Rapid Eye Movement Sleep In Patients Research Articles

Cluster Headache Characteristics and the Severity of Obstructive Sleep Apnea: Insights from Polysomnography Analysis

Purpose: Cluster headache (CH) is characterized by circadian rhythmicity of the attacks, and it is known to respond exceptionally well to oxygen therapy. Furthermore, obstructive sleep apnea (OSA) frequently co-occurs with CH, and both conditions may be parallel outcomes of hypothalamic dysfunction rather than being causally related. The aim of this study was to analyze the association between CH characteristics and polysomnographic factors stratified by the severity of OSA in patients diagnosed with CH and OSA.Methods: We retrospectively analyzed the data of OSA patients with CH who were enrolled in the Korean Cluster Headache Registry and underwent polysomnography due to clinical suspicion of OSA. Basic demographic data, headache-related parameters, and polysomnographic parameters were analyzed according to the severity of OSA (apnea-hypopnea index: <15 or ≥15 per hour).Results: Twelve CH patients with OSA were evaluated. The onset age of CH was higher (38.5 years vs. 19.0 years, p=0.010), and the maximal duration of cluster bouts was longer (156.5 days vs. 47.0 days, p=0.037) in the moderate-to-severe OSA group than in the mild OSA group. Unlike other polysomnographic parameters, the apnea-hypopnea index and respiratory arousal index during rapid eye movement (REM) sleep were comparable across different OSA severity levels.Conclusion: The onset age and duration of cluster bouts were associated with the severity of OSA in CH patients. Additionally, the relatively high susceptibility to hypoxia during REM sleep in patients with mild OSA implies that interventions may be potentially advantageous, even in CH patients with mild OSA.

Focal epilepsy impacts rapid eye movement sleep microstructure.

Whereas there is plenty of evidence on the influence of epileptic activity on non-rapid eye movement (NREM) sleep macro- and micro-structure, data on the impact of epilepsy on rapid eye movement (REM) sleep remains sparse. Using high-density electroencephalography (HD-EEG), we assessed global and focal disturbances of sawtooth waves (STW) as cortically generated sleep oscillations of REM sleep in patients with focal epilepsy. Twenty-two patients with drug-resistant focal epilepsy (13 females; mean age, 32.6 ± 10.7 years; 12 temporal lobe epilepsy) and 12 healthy controls (3 females; 24.0 ± 3.2 years) underwent combined overnight HD-EEG and polysomnography. STW rate, duration, frequency, power, spatial extent, IED rates and sleep homeostatic properties were analyzed. STW rate and duration were reduced in patients with focal epilepsy compared to healthy controls (rate: 0.64/min ± 0.46 vs. 1.12/min ± 0.41, p = .005, d = -0.98; duration: 3.60 s ± 0.76 vs. 4.57 ± 1.00, p = .003, d = -1.01). Not surprisingly given the fronto-central maximum of STW, the reductions were driven by extratemporal lobe epilepsy patients (rate: 0.45/min ± 0.31 vs. 1.12/min ± 0.41, p = .0004, d = -1.35; duration: 3.49 s ± 0.92 vs. 4.57 ± 1.00, p = .017, d = -0.99) and were more pronounced in the first vs. the last sleep cycle (rate first cycle patients vs. controls: 0.60/min ± 0.49 vs. 1.10/min ± 0.55, p = .016, d = -0.90, rate last cycle patients vs. controls: 0.67/min ± 0.51 vs. 0.99/min ± 0.49, p = .11, d = -0.62; duration first cycle patients vs. controls: 3.60s ± 0.76 vs. 4.57 ± 1.00, p = .003, d = -1.01, duration last cycle patients vs. controls: 3.66s ± 0.84 vs. 4.51 ± 1.26, p = .039, d = -0.80). There was no regional decrease of STWs in the region with the epileptic focus vs. the contralateral side (all p > .05). Patients with focal epilepsy and in particular extratemporal lobe epilepsy show a global reduction of STW activity in REM sleep. This may suggest that epilepsy impacts cortically generated sleep oscillations even in REM sleep when epileptic activity is low.

