Abstract: OBJECTIVE: To clarify the relationship between sleep instability and subjective complaints in patients with upper airway resistance syndrome (UARS). METHODS: Thirty subjects (15 women) with UARS and 30 age- and sex-matched controls in a prospective, single-blind, case-control study. Blinded cyclic alternating pattern (CAP) electroencephalogram analysis and scales of fatigue and sleepiness were completed. ANALYSIS: Mann-Whitney U tests for independent, nonparametric variables between groups and chi2 tests for nonparametric variables with defined standard values. RESULTS: Patients with UARS had significantly more complaints of fatigue and sleepiness, compared with controls, demonstrated on their Fatigue Severity Scale (P < 0.001) and Epworth Sleepiness Scale (P < 0.001). By design, the mean apnea-hypopnea index was normal in both groups, whereas the respiratory disturbance index was greater in patients with UARS than in those without (14.5 +/- 3.0 vs 9 +/- 5.2, respectively [P < 0.001]). CAP analysis demonstrated abnormal non-rapid eye movement sleep with abnormally increased CAP rate, electroencephalogram arousals, A2 index, and A3 index. Decreased A1 index in controls was consistent with their more normal progression of sleep. CAP rate correlated with both the Epworth Sleepiness Scale (r = 0.38, P < 0.01) and the Fatigue Severity Scale (r = 0.51, P < 0.0001), and there was a positive trend between the Fatigue Severity Scale and phase A2 index (r = 0.29, P < 0.05). CONCLUSION: Compared with age- and sex-matched controls, patients with UARS have higher electroencephalogram arousal indexes and important non-rapid eye movement sleep disturbances that correlate with subjective symptoms of sleepiness and fatigue. These disturbances are identifiable with sensitive measures such as CAP analysis but not with traditional diagnostic scoring systems.
Abstract: This review presents traditional and cutting-edge interventions in sleep research, including descriptions of the relationship of rapid eye movement-non-rapid eye movement sleep with the autonomous nervous system, and dream research methodology. Although sleep and dreaming are overlapping and non- separable phenomena, they are not typically addressed simultaneously in the scientific sleep research literature. Therefore, a more extensive overview of dream research has been included with a focus on objective dream content analysis and the theory of neurocognitive analysis. A bridge is made between dream content analysis and current sleep research methodologies.
Abstract: BACKGROUND AND PURPOSE: Thirty-two chronic sleepwalkers who were part of a larger, previously reported sleepwalking group all achieved control of sleepwalking after undergoing treatment for an associated sleep disorder. In the current study, all records were blindly scored to perform a cyclic alternating pattern (CAP) analysis. PATIENTS AND METHODS: Thirty-two young adult chronic sleepwalkers had polysomnography (PSG) on initial nights without sleepwalking events, as did age-matched normal controls and patients with mild sleep-disordered breathing (SDB). More than 90% of these patients with mild SDB had upper airway resistance syndrome (UARS). Ten randomly selected PSGs for sleepwalkers and matched controls also had quantitative electroencephalographic (EEG) analysis using Fast Fourier Transformation (FFT) with determination of delta power for each non-rapid eye movement (NREM)-REM sleep cycle. RESULTS: Compared to normal controls, an investigation of CAP in sleepwalkers demonstrated the presence of an abnormal CAP rate with a decrease in phase A1 and an increase in phases A2 and A3 on non-sleepwalking nights. The results of CAP analysis in sleepwalkers were similar to those obtained in age-matched UARS patients. Furthermore, the analysis of the first four NREM-REM sleep cycles reconfirmed the presence of an important decrease in delta power in sleep cycles 1 and 2 during a non-sleepwalking night in sleepwalkers compared to normal controls. CONCLUSIONS: The presence of both 'hypersynchronous slow delta' and 'burst of delta waves' have been reported in sleepwalkers, but their significance is controversial. These EEG patterns are similar to phase A1 (and possibly A2) of the CAP. Proper analysis of the sleep EEG of sleepwalkers should integrate CAP analysis. Sleepwalkers on a non-sleepwalking night present instability of NREM sleep, as demonstrated by this analysis. This instability is similar to the one noted in UARS patients. Subtle sleep disorders associated with chronic sleepwalking constitute the unstable NREM sleep background on which sleepwalking events occur. A subtle associated sleep disorder should be systematically searched for and treated in the presence of sleepwalking with abnormal CAP.
