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Biofuels from algae are highly interesting as renewable energy sources to replace, at least partially, fossil fuels, but great research efforts are still needed to optimize growth parameters to develop competitive large-scale cultivation systems. One factor with a seminal influence on productivity is light availability. Light energy fully supports algal growth, but it leads to oxidative stress if illumination is in excess. In this work, the influence of light intensity on the growth and lipid productivity of Nannochloropsis salina was investigated in a flat-bed photobioreactor designed to minimize cells self-shading. The influence of various light intensities was studied with both continuous illumination and alternation of light and dark cycles at various frequencies, which mimic illumination variations in a photobioreactor due to mixing. Results show that Nannochloropsis can efficiently exploit even very intense light, provided that dark cycles occur to allow for re-oxidation of the electron transporters of the photosynthetic apparatus. If alternation of light and dark is not optimal, algae undergo radiation damage and photosynthetic productivity is greatly reduced. Our results demonstrate that, in a photobioreactor for the cultivation of algae, optimizing mixing is essential in order to ensure that the algae exploit light energy efficiently.

Mixotrophy can be exploited to support algal growth over night or in dark-zones of a photobioreactor. In order to achieve the maximal productivity, however, it is fundamental also to provide CO(2) in excess to maximize photosynthetic activity and phototropic biomass production. The aim of this paper is to verify the possibility of exploiting mixotrophy in combination with excess CO(2). Two species with high biomass productivity were selected, Nannochloropsis salina and Chlorella protothecoides. Different organic substrates available at industrial scale were tested, and glycerol chosen for its ability to support growth of both species. In mixotrophic conditions, excess CO(2) stimulated photosynthesis but blocked the metabolization of the organic substrate, thus canceling the advantages of mixotrophy. By cultivating microalgae under day-night cycle, organic substrate supported growth during the night, but only if CO(2) supply was not provided. This represents thus a possible method to reconcile CO(2) stimulation of photosynthesis with mixotrophy., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Study Objectives: Pulse transit time (PPT) has been introduced as a useful screening tool to diagnose sleep disordered breathing (SDB). Since the prevalence of SDB increases with age, the question is whether PTT could be used to diagnose SDB in the elderly. We assess the effectiveness of PTT for SDB screening in a large healthy elderly population., Setting: Community-based sample in home and research clinical settings., Intervention: N/A., Participants: Seven hundred eighty volunteers, free of cardiac and neurologic disease, aged 68.6 ± 1.0 years, underwent ambulatory polygraphy to measure the apnea-hypopnea index (AHI). The presence of SDB was defined as an AHI of 15 or greater. The PTT was continuously monitored during the nocturnal study, and the overall autonomic arousal index (AAI) was calculated., Results: SDB was diagnosed in 447 (57.3%) subjects. In these subjects, the Bland-Altman plot for AAI revealed an underestimation with a bias of -8.04 ± 16.55 events per hour (mean ± 95% confidence interval). Receiver operating characteristic curves constructed for an AHI of 15 or greater defined an area under the curve of 0.67 and a cutoff point to AAI 32.3 events per hour, giving a sensitivity of 70.5% and a specificity of 54.7%. For prediction of an AHI of at least 30, the area under the curve was equal to 0.74 for a cutoff point of 56.3 events per hour, giving a better specificity (94.7%) but a lower sensitivity (32.2%)., Conclusions: In a healthy older population, the AAI showed moderate sensitivity for predicting SDB. This data does not allow us to use PTT as a screening tool for the diagnosis of SDB in the elderly., Clinical Trial Registration: NCT 00759304 and NCT 00766584.

Algae are interesting potential sources of biodiesel, although research is still needed to develop efficient large scale productions. One major factor affecting productivity is light use efficiency. The effect of different light regimes on the seawater alga Nannochloropsis gaditana was accessed monitoring growth rate and photosynthetic performances. N. gaditana showed the capacity of acclimating to different light intensities, optimizing its photosynthetic apparatus to illumination. Thanks to this response, N. gaditana maintained similar growth rates under a wide range of irradiances, suggesting that this organism is a valuable candidate for outdoor productions in variable conditions. In the conditions tested here, without external CO(2) supply, light intensity alone was not found to be a major signal affecting lipids accumulation showing the absence of a direct regulatory link between the light stress and lipids accumulation. Strong illumination can nevertheless indirectly influences lipid accumulation if combined with other stresses or in the presence of excess CO(2)., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Obstructive sleep apnoea (OSA) affects females and males differently, and increases in prevalence with age. The aim of the present study was to characterise clinical, anthropometric and polygraphic sex differences in a large elderly OSA population. A total of 641 subjects aged 68 yrs were examined. Measurements of fat mass, using dual-energy X-ray absorptiometry (DEXA) and polygraphy, were obtained in all subjects. An apnoea/hypopnoea index (AHI) of >15 events·h⁻¹ identified the presence of OSA. OSA was diagnosed in 57% of the sample, 34% having a mild form and 23% having an AHI of >30 events·h⁻¹. Females with OSA exhibited a lower AHI, less severe hypoxaemia and greater peripheral fat mass, and frequently reported anxiety and depression. Comparison of females with and without OSA did not reveal significant differences in clinical, anthropometric and DEXA data. After adjustment for body mass index, hypertension, diabetes, smoking, anxiety and depression, logistic regression analysis revealed that the presence of hypertension was significantly associated with OSA risk in females (OR 1.52, p = 0.04). In a general community healthy population, the prevalence of undiagnosed OSA in females increases with age, with a risk similar to that in males. In females, the clinical spectrum, anthropometric data and fat distribution appear to be more sex-related than OSA-dependent. The occurrence of OSA contributes to hypertensive risk in elderly females.

Idiopathic hypersomnia is an uncommon sleep disorder characterized by prolonged sleep time and excessive daytime sleepiness without cataplexy. This study concerned a case of familial occurrence. The proband expressed an idiopathic hypersomnia with long sleep time at the age of 12 years. Clinical interview and ad libitum polysomnographic study did not reveal any symptoms of narcolepsy or other sleep disorders. Family history revealed that a 20-year-old sister had experienced symptoms of hypersomnia from the age of 16 and their mother had been diagnosed with idiopathic hypersomnia previously. The diagnosis of idiopathic hypersomnia with long sleep time was confirmed in the sister by clinical interview and ad libitum polysomnography. Human leukocyte antigen (HLA) did not reveal the DQB1-0602 phenotype in the proband and relatives. This report confirms the hypothesis of a genetic predisposition in idiopathic hypersomnia.

Objective: In the elderly, obstructive sleep apnea (OSA) is frequently under diagnosed. This study was undertaken to assess the accuracy of the Berlin questionnaire to diagnose OSA in a large healthy elderly population., Patients and Methods: Six hundred forty-three participants aged 65.6 years were examined. All subjects completed the Berlin questionnaire and underwent at-home respiratory recording. Presence of OSA was defined by an AHI>15., Results: Of the respondents, 202 subjects (31.4%) were in an OSA high-risk group according to the Berlin questionnaire. The high-risk subjects were significantly heavier, had greater waist and hip circumferences, higher AHI, and reported more frequently hypertension and diabetes. Habitual snoring was present in 54% of the sample, sleepiness in 12% of participants, and a BMI>30 and a history of hypertension in 42.1%. Being in the high-risk group predicted an AHI>15 with a sensitivity of 77%, a specificity of 39%, a positive predictive value of 63% and a negative predictive value of 55%. Among Berlin questionnaire categories, snoring correctly classified 61% of the sample and explained the 5% variance of AHI., Conclusions: The Berlin questionnaire did not provide a high level of diagnostic specificity to discriminate OSA in an elderly population. Although not sufficiently accurate, this questionnaire can be used to identify subjects for sleep study assessment., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Cortical dysgenesis is increasingly recognised as a cause of epilepsy. We report a case with double cortex heterotopia and secondarily generalized seizures with a generalised spike wave pattern. During the course of the disease, the child developed electrical status epilepticus in slow wave sleep. From the first examination, sleep pattern revealed increased frequency and amplitude of spindle activity, more evident in anterior areas. The role of the thalamocortical pathway in increased sleep spindle activity is discussed with emphasis on the possible role of altered thalamocortical pathways in abnormal cortical migration. A strong suspicion of cortical dysgenesis may therefore be based on specific EEG sleep patterns.

