Autonomic control of the cardiovascular system during sleep in normal subjects

The autonomic control of heart rate and blood pressure during sleep is controversial: although it has been reported that vagal activity is more often lower in rapid eye movement sleep (REM) than in other stages of sleep (non-REM, NREM), the opposite has also been described. Initially, it was reported that baroreflex sensitivity (BRS) increases during sleep (REM and NREM), but in later studies, this was only partially confirmed. We therefore studied autonomic control of the cardiovascular (CV) system during sleep in 12 normal adults. The spectral components of the heart rate R-R interval, blood pressure (BP), and BRS were computed at low (LF) and actual breathing frequency (high frequency, HF). Analysis of sleep stage and a cycle-by-cycle stage II analysis were performed. CV variability is affected largely by sleep-stage and sleep-cycle organisation: NREM and the last cycle exhibit the greatest vagal activity and the lowest sympathetic activity. BRS estimation for both the LF and HF bands confirmed previous results obtained by pharmacological and spontaneous slope methods: BRS is greater during sleep than during nocturnal wake periods, and further increased in REM. BRS is frequency dependent: in NREM, the higher value of HF BRS compared to LF BRS favours the HF control of BP variability, whereas higher BRS HF and LF components contribute to the strongest control in REM. BRS variability exhibits no significant pattern during the night. Our results suggest that both sleep-cycle organisation and BRS estimation in the LF and HF bands should be considered in sleep studies of autonomic CV control. Electronic Publication     

A quantitative statistical analysis of the submentalis muscle EMG amplitude during sleep in normal controls and patients with REM sleep behavior disorder

The aim of this study was to evaluate quantitatively the amplitude of the submentalis muscle EMG activity during sleep in controls and in patients with idiopathic REM sleep behavior disorder (RBD) or with RBD and multiple system atrophy (MSA). We recruited 21 patients with idiopathic RBD, 10 with MSA, 10 age-matched and 24 young normal controls. The average amplitude of the rectified submentalis muscle EMG signal was used for the assessment of atonia and a Sleep Atonia Index was developed; moreover, also chin muscle activations were detected and their duration and interval analyzed. The Sleep Atonia Index was able to distinguish clearly REM from NREM sleep in normal controls with values very close to 1 in young normal subjects and only slightly (but significantly) lower in old controls. Idiopathic RBD patients showed a further significant decrease of this index; MSA patients showed the lowest values of REM Sleep Atonia Index, which were very well distinguishable from those of normal controls and of idiopathic RBD patients. The distribution of the duration of chin activations was monomodal in all groups, with idiopathic RBD patients showing the highest levels. This study is a really quantitative attempt to provide practical indices for the objective evaluation of EMG atonia during REM sleep and of EMG activations. Our proposed Sleep Atonia Index can have a practical application in the clinical evaluations of patients and represents an additional useful parameters to be used in conjunction with the other criteria for the diagnosis of this sleep motor disorder.     

Interpretation of normalized spectral heart rate variability indices in sleep research: a critical review

The normalized spectral heart rate variability (HRV) measures low-frequency (LF)nu and high-frequency (HF)nu are frequently used in contemporary sleep research studies to quantify modulation of the sympathetic and parasympathetic branches of the autonomic nervous system. The purpose of this tutorial and methodologic critique is to concisely demonstrate the structural algebraic redundancy inherent in the normalized spectral HRV measures with respect to each other, and also with respect to the well-known HRV index of sympathovagal balance, LF:HF ratio. The statistical problems and interpretational paradoxes related to the mathematical definitions of LFnu and HFnu are briefly outlined. Examples of use of normalized spectral HRV measures in recent articles from the sleep-relevant research literature are critically reviewed. LFnu, HFnu, and LF:HF ratio should be considered equivalent carriers of information about sympathovagal balance.

