Sleep latency and duration estimates among sleep disorder patients: variability as a function of sleep disorder diagnosis, sleep history, and psychological characteristics

STUDY OBJECTIVES: Insomnia patients often report greater sleep disturbance than found via polysomnography; yet the specific patient factors related to such sleep time misperceptions are poorly understood. We sought to characterize the extent to which a diverse group of patients complaining of insomnia (n=104) misperceive overnight total sleep time and sleep latency, and to identify patient factors associated with these variations. DESIGN: Cross-sectional. SETTING: University based sleep disorders center. PATIENTS: Sleep disorder groups consisted of patients with psychophysiological insomnia (n=19), sleep state misperception (n=8), insomnia with depressive disorder (n=11), insomnia secondary to Axis I psychiatric disorder other than depression (n=21), periodic limb movement disorder (n=24), and obstructive sleep apnea (n=21). MEASUREMENT AND RESULTS: Patients completed a sleep history questionnaire and the MMPI, underwent overnight diagnostic polysomnographic assessment, and then estimated their total sleep time and sleep latency the subsequent morning. On average, patients overestimated sleep latency, but were equally likely to underestimate vs. overestimate total sleep time. Sleep time misperception was associated with longer periods of wakefulness following sleep onset, greater self-perceived sleep impairment, as well as several psychological dimensions. CONCLUSIONS: Patient factors, including sleep quality, perceptions of habitual sleep time, and current psychopathology, potentially influence sleep time estimation. Whereas psychological factors may lead to exaggeration of sleep disturbance among some patients, sleep quality itself may also influence the congruence between subjective and objective indices of sleep.     

Measurement of heart-rate variability: Part 1—Comparative study of heart-rate variability analysis methods

A definition of heart-rate variability (h.r.v.) is given. The use of h.r.v. measurement in both clinical applications and the neural cardiovascular research is discussed. For the latter applications, four different signals describing h.r.v. are reviewed. It is shown that these signals are based on modifications of one model, namely the integral pulse frequency modulator. In Part 2, a hardware device for measuring h.r.v. based on one of these modifications is described.     

Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity

Study ObjectivesPatients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample.Methods1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates.ResultsPatients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009).ConclusionsTime-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients.Clinical Trial Information: A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966     

Plasma cytokine levels in patients with obstructive sleep apnea syndrome: a preliminary study

The levels of some pro- and anti-inflammatory cytokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, IL-6, IL-10, and transforming growth factor (TGF)-beta], were measured by enzyme-linked immunosorbent assay (ELISA) method in the plasma of patients affected by obstructive sleep apnea syndrome (OSAS) at 22:00 hours before polysomnographic recording and immediately after the first obstructive apnea causing an SaO2 below 85%. Significantly higher levels of TNF-alpha were found in OSAS patients assessed before polysomnography compared with the control group (P < 0.01). A slight but significant increase in the plasma levels of IL-6 was also present (P < 0.05). Conversely, a significant decrease in the plasma levels of IL-10 was evident at baseline in OSAS patients (P < 0.04). No significant difference emerged between the mean values of IL-1alpha and TGF-beta between OSAS patients and controls. The present data support a prevailing activation of the Th1-type cytokine pattern in OSAS patients, which is not associated with the severity and duration of OSAS. This can have important consequences for the outcome of OSAS patients, especially with regard to the increased risk for developing atherosclerosis and cardiovascular and cerebrovascular diseases. Immediately after the first obstructive apnea causing an SaO2 <85%, a significant variation was observed in the plasma levels of TNF-alpha in OSAS patients compared with those measured before the beginning of polysomnographic recording (P < 0.001). The role played by this further increase in TNF-alpha levels after the obstructive apnea in OSAS patients remains to be established in the light of the pathogenic mechanisms of this sleep disorder.     