Magnetic resonance imaging studies using voxel-based morphometry (VBM) have been inconsistent in demonstrating volumetric differences in patients with restless legs syndrome (RLS). Since treatment, age and selection of patients may introduce a methodological bias, we conducted optimized VBM analyses in unmedicated elderly subjects reporting RLS. Two hundred-four voluntaries, 65.9 +/- 0.6 year-old, free of any significant medical condition and without previous neurological or psychiatric medication, participated at the study. After exclusion of subjects having sleep-related breathing disorders and previous silent infarct, 71 subjects, 54 without RLS (RLS-) and 17 having RLS (RLS+) were analyzed. No structural change in gray matter density was found in RLS+ subjects compared to RLS- subjects. Subjects with RLS+ symptoms showed a small gray matter volume in the left occipital region without, however, statistical significance. VBM analysis did not show any significant change in subcortical and cortical gray matter in unmedicated elderly subjects with RLS symptoms. These results confirm the lack of specificity of thalamic and subcortical changes in restless legs syndrome.

Background: The occurrence of restless legs syndrome (RLS) in elderly individuals is well known but the incidence and the clinical correlates in these subjects are still unclear. The present study explores the prevalence of and assesses symptoms associated with RLS in an older French population., Methods: The study sample for this study comprised 318 subjects (219 women and 99 men), aged 68.6 +/- 0.8 years. All subjects underwent clinical assessment, nocturnal polygraphy, and cognitive and mood disorders evaluation. RLS was assessed with the standard validated criteria and severity was evaluated by the use of International Restless Legs Syndrome Study Group (IRLS) questionnaire., Results: RLS was present in 24.2% of the sample, prevalence being greater in women (29.7%) than in men (12.1%). The mean IRLS score was 16.6 +/- 4.8, 67% of cases having mild to moderate range. Participants with RLS reported greater hypnotic (p < .001) and antidepressant medication intake (p < .001) and had higher anxiety (p < .001) and depression (p < .001) scores. Participants with RLS had lower cognitive performances at Stroop and Verbal fluency tests than participants without RLS (p < .05 and p = .002, respectively). These associations remained significant after multivariate adjustment for medication, depression, and subjective sleep., Conclusions: Presence of undiagnosed RLS is higher in healthy elderly participants without previously diagnosed sleep disorders, affecting women more often than men. The presence of RLS increased the risk of anxiety and mood disorders and predispose to preclinical cognitive decline independently of anxiety, mood disorders, duration and quality of sleep, and medication.

Background and Purpose: An association between obstructive sleep apnoea/hypopnea (OSAH) and cardiovascular risk factors such as dyslipidemia has been described in adults and high-risk populations., Patients and Methods: We examined this association in a prospective cohort (SYNAPSE study) of 846 elderly (68.5+/-1.1 years) volunteers (41.6% of men). No subject presented with recognized OSAH syndrome, heart disease, or any neurological disorder. Unattended at-home polygraphy was done by all subjects. OSAH severity was defined as moderate (apnoea/hypopnea index: AHI>15/h) or severe (AHI>30/h). High-density lipoprotein cholesterol (HDL-c) was measured by immuno-separation-based homogenous assay., Results: The prevalence of severe cases reached 21.5% (AHI mean+/-SD: 43.5+/-11.9). Using univariate linear regression analysis, AHI (R=-0.172; p<0.0001), oxyhemoglobin desaturation index (ODI) (R=-0.108; p<0.002), mean SaO(2) (R=0.125; p<0.0003) and Nadir SaO(2) (R=0.094; p<0.007) were significantly associated with HDL-c. Multiple regression analysis demonstrated that male gender, BMI, waist to hip ratio, ODI, and AHI represent independent predictors of HDL-c. Logistic regression analysis showed a significant association between severe OSAH and low HDL-c serum levels (p<0.03) after adjustment for gender, BMI, hypertension, glycaemia, waist to hip ratio, alcohol intake and treated dyslipidemia. The association appears more evident in subjects free of lipid-lowering medications and beta-blockers (p<0.007). There was no independent association of OSAH syndrome with low-density lipoprotein (LDL) cholesterol., Conclusion: Unrecognized moderate to severe apnoea/hypopnea syndrome was independently associated with low HDL-c serum levels in the present cross-sectional based elderly population. This could explain the deleterious effect of OSAH syndrome on cardiovascular risk.

Elevated levels of C-reactive protein (CRP) have been reported in patients with sleep-disordered breathing (SDB) and may represent an inflammatory marker of cardiovascular risk. However, the association of CRP with SBD in presumed healthy elderly subjects is unknown. In total, 851 (58.5% females) 68-yr-old subjects, who were free of any known cardiac or sleep disorders, were prospectively examined. Subjects underwent unattended polygraphy, and the apnoea/hypopnoea index (AHI) and oxyhaemoglobin desaturation index (ODI) were assessed. Elevated levels of CRP were found on the morning after the sleep study in patients with more severe SDB. A significant correlation was found between CRP levels, time spent at night with arterial oxygen saturation <90% and ODI. No association was found between CRP levels and AHI. After adjustments for body mass index, smoking status, hypertension, diabetes and dyslipidaemia, a significant association remained between CRP levels and ODI >10 events.h(-1). CRP levels were frequently increased in a large sample of elderly subjects free of major cardiovascular disease. CRP levels were not correlated with the AHI and the indices of sleep fragmentation; the ODI >10 events.h(-1) was the strongest predictor of raised CRP level. The present results suggest that, in the elderly, intermittent hypoxaemia may underlie inflammatory processes leading to cardiovascular morbidity.

Background: Volume targeting by bi-level positive pressure ventilation (BPPV) has recently been made available by several manufacturers for home care ventilators. Although it may improve nocturnal ventilation, we hypothesized that increased pressure swings related to volume targeting may have a deleterious effect on sleep structure and patient comfort., Methods: Patients in stable clinical condition (n=12) treated by BPPV for obesity-hypoventilation (BMI: 44+/-8 kg/m(2)) for a median of 30 months (range: 2-138), underwent nocturnal polysomnography with transcutaneous capnography on 2 consecutive nights with either BPPV and usual ventilator settings or BPPV with volume targeting, in randomized sequence. Subjective quality of sleep (St. Mary's Hospital Questionnaire) and comfort of ventilation (VAS scales) were also assessed., Results: Mean IPAP, mean tidal volume, and total ventilation increased significantly with volume targeting. Control of nocturnal hypoventilation was slightly improved with volume targeting (nocturnal TcPCO(2): 42+/-9 vs. 45+/-5 mmHg, p=0.04). However, total sleep time and stage 2 sleep were greater without volume targeting, and wake after sleep onset and awakenings >20s increased with volume targeting. Subjectively, patients described a lighter sleep, of lesser quality and more frequent awakenings with volume targeting; ventilation was perceived as less comfortable, with an increased perception of leaks and of "too much air"., Conclusion: In stable patients treated by BPPV for obesity-hypoventilation, volume targeting improved control of nocturnal hypoventilation at the expense of a slight decrease in objective and subjective sleep quality, and comfort of ventilation.

Humans have an individual profile of the electroencephalographic power spectra at the 8 to 16 Hz frequency during non-rapid eye movement sleep that is stable over time and resistant to experimental perturbations. We tested the hypothesis that this electroencephalographic "fingerprint" is genetically determined, by recording 40 monozygotic and dizygotic twins during baseline and recovery sleep after prolonged wakefulness. We show a largely greater similarity within monozygotic than dizygotic pairs, resulting in a heritability estimate of 96%, not influenced by sleep need and intensity. If replicated, these results will establish the electroencephalographic profile during sleep as one of the most heritable traits of humans.