Citation:     

Interaction effect of obstructive sleep apnea and periodic limb movements during sleep on heart rate variability

We aimed at assessing cardiac autonomic function by heart rate variability during sleep in patients with obstructive sleep apnea and periodic limb movements during sleep, and to compare it with that of patients with obstructive sleep apnea only, periodic limb movements during sleep only, and controls. We also aimed at investigating the interaction effect between apnea–hypopnea index and periodic limb movement index on heart rate variability. Four groups of patients (n = 42 each, total = 168) were identified based on the presence/absence of obstructive sleep apnea and periodic limb movements during sleep: + obstructive sleep apnea/? periodic limb movements during sleep (5 ≤ apnea–hypopnea index < 30 events per hr), ? obstructive sleep apnea/+ periodic limb movements during sleep (periodic limb movement index > 15 events per hr), + obstructive sleep apnea/+ periodic limb movements during sleep, ? obstructive sleep apnea/? periodic limb movements during sleep (controls). All groups were matched for age, sex and body mass index. Time‐ and frequency‐domain heart rate variability measures were calculated over 5‐min periods of stable stage 2 non‐rapid eye movement sleep. In patients with both obstructive sleep apnea and periodic limb movements during sleep, LFnu and LF/HF ratio were higher than in those with obstructive sleep apnea only, periodic limb movements during sleep only, and controls, while HFnu was the lowest among the four groups. LFnu, HFnu and LF/HF ratio were significantly and independently associated with minimal oxygen saturation in the + obstructive sleep apnea/+ periodic limb movements during sleep group. There was a significant interaction effect between apnea–hypopnea index and periodic limb movement index on LF/HF ratio (p = 0.038) in patients with obstructive sleep apnea. Patients with elevated apnea–hypopnea index and elevated periodic limb movement index exhibited higher sympathovagal balance compared with those with high apnea–hypopnea index and low periodic limb movement index, and compared with those with low apnea–hypopnea index (regardless of periodic limb movement index). Increased sympathetic activation and decreased parasympathetic control appear to be related to the severity of oxygen desaturation. Apnea–hypopnea index and periodic limb movement index had interactive effects on increased sympathovagal balance in patients with obstructive sleep apnea.     

Age-related changes in cardiac autonomic control during sleep

Aging is commonly associated with decreased sleep quality and increased periodic breathing (PB) that can influence heart rate variability (HRV). Cardiac autonomic control, as inferred from HRV analysis, was determined, taking into account the sleep quality and breathing patterns. Two groups of 12 young (21.1 +/- 0.8 years) and 12 older (64.9 +/- 1.9 years) volunteers underwent electroencephalographic, cardiac, and respiratory recordings during one experimental night. Time and frequency domain indices of HRV were calculated in 5-min segments, together with electroencephalographic and respiratory power spectra. In the elderly, large R-R oscillations in the very-low frequency (VLF) range emerged, that reflected the frequency of PB observed in 18% of the sleep time. PB occurred more frequently during rapid eye movement sleep (REM) sleep and caused a significant (P < 0.02) increase in the standard deviation of normal R-R intervals (SDNN) and absolute low-frequency (LF) power. With normal respiratory patterns, SDNN, absolute VLF, LF, and high frequency (HF) power fell during each sleep stage (P < 0.01) compared with young subjects, with no significant sleep-stage dependent variations. An overall decrease (P < 0.01) in normalized HF/(LF + HF) was observed in the elderly, suggesting a predominant loss of parasympathetic activity which may be related to decreased slow-wave sleep duration. These results indicate that two distinct breathing features, implying different levels of autonomic drive to the heart, influence HRV in the elderly during sleep. The breathing pattern must be considered to correctly interpret HRV in the elderly.     

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.     

Cardiac autonomic function during sleep in psychogenic and organic erectile dysfunction

The present study investigated the sympathetic/parasympathetic balance during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in patients with psychogenic and organic erectile dysfunction. The cardiac autonomic balance was assessed from the power of the low frequency (LF) and high frequency (HF) spectral components of heart-rate variability in 11 patients with psychogenic erectile dysfunction and 11 patients with organic erectile dysfunction as determined by monitoring sleep-related erections. Spectral analysis of heart-rate variability was calculated for at least four successive 4-min epochs of electrocardiogram recordings during NREM sleep and for all available 4-min epochs during REM sleep. Statistical analysis revealed that organic patients had a significantly higher LF/HF ratio (P < 0.01) during both stages of sleep, which resulted from a significantly lower power in the HF component (P < 0.004) and higher power in the LF component (P < 0.01) in these patients, in both REM and NREM sleep stages. These results demonstrate that patients complaining of daytime sexual dysfunction and found by sleep-related erection monitoring to suffer from organic erectile dysfunction, have altered cardiac autonomic balance during both stages of sleep.     

