Atrial fibrillation is a major cause of stroke in apneic patients: a prospective study.

OBJECTIVES: Large prospective studies have established that sleep-disordered breathing (SDB) is associated with an increased incidence of cardiovascular and cerebrovascular diseases. Heterogeneous results have been published about SDB and ischaemic stroke mechanism. The aim of this study was to evaluate the relationship between poststroke apneic syndrome and stroke aetiologies according to the ASCO classification. METHODS: A total of 134 patients with acute ischaemic cerebrovascular events were prospectively included. Patients with severe or infratentorial infarctions were excluded. Stroke risk factors and clinical characteristics were recorded in all patients. An overnight polygraphy was recorded (Embletta PDS). Apneic patients were defined if the polygraphy reported an apnea-hypopnea index ≥15. A standardized diagnosis workup, including serum biological investigation, evaluation of extra and intracranial arteries and heart morphology and function, was performed. Stroke mechanism was defined using ASCO and TOAST classifications. RESULTS: A proportion of 42% (56 of 134) of the patients were diagnosed as having sleep apneas. Apneic patients were older (p < 0.001), had higher BMI (p = 0.02), and more were hypertensive (p < 0.001). Using ASCO classification, a major cardioembolic source of stroke, mainly atrial fibrillation, was more frequently observed in apneic patients (41.1% vs. 20.5%, p < 0.05), while no difference was observed when considering atherosclerosis or small-vessel disease mechanisms. Univariate analysis showed that cardioembolic stroke depends on sex, age, left atrial size and OSA; however, age remained the only significant factor in multivariate analysis. CONCLUSION: This study confirms the high prevalence of sleep apneas in stroke-affected patients and identifies atrial fibrillation as a major source of stroke in this population. The strong correlation between age and SDB seems to drive the increased frequency of stroke related to atrial fibrillation in this population.

Association between reported sleep need and sleepiness at the wheel: comparative study on French highways between 1996 and 2011.

OBJECTIVE: To investigate the evolution over 15 years of sleep schedules, sleepiness at the wheel and driving risk among highway drivers. METHODS: Comparative survey including questions on usual sleep schedules and before the trip, sleepiness at the wheel, the Epworth sleepiness scale, Basic Nordic Sleep Questionnaire (BNSQ) and a travel questionnaire. RESULTS: 80% of drivers stopped by the highway patrol agreed to participate in both studies with a total of 3545 drivers in 2011 and 2196 drivers in 1996 interviewed. After standardisation based on sex, age and mean annual driving distance, drivers in 2011 reported shorter sleep time on week days (p<0.0001), and week-ends (p<0.0001) and shorter optimal sleep time (p<0.0001) compared to 1996 drivers. There were more drivers sleepy at the wheel in 2011 than in 1996 (p<0.0001) and 2.5 times more drivers in 2011 than in 1996 had an Epworth sleepiness score >15 indicating severe sleepiness. CONCLUSIONS: Even if drivers in 2011 reported good sleep hygiene prior to a highway journey, drivers have reduced their mean weekly sleep duration over 15 years and have a higher risk of sleepiness at the wheel. Sleep hygiene for automobile drivers remains an important concept to address.

Is self-reported morbidity related to the circadian clock?

Morningness and eveningness preference, an endogenous component of the circadian clock, is characterized by an interindividual difference in circadian phase and requires of humans a specific timing of behavior. The biological rhythms of morning and evening types are consequently phase shifted with fixed socioeconomic constraints. The impact of this phase shift on health is widely debated. The purpose of the authors' study was to determine the influence of morningness/eveningness preference on self-reported morbidity and health in an active population. A total of 1165 nonshift workers of the French national electrical and gas company, enrolled in the GAZEL cohort and aged 51.3+/-3.3 years, were included in this study. They replied by mail with a completed questionnaire, including morningness/eveningness preference, self-reported morbidity, subjective sleep patterns, and daytime somnolence and sleeping schedules for 3 weeks, during the spring of 1997. Annual self-reported health impairments were assessed with the annual general questionnaire of the GAZEL cohort for 1997. After adjustment for age, sex, and occupational status, morningness-like and eveningness-like participants reported a specific worse self-reported morbidity. Whereas morningness was associated with worse sleep (p = 0.0001), eveningness was associated with feeling less energetic (p = 0.04) and physical mobility (p = 0.02). These relationships were observed even in good sleepers, except for physical mobility. After adjustment for confounding variables, eveningness-like participants reported more sleep (p = 0.0004) and mood (p = 0.00018) disorders than morningness-like participants. Morningness/eveningness preference was related to specific chronic complaints of insomnia: morningness was related with difficulty in maintaining sleep (p = 0.0005) and the impossibility to return to sleep in the early morning (p = 0.0001) (sleep phase-advance syndrome); eveningness was related to difficulty in initiating sleep (p = 0.0001) and morning sleepiness (p = 0.0001). In good sleepers, morningness was related with sleep phase-advance syndrome (p = 0.0001) and eveningness with morning sleepiness (p = 0.0001). In conclusion, the expression (phase advance or delay) of the circadian clock could be related to worse self-reported morbidity and health. These findings must be verified by further epidemiological studies, but they suggest that the impossibility to return to sleep in the early morning is not only associated with age.