Abstract: The classification of short duration events in the EEG during sleep, as the A stage of the cyclic alternating pattern (CAP) is a tedious and error prone task. The number of events under normal conditions is large (several hundreds), and it is necessary to mark the limits of the events with precision, otherwise the time sensitive classification of the CAP phases (A and B) and specially the scoring of different types of A phases will be compromised. The objective of this study is to verify the feasibility of visual CAP scoring with only one channel of EEG, the evaluation of the inter-scorer agreement in a variety of recordings, and the comparison of the visual scorings with a known automatic scoring system. Sixteen hours of one channel (C4-A1 or C3-A2) of NREM sleep were extracted from eight whole night recordings in European Data Format and presented to the different scorers. The average inter-scorer agreement for all scorers is above 70%, the pair wise inter-scorer agreement found was between 69% up to 77.5%. These values are similar to what has been reported in different type studies. The automatic scoring system has similar performance of the visual scorings. The study also has shown that it is possible to classify the CAP using only one channel of EEG.
Abstract: BACKGROUND AND PURPOSE: To investigate the complaint of unrefreshing sleep with study of sleep electroencephalogram (EEG) in patients with chronic fatigue. PATIENTS AND METHODS: Fourteen successively seen patients (mean age: 41.1 9.8) who complained of chronic fatigue but denied sleepiness and agreed to participate were compared to 14 controls (33.6+/-10.2 years) who were monitored during sleep recorded in parallel. After performing conventional sleep scoring we applied Fast Fourier Transformation (FFT) for the delta 1, delta 2, theta, alpha, sigma 1, sigma 2, beta EEG frequency bands. The presence of non-rapid eye movement (NREM) sleep instability was studied with calculation of cyclic alternating pattern (CAP) rate. Two-way analysis of variance (ANOVA) was performed to analyze FFT results and Mann-Whitney U-test to compare CAP rate in both groups of subjects. RESULTS: Slow wave sleep (SWS) percentage and sleep efficiency were lower, but there was a significant increase in delta 1 (slow delta) relative power in the chronic fatigue group when compared to normals (P<0.01). All the other frequency bands were proportionally and significantly decreased compared to controls. CAP rate was also significantly greater in subjects with chronic fatigue than in normals (P=0.04). An increase in respiratory effort and nasal flow limitation were noted with chronic fatigue. CONCLUSIONS: The complaints of chronic fatigue and unrefreshing sleep were associated with an abnormal CAP rate, with increase in slow delta power spectrum, affirming the presence of an abnormal sleep progression and NREM sleep instability. These specific patterns were related to subtle, undiagnosed sleep-disordered breathing.
Abstract: Cases of violent behavior during sleep have been reported in the literature. However, the incidence of violent behavior during sleep is not known. One epidemiological study showed that approximately 2% of the general population, predominantly males, presented violent behavior while asleep. In the present study, the authors describe clinical and medico-legal aspects involved in violent behavior investigation. Violent behavior refers to self-injury or injury to another during sleep. It happens most frequently following partial awakening in the context of arousal disorders (parasomnias). The most frequently diagnosed sleep disorders are REM behavior disorder and somnambulism. Violent behavior might be precipitated by stress, use of alcohol or drugs, sleep deprivation or fever.