Objective: Several factors, such as homeostatic and circadian influences, may affect the density of cortical and subcortical arousals (AR). The purpose of this study was to examine the time-of-night and the first night effect on AR response., Methods: AR were classified into microarousals (MA), phases of transitory activation (PAT), delta (D-burst) and K-complex burst (K-burst). The AR density and duration was analyzed during two consecutive nights with the analysis of sleep stage and sleep cycle in thirty-six healthy subjects., Results: D- and K-burst showed a trend toward progressive decline across sleep cycles (p<0.0001). While MA rate was unaffected throughout sleep cycles, PAT index increased across the night (p=0.002). The density and duration of each group of AR exhibited reproducibility without significant differences between nights. An individual inter-night variability in AR density was found independently of night and sleep structure., Conclusions: While homeostatic and circadian influences affect nighttime subcortical and MA responses, a wakefulness drive modulates the occurrence of AR with movements. Although the pattern of AR responses was highly reliable from the first to second night, the substantial inter-individual variability suggests the existence of an individual susceptibility., Significance: The first night effect on arousal response is affected by individual susceptibility and circadian and homeostatic influences.

In the last two decades quantitative electroencephalogram (EEG) analysis has been widely used to investigate the neurophysiological characteristics of insomnia. These studies provided evidence in support of the hypothesis that primary insomnia is associated with hyperarousal of central nervous system and altered sleep homeostasis. However, we have here underlined that these results have intrinsic methodological problems, mainly related to constraints of standard assessment in clinical research. We have proposed that future studies should be performed on larger samples of drug-free patients, using within-subjects designs and longitudinally recording patients adapted to sleep laboratory. All these methodological improvements will allow to partial out the contribution of individual differences, pharmacological influences and first-night effects on EEG frequencies. Moreover, we have discussed the potential relevance of recent findings from basic research concerning local changes during physiological sleep, which could be extended to the study of insomnia. We have suggested that, if normal sleep exhibits specific regional characteristics, also disorders in initiating and maintaining sleep should be characterized by local changes. The extension of this theoretical framework to the study of insomnia could provide new insights on the underlying pathophysiological mechanisms. As a first step toward the integration of knowledge from basic and clinical research focused on local sleep changes, here we showed some preliminary data from sleep onset recordings of patients with paradoxical insomnia. This approach supports the heuristic potential of our proposal, pointing to a local functional impairment in the process of synchronization in insomniac patients compared to normal subjects, the former exhibiting more beta and less delta and sigma power on anterior scalp locations than the latter.

New insights into the physiopathological correlates of arousal and sleep fragmentation have recently been gained through experimental and clinical studies in healthy individuals and in patients with sleep disorders. The development of new analyses of autonomic system during sleep, has enriched the knowledge of sleep fragmentation derived from electroencephalographic analysis and has made possible the characterization of other phasic events arising from sleep, such as autonomic arousals. All of these studies provide evidence in support of the hypothesis that autonomic activations without cortical involvement are an epiphenomena of sleep fragmentation and altered sleep continuity, similar to that induced by cortical activation. This review begins by describing the latest findings on type of arousal response, with regards to the effect of arousing stimuli on the brain and the autonomic system. It then focuses on the hotly debated issue on experimental and clinical physiopathology of the arousals without cortical activation, highlighting the results of novel studies on the neural substrates mediating these response. Finally, we address the current question on clinical significance of sleep fragmentation to understand if arousal per se, cortical or autonomic, has an impact on daytime functioning, cardiovascular consequences and cognitive sequelae.

Amebic abscess is a common manifestation of extraintestinal amebiasis and it is associated with relatively high morbidity and mortality. We present three cases seen in Bari, Southern Italy, one of which was autochthonous and the other two were not. Diagnosis was performed by elevated antibody titre for E. histolytica through immunofluorescence assay and positive antigen determination by ELISA in stools and in abscess aspirate. Fever often accompanied by chills, abdominal pain, weight loss and hepatomegaly were present. Laboratory findings also revealed leukocytosis with neutrophilia. Pleural effusion was observed in two patients. In all our patients multiple abscesses were observed. All the patients were treated with metronidazole and two of them also underwent the aspiration of the amoebic abscess. In all of them there was improvement of the clinical picture, as demonstrated by computerized tomography.

Background and Purpose: To evaluate the test-to-test variability of the suggested immobilization test (SIT) in patients with restless legs syndrome (RLS)., Patients and Methods: Twenty patients with primary RLS (12 men and eight women; age: 53.3+/-11.3 years) were selected for the study. We compared the results of two SITs performed on two consecutive evenings prior to polysomnographic recordings., Results: Overall, the periodic leg movement index during the SIT (SIT PLM) and the SIT PLM index associated with sensory manifestations (SIT PLM+) were not significantly different between tests. The number of PLM sequences per SIT, the mean PLM duration and the PLM interval did not significantly change between the two consecutive tests. The pattern of temporal evolution of motor activity across the SIT was very reproducible, SIT PLM showing a clear tendency to a progressive increase across the test, with the SIT PLM+ index decreasing in the second half of the test. Despite good reproducibility, there were marked intra-individual differences. Considering the proposed cut-off value of 12 for the SIT PLM index to confirm RLS, 11 patients were positive at the first test and four additional patients became positive at the second test. SIT PLM index changes did not correlate with age, severity of disease and polysomnographic measures., Conclusions: Quantitative analysis of motor activity during two consecutive SITs in RLS patients showed a significant inter-test intra-individual variability unrelated to demographic, clinical or polysomnographic parameters. SIT PLM index variability suggests that a single test would not be sensitive enough for diagnostic purposes in unclear cases and that new criteria need to be applied to increase its specificity and sensitivity.

Restless legs syndrome (RLS) is a common sleep disorder characterized by dysesthesias and paresthesias in the legs, occurring at rest, worsening at evening and night and alleviated by movements. Apart from idiopathic cases, RLS and psychiatric diseases share a common association and recent studies have shown a strong association between RLS and antidepressants. The effects of antidepressants such as selective serotonin reuptake inhibitors and venlafaxine on worsening RLS have been widely studied and their use should be avoided. The clinical spectrum of RLS and the physiopathological link with antidepressant will be discussed in this review in order to provide new preventive strategy in clinical practice to improve diagnosis, orientating therapeutic decision and evaluating efficacy of treatment.

Objective: The existence of a rapid eye movement (REM)-specific sleep-disordered breathing (SDB) has been suggested based on the finding of an association between sleepiness and respiratory disturbances confined primarily to REM sleep. The aim of the study was to define the frequency and the clinical and polysomnographic features of REM SDB in a large clinical population., Methods: Anthropometric, clinical, and polysomnographic characteristics of 415 patients undergoing polysomnography for SDB were examined. For all patients the apnea-hypopnea index (AHI) during total sleep time, the AHI during REM (AHI-REM), and the AHI during non-REM sleep (AHI-NREM) were calculated. REM SDB was defined as an AHI-REM/AHI-NREM ratio >2. Patients were stratified according to the severity of disease in mild, moderate, and severe cases. Daytime sleepiness was assessed subjectively by the Epworth sleepiness scale (ESS), and objectively, in a subgroup of 228 patients, by the maintenance wakefulness test (MWT)., Results: Of the initial sample, 36.4% of cases (n = 151) fulfilled the REM SDB criteria. No significant differences in subjective complaints, medical history, and drug intake were present between REM and non-REM SDB patients, and no significant differences were found in ESS scores and mean sleep latency of the MWT between groups. A high occurrence of REM SDB was found in mild (73.1%) and moderate cases (47.2%). While in the entire group and in non-REM SDB patients a strong male prevalence was found, the incidence of REM SDB was similar in men and women., Conclusion: Our results show that neither clinical history nor daytime sleepiness differentiate patients with REM SDB from non-REM SDB patients. The disorder is more common in mild and moderate cases; there is an equal incidence in women and men. These findings may suggest that REM-related SDB is a part of the spectrum of SDB.

