleep without atonia but a lower REM density than patients with narcolepsy and normal controls. Based on a threshold of 80% for percentage of REM sleep with atonia, 50% of narcoleptics and 87.5% of RBD patients had abnormal REM sleep muscle activity. No significant behavioral manifestation in REM sleep was noted in either narcoleptics or controls. We also found a higher frequency of periodic leg movements during wake (PLMW) and during sleep (PLMS) in narcoleptic patients compared to controls. CONCLUSIONS: The present study demonstrates abnormalities in REM sleep motor regulation with an increased frequency of REM sleep without atonia, phasic EMG events and PLMS in narcoleptic patients when compared to controls. These abnormalities were seen more prominently in patients with RBD than in narcoleptics, with the exception of the PLMS index. We proposed that dysfunctions in hypocretin/dopaminergic system may lead to motor dyscontrol in REM sleep that results in dissociated sleep/wake states.     

Analysis of automated quantification of motor activity in REM sleep behaviour disorder

Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by dream enactment and REM sleep without atonia. Atonia is evaluated on the basis of visual criteria, but there is a need for more objective, quantitative measurements. We aimed to define and optimize a method for establishing baseline and all other parameters in automatic quantifying submental motor activity during REM sleep. We analysed the electromyographic activity of the submental muscle in polysomnographs of 29 patients with idiopathic RBD (iRBD), 29 controls and 43 Parkinson's (PD) patients. Six adjustable parameters for motor activity were defined. Motor activity was detected and quantified automatically. The optimal parameters for separating RBD patients from controls were investigated by identifying the greatest area under the receiver operating curve from a total of 648 possible combinations. The optimal parameters were validated on PD patients. Automatic baseline estimation improved characterization of atonia during REM sleep, as it eliminates inter/intra‐observer variability and can be standardized across diagnostic centres. We found an optimized method for quantifying motor activity during REM sleep. The method was stable and can be used to differentiate RBD from controls and to quantify motor activity during REM sleep in patients with neurodegeneration. No control had more than 30% of REM sleep with increased motor activity; patients with known RBD had as low activity as 4.5%. We developed and applied a sensitive, quantitative, automatic algorithm to evaluate loss of atonia in RBD patients.     

REM sleep behavior disorder and REM sleep without atonia in patients with progressive supranuclear palsy

STUDY OBJECTIVE: To compare sleep characteristics, rapid eye movement (REM) sleep without atonia, and REM sleep behavior disorder (RBD) in patients with progressive supranuclear palsy (tauopathy), patients with Parkinson's disease (a synucleinopathy), and control subjects. DESIGN: Sleep interview, overnight polysomnography, and Multiple Sleep Latency Tests. PATIENTS: Forty-five age- and sex-matched patients with probable progressive supranuclear palsy, (n=15, aged 68 +/- 8 years, 7 men), patients with Parkinson disease (n=15), and control subjects (n=15). SETTINGS: Tertiary-care academic hospital. INTERVENTION: N/A. RESULTS: Compared to the 2 other groups, patients with progressive supranuclear palsy had a longer duration of wakefulness after sleep onset and twice as much sleep fragmentation and percentage of stage 1 sleep but had similar apnea-hypopnea indexes, periodic leg movements indexes, and mean daytime sleep latencies. REM sleep percentage was as low in patients with progressive supranuclear palsy (8% +/- 6% of total sleep time) as in patients with Parkinson disease (10% +/- 4%), versus 20% +/- 6% in controls (analysis of variance, P < .0001). Interestingly, patients with progressive supranuclear palsy had percentages of REM sleep without atonia (chin muscle activity: 33% +/- 36% of REM sleep) similar to those of patients with Parkinson disease (28% +/- 35%) and dramatically higher than those of controls (0.5% +/- 1%, analysis of variance, P = .008). Four (27%) patients with progressive supranuclear palsy had more than 50% REM sleep without atonia (as did a similar number of patients with Parkinson disease), and 2 of them (13%, vs 20% of patients with Parkinson disease) had clinical RBD. The four patients with progressive supranuclear palsy with excessive daytime sleepiness slept longer at night than the 11 patients with progressive supranuclear palsy who were alert (442 +/- 14 minutes vs 312 +/- 74 minutes, student t tests, P = .004), suggesting a primary nonnarcoleptic hypersomnia. CONCLUSION: REM sleep without atonia and RBD were as frequent in patients with progressive supranuclear palsy as in patients with Parkinson disease. It suggests that the downstream cause of parkinsonism, rather than its primary neuropathology (synucleinopathy vs tauopathy), is a key factor for REM sleep behavior disorder.     