Rapid eye movement sleep in adolescent females with borderline personality disorder

Objective: The aim of the study was detecting Rapid Eye Movement (REM) sleep abnormalities in adolescent females with borderline personality disorder (BPD). Method: A case control study included a convenient sample of 30 adolescent females with BPD compared to 30 matched healthy controls. Pittsburgh Sleep Quality Index and an overnight sleep lab polysomnographic study were applied to both groups to assess sleep. Results: Patients with BPD were subjectively dissatisfied with the quality of sleep compared to controls (p<0.001). Abnormalities in REM sleep in patients when compared to controls were higher REM percent (p=0.001), shorter REM latency (p=0.001), higher REM density (p=0.001) and higher number of REM periods in the first half of the night (p=0.000). Conclusion: REM sleep abnormalities are found in adolescent patients with BPD, which may be considered as trait markers for BPD.

Targeted Memory Reactivation During REM Sleep in Patients With Social Anxiety Disorder.

BackgroundSocial anxiety disorder (SAD) is characterized by a significant amount of fear when confronted to social situations. Exposure therapy, which is based on fear extinction, does not often lead to full remission. Here, based on evidence showing that rapid eye movement (REM) sleep promotes the consolidation of extinction memory, we used targeted memory reactivation (TMR) during REM sleep to enhance extinction learning in SAD.MethodsForty-eight subjects with SAD were randomly assigned to two groups: control or TMR group. All patients had two successive exposure therapy sessions in a virtual reality (VR) environment, where they were asked to give a public talk in front of a virtual jury. At the end of each session, and only in the TMR group (N = 24), a sound was paired to the positive feedback phase of therapy (i.e., approval of their performance), which represented the memory to be strengthened during REM sleep. All participants slept at home with a wearable headband device which automatically identified sleep stages and administered the sound during REM sleep. Participants' anxiety level was assessed using measures of parasympathetic (root mean square of successive differences between normal heartbeats, RMSSD) and sympathetic (non-specific skin conductance responses, ns-SCRs) activity, and subjective measures (Subjective Units of Distress Scale, SUDS), during the preparation phase of their talks before (T1) and after (T2) one full-night's sleep and after 1 week at home (T3). Participants also filled in a dream diary.ResultsWe observed an effect of time on subjective measures of anxiety (SUDS). We did not find any difference in the anxiety levels of the two groups after 1 week of TMR at home. Importantly, the longer the total duration of REM sleep and the more stimulations the TMR group had at home, the less anxious (increased RMSSD) these participants were. Finally, fear in dreams correlated positively with ns-SCRs and SUDS at T3 in the TMR group.ConclusionTMR during REM sleep did not significantly modulate the beneficial effect of therapy on subjective anxiety. Yet, our results support that REM sleep can contribute to extinction processes and substantiate strong links between emotions in dreams and waking stress levels in these patients.

Effects of Continuous Positive Airway Pressure on Sleep EEG Characteristics in Patients with Primary Central Sleep Apnea Syndrome.

This study aimed to investigate the effects of continuous positive airway pressure (CPAP) on the electroencephalographic (EEG) characteristics of patients with primary central sleep apnea syndrome (CSAS). Nine patients with primary CSAS were enrolled in this study. The raw sleep EEG data were analyzed based on two main factors: fractal dimension (FD) and zero-crossing rate of detrended FD. Additionally, conventional EEG spectral analysis in the delta, theta, alpha, and beta bands was conducted using a fast Fourier transform. The FD in patients with primary CSAS who underwent CPAP treatment was significantly decreased during nonrapid eye movement (NREM) sleep but increased during rapid eye movement (REM) sleep (p < 0.05). Regarding the EEG spectral analysis, the alpha power increased, while the delta/alpha ratio decreased during REM sleep in patients with CSAS (p < 0.05). In conclusion, CPAP treatment can reduce FD in NREM sleep and increase FD during REM sleep in patients with primary CSAS. FD may be used as a new biomarker of EEG stability and improvement in brain function after CPAP treatment for primary CSAS.

Abnormal Gray Matter Volume and Functional Connectivity in Parkinson's Disease with Rapid Eye Movement Sleep Behavior Disorder.