Background and Purpose: Restless legs syndrome (RLS) is usually associated with periodic leg movements (PLM) occurring during wakefulness and sleep. The PLM index obtained by the polysomnographic method reflects the degree of motor symptoms and their consequences on sleep structure. Automated analysis of PLM using actigraphy can assess this condition and can therefore be used to assess therapeutic effects in clinical trials. In the current study we assessed the reliability of the PAM-RL, an ambulatory device measuring limb movements and PLM with a high-time resolution., Patients and Methods: Forty-three patients consecutively referred to the sleep laboratory for insomnia and/or excessive daytime sleepiness underwent one or two nights of polysomnography (PSG) with simultaneous bilateral recording of limb activity by the PAM-RL device. The PSG recordings were blinded and manually analyzed for PLM, while limb actimetry was scored automatically based on the manufacturer's algorithm., Results: There was a significant correlation between PLM derived from PSG and actimetry (r=0.87, P<0.0001) with good agreement across a wide range of values. The sensitivity and specificity of the PAM-RL device in detecting patients having a polysomnographic PLM index >10 were, respectively, 0.88 and 0.76 with a receiving operating curve having an area under the curve (AUC) of 0.86 for the entire group of patients. All patients with clinically definitive RLS and primary PLM disorder (PLMD) had a PLM index >10 on PSG, but among patients with sleep-related breathing disorders (SRBD) 60% reached this cut-off value. Conversely, only 50% of those patients with an actigraphically assessed PLM index >10 had clinically definitive RLS or PLMD, and 40% had SRBD., Conclusions: We demonstrate that automatic detection of PLM derived from the PAM-RL device is highly reliable when compared to the 'gold standard' of polysomnography in patients with RLS and PLMD. Therefore, limb actigraphy can be used routinely to assess motor restlessness in patients with RLS and PLMD. The higher discrepancy in patients with SRBD and insomnia may preclude the use of the device in these patients.

Background: QT rate dependence is one of the major properties of ventricular repolarization, with its circadian and autonomic modulations. The alteration of cardiac autonomic tone occurring in obstructive sleep apnea syndrome (OSAS) patients could explain the altered rate-dependent adaptation of the myocardial repolarization. Thus, we postulated that dynamic alterations in QT interval adaptation could be ameliorated in OSAS patients under continuous positive airway pressure (CPAP) treatment. To assess ventricular repolarization features in patients with OSAS, we compared QT parameters and their dynamicities along RR intervals from 24-hour ECG., Methods: The study groups consisted of 38 consecutive OSAS patients and 38 healthy age-matched subjects. The syndrome was confirmed for OSAS patients according to standard polysomnographic criteria (apnea plus hypopnea index: 56.9 +/- 28.4/h). A second polysomnography synchronized with 24-hour ECG Holter and realized under efficient CPAP therapy confirmed the control of sleep-related breathing disorder., Results: QT length related to heart rate was found significantly altered in patients with OSAS compared with controls (QTend/RR slope: -0.126 +/- 0.031 vs -0.173 +/- 0.038; P < 0.01). This flattened relationship was significantly improved with the treatment of the OSAS (-0.151 +/- 0.051; P < 0.01 vs pretreatment status). There was no significant impact of CPAP therapy on ventricular ectopic activity as well as on static repolarization parameters (QT, RT, QTc, RTc) measured separately over daytime and nighttime., Conclusions: The prognostic implications of such findings and the protective role of CPAP treatment to prevent sudden cardiac death in OSAS need to be evaluated.

Background and Purpose: Although a night-to-night variability in periodic leg movements (PLM) occurrence has been described in patients with primary PLM disorder and sleep apnea syndrome, no study has apparently considered the inter-night effect on PLM index during wakefulness and sleep in patients with Restless Legs Syndrome (RLS). Moreover, no study has examined the night-to-night variability in PLM index according to sleep stage and time of night. We therefore examined changes in PLM index during wakefulness and sleep during two consecutive nights in a group of untreated RLS patients., Patients and Methods: Twenty-eight drug-free RLS patients, aged 53.4+/-2.3 yr, with a mean International Restless Legs Syndrome Study Group (IRLSSG) severity score of 20.2+/-1.6, were studied during two consecutive nights. PLM duration and interval, PLM index during wakefulness (PLMWI), during total sleep time (PLMSI), as well as during each sleep stage were measured. Analysis was also extended to examine PLM occurrence during sleep cycles., Results: In the group of patients as a whole, the PLMW and PLMS index, duration and interval did not show significant difference between nights, these measures being consistently similar for both nights. Comparison of PLMS index between different sleep stages did not reveal inter-night differences. Nocturnal variation in PLM number, duration and interval for total recording time and sleep period revealed a progressive decline across the night for PLM index (P

Objective: Changes in cardiovascular measures have been advocated as sensitive markers of phasic events arising from sleep. The current study was aimed to analyse the effects of periodic leg movements (PLMS) on heart rate variability (HRV) during NREM sleep in patients having restless legs syndrome and periodic leg movements during sleep., Methods: The absolute and normalized high- and low-frequency peaks from spectral analysis (FFT) of R-R intervals, the HRV changes using wavelet transform, the geometric and time domain HRV were measured in 14 patients with restless legs syndrome and PLMS. The analysis was done comparing one hundred, 10 min periods with PLMS (PLMS+) and 60 periods without PLMS (PLMS-) in stage 2 of NREM sleep. In 8 patients analysis was also done in slow wave sleep (SWS)., Results: Occurrence of PLMS induced changes in geometrical indices of HRV, with a rise of the triangular index and the triangular interpolation of R-R intervals in PLMS+ periods (P < 0.0001). Small changes in time domain indices were found during PLMS+ periods, while the SD of the R-R intervals (SDNN), reflecting global HRV, was significantly higher (P = 0.001). While the low frequency (LF) power significantly increased in PLMS+ periods (P < 0.0001), high frequency (HF) power showed a weak and not significant reduction. The rise in sympathetic activity as detected by frequency domain HRV analysis was related to density and interval of PLMS. Comparison between sleep stages of NREM sleep demonstrated lower values of HRV measures when PLMS+ periods occur in SWS., Conclusions: Overall, PLMS occurrence was associated with a shift to increased sympathetic activity without significant changes in cardiac parasympathetic activity. The frequency domain analysis of HRV appears to be an easy tool to estimate the autonomic changes related to PLMS and PLMS- arousals and to differentiate their occurrence during stage 2 and deep sleep., Significance: Spectral HRV measures may offer a simple approach to estimate the degree of autonomic changes occurring in relation to periodic leg movements in restless legs patients.

The maximal inspiratory effort recorded at the end of apnea has been considered as an index of arousal threshold in obstructive sleep apnea syndrome (OSAS). Previous investigations have shown that the arousal threshold is higher in patients with OSAS than in normal subjects. The aim of the present study was to investigate the effect of continuous positive airway pressure (CPAP) treatment on the inspiratory-effort-related arousal threshold in patients with OSAS. In ten male patients, 40 episodes of apnea during stage 2 non-REM (NREM) sleep were analyzed. Apnea duration (t), esophageal pressure (Pes) at the first occluded breath (Pes1), the minimum of the three initial Pes swings (Pes min), the maximum of the three final Pes swings (Pes Max), DeltaPes (Pes Max-Pes min), RPes (rate of increase of intrathoracic pressure, DeltaPes/t), n (number of occluded breaths during apnea), DeltaPes/n, n/t, and SaO(2) were determined before and after occlusion. These apneic episodes were compared to ten episodes of apnea provoked by a mask occlusion device after 1, 7, 30, and 90 days of CPAP treatment. The therapy resulted in a decrease in the inspiratory-effort-related arousal threshold, as measured by a reduction of Pes Max, without significant changes in apnea duration and apnea-related hypoxemia. Pes1 and DeltaPes/n, which are markers of respiratory drive, significantly decreased between observations. CPAP treatment decreases the inspiratory-effort-related arousal threshold and induces a decrease in ventilatory drive in response to upper airway occlusion.

