Cerebral autoregulation in patients with obstructive sleep apnea syndrome during wakefulness

Background and purpose:  Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for stroke. Impairment of cerebral autoregulation may play a potential role in the pre-disposition to stroke of OSAS patients. In this study, we aimed to assess dynamic cerebral autoregulation (DCA) during wakefulness in OSAS patients and a group of matched controls.
Methods:  Patients and controls were examined in the morning after an overnight complete polysomnography. Mean cerebral blood flow velocity (CBFV) in the middle cerebral artery and mean arterial blood pressure (ABP) were continuously recorded using transcranial Doppler and Finapres. DCA was assessed using the Mx autoregulatory index. Mx is a moving correlation coefficient between mean CBFV and mean ABP. More positive value of Mx indicates worse autoregulation.
Results:  Eleven OSAS patients (mean age ± SD; 52.6 ± 7.9) and 9 controls (mean age ± SD; 49.1 ± 5.3) were enrolled. The mean apnea–hypopnea index (AHI) in the OSAS group was of 22.7 ± 11.6. No significant difference was found between the two groups as for age, body mass index, mean ABP and endtidal CO₂ pressure. Cerebral autoregulation was impaired in OSAS patients compared with controls (Mx index: 0.414 ± 0.138 vs. 0.233 ± 0.100; P  = 0.009). The severity of autoregulation impairment correlated to the severity of the sleep respiratory disturbance measured by the AHI ( P  = 0.003).
Conclusion:  Cerebral autoregulation is impaired in patients with OSAS during wakefulness. Impairment of cerebral autoregulation is correlated with the severity of OSAS.     

Factors influencing subjective sleepiness in patients with obstructive sleep apnea syndrome

The aim of the present paper was to clarify the factors influencing subjective daytime sleepiness in patients with obstructive sleep apnea syndrome (OSAS). Subjects included 230 adult male OSAS patients aged 20-73 years. Single and multiple linear regression analyses were performed to estimate the association between the Epworth Sleepiness Scale (ESS) and the following variables: Minnesota Multiphasic Personality Inventory (MMPI), Self-Rating Depression Scale (SDS), age, body mass index (BMI), sleep duration during the preceding month and apnea-hypopnea index (AHI). Single linear regression analysis showed that age had a negative association with ESS score, while BMI, AHI, SDS, hypochondriasis (Hs), hysteria, psychopathic deviant, psychasthenia, schizophrenia and hypomania on the MMPI had a positive association with ESS score. However, the other remaining parameters such as nocturnal sleep duration during the preceding month, depression, masculinity-femininity, paranoia, social introversion on the MMPI had no statistical association with ESS score. Multiple linear regression analysis with stepwise elimination method was applied to choose the significant factors associated with ESS. It was found that three variables including age, AHI and Hs scores were independent factors influencing ESS score. The R(2) for the model was 0.14, suggesting that these factors account for 14% of possible variance of subjective daytime sleepiness of OSAS patients. These results suggest that subjective daytime sleepiness in patients with OSAS may be influenced not only by the severity of respiratory disorder indices but also by certain personality characteristics affecting Hs score and by age.     

A new EEG biomarker of neurobehavioural impairment and sleepiness in sleep apnea patients and controls during extended wakefulness

ObjectiveTo explore the use of detrended fluctuation analysis (DFA) scaling exponent of the awake electroencephalogram (EEG) as a new alternative biomarker of neurobehavioural impairment and sleepiness in obstructive sleep apnea (OSA).MethodsEight patients with moderate–severe OSA and nine non-OSA controls underwent a 40-h extended wakefulness challenge with resting awake EEG, neurobehavioural performance (driving simulator and psychomotor vigilance task) and subjective sleepiness recorded every 2-h. The DFA scaling exponent and power spectra of the EEG were calculated at each time point and their correlation with sleepiness and performance were quantified.ResultsDFA scaling exponent and power spectra biomarkers significantly correlated with simultaneously tested performance and self-rated sleepiness across the testing period in OSA patients and controls. Baseline (8am) DFA scaling exponent but not power spectra were markers of impaired simulated driving after 24-h extended wakefulness in OSA (r = 0.738, p = 0.037). OSA patients had a higher scaling exponent and delta power during wakefulness than controls.ConclusionsThe DFA scaling exponent of the awake EEG performed as well as conventional power spectra as a marker of impaired performance and sleepiness resulting from sleep loss.SignificanceDFA may potentially identify patients at risk of neurobehavioural impairment and assess treatment effectiveness.     