Serum cholesterol levels and panic symptoms in patients with panic disorder: a preliminary study

BACKGROUND: Although some previous research has focused on the relationship between panic disorder (PD) and a high total cholesterol (TC) level, it is still controversial. Recently, researchers have reported the heterogeneity of clinical symptoms in PD and the complexity of the correlations found among them. Therefore, the controversy on the TC level in PD may be due to the existence of clinical subgroups in PD. It is important to ascertain whether or not an elevated TC level in patients with PD is associated with specific panic symptoms. METHODS: In 104 drug-free patients with PD, we examined the relationship between TC level and each of several panic symptoms occurring at the time of panic attacks (PAs), which included anticipatory anxiety, agoraphobia, and 13 panic symptoms based on the DSM-III-R. RESULTS: Stepwise regression analysis revealed a significant effect of the presence of the symptom 'fear of dying' on TC levels. Patients with a fear of dying had a significantly higher TC level than those without it. LIMITATIONS: The relatively small sample size may limit the generalizability of our findings. DISCUSSION: These data suggest that TC level may be associated with panic symptoms in patients with PD.     

Microsleep as a marker of sleepiness in obstructive sleep apnea patients

We hypothesized that: (a) the presence of microsleep (MS) during a Maintenance Wakefulness Test (MWT) trial may represent a reliable marker of sleepiness in obstructive sleep apnea (OSA) patients; (b) the number of MSs will be higher in sleepy versus non‐sleepy patients with a borderline MWT mean sleep latency; and (c) scoring MS during MWT analysis may help physicians to recognize patients with a higher degree of sleepiness. We analysed the MWT data of 112 treatment‐naïve OSA patients: 20 with short sleep latency (SL, sleep latency <12.8 min), 43 with borderline latency (BL, sleep latency between 12.8 and 32.6 min) and 49 with normal latency (NL, sleep latency >32.6 min). Microsleep was identified in all SL, in 42 BL and in 18 NL patients, with a median latency of 5.6 min. Accordingly, patients were classified into two subgroups: group A (n = 43) with microsleep latency <5.6 min and group B (n = 69) with microsleep latency >5.6 min when present. The mean sleep latency in the MWT was 14.5 ± 7.5 min in group A and 34.6 ± 7.4 min in group B (p < 0.0001). The number of microsleep episodes during each MWT trial was higher in group A than in group B. Sleep latency survival curves demonstrated different patterns of sleep latency in these groups (log‐rank test <0.0001). This finding was confirmed in a Cox proportional hazard analysis: the presence of a mean MS latency <5.6 min is associated with an increasing risk of falling asleep during the MWT (RR, 1.93; 95 CI 1.04–3.6; p = 0.03). We conclude that the detection of microsleep may help in discriminating OSA patients with and without daytime vigilance impairment.     

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.     

Subjective sleep quality in relation to inhibition and heart rate variability in patients with panic disorder

Background

Patients with panic disorder (PD) are known to report impaired sleep quality and symptoms of insomnia. PD is an anxiety disorder characterised by deficient physiological regulation as measured by heart rate variability (HRV), and reduced HRV, PD and insomnia have all been related to impaired inhibitory ability. The present study aimed to investigate the interrelationships between subjectively reported sleep impairment, cognitive inhibition and vagally mediated HRV in a sample characterised by variability on measures of all these constructs.

Methods

Thirty-six patients with PD with or without agoraphobia were included. Cognitive inhibition was assessed with the Color–Word Interference Test from the Delis–Kaplan Executive Function System (D-KEFS), HRV was measured using high frequency (HF) power (ms²), and subjectively reported sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI).

Results

Cognitive inhibition was related to both Sleep latency and Sleep disturbances, whereas HRV was only related to Sleep disturbances. These relationships were significant also after controlling for depression.

Limitations

Correlational design.

Conclusion

Cognitive inhibition is related to key insomnia symptoms: sleep initiation and sleep maintenance. The data supports the psychobiological inhibition model of insomnia, and extends previous findings. Possible clinical implications of these findings are discussed.     