Objective Rapid eye movement (REM) sleep behavior disorder (RBD) is a common symptom in Parkinson's disease (PD), and patients with PD-RBD tend to have an increased risk of cognitive decline and have the tendency to be akinetic/rigidity predominant. At the same time, the mechanisms of RBD in patients with PD remain unclear. Therefore, this study aimed to detect the structural and functional differences in patients with PD-RBD and PD without RBD (PD-nRBD). Methods Twenty-four polysomnography-confirmed patients with PD-RBD, 26 patients with PD-nRBD, and 26 healthy controls were enrolled. Structural and functional patterns were analyzed based on voxel-based morphometry and seed-based functional connectivity (FC). Correlations between altered gray matter volume (GMV)/FC values and cognitive scores and motor impairment scores in PD subgroups were assessed. Results Compared with patients with PD-nRBD, patients with PD-RBD showed relatively high GMV in the cerebellar vermis IV/V and low GMV in the right superior occipital gyrus (SOG). For the FC, patients with PD-RBD displayed lower FC between the right SOG and the posterior regions (left fusiform gyrus, left calcarine sulcus, and left superior parietal gyrus) compared with the patients with PD-nRBD. The GMV values in the right SOG were negatively correlated with the Unified PD Rating Scale-III scores in patients with PD-RBD but positively correlated with delayed memory scores. The GMV values in the cerebellar vermis IV/V were positively correlated with the tonic chin EMG density scores. There were positive correlations between the FC values in the right SOG-left superior parietal gyrus and MoCA and visuospatial skills/executive function scores and in the right SOG-left calcarine sulcus and delayed memory scores. Conclusion Higher GMV in the cerebellum may be linked with the abnormal motor behaviors during REM sleep in patients with PD-RBD, and lower GMV and FC in the posterior regions may indicate that PD-RBD correspond to more serious neurodegeneration, especially the visuospatial–executive function impairment and delayed memory impairment. These findings provided new insights to learn more about the complicated characteristics in patients with PD-RBD.

0735 Hyperglycemia Is Associated With An Altered Sleep Structure In Patients With Obstructive Sleep Apnea

Abstract Introduction Although obstructive sleep apnea (OSA) is associated with abnormal glycometabolism, current evidence on the association between hyperglycemia and abnormal sleep structure is still limited among patients with OSA. We sought to evaluate whether hyperglycemia was associated with abnormal sleep architecture. Methods A total of 452 patients with OSA, who were free of previously diagnosed diabetes mellitus, were consecutively recruited. All participants underwent overnight polysomnography and 75-g oral glucose tolerance test. Patients were divided into normal glucose tolerance (NGT) and hyperglycemia (i.e. prediabetes and type 2 diabetes) according to the ADA criteria. The association between hyperglycemia and sleep architecture was examined using logistic regression model. Results Of 452 patients, 283 (63%) had hyperglycemia (age 43.9 ± 11.1) and 169 (37%) had NGT (age 40.1 ± 11.1). Compared to the NGT group, the hyperglycemia group had older age (P &amp;lt; 0.05), higher body mass index (27.5 ± 4.1 vs. 26.33 ± 4.4; P &amp;lt; 0.05) and higher AHI (apnea-hypopnea index) (57.41 ± 28.6 vs. 48.3 ± 28.2; P &amp;lt; 0.05). There were no differences in total sleep time, the percentage of time spent in rapid eye movement (REM) or non-rapid eye movement (NREM) sleep between groups. However, patients with hyperglycemia had more microarousal events, especially during the NREM sleep (214 (range 19-662) events/h vs. 148 (range 37-600) events/h; P &amp;lt; 0.05). In addition, sleep variables related to oxygen saturation measures, such as the percentage of time spent with oxygen saturation ≤80%, were significantly greater during the REM sleep in patients with hyperglycemia (1.4 (total range 0-91.1) % vs. 1.1(0-78.6) %; P &amp;lt; 0.05). After adjusting potential confounders, logistic regression analyses showed that the presence of hyperglycemia was independently associated with the number of microarousals in NREM sleep (OR = 1.01, 95% CI = 1.00-1.02, P = 0.02). Conclusion Hyperglycemia is independently associated with abnormal sleep architecture among patients with OSA. Patients with hyperglycemia have significantly increased sleep fragmentation in NREM sleep and significantly increased hypoxia in REM sleep. Support This work was supported by the National Natural Science Foundation of China (81700087).

Obstructive sleep apnea during rapid eye movement sleep in patients after percutaneous coronary intervention: a multicenter study.

