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Disorders of excessive sleepiness. Treatment improves ability to stay awake but does not reduce sleepiness.

A total of 47 patients with sleep disorder (36 male and 11 female) with a mean age of 47.5 +/- 15 years were evaluated for daytime symptoms with a Multiple Sleep Latency Test (MSLT) and a Maintenance of Wakefulness Test (MWT) given on the same day--once at the time of their diagnostic evaluation and again after one to six months of treatment. The MSLT and MWT data are consistent with the notion that sleep tendency, as measured by the MSLT and ability to remain awake, as measured by the MWT, represent different physiologic processes. Data show a marked treatment-related improvement in ability to stay awake as measured by the MWT and no treatment-related improvement in sleepiness as measured by the MSLT. We conclude that there is a heterogeneous subpopulation of patients with sleep disorders whose symptoms of daytime sleepiness will show no treatment-related improvement in daytime symptoms if they are evaluated only by the MSLT. We suggest that, since ability to stay awake (and not ability to fall asleep) is a requisite for all job-related duties, an objective, physiologically based test such as the MWT should be used to assess the impact of sleep disorders in cases where there is a clinical concern about fitness to drive or work.

Antidepressive Agents, Tricyclic

Evaluation of daytime sleepiness.

In summary, the evaluation of the tired patient requires an awareness of the various meanings of tiredness. Furthermore, it is important to differentiate normal sleepiness that is a product of circadian rhythm variation in vigilance from pathologic sleepiness. Sleepiness that results from faulty habits, e.g., altered sleep scheduling, drugs, or sleep restriction, can be readily discerned with the aid of a sleep-wake diary. Because subjective sleepiness is often unappreciated, especially in patients with sleep apnea, methods that rely on self-ratings of the severity of sleepiness, e.g., visual analogue scale, 10-cm line, or SSS may not coincide with performance tasks, observer assessments, or such physiologic methods as the MSLT. Less commonly employed neurophysiologic methods include pupillometry and averaged evoked potentials. On the other hand, the MSLT is commonly used for the detection of physiologic sleepiness. Moreover, it is helpful in evaluating response to treatment. A variation of the MSLT, the MWT, which instructs the individual to remain awake, does not discriminate between sleep onset times for wakefulness and the MSLT for sleepiness in normal subjects. The MWT may be useful for the assessment of treatment responses for excessive daytime sleepiness, e.g., narcolepsy, and for determining the frequency of daytime sleep episodes. The differences that have been observed between behavioral measures and physiologic measures of sleepiness suggest that these techniques assess different aspects of sleepiness. HLA typing (DR2, DQw1) has been shown to be a useful method for corroborating narcolepsy-cataplexy, but the antigens are neither specific for the disorder nor for sleepiness alone.

Diagnosis, Differential

Daytime sleepiness and performance among healthy 80 and 20 year olds.

This study investigated the relationship of daytime sleepiness and performance on a vigilance test in a sample of 10 healthy men and 13 women in their 80s (mean age 83.0 +/- 3.1 years) and 18 men and 12 women in their 20s (25.0 +/- 3.1). We hypothesized that "successfully" aged healthy individuals would have more daytime sleepiness with differentially greater decrements in performance than a younger comparison group. Daytime sleepiness was measured physiologically by the Multiple Sleep Latency Test (MSLT) and through self-report by the Stanford Sleepiness Scale (SSS). Morning and evening performance was measured with the Mackworth Clock Test of vigilance. The major findings were the absence of correlation between either MSLT or SSS daytime sleepiness with performance measures, no difference in daytime sleepiness between the old and young groups and performance decrements among the healthy elderly on all parameters. Results suggest that the modest decrements in performance among the elderly cannot be attributed to daytime sleepiness.

Adult

Blue light therapy delivered through light glasses improves sleep quality and daytime sleepiness in Parkinson's disease: A randomized trial.