Sleep position training as treatment for sleep apnea syndrome: a preliminary study

Ten male patients selected as having sleep apnea predominantly of the obstructive type associated with the supine sleep position on their evaluation night were trained for 1 additional night to avoid the back sleep position by wearing a gravity-activated position monitor/alarm on the chest. This device emitted an auditory signal if the patient remained supine for more than 15 s. The number of apneic events was significantly reduced, as were the number of episodes of significant O2 desaturation. While wearing the alarm, the apnea index of seven patients remained within or near normal limits. On a follow-up night, with only instructions to maintain the lateral decubitus posture, five patients remained significantly improved. Sleep position training may be appropriate as a single or interim treatment for a significant number of sleep apnea patients who have position-related obstruction.     

特发性和继发性快速眼动睡眠行为障碍的睡眠结构研究

目的：探讨快速眼动睡眠行为障碍（REM sleep behavior disorder,RBD）患者的睡眠结构改变。方法：纳入的22例患者符合国际睡眠障碍协会（第2版）的RBD诊断标准,16例患者符合RBD主要诊断标准以及英国脑库的PD、2005年国际路易体痴呆协作组或者2008年多系统萎缩第2版的诊断标准。同时纳入年龄、性别匹配的健康对照19例。利用日本光电32信道9200K脑电图机,所有患者均完成多项睡眠图监测（PSG）,记录脑电图、眼球运动、下颌和肢体肌电活动、心电图、经鼻气流、胸腹部呼吸运动、血氧、鼾声等多个项目,并录像监测患者的行为。使用Polysmith软件和视觉评估分析睡眠结构、呼吸、运动等相关指标。结果：RBD患者展现了典型临床表现和电生理改变。特发性RBD组（72．7％）较继发性RBD组（43．8％）显示有更多的夜间活动和言语,差异有统计学意义（P=0．071）。特发性RBD在睡眠结构并未发生明显改变,仅有周期性腿动（PLM）指数增高。继发性RBD与特发性RBD和健康对照相比,总体睡眠时间缩短、睡眠效率减低、睡眠潜伏期和REM潜伏期延迟、Ⅱ期和REM睡眠减少、Ⅰ期睡眠增加、低通气指数增高、PLM指数增高。结论：特发性RBD患者具有更多的夜间行为异常,而睡眠结构无改变,仅有PLM指数增加;而继发性RBD出现明显的睡眠结构紊乱、呼吸紊乱以及PLM异常。     

Interleukin 6 as a marker of depression in women with sleep apnea

Depression is common in women with obstructive sleep apnea (OSA), but objective markers of depression have not yet been explored in such patients. We hypothesized that inflammation and antioxidant biomarkers may be associated with depression in a cohort of OSA women. We conducted a multicentre, cross‐sectional study in 247 women diagnosed with moderate‐to‐severe OSA. Depression was assessed by the depression subscale of the Hospital Anxiety and Depression Questionnaire (HAD‐D) and defined as a score ≥11. Associations between tumour necrosis factor α (TNFα), interleukin 6 (IL‐6), C‐reactive protein (CRP), intercellular adhesion molecule 1 (ICAM‐1), catalase (CAT), superoxide dismutase (SOD) and brain‐derived neurotrophic factor (BDNF) plasma levels and depression were assessed. The women had a median (25th‐75th percentiles) age of 58 (51–65) years, body mass index (BMI) of 33.5 (29.0–38.3) Kg/m², Epworth Sleepiness Scale (ESS) score of 10 (6–13) and apnea–hypopnea index (AHI) of 33.3 (22.8–49.3). Logistic regression analyses revealed that only IL6 levels were associated with the presence of depression (adjusted odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08–1.34), whereas linear regression further confirmed that IL6 levels were significantly associated with HAD‐D scores (β = .154; 95% CI, 0.03–0.30). Multivariate regression analysis showed that IL6 (OR, 1.22; 95% CI, 1.09–1.36), ESS (OR, 1.10; 95% CI 1.02–1.19) and physical activity <30 min/day (OR, 2.51; 95% CI, 1.25–5.05) were independent predictors of depression. Thus, we conclude that in a cohort of women with moderate‐to‐severe OSA, IL6 levels are independently associated with the presence of depression and correlate with depression scores. Low physical activity and higher ESS scores are also independent indicators of risk of depression in this population.     