Abstract: BACKGROUND AND PURPOSE: We questioned whether or not the sleep of pre-pubertal children with recurrent sleepwalking was different from that recorded in normal children. PATIENTS AND METHODS: Twelve pre-pubertal chronic sleepwalkers were compared to age- and gender-matched normal children. All children had a clinical evaluation covering pediatric, sleep, neuropsychiatric and otolaryngological fields. Two standardized sleep questionnaires were administered, and a minimum of two successive polysomnograms were performed with monitoring of sleep electroencephalographic (EEG) and cardiorespiratory variables. The research investigations were performed on nights without sleepwalking to search for the presence of other sleep disorders, including upper airway resistance syndrome (UARS). Sleep was scored using standard atlases, but it was also evaluated for the cyclic alternating pattern (CAP) rate. RESULTS: All sleepwalkers presented with either obstructive sleep apnea (n=2) or UARS (n=10). Compared to normal children, sleepwalkers had shorter total sleep time but no significant change in wake after sleep onset when considering all arousals > 3 s. CAP analysis showed a significantly higher CAP rate than in controls. CONCLUSIONS: Chronic sleepwalkers have instability of non-rapid eye movement (NREM) sleep detectable only by the calculation of CAP rate. Instability of NREM sleep was seen even on nights without sleepwalking and is probably related to the presence of the associated sleep disorders. We hypothesize that chronic NREM-sleep instability is a risk factor for occurrence of sleepwalking when further sleep disruption is triggered by external events.
Abstract: BACKGROUND AND PURPOSE: We questioned the role of respiratory events in obstructive sleep apnea syndrome (OSAS) and of upper airway resistance syndrome (UARS) on heart rate (HR) during sleep, paying specific attention to the termination of the abnormal breathing events and examining the presence of arousals or termination with only central nervous system (CNS) activation. PATIENTS AND METHODS: Twenty patients, 10 with UARS and 10 with mild OSAS, were studied. A nocturnal polysomnogram was performed including measurement of respiratory variables and pulse transit time (PTT). According to the presence or absence of a PTT event indicative of autonomic nervous system (ANS) activation, 148 events were extracted after having been randomly chosen in each represented sleep stage, with or without an electroencephalogram (EEG) arousal >1.5s. RR interval (RRI) in electrocardiogram (ECG) recordings, as well as heart rate variability, was calculated during 60 and 120s, respectively. Period amplitude analysis (PAA) was applied for RR-interval analysis, and fast Fourier transformation (FFT) was applied to perform HR variability analysis. RESULTS: Visually scored EEG arousal was significantly associated with an increase in sympathetic index of heart rate, while PTT was associated with a drop in parasympathetic index, after the respiratory events. Patients with mild OSAS presented persistently shorter RRI when compared to patients with UARS. The latter also exhibited a significant decrease in parasympathetic index (High Frequency (HF)) at the termination of a respiratory event. CONCLUSION: The HF component was only significantly decreased in patients with UARS, which indicates a predominant involvement of the parasympathetic tone in patients with UARS in comparison to those with OSAS.
Abstract: STUDY OBJECTIVES: The aim of this study is to complement the data on the expression and characteristics of cyclic alternating pattern (CAP) events in children, specifically in the peripubertal age group of 8 to 12 years and to analyze the association of CAP events with arousals. The study of CAP and arousal is a useful tool for assessing sleep instability and fragmentation in children. DESIGN: Descriptive study. PARTICIPANTS: Ten sex-matched healthy children, aged 8 to 12 years, underwent standard polysomnography after 1 adaptation night in the sleep laboratory. Sleep stages, CAP, and arousals were analyzed according to standard international rules. RESULTS: The mean CAP rate was 62.1% +/- 10.8% and the mean CAP cycle duration, 24.6 +/- 2.1 minutes. CAP A1 phase was the most numerous (85.5% +/- 3.9%), whereas the A2 phase was 9.1% +/- 4.7%, and the A3 phase as 5% +/- 2.3%, (P < .01). Differences between boys and girls were detected by analysis of variance, namely increases of phase A2 and A3 subtypes in girls (P < .001). Stronger phase A1 subtype expression in slow-wave sleep was verified in both sexes. Positive correlation between electroencephalogram arousals and the sum of phase A2 and A3 subtypes was also present. The overall CAP rate is higher in this age group than the rate previously reported in children aged 6 to 10 years (62.1% +/- 10.8% vs 33.4% +/- 5.3%). CONCLUSIONS: Our study provides normative data on CAP in children aged 8 to 12 years and indicates that age and Tanner stages must both be considered when investigating peripubertal children.