BackgroundSleep disturbances, including excessive daytime sleepiness (EDS) and fragmented nocturnal sleep, are common in Parkinson's disease (PD) and significantly reduce quality of life. This pilot study evaluated the efficacy of a novel approach using blue light, delivered via dedicated glasses with integrated LED lights, to improve sleep and non-motor symptoms.MethodsRandomised, placebo-controlled, single-blind pilot study with a 2-week light intervention. Participants were assessed at baseline, two weeks, and five weeks. The study was designed to evaluate between- and within-group changes. Participants were randomly allocated to receive blue light therapy (n&#x2009;=&#x2009;15) or red light placebo (n&#x2009;=&#x2009;15), delivered via LED-integrated glasses for one hour, twice daily, given for a 2-week period. Primary outcome was improvement in sleep quality, assessed via the Pittsburgh Sleep Quality Index. Secondary outcomes included diary-based sleep outcomes, excessive daytime sleepiness, mood, anxiety, and motor symptoms.ResultsThere was a significant group&#x2009;&#xd7;&#x2009;time effect with blue light therapy leading to better Pittsburgh Sleep Quality Index scores (p&#x2009;=&#x2009;0.021). Between-group analyses showed that at two weeks a trend toward significance was observed (p&#x2009;=&#x2009;0.065), while sleep quality significantly improved at five weeks compared to placebo (p&#x2009;=&#x2009;0.029) with a large effect size (0.896). Excessive sleepiness improved in the blue light group (p&#x2009;<&#x2009;0.001), with a reduction in clinically relevant sleepiness from 50.0% to 6.7% (p&#x2009;=&#x2009;0.005).ConclusionsBlue light therapy delivered through dedicated glasses appeared to show an improvement in sleep quality and daytime sleepiness in individuals with PD. Blue light therapy offers a promising alternative to traditional light therapy utilising lower light intensities and eliminating the need for light boxes.

Aged

Circadian variation in performance, subjective sleepiness, sleep, and oral temperature during an altered sleep-wake schedule.

The effect of an altered sleep-wake schedule on the interrelation of oral temperature, performance, and sleepiness was studied in 38 male Naval volunteers who maintained a 60 min treatment--160 min testing schedule for 40 consecutive hrs. During the 60 min treatment portion of each epoch, 8 subjected napped, 10 subjects exercised, and 20 subjects rested in bed. Sleep measures (for the nap subjects), oral temperature, performance on several tests, and Stanford Sleepiness Scale ratings were obtained at 10 equidistant intervals throughout the 40-hr period. Within-subject correlations showed that minimum oral temperature was significantly associated with maximum nap sleep time, errors on a vigilance task, and sleepiness ratings. In the nap subjects, errors and sleepiness ratings were highest following naps with high total sleep time, suggesting that sleep was detrimental to immediately subsequent performance and alertness. The distribution and interrelation of temperature, errors, and sleepiness, however, was similar in the three groups; this indicated that the synchronous circadian variation in these measures was responsible for the apparent detrimental effect of sleep in the nap subjects. When the diurnal effect was removed by holding time of day constant, the correlations among the variables fell to near-zero, indicating no causal relationship among the variables independent of the circadian rhythm.

Adolescent

Sleepiness and hypertension in obstructive sleep apnea.

In order to assess the complications of sleep apnea, we have reviewed a data base of 619 consecutive admissions to a university sleep disorders center. Although patients with obstructive sleep apnea (OSA) described more subjective sleepiness than patients with central sleep apnea (CSA) or primary snoring (PS), the multiple sleep latency test (MSLT) indicated similar levels of physiologic sleepiness in the two apneic groups, which was greater than among those with PS. There was no significant relationship between individual subjective estimates of habitual sleepiness and the MSLT values. Among the OSA patients the mean minimum arterial oxygen desaturation during REM sleep accounted for 65 percent of the variance of the mean sleep latency on the MSLT, with an additional, smaller, contribution of the disordered breathing rate per hour. Subjective reports of sleepiness were associated with sleep efficiency and the number of disordered breathing events in NREM sleep. Patients with OSA or CSA had similar diastolic blood pressures and frequencies of history of treatment for hypertension, which were significantly higher in OSA than in the PS group. In the OSA group the absolute minimum arterial oxygen desaturation during NREM sleep was the most significant contributor to waking diastolic blood pressure, with an additional small contribution by weight. A history of treatment for hypertension was most strongly associated with weight, without significant additional contributions by measures of disordered breathing events or oxygen desaturation; however, weight was highly intercorrelated with measures of the apnea/hypopnea index and minimum arterial oxygen desaturation. In summary, these data support recent findings which show a close relation of obesity to a history of hypertension in OSA, and extend to this group a previous observation that in regular heavy snorers, there may be a disparity between levels of physiologic and subjective sleepiness.

Analysis of Variance

Excessive daytime sleepiness in man: multiple sleep latency measurement in narcoleptic and control subjects.

