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.     

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.     

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.     

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.     

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.     

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.     

Validation of a polysomnographic score for REM sleep behavior disorder

STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) was described more than 2 decades ago, but only 1 report on 5 patients and 5 normal subjects has tested the effectiveness of a method by which relevant polysomnographic findings can be quantified. We sought to validate this method in a larger sample of patients and control subjects. DESIGN: Cross-sectional. SETTING: Academic hospital. INTERVENTIONS: A clinician interviewed 17 patients at risk for RBD secondary to neurodegenerative disorders and 6 controls to assess whether RBD was present by history. Bed partners completed a questionnaire that quantified RBD symptom severity. From 2 consecutive nocturnal studies in each patient, 2 different polysomnographic RBD scores were generated: the percentage of 30-second REM epochs with at least 15 seconds of tonically maintained electromyographic activity, and the percentage of 3-second REM mini-epochs that contained phasic electromyographic bursts. MEASUREMENTS AND RESULTS: The tonic and phasic measures, combined together, were higher in patients with clinical determinations of probable or possible RBD (n=9) than in patients judged unlikely to have RBD (n=4, P = .023). The overall polysomnographic measure correlated with the symptom scores (rho = 0.42, P = .048). Specific polysomnographic RBD measures on night 1 correlated highly with those on night 2 (rho > 0.70, P < .0001). CONCLUSIONS: This quantitative method to assess the severity of RBD polysomnographic features appears to be both valid and reliable in patients at risk for RBD because of neurodegenerative disorders.     

Time structure analysis of leg movements during sleep in REM sleep behavior disorder

STUDY OBJECTIVES: To compare the time structure of leg movements (LM) during sleep of patients with rapid eye movement (REM) sleep behavior disorder (RBD) with that of patients with restless legs syndrome (RLS) or control subjects. DESIGN: The polysomnographically recorded tibialis anterior activity during sleep was analyzed by means of a new approach able to consider duration, intermovement interval, sleep stage and time of night distribution, and periodicity. PATIENTS AND PARTICIPANTS: Twenty patients with idiopathic RBD, 37 with idiopathic RLS and 14 age-matched control subjects were consecutively recruited. MEASUREMENTS AND RESULTS: Most patients with RBD (85%) presented periodic leg movements during sleep (PLMS). PLMS occurred more frequently during non-REM sleep in patients with RLS and during REM sleep in patients with RBD. PLMS were shorter in duration, less often bilateral, and with a higher intermovement interval in patients with RBD compared to those with RLS. The number of PLMS decreased across the night in patients with RBD and in those with RLS, but not in control subjects. In all subjects, LM periodicity clearly depended on sleep state, with higher values during non-REM than during REM sleep. Patients with RBD showed a lower LM periodicity, compared with patients with RLS, in each of the sleep states. CONCLUSIONS: Significant differences, together with some similarities in LM time structure, were observed between patients with RBD and those with RLS; for this reason, our approach seems to indicate that their phenotype might be dependent on 2 factors: disease and sleep stage.     

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.     

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.     

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.     

REM sleep behavior disorder and narcoleptic features in anti-Ma2-associated encephalitis

A 69-year-old man with anti-Ma2 paraneoplastic encephalitis presented with subacute onset of severe hypersomnia, memory loss, parkinsonism, and gaze palsy. A brain magnetic resonance imaging study showed bilateral damage in the dorsolateral midbrain, amygdala, and paramedian thalami. Videopolysomnography disclosed rapid eye movement (REM) sleep behavior disorder, and a Multiple Sleep Latency Test showed a mean sleep latency of 7 minutes and 4 sleep-onset REM periods. The level of hypocretin-1 in the cerebrospinal fluid was low (49 pg/mL). This observation illustrates that REM sleep behavior disorder and narcoleptic features are 2 REM-sleep abnormalities that (1) may share the same autoimmune-mediated origin affecting the brainstem, limbic, and diencephalic structures and (2) may occur in the setting of the paraneoplastic anti-Ma2-associated encephalitis.     

Interictal, potentially misleading, epileptiform EEG abnormalities in REM sleep behavior disorder

STUDY OBJECTIVES: To examine the implications of interictal epileptiform abnormalities (IEA) in idiopathic REM-sleep behavior disorder (RBD), particularly the risk of misdiagnosing RBD episodes as epileptic nocturnal seizures. DESIGN: Observational analysis and review. SETTING: Tertiary sleep center. PATIENTS: Thirty patients (28 men; mean age 66.3 +/- 7.5 years) referred to our sleep unit for a definite diagnosis of nocturnal sleep-related motor and behavioral paroxysmal episodes. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All the patients were found to be affected by idiopathic RBD according to standard clinical and videopolysomnographic criteria. IEA(sporadic, fronto-temporal sharp-waves) were detected in 8 subjects (26.6%) during routine electroencephalogram and/or nocturnal in-lab videopolysomnography with extended EEG montages. In 2 of these 8 patients, IEA occurred during REM sleep. CONCLUSIONS: When only the clinical history is considered, RBD episodes may be confused with nocturnal epileptic focal seizures. The presence of IEA either on routine awake electroencephalograms, or during sleep electroencephalograms, may add support for a diagnosis of epileptic nocturnal seizures. Our data show that IEA may occur in wake and sleep (non rapid eye movement and rapid eye movement sleep) tracings of subjects with episodes of idiopathic RBD. However full-night extended electroencephalogram montages and polysomnography recording of an episode proved useful in establishing a definite diagnosis of RBD in these potentially misleading cases. Comparison of the patients' demographic data and RBD features revealed no differences between RBD with IEA and without IEA. On this basis-and given that these abnormalities have also been described in elderly people with wakefulness-related nonepileptic disorders-IEA in RBD could simply be interpreted as a nonspecific phenomenon, probably related to brain aging.