Daytime sleepiness and automobile accidents in patients with obstructive sleep apnea syndrome

Abstract We evaluated the rate of automobile accidents and daytime sleepiness using the Epworth sleepiness scale (ESS) in 44 patients with obstructive sleep apnea syndrome (OSAS). We defined the automobile accident score as a sum of two points for every one automobile accident and one point for every near-miss accident. Automobile accidents and near-misses were found in 54.5% and 50.0% in patients with OSAS. Automobile accident score was significantly correlated with the ESS score ( r = 0.56, P < 0.01). Our findings suggest that ESS score may be useful in detecting patients with the potential risk of automobile accidents associated with daytime sleepiness.     

Daytime sleepiness and polysomnography in obstructive sleep apnea patients

BackgroundExcessive daytime sleepiness (EDS) is the major complaint in subjects with obstructive sleep apnea syndrome (OSAS). However, EDS is not universally present in all patients with OSAS. The mechanisms explaining why some patients with OSAS complain of EDS whereas others do not are unknown.ObjectiveTo investigate polysomnographic determinants of excessive daytime sleepiness (EDS) in a large multicenter cohort of patients with obstructive sleep apnea (OSAS).MethodsAll consecutive patients with an apnea–hypopnea index greater than 5 h⁻¹ who were evaluated between 2003 and 2005. EDS was assessed using the Epworth Sleepiness Scale (ESS), and patients were considered to have EDS if the ESS was >10.ResultsA total of 1649 patients with EDS ((mean [±SD] Epworth 15 ± 3) and 1233 without EDS (Epworth 7 ± 3) were studied. Patients with EDS were slightly younger than patients without EDS (51 ± 12 vs 54 ± 13 years, p < 0.0001), had longer total sleep time (p < 0.007), shorter sleep latency (p < 0001), greater sleep efficiency (p < 0.0001) and less NREM sleep in stages 1 and 2 (p < 0.007) than those without EDS. Furthermore, patients with EDS had slightly higher AHI (p < 0.005) and arousal index (p < 0.001) and lower nadir oxygen saturation (p < 0.01).ConclusionsPatients with OSAS and EDS are characterized by longer sleep duration and increased slow wave sleep compared to those without EDS. Although patients with EDS showed a mild worsening of respiratory disturbance and sleep fragmentation, these results suggest that sleep apnea and sleep disruption are not the primary determinants of EDS in all of these patients.     

Periodic limb movements and sleepiness in obstructive sleep apnea patients

BACKGROUND AND PURPOSE: The aim of this study was to assess the possibility that periodic limb movements during sleep (PLMS) could play an additive role in the sleepiness associated with obstructive sleep apnea syndrome (OSAS) before treatment, or could account for residual sleepiness in successfully CPAP-treated patients. PATIENTS AND METHODS: In order to test this hypothesis, we compared objective sleepiness, assessed by the Multiple Sleep Latency Test (MSLT) and subjective sleep propensity, assessed by the Epworth Sleepiness Scale (ESS), in a clinical series of 57 patients consecutively diagnosed with OSAS (apnea/hypopnea index, 53.3+/-26.15), before and after 1 year of treatment with CPAP. RESULTS: Twenty-two patients (38.5%) had significant PLMS (at least 5 PLMS/h of sleep; mean 52.9+/-53.9) in absence of apneas (with CPAP). The two groups (with and without PLMS) were similar in gender distribution, BMI, apnea/hypopnea index or CPAP level. Patients with PLMS were older than those without PLMS. Sleepiness measurements following OSAS diagnosis and after 1 year of CPAP treatment were similar in patients PLMS compared to those without significant PLMS. There was no correlation in the PLMS patient group between the PLM index, Epworth Sleepiness Scale score and mean latency in the MSLT. CONCLUSION: In this study we did not find a link between PLMS and increased objective or self-evaluated sleepiness in OSAS patients, before or after treatment with CPAP.     