Objective: Arousal (AR) from sleep is associated with an autonomic reflex activation raising blood pressure and heart rate (HR). Recent studies indicate that sleep deprivation may affect the autonomic system, contributing to high vascular risk. Since in sleep disorders a sleep fragmentation and a partial sleep deprivation occurs, it could be suggested that the cardiovascular effects observed at AR from sleep might be physiologically affected when associated with sleep deprivation. The aim of the study was to examine the effect of sleep deprivation on cardiac arousal response in healthy subjects., Methods: Seven healthy male subjects participated in a 64 h sleep deprivation protocol. Arousals were classified into four groups, i.e. >3<6 s, >6<10 s, >10<15 s and >15 s, according to their duration. Pre-AR HR values were measured during 10 beats preceding the AR onset, and the event-related HR fluctuations were calculated during the 20 beats following AR onset. As an index of cardiac activation, the ratio of highest HR in the post-AR period over the lowest recorded before AR (HR ratio) was calculated., Results: For AR lasting less than 10 s, the occurrence of AR induces typical HR oscillations in a bimodal pattern, tachycardia followed by bradycardia. For AR lasting more than 10 s, i.e. awakenings, the pattern was unimodal with a more marked and sustained HR rise. The HR response was consistently similar across nights, during NREM and REM sleep, without difference between conditions., Conclusions: Overall, total sleep deprivation appeared to have no substantial effect on cardiac response to spontaneous arousals and awakenings from sleep in healthy subjects. Further studies are needed to clarify the role of chronic sleep deprivation on cardiovascular risk in patients with sleep disorders., Significance: In healthy subjects acute prolonged sleep deprivation does not affect the cardiac response to arousal.

Background and Purpose: Micro-arousals (MA) are commonly considered as sleep components reflecting sleep fragmentation. However, their elucidation is time-consuming, with considerable inter-observer variability. The aim of our study was to investigate the usefulness of a sleep fragmentation index (SFI) to detect sleep disruption in a large sample of patients., Patients and Methods: Five-hundred ninety-eight polysomnographic studies made in controls and patients were examined. The SFI was calculated as the total number of awakenings and sleep stage shifts divided by total sleep time., Results: In the whole group a significant correlation was found between the SFI and the MA index (MAI) (P<0.001) with good agreement across a wide range of values. When patients were stratified according to final diagnosis a significant relation was noted for patients with insomnia (P<0.001), parasomnia (P<0.001), circadian schedule disorders (P<0.001) and sleep related breathing disorders (P< 0.001). Lower values were found in controls (P<0.01) and in patients with periodic limb movement disorder and/or restless legs syndrome (P<0.05). In 111 patients having two consecutive recording nights, a good reproducibility was present with no differences between nights (P=ns) and with significant correlation (P<0.001)., Conclusions: The SFI seems to be an accurate, reproducible and easy method to detect sleep fragmentation in patients with sleep disorders. Further studies are needed to validate the usefulness of this tool in clinical practice.

Objective: Typical changes in spectral electroencephalographic (EEG) activity and heart rate (HR) have been described in periodic leg movements (PLM) associated with or without microarousals (MA). We aimed to determine the effects of sleep stage and wakefulness on these responses to ascertain whether a common pattern of EEG and HR activation takes place., Methods: The time course of EEG spectral activity and HR variability associated with PLM was analysed in 13 patients during light NREM sleep, rapid-eye-movement (REM) sleep and wakefulness. The same analysis was also conducted for PLM without MA occurring in stage 2., Results: A significant EEG and electrocardiogram (ECG) activation was found associated with PLM during sleep, but not during wakefulness. While in light NREM sleep, an increase in delta and theta bands was detected before the PLM onset, in REM sleep the EEG activation occurred simultaneously with the PLM onset. Moreover, during stage 1 and REM sleep, alpha and fast frequencies tended to remain sustained after the PLM onset. In contrast, during wakefulness, a small and not significant increase in cerebral activity was present, starting at the PLM onset and persisting in the post-movement period. A typical pattern of cardiac response was present during NREM and REM sleep, the autonomic activation being lesser and prolonged during wakefulness., Conclusions: We conclude that the EEG and HR responses to PLM differ between sleep stages and wakefulness with lesser changes found during wakefulness., Significance: These findings suggest that specific sleep state-dependent mechanisms may underlie the occurrence of PLM.

The prevalence of OSAHS (obstructive sleep apnoea/hypopnoea syndrome) is high in developed countries and it is estimated that the vast majority of patients remain undiagnosed. On the basis of physiological evidence, we evaluated the frequency component of HRI (heart rate increment) as a simple and inexpensive screening tool for OSAHS detection in a first group of patients (group 1) and validated their discriminant capacity in a second group (group 2). The predictive accuracy of hourly %VLFI (frequency-domain HRI variable obtained from nocturnal ECG Holter monitoring) was analysed by comparison with an hour-by-hour respiratory disturbances index assessed by complete polysomnography in 28 consecutive clinically suspected OSAHS patients for group 1 and in 35 patients for group 2. OSAHS was present in 20 patients according to a mean hourly apnoea plus hypopnoea index >10 in group 1, and prevalence reached 77.1% in group 2. Sensitivity, specificity and positive and negative predictive accuracy were calculated and an ROC (receiver operating characteristic) curve was constructed for several polysomnographic threshold values. In group 1, hourly %VLFI appeared as an evident predictor of the apnoea/hypopnoea index (W=0.848, P<0.0001; where W is the area under the curve obtained using ROC curve analysis). Using an appropriate threshold (value > or =3.2%), %VLFI demonstrated a sensitivity of 78.1% and a specificity of 70.4%. These thresholds applied to group 2 yielded a sensitivity of 73.9% and a specificity of 76.6%. Frequency-domain analysis of the HRI appears to be a powerful tool for OSAHS prediction. The simplicity of its analysis and use makes of it a particularly well-suited variable for routine mass screening in high-risk populations undergoing ECG Holter monitoring.

Heart rate fluctuations are a typical finding during obstructive sleep apnoea, characterised by bradycardia during the apnoeic phase and tachycardia at the restoration of ventilation. In this study, a time-frequency domain analysis of the nocturnal heart rate variability (HRV) was evaluated as the single diagnostic marker for obstructive sleep apnoea syndrome (OSAS). The predictive accuracy of time-frequency HRV variables (wavelet (Wv) decomposition parameters from level 2 (Wv2) to level 256 (Wv256)) obtained from nocturnal electrocardiogram Holter monitoring were analysed in 147 consecutive patients aged 53.8+/-11.2 yrs referred for possible OSAS. OSAS was diagnosed in 66 patients (44.9%) according to an apnoea/hypopnoea index > or = 10. Using receiver-operating characteristic curves analysis, the most powerful predictor variable was Wv32 (W 0.758, p<0.0001), followed by Wv16 (W 0.729, p<0.0001) and Wv64 (W 0.700, p<0.0001). Classification and Regression Trees methodology generated a decision tree for OSAS prediction including all levels of Wv coefficients, from Wv2 to Wv256 with a sensitivity reaching 92.4% and a specificity of 90.1% (percentage of agreement 91.2%) with this nonparametric analysis. Time-frequency parameters calculated using wavelet transform and extracted from the nocturnal heart period analysis appeared as powerful tools for obstructive sleep apnoea syndrome diagnosis.

Objective: The temporal evolution of periodic leg movements (PLM) and the relationship of their arousing effect on sleep episode has not been extensively investigated. We studied the nocturnal evolution of PLM associated or not with microarousal (MA) and associated with slow wave activity (PLM with slow wave activity) in 23 patients with PLM and/or restless legs syndrome (RLS)., Methods: All subjects had PLM associated with MA or with slow wave activity as well as without MA and all slept for 4 sleep cycles. Spectral electroencephalogrpahic (EEG) analysis was done for the 4 sleep cycles to assess the nocturnal variation in slow wave activity (SWA)., Results: Sixty percent of PLM were associated with MA, 4% were associated with slow wave activity whereas 36% showed no EEG changes. There was a clear prevalence of PLM with MA in stages 1 and 2 while PLM without MA were prevalent in slow wave sleep. The night-time PLM index progressively declined from the first to the last sleep cycle (P<0.005), without differences between PLM types, or between PLM and RLS patients. The decline of PLM duplicated the temporal trend in SWA over consecutive sleep cycles., Conclusions: PLM showed a typical pattern of progressive decline throughout the night following the exponential decline in SWA. These over-time variations occurred independently of changes in the rate of PLM associated or not with MA or associated with slow wave activity, suggesting that variations in arousal threshold and sleep propensity did not affect the PLM arousing effect. The PLM-related arousal response might be affected by interaction of circadian and sleep stage influences with the addition of sleep oscillatory processes.