Sleep polygraphic effects of trimipramine in depressed patients. Preliminary report.

Preliminary results are presented from an ongoing study in hospitalised depressed patients. Changes in sleep parameters were assessed on days 1 to 3 and 12 to 14 of a 4-week study in which patients received trimipramine 150 mg on day 1 and 100 mg thereafter. On days 1 to 3 and 12 to 14, 7 depressed patients had a significantly increased total sleep time and sleep efficiency index and a significantly decreased total wake time and number of intrasleep wake episodes per hour of sleep. Trimipramine treatment had no significant effect on REM sleep, percentage of REM sleep, REM duration and REM sleep stability index. However, a significant increase in REM latency was noted on days 1 to 3 but not on days 12 to 14. These polygraphic data suggest that trimipramine effects a very rapid and maintained sleep improvement in these depressed patients without significant alterations to the parameters of REM sleep.

Long distance driving and self-induced sleep deprivation among automobile drivers.

OBJECTIVE: To evaluate the sleep hygiene and prevalence of sleep deprivation among a large sample of automobile drivers. DESIGN: From the 15th of June to the 4th of August 1996, with the help of the French highway patrol, we randomly stopped automobile drivers at the toll booths of Bordeaux and Biarritz. All subjects completed a validated questionnaire on sleep/wake habits during the year. After answering the questionnaire, subjects completed a graphic travel and sleep log of the three days preceding the interview. PARTICIPANTS: We randomly stopped 2196 automobile drivers. Ninety-one percent of the sample (mean age 43 +/- 13 years) agreed to participate in the survey. RESULTS: Fifty percent of the drivers decreased their total sleep time in the 24 hours before the interview compared with their regular self-reported sleep time. 12.5% presented a sleep debt > 180 minutes, and 2.7% presented a sleep debt > 300 minutes. Being young, commuting to work, driving long distances, starting the trip at night, being an "evening" person, being a long sleeper during the week, and sleeping in on the week-end were risk factors significantly associated with sleep debt. CONCLUSION: The results of the study highlight variables (long-distance driving, youth, sleep restriction) that are frequently associated with sleep-related accidents.

Work and rest sleep schedules of 227 European truck drivers.

OBJECTIVE: To investigate the sleep-wake behavior and performance of a random sample of European truck drivers. METHODS: The drivers completed a questionnaire concerning sleep-wake habits and disorders experienced during the previous 3 months. In addition, they were asked to complete a sleep and travel log that included their usual work and rest periods during the previous two days. They answered questions concerning working conditions and reported their caffeine and nicotine intake during their trips. RESULTS: A total of 227 drivers, mean age 37.7+/- 8.4 years (96.2% acceptance rate), participated in the study. The drivers were found to have a fairly consistent total nocturnal sleep time during their work week, but on the last night at home prior to the new work week there was an abrupt earlier wake-up time associated with a decrease in nocturnal sleep time. Of the drivers, 12.3% had slept less than 6 h in the 24 h previous to the interview and 17.1% had been awake more than 16 h. CONCLUSIONS: Shifting sleep schedules between work and rest periods can generate long episodes of wakefulness. This type of sleep deprivation is rarely investigated. Its is usually not taken into consideration when creating work schedules, but affects the performance of drivers. Unsuspected shifts occur at the onset of a new workweek. Sleep hygiene education for professional drivers is still far from perfect.

Evolution of ambulatory measurement of blood pressure and parameters of arterial stiffness over a 1-year period in patients with systemic sclerosis: ERAMS study.