Excessive daytime sleepiness is a complaint characterizing many disorders of the wakefulness--sleep cycle. This paper addresses the complaint of sleepiness objectively by an attempt to differentiate a group of control subjects from a group of patients with unambiguous narcolepsy. Fourteen control and 27 narcoleptic subjects were evaluated by one of three protocols involving nocturnal recordings, detailed interviews, and 5 or more 20-min opportunities to sleep offered at 2-h intervals beginning at 10.00 o'clock, +/- 30 min. Each 20-min opportunity to sleep was given to subjects lying in a darkened quiet room and asked to try to fall asleep. Polysomnographic variables were monitored and sleep was scored in 30-sec epochs by standard criteria. The interval from the start of each test to the first epoch of NREM (including stage 1 sleep) or REM sleep was called sleep latency. In two of the protocols, the subjects were awakened immediately after sleep onset. In the third protocol, the subjects were awakened after 10 min of sleep. Narcoleptics consistently fell asleep much more readily than did control subjects. We conclude that the Multiple Sleep latency test, in addition to providing opportunities to clinically document sleep onset REM sleep periods, can demonstrate pathological sleepiness. Based on these data, we suggest that an average sleep latency less than 5 min be set as the minimum cutoff point for pathological sleepiness.

Adult

Sleep habits of children and the identification of pathologically sleepy children.

Sleep disorders and daytime sleepiness have been investigated only minimally in children. The sleep habits of 218 children, ages 10-13 years, were surveyed by a sleep habits questionnaire (SHQ). Our results demonstrate that total night time sleep on school nights begins to fall in early adolescence, whereas it remains relatively stable on non-school nights. Daytime sleepiness is not a common problem in this age group, in contrast to a college age population. We conclude that in adolescence chronic sleep deficits begin to occur which cumulatively affect later functioning. The potential use of the SHQ for depicting pathological sleepiness is also discussed.

Adolescent

Reliability and factor analysis of the Epworth Sleepiness Scale.

The Epworth Sleepiness Scale (ESS) is a self-administered eight-item questionnaire that has been proposed as a simple method for measuring daytime sleepiness in adults. This investigation was concerned with the reliability and internal consistency of the ESS. When 87 healthy medical students were tested and retested 5 months later, their paired ESS scores did not change significantly and were highly correlated (r = 0.82). By contrast, ESS scores that were initially high in 54 patients suffering from obstructive sleep apnea syndrome returned to more normal levels, as expected, after 3-9 months' treatment with nasal continuous positive airway pressure. The questionnaire had a high level of internal consistency as measured by Cronbach's alpha (0.88). Factor analysis of item scores showed that the ESS had only one factor for 104 medical students and for 150 patients with various sleep disorders. The ESS is a simple and reliable method for measuring persistent daytime sleepiness in adults.

Adolescent

Daytime sleepiness: a risk factor in community life.

The prevalence of daytime sleepiness and background factors associated with it were investigated in a study carried out at the UKK Institute. The inquiry took the form of a questionnaire mailed to 1600 people of middle age. Daytime sleepiness was found to be associated with disturbed night sleep. Women were more tired than men, but men slept more frequently during the day. Those suffering from tiredness complained of poor health more than other respondents. Traffic accidents and other mishaps attributable to tiredness had occurred in 1.3% of cases, and almost 5% of male respondents had dozed off while driving at least five times in their lives. The findings indicate a need for increased attention to disturbance of sleep and daytime sleepiness in routine health screening.

Accidents, Traffic

Steroid hormone biosynthesis and dietary related metabolites associated with excessive daytime sleepiness.

BACKGROUND: Excessive daytime sleepiness (EDS) is a complex sleep problem that affects approximately 33% of the United States population. Although EDS usually occurs in conjunction with insufficient sleep and other sleep and circadian disorders, recent studies have shown unique genetic markers and metabolic pathways underlying EDS. Here, we aimed to further elucidate the biological profile of EDS using large-scale single- and pathway-level metabolomics analyses. METHODS: Metabolomics data were available for 877 metabolites in 6071 individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). EDS was assessed using the Epworth Sleepiness Scale (ESS) questionnaire. We performed linear regression for each metabolite on the continuous ESS score, adjusting for demographic, lifestyle, and physiological confounders, and in sex specific groups. Subsequently, gaussian graphical modelling was performed coupled with pathway and enrichment analyses to generate a holistic interactive network of the metabolomic profile of EDS associations. FINDINGS: We identified seven metabolites belonging to steroids, sphingomyelin, and long-chain fatty acids sub-pathways in the primary model associated with EDS, and an additional three metabolites in the male-specific analysis. INTERPRETATION: Our findings indicate that an EDS metabolomic profile is characterised by endogenous and dietary metabolites within the steroid hormone biosynthesis pathway, with some pathways that differ by sex. These pathways may be useful for understanding the causes or consequences of EDS and related sleep disorders. FUNDING: Details regarding funding supporting this work and all studies involved are provided in the acknowledgements section.