Diurnal variation in daytime sleepiness of patients with sleep apnea syndrome

Diurnal variations in daytime sleepiness were studied in 26 men with sleep apnea syndrome (SAS) [age, 41.7 +/- 9.9 years (mean +/- SD); body mass index, 30.0 +/- 6.2 kg/m2; Epworth Sleepiness Score, 8.7 +/- 4.1; apnea-hypopnea index, 50.2 +/- 22.0]. Sleep latencies measured at 09.00 h, 11.00 h, 13.00 h, 15.00 h, and 17.00 h were 3.4 +/- 3.6 min, 4.7 +/- 5.5 min, 5.2 +/- 4.4 min, 5.3 +/- 5.4 min, and 9.3 +/- 7.2 min, respectively (ANOVA, P < 0.05). Daytime sleepiness in patients with SAS was more pronounced in the morning than in the afternoon and evening.     

Baroreflex modulation during sleep and in obstructive sleep apnea syndrome

This review focuses on the complex integration between cardiovascular reflexes and central autonomic influences controlling physiological sleep-dependent changes in arterial blood pressure and heart rate. A brief introduction on the anatomic and functional organization of the arterial baroreflex and the methods available to assess its function in humans is followed by an analysis of the functional interaction between autonomic nervous system and sleep mechanisms at the highest levels of brain organization. An insight into these interactions is important to shed light on the physiopathology of the most frequent complications of obstructive sleep apnea syndrome, such as sustained arterial hypertension, and excessive daytime sleepiness.     

Driving impairment in patients with obstructive sleep apnea syndrome

Drivers with obstructive sleep apnea syndrome (OSAS) have an increased risk of motor vehicle crashes. Unfortunately, neither clinical nor polysomnographic features allow clinicians to reliably identify high-risk drivers. One potential means of identifying these drivers is with the use of driving simulators. Several investigators have shown that OSAS patients perform worse than healthy control drivers and results from our studies have demonstrated declines in driving performance during EEG-defined "microsleeps." The use of simulators, and in-vehicle detection and alerting devices may mitigate some of the suffering caused by these crashes.     

睡眠呼吸暂停低通气综合征患者多导睡眠图特征及日间嗜睡分析

目的 通过对男女睡眠呼吸暂停低通气综合征（OSA）患者多导睡眠图特征及日间嗜睡程度的对比,探究OSA患者的多导睡眠图特征及日间嗜睡程度是否存在性别差异.方法 选取2011年5月～2013年2月在华西医院睡眠中心就诊,年龄在18～65岁之间,经整夜多导睡眠呼吸监测确诊为OSA（睡眠呼吸紊乱指数,AHI≥5次/h）的患者进行回顾性分析.按性别分为男性OSA患者及女性OSA患者两组,并对两组的年龄及AHI进行配对.比较两组患者多导睡眠图所示睡眠结构、缺氧状况、多次小睡潜伏时间试验（MSLT）及Epworth嗜睡量表（ESS）评分的差异.结果 共258名患者纳入研究,其中男性129名,平均年龄（49.4±11.3）岁,平均AHI指数（35.3±26.7）次/h;女性129名,平均年龄（49.7±11.8）岁,平均AHI指数（34.1±26.7）次/h.男女OSA患者相比,女性患者睡眠潜伏期更长[（19.2± 28.1）vs.（12.9±12.9）min],睡眠效率更低[（78.5±14.1）% vs.（84.5±9.7）%],睡后觉醒时间更长[（89.8±63.8）vs.（66.1±48.4）min],总睡眠时间更短[（396.9±78.8）vs.（ 427.6± 56.1）min],多次小睡平均潜伏期更长[（9.9±3.39）vs.（9.3±3.7）min],（P均＜0.05）.男女患者呼吸事件中低通气所占比例[（39.9±26.3）% vs.（53.4±27.7）%],阻塞性呼吸暂停所占比例为[（50.81±25.88）% vs.（41.03±26.72）%],（P均＜0.05）.结论 在AHI严重程度相一致的情况下,女性患者睡眠质量更差,但男性患者日间客观嗜睡程度更重.呼吸事件中女性患者多以低通气为主,而男性患者多以阻塞性呼吸暂停为主.     

Topographic mapping of EEG spectral power and coherence in delta activity during the transition from wakefulness to sleep

The present study examined the topographic characteristics in delta band activity during the transition from wakefulness to sleep, using topographic mapping of electroencephalogram (EEG) power and coherence corresponding to nine EEG stages. The dominant topographic components of delta band activity increased clearly from the vertex sharp-wave stage EEG stage 6) in the anterior-central area. Principal component maps revealed the scalp distribution of EEG. Delta activity in the sleep onset period were composed of two covariant components. One is a diffuse component widely distributed on the scalp and the other is a local component at the temporo-occipital area.     