Recent reports have suggested that altered quality of life and well-being are reported by patients with sleep-related breathing disorders (SRBD). There seems to be no data available in the literature on factors underlying these behavioural consequences. In this study, health-related quality of life (HRQL) scores were examined in SRBD patients in order to establish which factors are implicated in these disturbances. The study group consisted of 130 patients: 49 snorers and 81 patients with obstructive sleep apnoea. The Medical Outcome Survey Short Form-36 questionnaire was administered the morning after the sleep study and scores for the eight dimension scores were obtained. Patient's data were compared to normative sex- and age-matched data. In comparison with normal values, scores for all HRQL dimensions were decreased in SRBD patients, with a greater impact on subscores for "vitality", "physical role", "social functioning", "mental health" and "role emotional" dimensions. While impairment in physical function was mostly influenced by sleep stage and obesity, subjective daytime sleepiness mainly affected the other dimensions. The authors conclude that the altered health-related quality of life of sleep-related breathing disorder patients is a multifactorial phenomenon depending on the interaction of sleep stages, daytime sleepiness and obesity, with no significant contribution of sleep fragmentation, hypoxaemia and apnoea recurrence.

Objectives: A hierarchy in arousal response has been proposed for spontaneous arousal by analyzing the temporal changes in heart rate (HR) and electroencephalographic (EEG) activity. To address the question as to whether the same continuum may be proposed in sleep disorders, we performed temporal spectral EEG and HR analyses during periodic leg movements (PLM) associated or not with microarousal (MA)., Methods: Data were obtained in 12 patients with restless leg syndrome and/or PLM syndrome. PLMs were classified into 3 types including PLM associated with MA, PLM without MA, and PLM associated with delta or K-complex bursts. HR and EEG spectral analyses were done for 10s before and 10s after the PLM onset., Results: Each type of PLM was associated with a typical EEG and autonomic pattern consisting of an increase in HR and delta band activity before the PLM, regardless of the presence or absence of MA. Thereafter, a rise in delta, alpha and beta(2) activity was noted associated with tachycardia. This was greater when MA or bursts of slow wave activity were present. In the period following the PLM, HR, delta and alpha power showed a long-lasting decrease with values significantly below the baseline., Conclusions: From these data, we can conclude that: (1) cardiac and cerebral changes occur in association with PLM even when MA cannot be detected; (2) the combined increase in delta activity and HR before the onset of PLM suggests that these changes are part of the arousal response during PLM; (3) the graded arousal response during PLM confirms that the human arousal response involves a progression of central nervous system activation from brainstem to cortical level.

No data are available in the literature assessing the potential use of waking electroencephalographic (EEG) activity in the detection of excessive daytime sleepiness (EDS) in patients with sleep-related breathing disorders (SRBD). The aim of this study was to evaluate whether waking EEG spectral power reflects the level of EDS in SRBD patients. The study was performed in 48 patients in whom quantitative EEG analysis, including the alpha attenuation coefficient (AAC), was performed. Sleepiness was assessed by the Epworth Sleepiness Scale, the Stanford Sleepiness Scale, the Visual Analogue Scale and the maintenance of wakefulness test. Although AAC and EEG spectral power tended to vary throughout the day, none of these variations correlated with EDS measures. Waking EEG measures were not different between snorers and apnoeic patients. Compared to nonsleepy patients, sleepy patients had greater theta and slow alpha powers, but the differences did not reach statistical significance. The EEG slowing was independent of hypoxaemia, severity of SRBD, or degree of sleep disruption. The authors conclude that waking electroencephalographic measures are not sensitive enough to predict variation in alertness or to differentiate sleepy from nonsleepy sleep-related breathing disorders patients. The degree of electroencephalographic slowing was related neither to sleep disruption nor to severity of sleep-related breathing disorders.

Objective: The etiology of depression and personality disorders in patients with sleep-disordered breathing (SDB) is not well defined and it is still unclear if they are directly related to the severity of the disease. In this study we test the hypothesis as to whether daytime sleepiness largely contributes to appearance of mood disorders., Methods: Sixty patients diagnosed as having snoring (n=16) or OSA (n=44) were examined. Daytime sleepiness was assessed by the administration of the Epworth Sleepiness Scale (ESS) and by the Maintenance Wakefulness Test (MWT). The Hospital Anxiety (HAD-A) and Depression (HAD-D) Scale and the Temperament and Character Inventory (TCI) questionnaires were used for psychopathological evaluation., Results: The mean HAD-A score was 6.9+/-0.45 and the average HAD-D score was 4.6+/-0.48, with no significant difference between snorers and OSA patients. Anxiety was present in 16% of cases and depression in 7%. The HAD-D score was related to the ESS score (R=0.37, P=0.003), the mean sleep latency at the MWT (R=-0.34, P=0.04), and the mean low SaO(2), ESS score alone explaining the 17% of variance in the HAD-D score. Compared to controls, there were no differences in almost all TCI scores, with novelty-seeking temperament score higher in patients. No relationships were found between HAD or TCI scores and apnea density., Conclusions: We conclude that among patients evaluated for SDB, higher depression scores show an association with reduced daytime alertness, which therefore may have important effects on mood.

The aim of this study was to validate some recurring definitions of excessive daytime sleepiness (EDS) obtained from descriptive epidemiological studies. We devised questions concerning concepts such as "tiredness", "resistible sleepiness", "irresistible sleepiness" and "sudden sleep attacks". The validation was done by comparing the answers with the results of the Multiple Sleep Latency Test (MSLT), considered the gold standard, or criterion measure, for the diagnosis of EDS. The sample study comprised 73 subjects, 57 outpatients referred to our Sleep Center complaining of daytime sleepiness, snoring or sleep apnea and 16 inpatients admitted to our Neurological Institute for causes other than sleep disorders. A moderate correlation (p = -0.38, 95% confidence interval -0.57 to -0.19) was found between "irresistible sleepiness" and mean sleep latency (MSL). The best combinations of sensitivity and specificity in identifying EDS, for 5- and 8-min MSL cutoffs, were observed for the questions concerning "sudden sleep attacks" and "irresistible sleepiness" (areas under the receiver-operating characteristic curves = 66 and 67%, respectively). The subitems exploring the frequency and situations of occurrence of these symptoms improved the validity in identifying EDS. The items regarding "tiredness" and "resistible sleepiness" were not related to the results of the MSLT. In subgroup analysis, irresistible sleepiness failed to identify pathologic MSLT in sleep-disordered breathing subjects. According to previous observations, we suggest that the concept of sleepiness includes various domains heterogeneously related with MSL and that questionnaires must be tailored to the different populations studied., (Copyright 2001 S. Karger AG, Basel)

Previous studies indicate that upper airway (UA) sensory receptors play a role in the maintenance of UA patency and contribute to arousal in response to airway occlusion. An impairment of UA sensory function could therefore predispose to UA obstruction during sleep. We hypothesized that UA sensation is impaired in obstructive sleep apnea (OSA), and that sensation improves after treatment with nasal continuous positive airway pressure (CPAP). We measured two-point discrimination (2PD) and vibratory sensation thresholds (VT) in 37 patients with OSA (mean [+/- SE] apnea- hypopnea index [AHI] = 39 +/- 5 events/h), 12 nonapneic snorers (SN), and 15 control subjects (CL). Sensory thresholds were determined in the UA and on the lip and hand as control sites. Both 2PD and VT were similar among the three groups at the lip and hand sites but were significantly reduced in the UA of OSA and SN subjects versus CL (p < 0.05). Values for 2PD and VT in the UA of OSA versus SN were not significantly different. Sensory measures were repeated after 6 mo in 23 OSA patients treated with CPAP as well as in 18 untreated patients. Thresholds for 2PD and VT at control sites remained identical in both groups, as did 2PD for the UA. However, VT in the UA showed a significant improvement in treated (4.4 +/- 0.2 pre-CPAP versus 3.8 +/- 0.2 mm post-CPAP, p < 0.05) but not untreated patients. These findings indicate the presence of a selective impairment in the detection of mechanical stimuli in the UA of patients with OSA and SN, which is partially reversible after treatment with nasal CPAP in patients with OSA.