Effect of upper airway surgery on heart rate variability in patients with obstructive sleep apnoea syndrome

To determine whether surgery influences cardiovascular autonomic modulation in obstructive sleep apnoea syndrome (OSAS), the present study was performed to evaluate the effect of upper airway (UA) surgery on heart rate variability (HRV) using frequency domain analysis for patient groups who have had either successful or unsuccessful surgery. We compared body mass index (BMI), polysomnographic [apnoea index (AI), apnoea-hypopnoea index (AHI), minimum SaO(2)] and HRV [very low frequency (VLF) power, low frequency (LF) power, high frequency (HF) power, HF/LF ratio, LFnu = LF/(LF + HF), HFnu = HF/(LF + HF)] parameters between the unsuccessful (n = 14) and successful (n = 22) surgical groups before and after UA surgery. Significant changes were observed for the successful patient group with respect to mean AI (from 29.1 ± 21.3 to 2.0 ± 3.2 events h(-1), P < 0.001), AHI (from 38.6 ± 20.0 to 5.6 ± 5.1 events h(-1), P < 0.001), minimum SaO(2) (from 73.3 ± 12.7 to 86.3 ± 6.5%, P < 0.001), VLF power (from 25599 ± 12906 to 20014 ± 9839 ms(2), P = 0.013), LF power (from 17293 ± 7278 to 14155 ± 4980 ms(2), P = 0.016), LFnu (from 0.700 ± 0.104 to 0.646 ± 0.128, P = 0.031) and HFnu (from 0.300 ± 0.104 to 0.354 ± 0.128, P = 0.031); however, mean BMI, HF power and LF/HF ratio did not change significantly after UA surgery. No significant changes were observed in the unsuccessful surgical group. Successful UA surgery may improve cardiac sympathetic and parasympathetic modulation in patients with OSAS.     

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.     

Heart rate variability during waking and sleep in healthy males and females

STUDY OBJECTIVES: The study goal was to investigate autonomic activity with heart rate variability analysis during different sleep stages in males and females. DESIGN: The study utilized a 2 Groups (males, females) x 4 States (waking, stage 2 sleep, stage 4 sleep, rapid-eye movement sleep) mixed design with one repeated, within-subjects factor (i.e., state). SETTING: The study was carried out in the sleep laboratory of the Thomas N. Lynn Institute for Healthcare Research. PARTICIPANTS: Twenty-four healthy adults (fourteen females and ten males). INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: All participants underwent polysomnographic monitoring and electrocardiogram recordings during pre-sleep waking and one night of sleep. Fifteen-minute segments of beat-to-beat heart rate intervals during waking, stage 2 sleep, stage 4 sleep, and REM sleep were subjected to spectral analysis. Compared to NREM sleep, REM sleep was associated with decreased high frequency (HF) band power, and significantly increased low frequency (LF) to (HF) ratio. Compared to females, males showed significantly elevated LF/HF ratio during REM sleep. Males also demonstrated significantly decreased HF band power during waking when compared to females. No significant sleep- or gender-related changes in LF band power were found. CONCLUSIONS: The results confirmed changes in autonomic activity from waking to sleep, with marked differences between NREM and REM sleep. These changes were primarily due to stage-related alterations in vagal tone. REM sleep was characterized by increased sympathetic dominance, secondary to vagal withdrawal. The data also suggested gender differences in autonomic functioning during waking and sleep, with decreased vagal tone during waking and increased sympathetic dominance during REM sleep in the males.     