Abstract: The nocturnal recordings of breathing, and sleep and daytime multiple sleep latency tests over the 5 year follow-up of a patient with post encephalitis hypersomnia are presented. EEG power spectrum analysis was performed on the last polysomnographic recording, and the results were compared with those obtained for a matched control subject. The patient presented initially a hypoventilation syndrome controlled by nasal bilevel positive pressure at night. The syndrome progressively improved, but daytime sleepiness stayed unchanged with limited help from stimulants. Fast Fourier transformation analysis of the last nocturnal recording demonstrates a decrease in absolute power for all frequency bands in all sleep stages, but a cyclical presence of the NREM/REM.
Abstract: OBJECTIVES: Upper airway resistance syndrome (UARS) and obstructive sleep apnea syndrome (OSAS) are associated with arousals and autonomic activation. Pulse transit time (PTT) has been used to recognize transient arousals. We examined the accuracy of PTT to recognize arousals, and the relationship between PTT deflection and visual and non-visual arousals.METHODS: Ten UARS and 10 mild OSAS subjects were studied via polysomnography including measurement of esophageal pressure. Electroencephalogram (EEG) spectral power was obtained from central leads. Seven types of events were identified, depending upon the presence or absence of: a sleep-related respiratory event (SRRE), i.e. apnea, hypopnea, and abnormal breathing effort; a PTT signal; or a visually scored arousal (>1.5s).RESULTS: One thousand four hundred forty-six events were identified in 20 subjects. Fifty-nine percent of all SRREs were associated with a PTT signal and a visual EEG arousal. Nineteen percent of SRREs had no EEG arousals at their termination, and 7.4% had no associated PTT signal. Delta power was significantly increased when non-visual EEG arousals were scored. The time delay for PTT was determined by the presence or absence of EEG arousal. The sensitivity of PTT to recognize EEG arousal was 90.4% and the specificity was 16.8%. The sensitivity and specificity of PTT to recognize SRRE was 90.7 and 21.9%, respectively.CONCLUSIONS: These results preclude the use of PTT by itself. SRREs induce an activation with positive PTT response but without arousal in 14% of cases. This PTT response, however, is much slower than that occurring with arousal. UARS and mild OSAS do not respond in the same way to SRREs, particularly during rapid eye movement sleep.
Abstract: After being released from transcription sites, messenger ribonucleoprotein particles (mRNPs) must reach the nuclear pore complexes in order to be translocated to the cytoplasm. Whether the intranuclear movement of mRNPs results largely from Brownian motion or involves molecular motors remains unknown. Here we have used quantitative photobleaching techniques to monitor the intranuclear mobility of protein components of mRNPs tagged with GFP. The results show that the diffusion coefficients of the poly(A)-binding protein II (PABP2) and the export factor TAP are significantly reduced when these proteins are bound to mRNP complexes, as compared with nonbound proteins. The data further show that the mobility of wild-type PABP2 and TAP, but not of a point mutant variant of PABP2 that fails to bind to RNA, is significantly reduced when cells are ATP depleted or incubated at 22 degrees C. Energy depletion has only minor effects on the intranuclear mobility of a 2,000-kD dextran (which corresponds approximately in size to 40S mRNP particles), suggesting that the reduced mobility of PABP2 and TAP is not caused by a general alteration of the nuclear environment. Taken together, the data suggest that the mobility of mRNPs in the living cell nucleus involves a combination of passive diffusion and ATP-dependent processes.