REM sleep behavior disorder and REM sleep without atonia in probable Alzheimer disease

STUDY OBJECTIVE: To determine the frequency of rapid eye movement (REM) sleep behavior disorder (RBD) and REM sleep without atonia among patients with Alzheimer disease and control subjects. DESIGN: Overnight polysomnography. SETTINGS: Sleep laboratory. PATIENTS: Fifteen patients with probable Alzheimer disease (mean age +/-SD, 70.2+/-5.6) and 15 age-matched healthy control subjects (mean age +/- SD, 67.9 +/-5.4). INTERVENTION: N/A. RESULTS: Four patients with Alzheimer disease presented REM sleep with-out atonia. One of these patients had all the polysomnographic features of RBD, including behavioral manifestations during REM sleep. CONCLUSION: RBD is rare, but REM sleep without atonia is relatively fre-quent in patients with probable Alzheimer disease, a tauopathy.     

Brainstem proton magnetic resonance spectroscopy in idopathic REM sleep behavior disorder

STUDY OBJECTIVES: Rapid-eye-movement (REM) sleep behavior disorder (RBD) is thought to result from a dysfunction of the brainstem structures that regulate physiologic REM sleep muscle atonia. Proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive method that allows detection of in vivo neuronal dysfunction in localized brain areas. The aim of our study was to investigate whether 1H-MRS can detect brainstem abnormalities in patients with idiopathic RBD. DESIGN: 1H-MRS centered on the midbrain and the pontine tegmentum was acquired in 15 patients with idiopathic RBD and 15 control subjects matched for age and sex. SETTING: University hospital sleep laboratory center. PARTICIPANTS: Fifteen untreated patients with chronic RBD diagnosed by history and video-polysomnography, normal neurologic examination, and normal cranial MRI. Fifteen healthy controls with no sleep complaints and normal polysomnography and brain MRI. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The metabolic peaks detectable with 1H-MRS, N-acetylaspartate (NAA), creatine-phosphocreatine (Cr), choline-containing compounds (Cho) and myoinositol (mI), and the ratios of NAA, Cho and ml to Cr were evaluated both in the midbrain and pontine tegmentum. No significant differences in N-acetylaspartate/creatine, choline/creatine and myoinosito/creatine ratios were found between patients and controls. CONCLUSIONS: The results do not suggest that marked mesopontine neuronal loss or 1H-MRS detectable metabolic disturbances occur in idiopathic RBD.     

Aktuelle semiautomatische und automatische polysomnographische Auswertemethoden und Klassifikationsmodelle der REM-Schlafverhaltensstörung

The REM sleep behavior disorder (RBD) has been newly classified in the International Classification of Sleep Disorders 3 (2014) and the scoring rules are described by the American Academy of Sleep Medicine (2012). The scoring rules for RBD are based on the detection target muscle activity in REM sleep as REM sleep without atonia (RSWA). Until now a differentiation was made between phasic and tonic muscle activity in REM sleep but recent literature has shown that the scoring of any muscle activity leads to comparable results. Until recently muscle activity was scored manually but semiautomatic scoring algorithms now allow exact and fast scoring of RSWA. Italian and German algorithms are based on the creation of envelope curves of muscle activity, whereas a Danish algorithm uses an outlier detection method, where the outliers represent RSWA and the inliers normal REM sleep atonia. A polysomnographic (PSG) analysis of RBD shows slowing of the electroencephalography (EEG) basal activity and reduction of spindle density. These changes are similar to those seen in neurodegenerative disorders, into which up to 90?% of idiopathic RBD convert within 10–20 years after onset. The new semiautomatic scoring algorithms allow faster evaluation of PSGs not only for RSWA but also for other graphoelements which can serve as predictors for neurodegenerative diseases.     