Outcome of sleepiness and fatigue scores in obstructive sleep apnea syndrome patients with and without restless legs syndrome after nasal CPAP

BACKGROUND & PURPOSE: The association of obstructive sleep apnea syndrome (OSAS) and restless legs syndrome (RLS) has been reported in the literature for many years. Both conditions may be responsible for fatigue and somnolence complaints secondary to nocturnal sleep disruption. The primary concern of this study is to evaluate the outcome of fatigue and daytime sleepiness symptoms at baseline and after continuous positive air pressure (CPAP) treatment in OSAS patients with and without RLS. METHOD: A prospective and comparative study between a group of 13 patients with OSAS and a group of 17 patients with OSAS+RLS. Laboratory blood tests and polysomnography were performed at baseline. The Epworth Sleepiness Scale (ESS) and the Pichots questionnaire of fatigue/depression (PIC) were applied before and after 3 months of CPAP treatment. Results were compared. RESULTS: No significant differences were found on PSG and laboratory results at baseline. Both groups had similar ESS and PIC scores at baseline (p=0.73 and 0.08, respectively). After n-CPAP, OSAS+RLS patients showed higher ESS and PIC scores (p=0.017 and 0.03, respectively). CONCLUSIONS: Despite a favorable general response, n-CPAP seemed less effective in treating fatigue and sleepiness in the OSAS+RLS group.     

Causes of excessive daytime sleepiness in hypercapnic and normocapnic obstructive sleep apnea patients

Daytime sleepiness assessed using the Epworth sleepiness scale (ESS) and polysomnography results were compared in 43 patients with obstructive sleep apnea (OSA) with concomitant chronic hypercapnia (PaCO2 53 +/- 6 mmHg), and in 58 patients with the OSA syndrome accompanied by normocapnia (PaCO2 < or = 45 mmHg, mean 39 +/- 3 mmHg). The OSA patients with hypercapnia were more sleepy than those with normocapnia (ESS 18 +/- 7 vs 15 +/- 7, p < 0.05), but apnea index values were similar in both groups (54 +/- 20 and 49 +/- 17). The following parameters of electrophysiological sleep structure were obtained in the hypercapnic OSA patients: sleep stage 1: 66 +/- 28%, stage 2: 28 +/- 27%, stage 3 + 4: 1 +/- 1%, REM sleep 5 + 6% of the total sleep time, while in the OSA patients with normocapnia: stage 1: 39 +/- 19%, stage 2: 28 +/- 27%, stage 3 + 4: 2 +/- 2%, and REM sleep 6 +/- 7% of the total sleep time. Stage 1 NREM sleep was found to be longer, and stage 2 NREM--shorter in hypercapnic than in normocapnic OSA patients (p < 0.01). CONCLUSION: Increased daytime sleepiness in both groups patients with the OSA syndrome is due to sleep fragmentation as well as to deficiency of deep and paradoxical sleep (almost absent deep sleep and extremely shortened REM sleep). Hypercapnic OSA patients' more marked sleepiness may result from a more pronounced disturbance of their sleep macrostructure, with a considerable predomination of stage I NREM sleep.     

Cardiac arrhythmias during normal sleep and in obstructive sleep apnea syndrome

Normal sleep is associated with a slowing in heart rate due to a relative shift from sympathetic to parasympathetic neural dominance. Bradyarrhythmias consisting of sinus bradycardia, sinus arrest and second degree (Mobitz type 1) heart block are not uncommon in young adults. With aging, bradyarrhythmias decrease in frequency while atrial arrhythmias and ventricular ectopy increases. Patients with obstructive sleep apnea (OSA) have been demonstrated to have bradyarrhythmias and increased ventricular ectopy in association with apneas when oxyhemoglobin desaturations become severe. Although retrospective studies have suggested that cardiovascular mortality may be increased in patients with OSA, this remains to be proven in prospective clinical studies. Sudden death during sleep secondary to apnea related brady or ventricular tachyarrhythmias may occur. However, this is likely to be a very rare event that remains to be documented in the literature.     