UNLABELLED: Patients with systemic sclerosis commonly exhibit increased arterial stiffness, which may be predictive of the overall severity of the disease. The aim of the present study was to check the stability of parameters of arterial stiffness after 1 year in this population. ERAMS is a French multicentric prospective study designed to identify a link between arterial distensibility and outcome in 100 patients with systemic sclerosis. Arterial distensibility was evaluated by 24-h ambulatory monitoring of QKD interval along with blood pressure (BP) and heart rate (HR) (four measurements/hour). The index QKD(100-60), which is linked to aortic distensibility, was calculated automatically. QKD(100-60) is the value of QKD (which depends on pulse wave velocity) for 100 mm Hg sBP and 60 bpm HR. The reproducibility of QKD(100-60) was assessed on the first patients to be followed up for a complete year. So far the 100 patients have been recruited from 14 participating centres and 48 were re-evaluated after 1 year. QKD(100-60) was highly reproducible: 201 +/- 6 vs202 +/- 18 msec, standard deviation of difference = 13 msec. IN CONCLUSION: determination of QKD(100-60) to assess arterial stiffness gives stable results over 1 year in patients with systemic sclerosis.

Effect of fatigue on performance measured by a driving simulator in automobile drivers.

OBJECTIVE: To identify risk factors of performance decrement in automobile drivers. METHODS: 114 drivers (age <30 years, n=57; age > or =30 years, n=57) who stopped at a rest stop area on a freeway were recruited for the study. They filled out a questionnaire on their journey, sleep/wake patterns and performed a 30-min test on a driving simulator. The test evaluates, by computerized analysis, the lateral deviation of a virtual car from an appropriate trajectory on a virtual road. A sex/age matched control group was recruited in the community. Control subjects were studied at the same time of day as the index case driver. Controls had normal sleep wake schedule, absence of long driving and performed the same driving test. RESULTS: Drivers performed significantly worse than controls on the driving test. Age and duration of driving were the main factors associated with decreased performance. CONCLUSION: Our driving simulator can identify fatigue generated by driving but results must be considered in relation with age of subjects.

Heart rate circadian rhythm as a biological marker of desynchronization in major depression: a methodological and preliminary report.

Heart rate (HR) was continuously monitored during successive 24-hr periods in 19 healthy subjects and 26 major depressed patients (DSM III-R). Recordings were performed after a 2-week wash-out period and the morningness or eveningness typology of each subject was determined. The chronobiological parameters and rhythm percentage (RP) were calculated by the single cosinor method from the smoothed HR curves of each subject. In normal subjects, HR follows a circadian rhythm (RP greater than 65%) with the lowest values at night. Morning type subjects have an earlier peak time (13:30) than evening type subjects (17:30). Major depressive patients were split into two groups; in the first one HR circadian rhythm was still present (RP greater than 63%) with a decrease in amplitude (24%) while in the second group, no circadian rhythm of HR could be detected (RP less than 25%, decrease in amplitude greater than 70%). In the group of patients with a persisting HR circadian rhythm, no veritable phase advance was observed. Our results suggest that circadian HR rhythm, which can be easily studied with non-invasive methods, might represent a chronobiological marker of some depressions. Given the lag that exists between the rhythms of morning type and evening type subjects, our study also stresses the importance of taking into account this behavioural trait in chronobiological studies.

Sleep and heart rate circadian rhythm in depression: the necessity to separate.

In order to determine whether a decrease in the amplitude of heart rate circadian rhythm (HRCR) could represent a chronobiological marker of depression and to answer the question of the possible role of this alteration in the reduction of rapid eye movement sleep latency (REM latency) observed in depression, 22 major depressed patients (DSM III R, Montgomery Asberg Depression Rating Scale) and 11 healthy volunteers entered this study, which included the simultaneous recordings of sleep and heart rate (HR) during two consecutive 24-h periods. After a smoothing procedure, the HR data, obtained from a portable device providing mean HR/min, were computed with the single cosinor method for the classical circadian parameters. We also determined the cosinor fitting index (CFI = percentage to fit). When studied as a single group and compared to the control group, the depressed patients, who had difficulties in sleep initiation and whose REM latencies were within normal limits, were characterized by a dampening of the amplitude HRCR and of the day-night HR difference. This was linked to a lesser increase of HR during the day and a reduced decrease at night. No significant phase modification of HRCR was observed in this group of depressives. In a second step, the depressives were divided into a depressed arrhythmic group (DAG, CFI < 50%, 11 patients) and a depressed rhythmic group (DRG, CFI > 50%, 11 patients) who did not differ on MADRS scores. Even though the amplitude of HRCR was reduced in the DAG only, with HR higher at night and lower during the daytime than for controls, both DAG and DRG significantly differed from controls on those items related to sleep induction and maintenance. In the DAG only was there a tendency toward a reduction of total sleep time and REM sleep time while REM latency was normal. This finding suggests that sleep problems are not responsible for the differences in HRCR parameters between the two depressed groups. These differences in HR and sleep parameters between two groups of similarly depressed patients also suggest that a short REM latency does not systematically imply a disruption of all circadian clocks.