Study Objectives: To estimate the course of slow-wave activity (SWA), its amount during the night, and its correlation with daytime sleepiness in sleep apnea syndrome (SAS) patients. This study also verified whether continuous positive airway pressure (CPAP) treatment also restores a normal pattern of SWA in severe SAS patients., Participants: Ten patients with a diagnosis of severe SAS who showed a good clinical response to CPAP after approximately 9 months of treatment were included in this study. These patients were matched for sex and age with 10 control subjects., Design: All subjects underwent 1 night of polysomnography (PSG), followed by the multiple sleep latency test (MSLT) the next day. For the SAS patients only, the same procedure was repeated after 9 +/- 0.7 months of CPAP treatment. In addition to traditional scoring of sleep stages, apneas, hypopneas, and microarousals, the SWA, defined as the power in the 0.75- to 4.5-Hz frequency band, was evaluated., Results: A positive correlation between SWA of the first cycle and the MSLT (r = 0.56; p = 0.045) was found before treatment. Moreover, SAS patients significantly increased their mean SWA after CPAP treatment in the first (p = 0.024) and second (p = 0.002) sleep cycles and restored a more physiologic decay of SWA across the night., Conclusions: These results suggest that daytime sleepiness in SAS patients may be the result of a lack of SWA during the first part of the night, and show that CPAP restores a more physiologic pattern of SWA across the night.

This study describes the technical steps for the making of a mandibular advancement device for sleep disordered patients (apnea index < 10). In a second part of the study, a group of 21 patients with sleep disordered breathing treated successfully with a mandibular advancement device is compared to a homologous control group. The experimental group showed cephalometric characteristics approaching those seen in patients with sleep apnea syndrome. The mandibular advancement device moved the mandibule forward (SNB angle increases by 1.7 degrees) and downward (mandibular plane angle increases by 3 degrees, which can be related to the 7.4 mm anterior vertical height increase). The hyoid bone adopted a more distant position from the cervical vertebrae. Important individual variations were seen among the patients for the optimal repositioning of the mandible.

Objectives: One major subject of discussion in sleep studies is whether bursts of K-complexes (K-bursts) and delta waves (D-bursts), expressions of a subcortical arousal, truly reflect an arousal response during sleep. To address this question we studied the changes in heart rate (HR) during spontaneous arousals in healthy subjects., Methods: Twenty-seven healthy adults were examined. Arousals were graded in 4 levels, including the standard definition of a microarousal (MA), phases of transitory activation (PAT), D-bursts and K-bursts. HR was analyzed for 10 beats before and 20 beats during arousal. EEG spectral analysis was performed for all types of arousals, including in the analysis the 20 s period preceding the actual event., Results: Each type of arousal was associated with HR changes consisting of a tachycardia followed by a bradycardia. Changes were more pronounced during MA and PAT. Detailed analysis of the HR response showed that HR always increased before MA and PAT onset, associated with a rise in delta, theta and fast EEG activities, and suggesting a cerebral activation., Conclusions: Our data suggest that such subcortical arousals represent a real arousal response inducing cardiac activation similar to that found during MA and PAT. During MA and PAT, a rise in HR appears before the onset of the actual arousal associated with an increase in EEG slow and fast activity. The link between EEG and HR variation during MA and PAT and the fluctuations in HR during subcortical arousal suggest a continuous spectrum in the arousal mechanisms, starting at the brainstem level and progressing to cortical areas.

Objective: To determine whether the spectral activity during sleep of patients with idiopathic hypersomnia (IH) differs from that of healthy subjects., Methods: Spectral analysis of the electroencephalogram (EEG) was performed in 10 patients with IH and in 10 age-matched control subjects. We compared the time course of absolute power for slow wave activity (SWA: 0.75-4.5 Hz), and for theta, alpha, sigma and beta bands for the first 4 non-rapid-eye movement (NREM) episodes., Results: Compared to controls, IH patients had less SWA across the night although the exponential decay was preserved. The fall in SWA was statistically significant for the first two NREM episodes only. The lower power of SWA was related to lower amounts of stages 3 and 4 of NREM sleep during the sleep episodes. No correlation was found between SWA during the night and the mean sleep latency on the multiple sleep latency test (MSLT)., Conclusions: These results showed that, in IH patients, the homeostatic sleep regulatory mechanisms are preserved but the sleep pressure, indicated by SWA, is lower.

Increased pharyngeal collapsibility and abnormal anatomic structures have been postulated to contribute to the pathophysiology of obstructive sleep apnea (OSA) syndrome. It is unclear whether the abnormal craniofacial and soft tissue features may affect the pharyngeal collapsibility and contribute to the apnea density. In the present study we examine the relationship between pharyngeal collapsibility and cephalometric variables in a group of 57 male OSA patients. Pharyngeal collapsibility was measured during the night of nasal continuous positive airway pressure (nCPAP) titration by analyzing the pressure-flow relationship. Pharyngeal critical pressure (Pcrit) was calculated as the extrapolated pressure at zero flow. The patients, age 52.0 +/- 9.0 yr, had an average apnea-hypopnea index (AHI) of 72.6 +/- 31.8 and a mean Pcrit of 2.4 +/- 1.0 cm H(2)O. A significant correlation was found between Pcrit and the soft palate length (SPl) (r = 0.27, p = 0.04), the distance from the hyoid bone to the posterior pharyngeal wall (H-Ph) (r = 0. 29, p = 0.03), and the distance from the hyoid bone to posterior nasal space (H-Pns) (r = 0.32, p = 0.02). While in obese patients Pcrit was related to SPl and neck circumference, the distance of the hyoid bone to the mandibular plane (H-MP) affected Pcrit in nonobese patients. Our results show that both pharyngeal soft tissue abnormalities and the lower position of the hyoid bone affect Pcrit in OSA patients, suggesting that an anatomic narrowing contributes to the upper airway collapsibility.

Effective compliance (time spent at the effective pressure) with nasal CPAP in obstructive sleep apnea has been reported to be poor. The aim of our study was to evaluate effective compliance in a large European multicenter study. One hundred twenty-one consecutive newly treated patients (initial apnea-hypopnea index [AHI] = 62.0 +/- 29. 5/h, AHI under CPAP = 6.4 +/- 8.1/h, CPAP pressure = 8.7 +/- 2.6 cm H(2)O, BMI = 33.1 +/- 6.8 kg/m(2)) were randomly allocated to a group with (MC(+)) (n = 58) or without (MC(-)) (n = 63) a control unit measuring effective compliance at 1, 2, and 3 mo, which was compared with the built-in time counter data. MC(+) data were 94 +/- 10, 98 +/- 5, and 96 +/- 9% of counter data at 1, 2, and 3 mo, respectively. Using criteria of regular use already reported in the literature (at least 4 h of nCPAP per day of use and nCPAP administered more than 70% of the days) we found 77, 82, and 79% compliant patients at 1, 2, and 3 mo, respectively, 79% of the patients meeting these criteria each month. Although there were no pulmonary functions or polysomnographic differences between the two subgroups, the compliant patients did report a greater improvement in minor symptoms. We found a close correlation between effective use of CPAP and the machine run time. The main result of our study was a higher effective compliance than previously reported, approximately 80% of the patients being regular users versus 46% in a previously published study. This may result from different technical and medical follow-up.

The aim of the present study was to determine survival rates of obstructive sleep apnoea patients treated with continuous positive airway pressure (CPAP) and to investigate the prognostic value of pretreatment lung function and pulmonary haemodynamics. Two hundred and ninety-six patients, exhibiting > or = 20 apnoeas plus hypopnoeas per hour of sleep, were included. Patients were treated with nasal CPAP and regularly followed up. The cumulative survival rates were 0.96 (95% confidence interval (CI): 0.94-0.99) at 3 yrs and 0.93 (95% CI: 0.91-0.97) at 5 yrs. Most patients died from cardiovascular disease. Apart from age, covariates associated with a lower survival were the presence of a heavy smoking history, a low vital capacity, a low forced expiratory volume in one second (FEV1) and a high mean pulmonary artery pressure. Only three covariates were included by forward stepwise selection in the multivariate analysis, smoking habit (>30 pack-yrs), age and FEV1. The observed survival rates of the group as a whole were similar to those of the general population matched in terms of age, sex and smoking habit, except for patients between 50 and 60 yrs old who had reduced survival. This difference disappeared when patients of the present study with an associated chronic obstructive pulmonary disease were excluded from the comparison. In conclusion, survival of obstructive sleep apnoea patients treated with nasal continuous positive airway pressure is near to that of the general population. The prognosis is worse in subgroups of patients with a history of heavy smoking and with an associated chronic obstructive pulmonary disease.