特发性和继发性快速眼动睡眠行为障碍的睡眠结构研究

目的：探讨快速眼动睡眠行为障碍（REM sleep behavior disorder,RBD）患者的睡眠结构改变。方法：纳入的22例患者符合国际睡眠障碍协会（第2版）的RBD诊断标准,16例患者符合RBD主要诊断标准以及英国脑库的PD、2005年国际路易体痴呆协作组或者2008年多系统萎缩第2版的诊断标准。同时纳入年龄、性别匹配的健康对照19例。利用日本光电32信道9200K脑电图机,所有患者均完成多项睡眠图监测（PSG）,记录脑电图、眼球运动、下颌和肢体肌电活动、心电图、经鼻气流、胸腹部呼吸运动、血氧、鼾声等多个项目,并录像监测患者的行为。使用Polysmith软件和视觉评估分析睡眠结构、呼吸、运动等相关指标。结果：RBD患者展现了典型临床表现和电生理改变。特发性RBD组（72．7％）较继发性RBD组（43．8％）显示有更多的夜间活动和言语,差异有统计学意义（P=0．071）。特发性RBD在睡眠结构并未发生明显改变,仅有周期性腿动（PLM）指数增高。继发性RBD与特发性RBD和健康对照相比,总体睡眠时间缩短、睡眠效率减低、睡眠潜伏期和REM潜伏期延迟、Ⅱ期和REM睡眠减少、Ⅰ期睡眠增加、低通气指数增高、PLM指数增高。结论：特发性RBD患者具有更多的夜间行为异常,而睡眠结构无改变,仅有PLM指数增加;而继发性RBD出现明显的睡眠结构紊乱、呼吸紊乱以及PLM异常。     

REM sleep behavior disorder in patients with guadeloupean parkinsonism, a tauopathy

STUDY OBJECTIVE: To describe sleep characteristics and rapid eye movement (REM) sleep behavior disorder in patients with Guadeloupean atypical parkinsonism (Gd-PSP), a tauopathy resembling progressive supranuclear palsy that mainly affects the midbrain. It is possibly caused by the ingestion of sour sop (corossol), a tropical fruit containing acetogenins, which are mitochondrial poisons. DESIGN: Sleep interview, motor and cognitive tests, and overnight videopolysomnography. PATIENTS: Thirty-six age-, sex-, disease-duration- and disability-matched patients with Gd-PSP (n = 9), progressive supranuclear palsy (a tauopathy, n = 9), Parkinson disease (a synucleinopathy, n = 9) and controls (n = 9). SETTINGS: Tertiary-care academic hospital. RESULTS: REM sleep behavior disorder was found in 78% patients with Gd-PSP (43% of patients reported having this disorder several years before the onset of parkinsonism), 44% of patients with idiopathic Parkinson disease, 33% of patients with progressive supranuclear palsy, and no controls. The percentage of muscle activity during REM sleep was greater in patients with Gd-PSP than in controls (limb muscle activity, 8.3%+/-8.7% vs 0.1%+/- 0.2%; chin muscle activity, 24.3%+/- 23.7% vs 0.7%+/-2.0%) but similar to that of other patient groups. The latency and percentage of REM sleep were similar in patients with Gd-PSP, patients with Parkinson disease, and controls, whereas patients with progressive supranuclear palsy had delayed and shortened REM sleep. CONCLUSION: Although Gd-PSP is a tauopathy, most patients experience REM sleep behavior disorder. This suggests that the location of neuronal loss or dysfunction in the midbrain, rather than the protein comprising the histologic lesions (synuclein versus tau aggregation), is responsible for suppressing muscle atonia during REM sleep. Subjects with idiopathic REM sleep behavior disorder should avoid eating sour sop.     