Improvement in excessive daytime sleepiness after surgical treatment for obstructive sleep apnea syndrome

Abstract The author's goal was to investigate the effects of surgical treatment on psychophysiological measurements in 17 patients with obstructive sleep apnea syndrome (OSAS) and also to clarify the improvement process of each evaluation. Given the changes in respiratory disturbance and sleep architecture, it was obvious that surgical treatment had therapeutic effects on OSAS patients a few months after the surgery. In that process, a dissociation between objective and subjective sleepiness was observed. The improvement in objective sleepiness [multiple sleep latency test (MSLT)] was more delayed than the improvement in subjective sleepiness (Stanford Sleepiness Scale, Spaceaeromedicine fatigue checklist). The improvement of MSLT was associated with an improvement in sleep fragmentation. This finding suggests that the disruption of sleep continuity accompanied by respiratory disturbance might be responsible for the occurrence of objective sleepiness. It can be concluded that the effective management of OSAS needs to address the full range of psychophysiological manifestations, especially objective measurement of daytime sleepiness.     

Persistent sleepiness in CPAP treated obstructive sleep apnea patients: evaluation and treatment

Nasal continuous positive airway pressure (CPAP) is an effective treatment for most patients with obstructive sleep apnea syndrome (OSAS), improving sleepiness, cognitive function and mood. A number of patients, however, complain about persistent sleepiness after CPAP. In these cases another clinical history should be carried out to confirm the diagnosis of OSAS, to check CPAP compliance and to exclude associated conditions such as poor sleep hygiene, depression, narcolepsy or idiopathic hypersomnia. If necessary, a full polysomnography (PSG) followed by a multiple sleep latency test or even a full PSG with CPAP titration should be performed. Experimental data in animals suggest that long-term intermittent hypoxia related to the apneic events could deteriorate the brain structures that regulate alertness. This impairment, if present in humans, could be another reason for residual sleepiness after CPAP. Modafinil has been shown to reduce subjective sleepiness after CPAP in OSAS patients. Further studies are warranted to clarify the way in which CPAP modifies sleepiness.     

Placebo and modafinil effect on sleepiness in obstructive sleep apnea

INTRODUCTION: Previous studies have evaluated the effect of modafinil on residual excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea syndrome (OSAS) under effective CPAP treatment. Even though those trials also used placebo groups, we suppose that the placebo effect might influence the patients' response to modafinil. METHODS: Twenty sleepy patients with OSAS under CPAP treatment were selected. All of them had Epworth Sleepiness Scale (ESS) >10. Following baseline evaluation (T1), all subjects were instructed to take placebo for 7 days. After this single-blind placebo phase and second evaluation (T2), patients were randomly allocated to placebo or modafinil treatment for 21 days in a double-blind protocol. Patients underwent a final evaluation (T3) on the last day of drug intake. The evaluations at T1, T2 and T3 consisted of: medical and laboratory examinations, nocturnal polysomnography, ESS, maintenance of wakefulness test (MWT) and complex reaction time (CRT-NY). In addition, in T2 and T3 the change of illness severity scale (CGI-C) and the evaluation of quality of life (SF-36) were applied. RESULTS: The comparison between the two groups during the three periods studied, showed the following results: in the modafinil group, ESS score did not change during the initial placebo period, but there was a significant reduction during the modafinil treatment period (p=0.0006); in the placebo group a significant reduction occurred during the initial placebo period (p=0.05), and no further change was observed in the treatment (placebo) period. A significant difference was found between the two groups after the placebo period (T2) (p=0.02). Three patients (33%) of the modafinil group and 9 patients (81%) of the placebo group were classified as placebo-responsive (X2: p=0.039). In the treatment period, reaction time was significantly reduced in the modafinil group compared to the placebo group (p<0.02). There was a trend toward improvement in overall clinical condition and also in some domains of SF-36 in the modafinil group. CONCLUSION: In summary, our study confirms that modafinil used adjunctively with CPAP therapy improves subjective daytime sleepiness in patients with OSAS who were regular users of CPAP therapy but still experienced sleepiness. Moreover, it could help in the improvement of objective measures of behavioral alertness and reduce functional impairments. The usefulness of a blinded placebo period for systematic investigation of placebo role in studies based on subjective response is a point that should be considered in this type of drug trial.