[Study of the real situation of improvement by Zopiclone in treatment of insomnia among persons working during night shifts]. / Etude en situation réelle de l'amélioration par la Zopiclone des insomnies chez les personnes travaillant en équipes de nuit.

UNLABELLED: We investigated the effect of adapted management of sleep on the duration and quality of sleep in shift workers working the night shift. Twenty-nine shift workers suffering from insomnia were included and treated with zopiclone (7.5mg/day) or placebo according to a random double-blind protocol. Patients completed a sleep diary and a wrist actigraph was used to evaluate episodes of rest/activity. A self-administered subjective sleep questionnaire was filled out just after awakening. Zopicone was found to increase the duration of sleep significantly (p<0.05) over the baseline duration after the first and second night on duty. Subjective estimation of sleep was better in patients taking zopiclone who exhibited a smaller number of shorter awakening episodes. IN CONCLUSION: zopiclone improves the quality and duration of sleep in shift workers suffering from insomnia.

[Sleep apnea syndrome: psychiatric aspects]. / Syndrome d'apnées du sommeil. Aspects psychiatriques.

The prognosis of sleep apnea syndrome (SAS) is dominated by cardiovascular complications. However, this disease is concerned with psychiatric field through specific clinical patterns. Nocturnal respiratory arrests are responsible for hypoxic and hypercapnic events including sleep fragmentation, reduction of slow wave sleep and rapid eye movement sleep. Alertness disturbances and sleep disorders are the most common functional complaints. Memory and cognitive disorders, personality changes and anxiodepressive syndromes may occur but are often neglected due to the increase of frequency with age together with the frequency of SAS; clinicians should consequently be aware of the fact that such troubles may be related to sleep respiratory disorders. In this case polysomnography should be performed before prescribing hypnotics, tranquilizers or sedative antidepressants.

Reliability of simulator driving tool for evaluation of sleepiness, fatigue and driving performance.

STUDY OBJECTIVE: To compare the impact of extended wakefulness (i.e., sleepiness) and prolonged driving (i.e., fatigue) at the wheel in simulated versus real-life driving conditions. DESIGN: Participants drove on an INRETS-MSIS SIM2 simulator in a research laboratory or an open French highway during 3 nocturnal driving sessions. A dose-response design of duration of nocturnal driving was used: a 2 h short driving session (3-5 AM), a 4 h intermediate driving session (1-5 AM) and an 8 h long driving session (9 PM-5 AM). PARTICIPANTS: Two groups of healthy male drivers (20 for simulated driving and 14 drivers for real driving; mean age±SD=22.3±1.6 years), free of sleep disorders. MEASUREMENTS: Number of inappropriate line crossings, self-rated fatigue and sleepiness were recorded in the last hour of driving sessions to control the effects of prior waking time and time of day. RESULTS: Compared to the daytime reference session, both simulated and real driving performance were affected by a short nocturnal driving session (P<.05 and P<.001, respectively). Extension of nocturnal driving duration affected simulated performance nonlinearly and more severely than that of real driving (P<.001). Compared to the daytime reference session, short nocturnal simulated and real driving sessions increased self-perceived fatigue and sleepiness. Real and simulated driving conditions had an identical impact on fatigue and sleepiness during extended periods of nocturnal driving. CONCLUSIONS: In healthy subjects, the INRETS-MSIS SIM2 simulator appropriately measures driving impairment in terms of inappropriate line crossings related to extended wakefulness but has limitations to measure the impact of extended driving on drivers' performance.

Is there a link between alertness and fatigue in patients with traumatic brain injury?