Unusual sleep experiences and dissociation as mediators between sleep quality and proneness to hallucinations in a nonclinical population sample: a preliminary study

Introduction: The purpose of this study was to examine the relationship of sleep quality to proneness to hallucinations and the mediating role of dissociation and unusual sleep experiences in a nonclinical sample.

Methods: One hundred and seventy-seven participants completed a questionnaire on sleep quality, a dissociative experiences scale, an unusual sleep experiences scale and a hallucination proneness scale.

Results: The results showed a significant positive association between quality of sleep and hallucination proneness, dissociation and unusual sleep experiences, and that dissociation and unusual sleep experiences fully mediated between sleep quality and hallucination proneness.

Conclusions: Our study highlights the importance of variables related to sleep quality and unusual sleep experiences and dissociation in understanding hallucinations, and the importance of taking these variables into consideration in designing intervention directed at reducing distress caused by hallucinations.     

Comorbid insomnia and sleep apnea in children: a preliminary explorative study

Insomnia and sleep-disordered breathing (SDB) are prevalent sleep disorders. These disorders can therefore be concurrently present – comorbid insomnia and sleep apnea (COMISA). The prevalence of COMISA in the paediatric age range is unclear. As such, phenotypic constructs should help better define this comorbid condition if it exists in children and improve both diagnostic sensitivity and ultimately clinical care outcomes. We aimed to evaluate the frequency of insomnia in children and adolescents referred for evaluation of sleep symptoms suggestive of SDB in one initial (Cohort#1) and verify such findings in an independent cohort (Cohort#2) using a retrospective cross-sectional approach in patients aged 9–19 years presenting at a sleep centre to be evaluated for symptoms of SDB. Cohort #1 comprised 50 consecutive children (58% males; mean [SD] age 13.6 [3.3] years; median [interquartile range, IQR] Epworth Sleepiness Scale score 10 [6–12]) who were evaluated using validated SDB and insomnia questionnaires. Cohort#2 was extracted from electronic medical records and included 384 polysomnographically evaluated children (mean [SD] age 12.9 [3.6] years; mean [SD] body mass index z score 1.27 [0.28]; median Epworth Sleepiness Scale score 9.7 [4–17]). In Cohort #1, 56% were at high risk of SDB, 36% had insomnia alone, and 18% were at high risk of COMISA. The prevalence of COMISA in Cohort #2 was 16%, 72% had SDB alone, and 12% had insomnia alone. In both cohorts, COMISA manifested as increased propensity for sleepiness and fatigue during both waking and daytime. Thus, the presence of COMISA is frequent in the paediatric age range and accompanied by a more prominent symptomatic phenotype.     

Melatonin profiles and sleep characteristics in boys with fragile X syndrome: a preliminary study

Sleep patterns and endogenous melatonin profiles in 13 fragile X boys between the age of 4.7 and 11.0 years were compared to those of 8 age-matched, normal control boys. Parents recorded sleep patterns on a Sleep Diary Chart for 14 consecutive days. Twelve saliva samples were obtained from 8 fragile X participants and all of the controls over 48 hours for the assessment of salivary melatonin profiles. The results showed greater variability in total sleep time and difficulty in sleep maintenance in fragile X boys compared with the control participants. Nocturnal melatonin production, expressed as both peak level and area under the concentration-time curve between 20:00 h and 08:00 h, were found to be significantly larger in fragile X boys than in controls. Additionally, the mean of the minimum daytime melatonin levels recorded was significantly higher for the fragile X group. Elevated levels in some fragile X boys relative to the range seen in controls, occurring either during the day or at night, or in both segments of the secretory profile for some individuals, may be due in part to overactivity of the sympathetic nervous system. Alternative molecular mechanisms leading to changes in melatonin profiles in fragile X are also discussed.     

Premenstrual dysphoric disorder and risk for major depressive disorder: a preliminary study.