Abstract: OBJECTIVES: It is known that the number of arousals per hour of sleep increases linearly across life, while the amount of cyclic alternating pattern (CAP) undergoes a u-shaped evolution. The present study aimed at investigating the differences, overlaps and age-related distribution of arousals and CAP components, i.e. subtypes A1, A2, A3. The relationship between the phase A subtypes and the structural organization of sleep was also evaluated. METHODS: Forty healthy subjects were examined. Polysomnographic analysis was performed according to the scoring rules for sleep stages, CAP and American Sleep Disorders Association arousals. RESULTS: Arousals occurred more frequently during CAP (40 events per hour) than in total sleep time (18 events per hour), non-rapid eye movement (NREM) sleep (20 events per hour), and rapid eye movement (REM) sleep (12 events per hour). Within CAP, arousals always coincided with a subtype A2 or A3. Both arousals and subtypes A2 and A3 showed a similar evolution with relation to age (linear positive), and to the amounts of light NREM sleep (linear positive) and deep NREM sleep (linear negative). In contrast, subtypes A1 showed a u-shaped profile across the life span and appeared closely related (linear positive) to the time spent in stages 3 and 4. Almost 90% of arousals occurring in NREM sleep were preceded in the previous 3s by a K-complex or a delta burst, indicating a topical involvement of slow electroencephalographic (EEG) components in the arousal build-up. CONCLUSIONS: Arousals show only one side of the multi-faceted activation complexes, whereas the three subtypes of CAP provide a graded picture of arousal features from the strongest A3 subtypes, showing a prevalence of EEG desynchrony, to the weakest A1 phases, which are dominated by EEG synchrony and represent the prevalent components of CAP (60% of all the phase A subtypes).
Abstract: Gene expression can be silenced by proximity to heterochromatin blocks containing centromeric alpha-satellite DNA. This has been shown experimentally through cis-acting chromosome rearrangements resulting in linear genomic proximity, or through trans-acting changes resulting in intranuclear spatial proximity. Although it has long been been established that centromeres are nonrandomly distributed during interphase, little is known of what determines the three-dimensional organization of these silencing domains in the nucleus. Here, we propose a model that predicts the intranuclear positioning of centromeric heterochromatin for each individual chromosome. With the use of fluorescence in situ hybridization and confocal microscopy, we show that the distribution of centromeric alpha-satellite DNA in human lymphoid cells synchronized at G(0)/G(1) is unique for most individual chromosomes. Regression analysis reveals a tight correlation between nuclear distribution of centromeric alpha-satellite DNA and the presence of G-dark bands in the corresponding chromosome. Centromeres surrounded by G-dark bands are preferentially located at the nuclear periphery, whereas centromeres of chromosomes with a lower content of G-dark bands tend to be localized at the nucleolus. Consistent with the model, a t(11; 14) translocation that removes G-dark bands from chromosome 11 causes a repositioning of the centromere, which becomes less frequently localized at the nuclear periphery and more frequently associated with the nucleolus. The data suggest that "chromosomal environment" plays a key role in the intranuclear organization of centromeric heterochromatin. Our model further predicts that facultative heterochromatinization of distinct genomic regions may contribute to cell-type specific patterns of centromere localization.
Abstract: A multimedia Sleep tutorial for General Practitioners was implemented from scratch. The implementation had into account the following features: 1) Specific needs of GPs evaluated in 3 different countries, related with Tutorial contents and technical features; 2) Multinational authorship from European experts; 3) Multilingual possibilities; 4) User friendliness and easy navigation. The tutorial was implemented and tested and its gama version is now available for commercialization.
Abstract: OBJECTIVES: The analysis of cyclic alternating pattern (CAP) provides important microstructural information on arousal instability and on EEG synchrony modulation in the sleep process. This work presents a methodology for automatic classification of the micro-organization of human sleep EEG, using the CAP paradigm. METHODS: The classification system is composed of 3 parts: feature extraction, detection and classification. The feature extraction part is an EEG generation model-based maximum likelihood estimator. The detector part for the CAP phases A and B is done by a variable length template matched filter, while the classification criteria part is implemented on a state machine ruled-based decision system. RESULTS AND CONCLUSIONS: The preliminary results of the automatic classifier on a group of 4 middle-aged adults are presented. The high agreement between the detector and visual scoring is very promising in the achievement of a fully automated scoring system, although a more exhaustive evaluation program is needed.