OBJECTIVES: Many patients with traumatic brain injury (TBI) report chronic fatigue, and previous studies showed a potential relationship between sleepiness and fatigue in these patients. Our study first looked at the impact of objective and subjective sleepiness on fatigue in patients with TBI. We then investigated how fatigue could affect driving performance in these patients. METHODS: Nocturnal polysomnography, the Fatigue Severity Scale (FSS), the Epworth Sleepiness Scale (ESS), and five 40-minute maintenance of wakefulness tests (MWT) were collected in 36 patients with TBI. Fitness to drive was assessed in a subsample of 22 patients compared to 22 matched controls during an hour simulated driving session. RESULTS: In patients with TBI, FSS, ESS, and mean MWT scores (+/-SD) were 27 +/- 10, 8 +/- 4, and 35 +/- 7 minutes vs 15 +/- 2.5, 5 +/- 3, and 37 +/- 5 minutes in controls. Patients with TBI reported more chronic fatigue (W = 99, p < 0.001) than controls, and, unlike in controls, the level of chronic fatigue was correlated to their MWT scores. Patients' driving performances were worse than the controls' (W = 79, p < 0.001). The best predictive factors of driving performance were fatigue scores and body mass index (multiple R = 0.458, 41.8% of explained variance). CONCLUSION: In patients with TBI, chronic fatigue is significantly related to subjective and objective levels of alertness, even though these levels are not highly pathologic. This might suggest that a small level of sleepiness (i.e., MWT scores between 33 and 39 minutes) worsens fatigue in these patients. Chronic fatigue and body mass index could predict driving simulator performance in patients with TBI.

An animal model of a spontaneously reversible obstructive sleep apnea syndrome in the monkey.

The anatomies of the tongue and uvula in monkeys share many similarities with humans, such that this species has the closest approximation to the human upper airway than any other species. In this study, we investigated the feasibility of using small monkeys as experimental animals for an obstructive sleep apnea model. Monkeys received intradermal injections of liquid collagen in the uvula, tongue, and lateral pharyngeal walls every 2 weeks. Polysomnography was performed bi-monthly in order to control the impact of injections on breathing events, respiratory effort (as measured by esophageal pressure), and sleep. Before injections, the three animals showed normal breathing during sleep with a mean of 4.8 +/- 2.0 events/h. After injections, a mean of 27.9 +/- 19.7 hypopneas/h was recorded (P = 0.023). Total sleep time was significantly reduced, with a decrease of REM sleep and stage II sleep; however, stage I sleep increased. Collagen injections in monkey's upper airways can create sleep-disordered breathing and abnormal sleep, as seen in sleep apneic patients.

Morningness/eveningness and the need for sleep.

The purpose of this study was to determine, in a large sample of adults of all ages (17-80 years), the effect of morningness/eveningness on sleep/wake schedules, sleep needs, sleep hygiene and subjective daytime somnolence. A total of 617 subjects (219 subjects per chronotype group) matched for age, sex and employment status, completed an abridged morningness/eveningness questionnaire, a questionnaire on sleep habits and the quality of sleep, and the Epworth Sleepiness Scale. Eveningness was associated with a greater need for sleep, less time in bed during the week compared to ideal sleep needs, more time in bed at the weekend, a later bedtime and waking-up time especially at the weekend, more irregular sleep/wake habits and greater caffeine consumption. These subjects built up a sleep debt during the week and extended their duration of sleep at the weekend. They did not, however, rate themselves more sleepy than other types, despite the fact that our results showed a clear link between subjectively evaluated daytime somnolence and sleep debt. Why they were less affected by sleep deprivation is not clear. This raises the question of individual susceptibility to the modification of sleep parameters.

Melatonin is able to influence its secretion in humans: description of a phase-response curve.

A single physiological dose of melatonin (20 micrograms for 3 h given intravenously at different times of the day (04.00-12.00, 16.00 and 20.00 h) was able to shift the endogenous plasma melatonin profile of healthy volunteers under entrained conditions according to a phase-response curve (PRC). ANOVA showed an effect of the time of administration on the onset, the acrophase or the offset of the melatonin profiles. These profiles were significantly delayed when the infusion was administered at 12.00 h and advanced when the infusion was given at 20.00 h. Further, the AUCs evaluated on the nocturnal melatonin profiles were increased after the 04.00 h infusion (+20.5%, p < 0.05), whereas they were decreased after the 12.00 h infusion (-20%, p < 0.05). Lastly, no alteration was observed for cortisol rhythm, whatever the time of melatonin administration. These results, which show that according to a PRC the system regulating melatonin secretion is sensitive to a single short-term administration of the hormone given at a low dose, support the paradigm of the endogenous synchronizer melatonin.