Obstructive sleep apnea (OSA) during the rapid eye movement (REM) stage of the sleep cycle is associated with intense hypoxemia and cardiovascular instability. We characterized OSA during REM sleep in patients after percutaneous coronary intervention. In this multicenter study, 204 patients who had undergone percutaneous coronary intervention in the prior 6 to 36months were recruited for in-laboratory polysomnography. The primary measure was respiratory events during REM sleep. The patients were divided into 2 groups: (1) OSA during REM sleep (≥ 15 events/h) and (2) absence of OSA during REM sleep (< 15 events/h). Based on the overall apnea-hypopnea index ≥ 15, 148 patients (74.0%) had OSA. After excluding patients with failed polysomnography or REM sleep < 30min, 163 patients formed the cohort for this analysis. OSA during REM sleep was diagnosed in 132 patients (81%). Compared with the patients without OSA during REM sleep, those with OSA during REM sleep had a higher body mass index (p = 0.003) and systolic blood pressure (p = 0.041), and a higher prevalence of diabetes mellitus (p = 0.029). Logistic regression analysis, including age, sex, diabetes mellitus, indication for percutaneous coronary intervention, and indication for multi-vessel percutaneous coronary intervention, showed that diabetes mellitus was the only independent predictor of OSA during REM sleep (odds ratio 2.83; 95% CI, 1.17 to 6.83; p = 0.021). In patients treated with percutaneous coronary intervention, there was a high prevalence of OSA during REM sleep. Diabetes mellitus was an independent predictor of OSA during REM sleep.

Supine Alarm Device can Restore REM Sleep in Patients with Obstructive Sleep Apnea

The obstructive sleep apnea syndrome (OSAS) is a type of sleep-related breathing disorder and a highly prevalent disease. Because of frequent arousals during the night, OSAS leads to a fragmentation of sleep and the loss of its restorative function. Being in the supine position during sleep makes the individual more susceptible to obstructive apneic events. This influence of sleeping position on OSAS is thought to be generally greater in rapid eye movement (REM) sleep than in non-rapid eye movement (NREM) sleep stages. The aim of the present study was to evaluate the effect of a supine alarm device that combines an auditory and vibrational signal to discourage patients with OSAS from lying in the supine position during sleep. Thirteen participants with OSAS spent two nights in the sleep laboratory, one night with the device activated and the other night with it deactivated in randomized order. Full-night polysomnography, evening and morning blood pressure, and subjective sleep quality were assessed. Under treatment with the activated supine alarm device, participants had significantly fewer respiratory events, a higher baseline blood oxygenation level, fewer oxygen desaturations, and a significant increase in REM sleep compared to the control condition. Subjective sleep quality significantly improved, whereas psychosomatic symptoms during sleep decreased. Treatment with the supine alarm device appears to improve the amount of REM sleep and subjective sleep in patients with OSAS. Future research would benefit of evaluating patient acceptance and adherence to treatment in the home setting and long-term outcomes.

Continued Presence of Period Limb Movements During REM Sleep in Patients With Chronic Static Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS).

A major component of pediatric acute-onset neuropsychiatric syndrome (PANS) is disruption of sleep. These disturbances have been reported in the acute phase of diagnosis but it is unknown if these sleep disruptions persist, especially in patients with chronic static symptoms. This retrospective chart review sought to review polysomnography (PSG) tests of patients in whom PANS has been clinically diagnosed in order to assess sleep architecture, periodic limb movements, and presence of rapid eye movement (REM) sleep without atonia (RSWA) after a chronic static course of symptoms, which were refractory to immunomodulatory interventions. Patients were retrospectively identified through the PANS clinic at our institution and had to have fully completed a PSG study and be younger than 18 years. PSG with video were reviewed and scored based on established criteria. We identified 9 patients who met inclusion criteria. The median time from presentation to PSG was 4 years. This study identified PSG-measured periodic limb movement index (PLMI) > 5 events/h in REM sleep in 7 of 9 patients. Two patients with elevated PLMI also demonstrated RSWA, although neither fit a clinical diagnosis of REM sleep behavior disorder. This cohort also demonstrated increased onset of REM sleep (median 134 minutes), insomnia (median total sleep time of 389 minutes), and decreased sleep efficiency (77%). This study identifies continued sleep disturbances in patients with refractory PANS symptoms several years after diagnosis and treatment. Continued sleep disturbances after presentation and treatment in patients with chronic static PANS may be a contributing factor in prolonged symptomatology of this disease process.