Objective: To investigate other physiologic changes that occur with periodic leg movements during sleep (PLMS) that might be considered to be more sensitive indices of sleep fragmentation., Background: Although PLMS are associated with recurrent microarousals (MA), the frequency of PLMS with MA does not correlate with objective daytime sleepiness. It is postulated that the lack of correlation results from the low sensitivity of the standard criteria used to score MA., Methods: Ten drug-free patients with a polygraphic and clinical diagnosis of restless legs syndrome (RLS) and PLMS were examined. The EEG correlates of PLMS were analyzed by visual scoring and spectral analysis during PLMS that ended in a visible microarousal (PLMS with MA) or not (PLMS without MA). The R-R interval in the EKG signal was also examined., Results: A total of 34% of PLMS were associated with MA lasting >3 seconds, and 3% of PLMS were associated with MA lasting <3 seconds. Although PLMS with MA were associated with an increase in alpha activity, for PLMS without MA a significant increase in delta and theta activity was present. Both types of PLMS induced a shortening of the R-R interval; this was particularly more marked for PLMS with MA., Conclusions: First, visual scoring of MA that include a duration of less than 3 seconds has little effect on the detection of PLMS with MA. Second, EEG activation and tachycardia are present during both types of PLMS. Third, a hierarchy in the arousal response is present-going from autonomic activation to bursts of delta activity to alpha activity to a full awakening.

A study comparing actigraphy and polysomnography in the detection of leg movements was performed in a group of 35 patients with sleep disorders. Visual scoring used epochs of 5-second duration, and in each epoch, electromyographic activity of tibialis anterior muscle was classified in eight types on the basis of its duration and amplitude. Activity levels of the actigraphic data were logged in 5-second intervals and stored in memory for computer retrieval. To assess the reproducibility of actigraphic detection scoring, in 10 patients actigraphic and polysomnographic data were compared during two consecutive nights. Despite a high correlation between polysomnography and actigraphy in the detection of muscular activity (r = 0.78; P = 0.001), no agreement was obtained between the two analyses according to the Bland and Altman method of concordance (mean bias: -117.5). The greater agreement was found for electromyographic activity lasting more than 3 seconds and with an amplitude of more than 50 microV. In the group of patients examined during two consecutive nights the scoring error did not differ significantly. The results demonstrated that (1) despite a significant correlation between actigraphic and polysomnographic data, actigraphy substantially underestimated leg electromyographic activity and therefore could not be used routinely for diagnostic purposes; and (2) because error scoring did not undergo significant changes across the two nights, actigraphy may be used for follow-up evaluation.

It has recently been described that the maximal respiratory effort developed at the end of an apnea (Pesmax)--which is regarded as an index of arousal threshold in patients with obstructive sleep apnea syndrome (OSA)--increases progressively during the night, probably as a consequence of associated sleep fragmentation. In order to find out whether the nocturnal trend of Pesmax may be more influenced by a sleep-dependent circadian rhythm than by sleep fragmentation, we revised the polygraphic recordings of 37 patients in whom obstructive apneas were recorded for at least 7 hours. In 15 of these patients, analysis was made for eight hours of the night. During each hour we analyzed at least 7 obstructive apneas, in which we measured the minimal esophageal pressure at the start of the apnea, the maximum value recorded at the end of the apnea (Pesmax), the difference from the minimum to the maximum (delta Pes), and the rate of increase in esophageal pressure (RPes). As indices of sleep fragmentation, we defined the number of arousals, awakenings and sleep state transitions. In the group of patients as a whole, we found a trend toward a gradual increase for apnea duration (F = 98.8, p < 0.001) and Pesmax F = 31.6, p < 0.001) which was significant from the first to the last hour. The time-dependent evolution of apnea duration and Pesmax showed that the rise in these two variables peaked during the first 3 hours of sleep, followed by a plateau and a decrease in the last hour of the night. This temporal profile was more evident when the analysis was available for 8 hours. No significant changes across the night were found for nocturnal hypoxemia and number of arousals. Considering the slope of Pesmax changes across the night, we saw that neither the apnea+hypopnea index nor the indices of sleep fragmentation affected the nocturnal trend. The present data demonstrate the presence of a nocturnal trend in arousal threshold in OSA patients independent of sleep fragmentation. The biphasic evolution of the arousal threshold may be caused by factors that influence the circadian and homeostatic processes.

Current evidence suggests that patients with obstructive sleep apnea (OSA) may have greater pharyngeal critical pressure (Pcrit), which reflects the increase in upper airway collapsibility. The contribution of Pcrit to the severity of OSA and to the efficacious continuous positive pressure (nCPAPeff) therapy has never been extensively described and no data are available about the interaction of Pcrit, age, and anthropometric variables. To determine the relationship between Pcrit, severity of the disease, nCPAPeff, and anthropometric variables we measured Pcrit in a group of 106 patients with OSA. Pharyngeal critical pressure was derived from the relationship between maximal inspiratory flow and nasal pressure, Pcrit representing the extrapolated pressure at zero flow. Upper airway resistance (Rus) was determined as the reciprocal of the slope (DeltaPn/DeltaVImax cm H2O/L/s) in the regression equation. In a subgroup of 68 patients, during the diagnostic night, we measured as indices of respiratory effort, the maximal inspiratory esophageal pressure (Pes) at the end of apnea (Pesmax), the overall increase from the minimum to the maximum (DeltaPes), and the rate of increase of Pes during apnea (RPes). As a group, the mean Pcrit was 2.09 +/- 0.1 cm H2O (range, 0 to 4.5) and the mean Rus was 11.1 +/- 0.5 cm H2O/L/s. Although men have greater Pcrit, pharyngeal collapsibility was influenced neither by neck size nor by body mass index (BMI). Although there was a significant relationship between Pcrit and apnea plus hypopnea index (AHI) (r = 0.23, p = 0.02), neck circumference was the stronger predictor of apnea frequency, with Pcrit contributing only to the 3% of the variance. In the group of patients as a whole, a model including AHI, BMI, Rus, and Pcrit explained the 36% of the variance in nCPAPeff, with a greater contribution of AHI, Pcrit accounting for only 3% of the variation. In patients for whom the measure of respiratory effort was obtained, 42% of the variance in nCPAPeff was explained by RPes (33%) and BMI. From these results we conclude that Pcrit alone does not yield a diagnostically accurate estimation of OSA severity and nCPAPeff. Although individual collapsibility may predispose to pharyngeal collapse, upper airway occlusion may require the combination of several factors, including obesity, upper airway structure, and abnormalities in muscle control.

The upper airway can be described as a collapsible segment (the pharynx) interposed between two rigid bony (the cavum) or cartilaginous (the trachea) segments. Due to this structure, the pharynx behaves as a collapsible tube, in which airflow does not depend on the downstream pressure, but is limited to a maximum value which depends only on the upstream pressure and on the pressure surrounding the collapsible segment; this behavior, known as a Starling resistor can be modeled by the waterfall effect. Thus, the upper airways can be in three different conditions: an occluded condition, in which no flow is possible, a patent condition, in which flow depends on the difference between upstream and downstream pressures (according to Poiseuille's law), and a situation in which flow is limited. The behavior of the upper airway is largely dependent on its anatomic structure, but functional factors play a critical role. Among these sleep state is both a determinant of the collapsibility of the pharynx, and determined by the simulation of upper airway mechanoreceptors whose activity depends on the activity of respiratory muscles. Thus the interplay of three factors: ventilatory drive, upper airway collapsibility, and arousal threshold can predict most of the situations of stable and unstable ventilatory behavior during sleep. The level of the arousal threshold governs the stability of the ventilatory pattern, as it determines whether a combination of slow, respiratory effort, and blood gases can be maintained or is interrupted by an arousal.