Investigators examined whether premenstrual dysphoric disorder (PMDD) poses a risk for major depressive disorder (MDD). In an initial study, women rated premenstrual symptoms and functional impairment daily for two menstrual cycles. A semistructured diagnostic interview was given to obtain psychiatric histories and differentiate PMDD from premenstrual exacerbations of other disorders. Participants in this pilot study were eight women with PMDD and a random subgroup without PMDD (n = 9) initially. Another semistructured interview was given to diagnose psychiatric disorders occurring during a two-year follow-up interval. In all, seven of the eight women with PMDD developed MDD within two years, including all those who had never had MDD before. The odds that a woman with PMDD developed MDD were 14 times the odds that a woman without PMDD developed MDD ( p <.05). Premenstrual dysphoric disorder may be a prodrome of or causal risk factor for MDD. Preliminary evidence for the diagnostic validity of PMDD is provided.     

Heart rate variability during sleep as a function of the sleep cycle

In this work, in order to evaluate whether autonomic differences distinguish REM sleep and NREM sleep through the whole sleeping period, statistical analysis on spectral power associated with low frequency and high frequency bands were performed on the whole polysomnographic recording, considering the sleep cycle as a unit of sleep. Our results from nine subjects show that power associated with low frequency is higher in REM sleep than in NREM sleep, while power associated with high frequency is significantly higher in NREM sleep than in REM sleep. Differences between REM sleep and NREM sleep are not of the same magnitude within the whole sleep episode and, independent of sleep stages, specific trends are observable in the autonomic control of heart rate during the night.     

Evaluation of frequency and time-frequency spectral analysis of heart rate variability as a diagnostic marker of the sleep apnoea syndrome

The sleep apnoea/hypopnoea syndrome (SAHS) elicits a unique heart rate rhythm that may provide the basis for an effective screening tool. The study uses the receiver operator characteristic (ROC) to assess the diagnostic potential of spectral analysis of heart rate variability (HRV) using two methods, the discrete Fourier transform (DFT) and the discrete harmonic wavelet transform (DHWT). These two methods are compared over different sleep stages and spectral frequency bands. The HRV results are subsequently compared with those of the current screening method of oximetry. For both the DFT and the DHWT, the most diagnostically accurate frequency range for HRV spectral power calculations is found to be 0.019-0.036 Hz (denoted by AB2). Using AB2, 15 min sections of non-REM sleep data in 40 subjects produce ROC areas, for the DFT, DHWT and oximetry, of 0.94, 0.97 and 0.67, respectively. In REM sleep, ROC areas are 0.78, 0.79 and 0.71, respectively. In non-REM sleep, spectral analysis of HRV appears to be a significantly better indicator of the SAHS than the current screening method of oximetry, and, in REM sleep, it is comparable with oximetry. The advantage of the DHWT over the DFT is that it produces a greater time resolution and is computationally more efficient. The DHWT does not require the precondition of stationarity or interpolation of raw HRV data.     

Evaluation of frequency and time-frequency spectral analysis of heart rate variability as a diagnostic marker of the sleep apnoea syndrome

The sleep apnoea/hypopnoea syndrome (SAHS) elicits a unique heart rate rhythm that may provide the basis for an effective screening tool. The study uses the receiver operator characteristic (ROC) to assess the diagnostic potential of spectral analysis of heart rate variability (HRV) using two methods, the discrete Fourier transform (DFT) and the discrete harmonic wavelet transform (DHWT). These two methods are compared over different sleep stages and spectral frequency bands. The HRV results are subsequently compared with those of the current screening method of oximetry. For both the DFT and the DHWT, the most diagnostically accurate frequency range for HRV spectral power calculations is found to be 0.019–0.036 Hz (denoted by AB₂). Using AB₂, 15 min sections of non-REM sleep data in 40 subjects produce ROC areas, for the DFT, DHWT and oximetry, of 0.94, 0.97 and 0.67, respectively. In REM sleep, ROC areas are 0.78, 0.79 and 0.71, respectively. In non-REM sleep, spectral analysis of HRV appears to be a significantly better indicator of the SAHS than the current screening method of oximetry, and, in REM sleep, it is comparable with oximetry. The advantage of the DHWT over the DFT is that it produces a greater time resolution and is computationally more efficient. The DHWT does not require the precondition of stationarity or interpolation of raw HRV data.