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.     

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.

     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Brainstem mechanisms of paradoxical (REM) sleep generation

Paradoxical sleep (PS) is characterized by EEG activation with a disappearance of muscle tone and the occurrence of rapid eye movements (REM) in contrast to slow-wave sleep (SWS, also known as non-REM sleep) identified by the presence of delta waves. Soon after the discovery of PS, it was demonstrated that the structures necessary and sufficient for its genesis are restricted to the brainstem. We review here recent results indicating that brainstem glutamatergic and GABAergic, rather than cholinergic and monoaminergic, neurons play a key role in the genesis of PS. We hypothesize that the entrance to PS from SWS is due to the activation of PS-on glutamatergic neurons localized in the pontine sublaterodorsal tegmental nucleus. The activation of these neurons would be due to a permanent glutamatergic input arising from the lateral and ventrolateral periaqueductal gray (vlPAG) and the removal at the onset of PS of a GABAergic inhibition present during W and SWS. Such inhibition would be coming from PS-off GABAergic neurons localized in the vlPAG and the adjacent deep mesencephalic reticular nucleus. The cessation of activity of these PS-off GABAergic neurons at the onset and during PS would be due to direct projections from intermingled GABAergic PS-on neurons. Activation of PS would depend on the reciprocal interactions between the GABAergic PS-on and PS-off neurons, intrinsic cellular and molecular events, and integration of multiple physiological parameters.     

Quantitative proton magnetic resonance spectroscopy of the bilateral frontal lobes in patients with bipolar disorder.

BACKGROUND: Using 31P and 1H magnetic resonance spectroscopy (MRS) we previously reported that phosphocreatine was decreased in the left frontal lobe and choline-containing compounds were increased in the basal ganglia in the depressive state in patients with bipolar disorder. We applied quantitative 1H-MRS for further characterization of biochemical alteration in the frontal lobes of bipolar patients. METHODS: Twenty-three bipolar patients and 20 normal controls were examined by 1H-MRS with a 1.5T MR system. All patients were examined in the euthymic state, and eight patients were also examined in the depressive state. Volumes of interest of 2.5 x 2.5 x 2.5 cm were selected in the left and right frontal lobes. Absolute concentrations of N-acetyl-1-aspartate, creatine plus phosphocreatine, and choline-containing compounds were calculated from each metabolite peak. RESULTS: Creatine concentration in the left frontal lobe in bipolar patients in the depressive state was significantly lower than that in the euthymic state. Creatine concentration in the right frontal lobe in the male patients was significantly higher than that in the female patients and a similar trend was also found in the control subjects. CONCLUSIONS: We found a state-dependent change of creatine metabolism in the left frontal lobe of bipolar patients. The present results are compatible with our previous report of decreased phosphocreatine measured by 31P-MRS in the left frontal lobe in bipolar disorder. We also found an effect of gender on the creatine concentration. There may be a gender difference in creatine transport function into the brain.