The association between daytime sleepiness and sleep-disordered breathing in NREM and REM sleep

BACKGROUND: Daytime sleepiness is common in patients with sleep-disordered breathing. Although respiratory events during sleep are associated with the occurrence of daytime sleepiness, the differential impact of these events during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep on daytime sleepiness has not been well characterized. STUDY OBJECTIVES: To determine the effect of respiratory events during REM sleep and NREM sleep on daytime sleepiness, as assessed by the multiple sleep latency test (MSLT). DESIGN: Cross-sectional study. SETTING: University-based sleep disorders laboratory. PARTICIPANTS: Patients referred for polysomnography and daytime MSLT (n=1,821). INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: The study sample was initially divided into quartiles based on the level of the apnea-hypopnea index (AHI) during NREM sleep. Within the first NREM-AHI quartile (NREM-AHI < 8.3 events/hr), the association between REM-related respiratory events and daytime sleepiness was examined using the method of Kaplan-Meier analysis and Cox proportional hazards regression. After adjusting for age, gender, body mass index, and the duration of NREM and REM sleep, REM-AHI was not associated with daytime sleepiness (Relative Risk: 1.01; 95%CI: 0.94-1.10). Similarly, no significant association was observed between REM-AHI and the MSLT in patients within the second through fourth NREM-AHI quartiles. In contrast, increasing severity of disordered breathing during NREM sleep was associated with daytime sleepiness. For a 10-point increase in NREM-AHI, the adjusted relative risks for daytime sleepiness in the second through fourth NREM-AHI quartile were 1.21 (95%CI: 1.01-1.46), 1.20 (95%CI: 1.05-1.37), and 1.10 (95%CI: 1.04-1.16), respectively. CONCLUSION: Sleep-disordered breathing during NREM sleep, but not REM sleep, is associated with increased risk of daytime sleepiness.     

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.     

Relationship between electroencephalogram slow-wave magnitude and heart rate variability during sleep in humans

To explore whether depth of sleep is related to changes in autonomic control, continuous power-spectral analysis of the electroencephalogram (EEG) and heart rate variability (HRV) was performed in ten normal subjects during nocturnal sleep. Quiet sleep (QS) was associated with an increase in high-frequency power (HF) of HRV (0.15-0.4 Hz) but a decrease in low-frequency power (LF) (0.04-0.15 Hz) to HF ratio (LF/HF) compared with awakening. During QS, LF/HF was significantly and negatively correlated with delta power of EEG (0.5-4.0 Hz), whereas mean R-R interval and HF were not. We conclude that during QS, cardiac sympathetic regulation is negatively related to the depth of sleep, although vagal regulation is not. Our methodology offers a quantitative analysis to study the interaction between cerebral cortical and autonomic functions.     

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-courses in renin and blood pressure during sleep in humans

We previously described a strong concordance between nocturnal oscillations in plasma renin activity (PRA) and the rapid eye movement (REM) and non-REM (NREM) sleep cycles, but the mechanisms inducing PRA oscillations remain to be identified. This study was designed to examine whether they are linked to sleep stage-related changes in arterial blood pressure (ABP). Analysis of sleep electroencephalographic (EEG) activity in the delta frequency band, intra-arterial pressure, and PRA measured every 10 min was performed in eight healthy subjects. Simultaneously, the ratio of low frequency power to low frequency power + high frequency power [LF/(LF + HF)] was calculated using spectral analysis of R--R intervals. The cascade of physiological events that led to increased renin release during NREM sleep could be characterized. First, the LF/(LF + HF) ratio significantly (P < 10(-4) decreased, indicating a reduction in sympathetic tone, concomitantly to a significant (P < 10(- 3) decrease in mean arterial pressure (MAP). Delta wave activity increased (P < 10(-4) 10-20 min later and was associated with a lag of 0-10 min with a significant rise in PRA (P < 10(-4) . Rapid eye movement sleep was characterized by a significant increase (P < 10(-4) in the LF/(LF + HF) ratio and a decrease (P < 10(-4) in delta wave activity and PRA, whereas MAP levels were highly variable. Overnight cross-correlation analysis revealed that MAP was inversely correlated with delta wave activity and with PRA (P < 0.01 in all subjects but one). These results suggest that pressure-dependent mechanisms elicit the nocturnal PRA oscillations rather than common central processes controlling both the generation of slow waves and the release of renin from the kidney.     

Uterine activity during sleep

REM-related increases in uterine activity were found in 10 healthy young adult volunteer subjects. Contraction baseline pressures were elevated compared with NREM sleep, stage 2 sleep, stages 3 and 4 slow wave sleep (SWS), and stage 0. Contraction amplitudes during REM sleep were greater than those during SWS and stage 0, while contraction rates differed only between REM sleep and SWS. The results strongly indicated a cycle of genital activity in women that parallels the penile erection cycle in men. The implications of this finding and suggestions for future research are discussed.     