Pervasive and diffuse muscle activity during REM sleep and non-REM sleep characterises multiple system atrophy in comparison with Parkinson's disease

Multiple system atrophy (MSA) and Parkinson's disease (PD) may share overlapping features particularly at early disease stage, including sleep alterations, but have profoundly different prognoses. Certain sleep phenomena and disorders of motor control are more prevalent in multiple system atrophy, such as REM sleep behaviour disorder (RBD). We quantitatively tested whether pervasive muscle activity during sleep occurs in subjects with multiple system atrophy versus Parkinson's disease. Laboratory polysomnographic studies were performed in 50 consecutive subjects with Parkinson's disease and 26 age- and gender-matched subjects with multiple system atrophy at <5 years from disease onset. The distributions of normalised electromyographic activity of submentalis, wrist extensor, and tibialis anterior muscles in different wake–sleep states during the night were analysed. Subjects with multiple system atrophy had significantly higher activity of submentalis, wrist extensor, and tibialis anterior muscles than subjects with Parkinson's disease during non-REM sleep, including separately in stages N1, N2, and N3, and during REM sleep, but not during nocturnal wakefulness. The activity of wrist extensor and tibialis anterior muscles during non-REM sleep and the activity of tibialis anterior muscles during REM sleep were also significantly higher in subjects with multiple system atrophy and RBD than in subjects with Parkinson's disease and RBD. In conclusion, with respect to Parkinson's disease, multiple system atrophy is characterised by a pervasive and diffuse muscle overactivity that involves axial and limb muscles and occurs not only during REM sleep, but also during non-REM sleep and between subjects with comorbid RBD.     

Severe obstructive sleep apnea/hypopnea mimicking REM sleep behavior disorder

OBJECTIVE: To describe the clinical and video-polysomnographic (VPSG) features of a group of subjects with severe obstructive sleep apnea/hypopnea (OSAH) mimicking the symptoms of REM sleep behavior disorder (RBD). DESIGN: Evaluation of clinical and VPSG data. SETTING: University hospital sleep laboratory unit. PARTICIPANTS: Sixteen patients that were identified during routine first evaluation visits. Patients' PSG measures were compared with those of 20 healthy controls and 16 subjects with idiopathic RBD of similar age and sex distribution and apnea/hypopnea index lower than 10. INTERVENTIONS: NA. RESULTS: Sixteen subjects were identified presenting with dream-enacting behaviors and unpleasant dreams suggesting the diagnosis of RBD, in addition to snoring and excessive daytime sleepiness. VPSG excluded RBD showing REM sleep with atonia and without increased phasic EMG activity, and was diagnostic of severe OSAH with a mean apnea-hypopnea index of 67.5 +/- 18.7 (range, 41-105) demonstrating that the reported abnormal sleep behaviors occurred only during apnea-induced arousals. Continuous positive airway pressure therapy eliminated the abnormal behaviors, unpleasant dreams, snoring and daytime hypersomnolence. CONCLUSIONS: Our study shows that severe OSAH may mimick the symptoms of RBD and that VPSG is mandatory to establish the diagnosis of RBD, and identify or exclude other causes of dream-enacting behaviors.     

Excessive Muscle Activity Increases Over Time in Idiopathic REM Sleep Behavior Disorder

Study Objectives:

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by excessive electromyographic (EMG) activity due to dysfunction of the brainstem structures modulating REM sleep atonia. Patients with idiopathic RBD often develop a neurodegenerative disease, such as Parkinson disease, over the years, suggesting progression of an underlying pathologic process in the brainstem. It is unknown if the excessive EMG activity in REM sleep changes over time in patients with idiopathic RBD.

Setting:

University hospital sleep disorders center.

Participants:

Eleven patients with idiopathic RBD who were studied at baseline and after a mean follow-up of 5 years.

Interventions:

NA.