Differences in sleep architecture between left and right temporal lobe epilepsy.

To investigate whether seizure lateralization affects sleep macrostructure in patients with left and right temporal lobe epilepsy (TLE), as rapid eye movement (REM) sleep is shorter in patients with right hemispheric cerebral infarction than with left. We retrospectively analyzed data from 16 patients with TLE (6 men and 10 women aged 34.9±11.4years) who underwent polysomnography as well as long-term video electroencephalography. Ten patients were diagnosed with left TLE and six patients with right TLE. Sleep stages and respiratory events were scored based on the American Academy of Sleep Medicine criteria. Sleep and respiratory parameters were compared between the patient groups. Percentage of REM stage sleep was significantly (p<0.05) lower in patients with left TLE (median 8.8%, interquartile range 5.5-13.8%) than in patients with right TLE (median 17.0%, interquartile range 14.1-18.3%). The other parameters showed no significant differences. Shorter REM sleep in patients with left TLE sharply contrasts with the previous report of shorter REM sleep in patients with right cerebral infarction. Laterality of the irritative epileptic focus versus destructive lesion may have different effects on the sleep macrostructures.

The diagnostic value of power spectra analysis of the sleep electroencephalography in narcoleptic patients

ObjectiveManifestations of narcolepsy with cataplexy (NC) include disturbed nocturnal sleep – hereunder sleep–wake instability, decreased latency to rapid eye movement (REM) sleep, and dissociated REM sleep events. In this study, we characterized the electroencephalography (EEG) of various sleep stages in NC versus controls. MethodsEEG power spectral density (PSD) was computed in 136 NC patients and 510 sex- and age-matched controls. Features reflecting differences in PSD curves were computed. A Lasso-regularized regression model was used to find an optimal feature subset, which was validated on 19 NC patients and 708 non-NC patients from a sleep clinic. Reproducible features were analyzed using receiver operating characteristic (ROC) curves. ResultsThirteen features were selected based on the training dataset. Three were applicable in the validation dataset, indicating that NC patients show (1) increased alpha power in REM sleep, (2) decreased sigma power in wakefulness, and (3) decreased delta power in stage N1 versus wakefulness. Sensitivity of these features ranged from 4% to 10% with specificity around 98%, and it did not vary substantially with and without treatment. ConclusionsEEG spectral analysis of REM sleep, wake, and differences between N1 and wakefulness contain diagnostic features of NC. These traits may represent sleepiness and dissociated REM sleep in patients with NC. However, the features are not sufficient for differentiating NC from controls, and further analysis is needed to completely evaluate the diagnostic potential of these features.

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.

Increased Corticomuscular Coherence in Idiopathic REM Sleep Behavior Disorder

The authors hypothesized that if locomotor drive increases along with rapid eye movement (REM) sleep without atonia in idiopathic REM sleep behavior disorder (RBD), then RBD patients would have greater corticomuscular coherence (CMC) values during REM sleep than at other sleep stages and than in healthy control subjects during REM sleep. To explore this hypothesis, we analyzed beta frequency range CMC between sensorimotor cortex electroencephalography (EEG) and chin/limb muscle EMG in idiopathic RBD patients. Eleven drug naive idiopathic RBD patients and 11 age-matched healthy control subjects were included in the present study. All participants completed subjective sleep questionnaires and underwent polysomnography for one night. The CMC value between EEGs recorded at central electrodes and EMGs acquired at leg and chin muscles were computed and compared by repeated measures analysis of variance (ANOVA). Sleep stages and muscle (i.e., chin vs. leg) served as within-subject factors, and group served as the between-subject factor. Repeated measures ANOVA revealed no significant main effect of group (F1,20 = 0.571, p = 0.458) or muscle (F1,20 = 1.283, p = 0.271). However, sleep stage was found to have a significant main effect (F2.067,41.332 = 20.912, p < 0.001). The interaction between group and sleep stage was significant (F2.067,41.332 = 3.438, p = 0.040). RBD patients had a significantly higher CMC value than controls during REM sleep (0.047 ± 0.00 vs. 0.052 ± 0.00, respectively, p = 0.007). This study reveals increased CMC during REM sleep in patients with RBD, which indicates increased cortical locomotor drive. Furthermore, this study supports the hypothesis that sufficient locomotor drive plays a role in the pathophysiology of RBD in addition to REM sleep without atonia.