Abstract: Although various investigators have suggested algorithms for the automatic detection of eye movements during sleep, objective comparisons of the proposed methods have previously been difficult due to different recording arrangements of different investigators. In this study the results of five eye movement detection algorithms applied to the same data were compared to visually scored data. The percentages of true and false detections are given for various threshold levels in rapid and slow eye movement detections. The methods gave best results when they were used with the same electrode montage they were designed for but the performance decreased when other montages were used. Subtracting the cross-talk of EEG delta activity improved the correctness of eye movement detections.
Abstract: Among psychiatric entities, dysthymic patients provide a good model for studies on minor disturbances in sleep organization because they present borderline abnormalities in their night sleep that concern mainly slow wave sleep. A study on sleep phasic events was performed to evaluate abnormalities in sleep microstructure. Therefore, for all subjects--normal controls and dysthymic patients--the following phasic activities were scored: K-complexes, vertex sharp transients, posterior occipital transients, delta paroxysms, theta bursts, microarousals, and awakenings. Furthermore, other sleep EEG patterns, such as REM with spindles, and intermediate stages, were assessed. The following results were obtained: 1) dysthymic patients have less K-complexes and vertex sharp transients, with lower densities of these events; 2) they have a reduced number of microarousals, with an increased rate of awakenings; 3) patients present a higher incidence of other events such as theta bursts, POSTs, REM with spindles, and intermediate stages. These results suggest that the analysis of phasic events is useful for the discrimination between normal and pathologic sleep, even when there are only minor differences in terms of macrostructure.
Abstract: A model-based automatic K-complex (Kc) detector was applied to all-night single-channel sleep electroencephalographic (EEG) recordings from normal and dysthymic patients. The performance of the detector was analyzed in the two groups, and the differences obtained were discussed. The results showed that the detection rate of Kc in the normal group was around 92% through all stages of non-rapid eye movement (NREM) sleep, but with high numbers of "false" positives in stage 4 NREM, which reached 57%. In the dysthymic patients "true" detection included 85% of the Kc, but the percentage of "false" positives dropped to 25% in stage 4 NREM. Most of the "false" detections in the normal group were due to sharp delta activity during slow wave sleep (SWS). The results in the patient group were expected, because sleep in dysthymics showed a reduction in SWS when compared to normals. The behavior and automatic artifact rejection mechanisms of the detector are briefly presented. The model-based Kc detector performed significantly better than other automatic detectors described in the literature; it was found to be a useful tool for routine sleep EEG studies.
Abstract: A simple digital format supporting the technical aspects of exchange and storage of polygraphic signals has been specified. Implementation of the format is simple and independent of hard- or software environments. It allows for any local montages, transducers, prefiltering, sampling frequencies, etc. At present, 7 laboratories in various countries have used the format for exchanging sleep-wake recordings. These exchanges have made it possible to create a common database of sleep records, to compare the analysis algorithms local to the various laboratories to each other by applying these algorithms to identical signals, and to set up a computer-aided interlaboratory evaluation of manual and automatic analysis methods.
Abstract: A model of sleep phasic events such as vertex waves, K complexes, delta waves and sleep spindles is proposed. It consists of feedback loops that are driven by white noise (simulating tonic delta and sigma activity) and by isolated random impulses, simulating vertex waves or K complexes, depending on the background tonic activity. A model-based method for the detection of sleep phasic events was implemented in a personal computer. Its performance was investigated using simulated and real whole-night EEG signals. The method was able to detect K complexes and vertex waves in a reliable way in spite of their variable shapes and in the presence of a variety of background activities. The detector appears to have superior performance to those so far reported in the literature. The performance of the detector was also compared to that of an electroencephalographer using normal sleep EEG records of 8 h duration from 6 subjects. The performance was satisfactory both in terms of accuracy and reliability. The problem of detecting K complexes in stages 3 and 4 of sleep is discussed.