Measurements and Results:

Eleven patients with idiopathic RBD underwent polysomnography (PSG) at the moment of the diagnosis of RBD (PSG1) and after a mean follow-up of 5 years (PSG2). Tonic EMG activity in PSG1 and PSG2 was blindly quantified and compared in the mentalis muscle during REM sleep. Phasic EMG activity in PSG1 and PSG2 was blindly quantified and compared in the mentalis muscle, both biceps brachii, and both anterior tibialis during REM sleep. Patients were 9 men and 2 women with a mean age of 73.2 ± 5.4 years and a mean RBD duration of 10.7 ± 5.3 years at PSG2. In each of the 5 muscles and combination of muscles evaluated, phasic EMG activity was significantly greater in PSG2 than in PSG1 (P < 0.022 in all muscles studied). Mentalis tonic EMG activity increased from 30% to 54% (P = 0.013). No correlation was found between age of the patients and quantity of EMG activity at PSG1 (tonic; P = 0.69, phasic P = 0.89) and at PSG2 (tonic; P = 0.16, phasic; P = 0.42).

Conclusion:

Excessive tonic and phasic EMG activity during REM sleep increases over time in subjects with idiopathic RBD. This finding suggests that, in subjects with idiopathic RBD, there is an underlying progressive pathologic process damaging the brainstem structures that modulate REM sleep.

Citation:

Iranzo A; Ratti PL; Casanova-Molla J; Serradell M; Vilaseca I; Santamaria J. Excessive muscle activity increases over time in idiopathic REM sleep behavior disorder. SLEEP 2009;32(9):1149-1153.     

REM sleep behavior disorder (RBD)

Background

REM 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.

Objective

In this review article, the current knowledge regarding RBD diagnosis and treatment is presented.

Methods

A selective literature search was carried out.

Results and discussion

Although 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.

     

EMG variance during polysomnography as an assessment for REM sleep behavior disorder

STUDY OBJECTIVES: In a previous study, we validated a polysomnographic assessment for REM sleep behavior disorder (RBD). The method proved to be reliable but required slow, labor-intensive visual scoring of surface electromyogram (EMG) activity. We therefore developed a computerized metric to assess EMG variance and compared the results to those previously published for visual scoring, bed partner-rated RBD symptom scores, and clinical assessments by sleep medicine specialists. DESIGN: Retrospective validation of new computer algorithm. SETTING: Sleep research laboratory PARTICIPANTS: Twenty-three subjects: 17 with neurodegenerative disorders (9 with probable or possible RBD), and 6 controls. INTERVENTIONS: N/A METHODS: We visually scored 2 consecutive nocturnal polysomnograms for each subject. A computer algorithm calculated the variance of the chin EMG during all 3-second mini-epochs, and compared variances during REM sleep to a threshold defined by variances during quiet NREM sleep. The percentage of all REM mini-epochs with variance above this threshold created a metric, which we refer to as the supra-threshold REM EMG activity metric (STREAM) for each subject. RESULTS: The STREAM correlated highly with the visually-derived score for RBD severity (Spearman rho = 0.87, P < 0.0001). A clinical impression of probable or possible RBD was associated to a similar extent with both STREAM (Wilcoxon rank sum test, P = 0.009) and the visually-derived score (P = 0.018). An optimal STREAM cutoff identified probable or possible RBD with 100% sensitivity and 71% specificity. The RBD symptom score correlated with both STREAM (rho = 0.42, P = 0.046) and the visual score (rho = 0.42, P = 0.048). CONCLUSIONS: These results suggest that a new, automated assessment for RBD may provide as much utility as a more time-consuming manual approach.     