Sleep and cognition at baseline and the effects of REM sleep diminution after 1 week of antidepressive treatment in patients with depression

It has been hypothesized that non-rapid eye movement (NREM) sleep facilitates declarative memory consolidation, and rapid eye movement (REM) sleep is particularly important in promoting procedural learning. The aim of this study was to examine the effects of pharmacological REM sleep suppression on performance in different neuropsychological tasks. For our baseline, we chose 41 moderately depressed patients (age range 19-44 years), who were not taking antidepressants. In the morning after polysomnography, we tested memory recall and cognitive flexibility by assessment of verbal and figural fluency, a shift of attention task and the Trail Making Test B. After recording baseline values, patients were assigned randomly to one of three treatment groups: medication with citalopram; medication with reboxetine; or exclusive treatment with psychotherapy. Retesting took place 1 week after onset of treatment. The main results were: (1) an association of slow-wave sleep with verbal memory performance at baseline; (2) a suppression of REM sleep in patients taking citalopram and reboxetine; (3) no differences regarding neuropsychological performance within the treatment groups; and (4) no association of REM sleep diminution with decreases in memory performance or cognitive flexibility in patients treated with citalopram or reboxetine. In line with other studies, our results suggest that there are no negative effects of a decrease in REM sleep on memory performance in patients taking antidepressants.

Motor disturbance during REM sleep in group A xeroderma pigmentosum.

We investigated motor phenomena during rapid eye movement (REM) sleep in 13 patients with group A xeroderma pigmentosum aged from 11 to 39 months, and compared them with those obtained from 12 age-matched controls. At the time of sleep study, they had no abnormality on routine electrophysiological examinations. The amount of REM sleep and the incidence of motor phenomena during REM sleep in patients were similar to those in age-matched controls. However using the newly designated indices, we demonstrated disturbance on both the tonic motor inhibition occurring during the whole REM sleep period and the phasic one acting simultaneously with horizontal rapid eye movements in these patients. Since the motor inhibition during REM sleep is mediated by the subcortical structures, our study indicate that these structures are functionally impaired in group A xeroderma pigmentosum even during the early stage of the illness.

Time Structure Analysis of Leg Movements During Sleep in REM Sleep Behavior Disorder

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. 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. Twenty patients with idiopathic RBD, 37 with idiopathic RLS and 14 age-matched control subjects were consecutively recruited. 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. 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.

Efficacy of Mirtazapine in Obstructive Sleep Apnea Syndrome

Decreased serotonergic facilitation of upper-airway motor neurons during sleep has been postulated as an important mechanism rendering the upper airway vulnerable to obstruction in patients with obstructive sleep apnea syndrome (OSA). Although serotonin reuptake inhibitors have been shown to produce modest reductions in the apnea-hypopnea index (AHI) during non-rapid eye movement (NREM) sleep, they have not been proven to be generally effective as treatments for OSA. Conversely, antagonists of type 3 (5-HT3) serotonin receptors effectively have been shown to reduce the frequency of central apneas during rapid eye movement (REM) sleep in a rodent model of sleep-related breathing disorder. We sought to determine whether mirtazapine, a mixed 5-HT2/5-HT3 antagonist that also promotes serotonin release in the brain would effectively reduce AHI during both NREM and REM sleep in patients with OSA. A randomized, double-blind, placebo-controlled, 3-way crossover study of mirtazapine in patients with OSA. Laboratory studies were conducted in the Center for Sleep and Ventilatory Disorders at the University of Illinois Medical Center. Seven adult men and 5 adult women with newly diagnosed (treatment-naïve) and medically uncomplicated OSA were randomized into the study. Each subject self-administered oral medications 30 minutes before bedtime each night for 3 consecutive 7-day treatment periods. These treatments comprised (1) placebo, (2) 4.5 mg per day of mirtazapine, and (3) 15 mg per day of mirtazapine. The order of treatments was randomized for each subject, and orders were counterbalanced for the overall study. Each subject charted his or her sleep-wake schedule throughout the study and completed the Stanford Sleepiness Scale every 2 hours during the seventh day of each treatment period. Subjects were studied by laboratory polysomnography on the seventh night of each treatment period. With respect to placebo treatment, 4.5 mg of mirtazapine significantly reduced the AHI in all sleep stages to 52%, with 11 of 12 subjects showing improvement over placebo; 15 mg of mirtazapine reduced the AHI to 46%, with 12 of 12 subjects showing improvement over placebo. Sleep fragmentation was reduced only by the higher dose of mirtazapine. Gross changes in sleep architecture were unremarkable. Daily administration of 4.5 to 15 mg of mirtazapine for 1 week reduces AHI by half in adult patients with OSA. This represents the largest and most consistent drug-treatment effect demonstrated to date in a controlled trial. These findings suggest the therapeutic potential of mixed-profile serotonergic drugs in OSA and provide support for future studies with related formulations. Mirtazapine also is associated with sedation and weight gain-2 negative side effects in patients with OSA. In view of the above, we do not recommend use of mirtazapine as a treatment for OSA.