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.     

Increased muscle activity during rapid eye movement sleep correlates with decrease of striatal presynaptic dopamine transporters. IPT and IBZM SPECT imaging in subclinical and clinically manifest idiopathic REM sleep behavior disorder,Parkinson's disease,and controls

STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by complex behavior during REM sleep. The etiology of this disorder is still unknown, but a recent study showed that RBD precedes symptoms of Parkinson disease (PD) by several years, and in a previous study, we found reduced striatal dopamine transporters in idiopathic clinically manifest RBD. DESIGN: Hypothesizing that subclinical RBD shows a less severe reduction of striatal dopamine transporters than clinically manifest RBD, we studied striatal postsynaptic dopamine D2-receptors with (S)-2hydroxy-3iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide labeled with iodine 123 (IBZM) and the striatal presynaptic dopamine transporters with (N)-(3-iodopropene-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane labeled with iodine 123 (IPT) using single-photon emission computed tomography (SPECT) in the following groups: 8 patients with idiopathic subclinical RBD, 8 patients with idiopathic clinically manifest RBD, 11 controls, and 8 patients with PD stage Hoehn & Yahr I. RESULTS: The IPT uptake was highest in controls. There was a significant decrease in IPT uptake from controls to patients with subclinical RBD, from patients with subclinical RBD to clinically manifest RBD, and from patients with clinically manifest RBD to patients with PD (controls: right = 4.07 +/- 0.29, left = 4.07 +/- 0.30; subclinical RBD: right = 3.56 +/- 0.21, left = 3.55 +/- 0.25; clinically manifest RBD: right = 3.18 +/- 0.43, left = 3.2 +/- 0.43; PD: ipsilateral to the clinically affected body side = 3.25 +/- 0.35, contralateral to the clinically affected body side = 2.51 +/- 0.28). Muscle activity during REM sleep lasting persistently longer than 0.5 seconds was independently associated with reduction of striatal dopamine transporters (P = 0.001). The IBZM uptake was not significantly different between the groups. CONCLUSIONS: This study suggests that there is a continuum of reduced striatal dopamine transporters involved in the pathophysiologic mechanisms causing increased muscle activity during REM sleep in patients with subclinical RBD.     

Changes in Cardiac Variability after REM Sleep Deprivation in Recurrent Nightmares

Study Objectives:

To assess whether dysfunctional autonomic regulation during REM sleep as indexed by heart rate variability (HRV) is a pathophysiological factor in frequent nightmares (NMs).

Design:

Monitoring with polysomnography (PSG) and electrocardiography (ECG) for 3 consecutive nights: Night 1 (N1), adaptation night; N2, administration of partial REM sleep deprivation; N3, recovery night. Differences between NM and control (CTL) groups assessed for ECG measures drawn from wakefulness, REM sleep, and Stage 2 sleep on both N1 and N3.

Setting:

Hospital-based sleep laboratory

Participants:

Sixteen subjects with frequent NMs ( ≥ 1 NM/week; mean age = 26.1 ± 8.7 years) but no other medical or psychiatric disorders and 11 healthy comparison subjects ( < 1 NM/month; mean age = 27.1±5.6 years).

Results:

NM and CTL groups differed on 2 REM sleep measures only on N1; the NM group had longer REM latencies and REM/NREM cycle durations than did the CTL group. No differences were found on time domain and absolute frequency domain ECG measures for either N1 or N3. However, altered HRV for the NM group was suggested by significantly higher LFnu, lower HFnu, and higher LF/HF ratio than for the CTL group.

Conclusions:

Results are consistent with a higher than normal sympathetic drive among NM subjects which is unmasked by high REM sleep propensity. Results also support a growing literature linking anxiety disorders of several types (panic disorder, posttraumatic stress disorder (PTSD), generalized anxiety disorder) to altered HR variability.

Citation:

Nielsen T; Paquette T; Solomonova E; Lara-Carrasco J; Colombo R; Lanfranchi P. Changes in cardiac variability after rem sleep deprivation in recurrent nightmares. SLEEP 2010;33(1):113-122.     

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.