A two‐part,double‐blind,placebo‐controlled trial of exogenous melatonin in REM sleep behaviour disorder

Rapid eye movement (REM) sleep behaviour disorder (RBD) has been suggested to predict the development of neurodegenerative disorders. Patients with RBD are acting out dream behaviour associated with loss of normal muscle atonia of REM sleep. The aim of the present study was to confirm that exogenous melatonin improves RBD. Eight consecutively recruited males (mean age 54 years) with a polysomnographically (PSG) confirmed diagnosis of RBD were included in a two‐part, randomized, double‐blind, placebo‐controlled cross‐over study. Patients received placebo and 3 mg of melatonin daily in a cross‐over design, administered between 22:00 h and 23:00 h over a period of 4 weeks. PSG recordings were performed in all patients at baseline, at the end of Part I of the trial and at the end of Part II of the trial. Compared to baseline, melatonin significantly reduced the number of 30‐s REM sleep epochs without muscle atonia (39% versus 27%; P = 0.012), and led to a significant improvement in clinical global impression (CGI: 6.1 versus 4.6; P = 0.024). Interestingly, the number of REM sleep epochs without muscle atonia remained lower in patients who took placebo during Part II after having received melatonin in Part I (–16% compared to baseline; P = 0.043). In contrast, patients who took placebo during Part I showed improvements in REM sleep muscle atonia only during Part II (i.e. during melatonin treatment). The data suggest that melatonin might be a second useful agent besides clonazepam in the treatment of RBD.     

Quantification of electromyographic activity during REM sleep in multiple muscles in REM sleep behavior disorder

STUDY OBJECTIVES: The aim of our study was to determine which muscle or combination of muscles (either axial or limb muscles, lower or upper limb muscles, or proximal or distal limb muscles) provides the highest rates of rapid eye movement (REM) sleep phasic electromyographic (EMG) activity seen in patients with REM sleep behavior disorder (RBD). SETTING: Two university hospital sleep disorders centers. PARTICIPANTS: Seventeen patients with idiopathic RBD (n = 8) and RBD secondary to Parkinson disease (n = 9). INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: Patients underwent polysomnography, including EMG recording of 13 different muscles. Phasic EMG activity in REM sleep was quantified for each muscle separately. A mean of 1459.6 +/- 613.8 three-second REM sleep mini-epochs were scored per patient. Mean percentages of phasic EMG activity were mentalis (42 +/- 19), flexor digitorum superficialis (29 +/- 13), extensor digitorum brevis (23 +/- 12), abductor pollicis brevis (22 +/- 11), sternocleidomastoid (22 +/- 12), deltoid (19 +/- 11), biceps brachii (19 +/- 11), gastrocnemius (18 +/- 9), tibialis anterior (right, 17 +/- 12; left, 16 +/- 10), rectus femoris (left, 11 +/- 6; right, 9 +/- 6), and thoraco-lumbar paraspinal muscles (6 +/- 5). The mentalis muscle provided significantly higher rates of excessive phasic EMG activity than all other muscles but only detected 55% of all the mini-epochs with phasic EMG activity. Simultaneous recording of the mentalis, flexor digitorum superficialis, and extensor digitorum brevis muscles detected 82% of all mini-epochs containing phasic EMG activity. This combination provided higher rates of EMG activity than any other 3-muscle combination. Excessive phasic EMG activity was more frequent in distal than in proximal muscles, both in upper and lower limbs. CONCLUSION: Simultaneous recording of the mentalis, flexor digitorum superficialis, and extensor digitorum brevis muscles provided the highest rates of REM sleep phasic EMG activity in subjects with RBD.     

Sleep and periodic leg movement patterns in drug-free patients with Parkinson's disease and multiple system atrophy

STUDY OBJECTIVE: To assess and compare polygraphic sleep measures and periodic leg movement (PLM) patterns in untreated patients with mild to moderate Parkinson's disease (PD), multiple system atrophy (MSA) and healthy age-matched controls. DESIGN: Polysomnographic recordings of 2 consecutive nights were performed in 10 patients with PD (mean age 65 years, mean Hoehn and Yahr stage 2.2), 10 patients with MSA (mean age 61 years) and in a control group of 10 healthy subjects (mean age 64 years). All patients and controls were free of antiparkinsonian medication and other centrally active drugs for 2 weeks prior to polysomnography. SETTING: NA. PATIENTS OR PARTICIPANTS: NA. INTERVENTIONS: NA. RESULTS: Sleep measures for the second night showed a significantly lower total sleep time, sleep efficiency and sleep period time in PD and MSA patients compared to healthy controls. PLM-indices during sleep and wakefulness were significantly higher in PD, but not in MSA patients compared to controls. Five patients with PD and 7 patients with MSA, but no control subject, showed abnormal rapid eye movement (REM) sleep features (i.e., REM sleep without atonia or behavioral manifestations typical for REM sleep behavior disorder). CONCLUSIONS: Sleep disruption and increased motor activity during REM and non REM sleep are a frequent finding in PD and MSA. An increased PLM index in untreated PD patients may be due to a dopaminergic deficit and is probably not associated with dopaminergic treatment.     