Effects of Sleep Fragmentation on the Arousability to Resistive Loading in NREM and REM Sleep in Normal Men

In healthy subjects, arousability to inspiratory resistive loading is greater during rapid eye movement (REM) sleep compared with non-REM (NREM) sleep but is poorest in REM sleep in patients with sleep apnea. We therefore examined the hypothesis that sleep fragmentation impairs arousability, especially from REM sleep. Two blocks of 3 polysomnographies (separated by at least 1 week) were performed randomly. An inspiratory-loaded night followed either 2 undisturbed control nights (LN(C)) or 2 acoustically fragmented nights (LN(F)) SETTING: Sleep laboratory. Sixteen healthy men aged 20 to 29 years. In both loaded nights, an inspiratory resistive load was added via a valved facemask every 2 minutes during sleep and turned off either when arousal occurred or after 2 minutes. During LN(F), arousability remained significantly greater in REM sleep (71% aroused within 2 minutes) compared with stage 2 (29%) or stage 3/4 (16%) sleep. After sleep fragmentation, arousability was decreased in stage 2 sleep (LN(F): 29%; LN(C): 38%; p < .05) and low in early REM sleep, increasing across the night (p < .01). In stage 3/4 sleep, neither an attenuation nor a change across the night was seen after sleep fragmentation. Mild sleep fragmentation is already sufficient to attenuate arousability in stage 2 sleep and to decrease arousability in early, compared with late, REM sleep. This means that sleep fragmentation affects the arousal response to increasing resistance and that the effects are different in stage 2 and REM sleep. The biologic reason for this increase in the arousal response in REM sleep across the night is not clear.

Decreased nonlinear complexity and chaos during sleep in first episode schizophrenia: a preliminary report

Schizophrenia is characterized by disturbed sleep architecture. It has been thought that sleep abnormalities may underlie information processing deficits associated with this disorder. Nonlinear analyses of sleep data can provide valuable information on sleep characteristics that may be relevant to the functions of sleep. This study examined the predictability and nonlinear complexity of sleep EEG time series in two EEG channels (C4 and F4) using measures of nonlinearity, such as symbolic dynamics and the largest Lyapunov exponent (LLE) in schizophrenia. A series of antipsychotic naı̈ve patients with first episode of schizophrenia or schizoaffective disorder and age-matched healthy controls were studied during awake period, stage 1/2, slow wave sleep (stage 3/4) and rapid eye movement (REM) sleep. Nonlinearity scores were significantly lower during awake stage in patients compared to controls suggesting that there may be a diminished interplay between various parameters for the genesis of waking EEG. Symbolic dynamics and LLE were significantly lower in patients during REM compared to healthy controls, suggesting decreased nonlinear complexity of the EEG time series and diminished chaos in schizophrenia. Decreased nonlinear complexity was also correlated with neurocognitive deficits as assessed by the Wisconsin card sorting test. Diminished complexity of EEG time series during awake and REM sleep in patients with schizophrenia may underlie the impaired ability to process information in psychotic disorders such as schizophrenia.