Serotonergic antidepressants are associated with REM sleep without atonia

STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is generally observed in older men and in individuals with specific neurologic diseases. There are case reports of RBD in individuals taking serotonergic antidepressants. Our objective was to assess electromyogram (EMG) activity during REM sleep in individuals taking serotonergic antidepressants and in a matched control group not on such medication. DESIGN: Chart review of clinical and polysomnographic data. SETTING: Sleep laboratory affiliated with a general hospital. PARTICIPANTS: 15 subjects taking a serotonergic antidepressant and 15 age-matched individuals not on such medication. MEASUREMENTS: Submental and anterior tibialis tonic and phasic EMG activity during REM sleep, REM latency, time in REM, apnea-hypopnea index, periodic leg movements of sleep index, and sleep-architecture measures. RESULTS: Tonic, but not phasic, submental EMG activity during REM sleep was significantly more common in the antidepressant-treated group than in the control group (P < .02). Tonic REM submental EMG activity correlated with REM latency (r = .42, P = .02) and inversely with REM time (r = -.36, P = .05). Subject age correlated with tonic REM submental EMG activity (r = .58, P = .02) in the antidepressant group There were also trends for more phasic activity in the anterior tibialis (P = .09) and submental (P = .07) EMG in REM sleep in the antidepressant group than in the control group. CONCLUSIONS: Subjects taking serotonergic antidepressants had more EMG activity in the submental lead during REM sleep than did controls. This correlated with measures of REM suppression and age. Individuals taking such medications may be at increased risk of developing REM sleep behavior disorder, particularly with increasing age.     

Cardiac autonomic regulation during sleep in idiopathic REM sleep behavior disorder

OBJECTIVE: To assess cardiac autonomic and respiratory changes from stage 2 non-rapid eye movement sleep (NREM) to rapid eye movement (REM) sleep in subjects with idiopathic REM sleep behavior disorder (RBD) and controls. We tested the hypothesis that REM-related cardiorespiratory activation is altered in subjects with RBD. DESIGN: Retrospective case-control study. SETTING: University hospital-based sleep research laboratory. PATIENTS: Ten subjects with idiopathic RBD (2 women, mean age 63.4 +/- 6.2 years) and 10 sex- and age-matched controls (mean age 63.9 +/- 6.3 years). INTERVENTION: One-night polysomnography was used to assess R-R variability during NREM and REM sleep. MEASUREMENTS AND RESULTS: Spectral analysis of R-R interval and respiration were performed. Mean R-R interval, low-frequency (LF) and high-frequency (HF) components in both absolute and normalized units (LFnu and HFnu), and the LF/HF ratio were obtained from 5-minute electrocardiogram segments selected during NREM and REM sleep under stable conditions (stable breathing pattern, no microarousals or leg movements). Respiratory frequency was also assessed. Values obtained were then averaged for each stage and analyzed by 2 x 2 analysis of variance with group (RBD subjects and controls) as factor and state (NREM and REM) as repeated measures. RR interval, HF, and HFnu components decreased from NREM to REM in controls but did not change in RBD subjects (Interaction P < 0.05). LFnu (interaction P < 0. 001), LF/HF (interaction P < 0. 001), and respiratory frequency (interaction P < 0. 05) increased from NREM to REM sleep in controls but remained stable in RBD subjects. CONCLUSION: REM-related cardiac and respiratory responses are absent in subjects with idiopathic RBD.