Humans

Altered states of consciousness in disorders of daytime sleepiness.

Patients with daytime sleepiness present altered states of consciousness. The occurrence of these states impairs their professional, social and familial activities and may threaten life itself. The automatic behavior syndrome is characterized by continuation of mechanical activity and complete amnesia. Episodes lasting from a few seconds to several hours are correlated with repetitive micro-sleep periods. During cataplectic attacks, patients may have a meshing of reality with hallucinatory dream contents. Sleep-induced apnea may lead to abnormal movement and abnormal ambulation during sleep as well as hallucinations in the early morning. These altered states of consciousness must be considered as diagnostic indexes in differentiating epileptic syndromes from syndromes of daytime sleepiness.

Adult

235 cases of excessive daytime sleepiness. Diagnosis and tentative classification.

A series of 235 consecutive patients refferred to the Stanford University Sleep Disorders Clinic with the complaint of excessive daytime sleepiness (EDS) were investigated extensively. A satisfactory final diagnosis involving a consistent syndrome or pathogenic process was made in all but 7 patients. In the course of this work a variety of tests, including prolonged polygraphic monitoring of multiple variables and CSF measurements before and after probenecid ingestion, were utilized. Different syndromes were confirmed (harmonious hypersomnia, subwakefulness syndrome); the definitions of others were clarified and extended (narcolepsy, drug dependency, periodic hypersomnia associated with menstruation, upper airway sleep apnea in children). Two new entities were tentatively identified (narcolepsy with sleep apnea, the neutral state syndrome). Narcolepsy and upper airway sleep apnea accounted for the majority of the cases (199). A strategic schema utilizing specific categories and frequency of occurrence in the case series is presented to improve the diagnosis of the complaint of excessive daytime sleepiness by the practicing physician. This case series was analysed in order to develop tentatively a meaningful nosology.

Adolescent

Daytime sleepiness after long-term continuous positive airway pressure (CPAP) treatment in obstructive sleep apnea syndrome.

A modified maintenance of wakefulness test was performed in 58 patients with obstructive sleep apnea (OSA) syndrome before treatment and after long-term (554 +/- 28 days) home therapy with nasal continuous positive airway pressure (CPAP). Before treatment the patients had a shorter mean sleep latency than controls (16 +/- 1 vs. 27 +/- 1 min, mean +/- SEM, P less than 0.001). After treatment, the mean sleep latency increased to 20 +/- 1 min (P less than 0.002 as compared to baseline), but was still shorter than in controls (P less than 0.001). The incomplete normalization of the mean latency contrasted with the patients' claim that they no longer felt sleepy. The improvement in daytime alertness was significantly correlated with the reduction in sleep fragmentation after CPAP treatment and with the baseline mean sleep latency. These results support the hypothesis that sleep disruption related to respiratory events plays a role in the pathogenesis of daytime sleepiness.

Electrocardiography

The effects of phenindamine tartrate on sleepiness and psychomotor performance.

Phenindamine, an H1-receptor antagonist that was developed almost 50 years ago, has been associated with both drowsiness and insomnia. Since its central nervous system profile has not been well characterized, we used a series of psychomotor tests to conduct two studies. In the first, 12 subjects received single oral doses of phenindamine (25 mg), diphenhydramine (50 mg), terfenadine (60 mg), or placebo in a four-way crossover study. Psychomotor tests included choice reaction time (CRT), tracking, and hand steadiness (HS). In the second trial, 15 subjects received single oral doses of phenindamine (25 mg), pseudoephedrine (60 mg), phenindamine and pseudoephedrine, diphenhydramine (50 mg), or placebo in a five-way crossover study. Psychomotor tests included CRT, HS, and a task that divided attention between tracking and reaction time. Introspective drowsiness was measured in both trials with use of a visual analog scale (VAS) and the Stanford Sleepiness Scale (SSS). All assessments were made before and 1, 3, and 5 hours after drug administration. In the first trial, diphenhydramine produced significant impairment relative to placebo (p < 0.05) in CRT, tracking, and HS tasks and higher SSS and VAS scores, with peak effect noted at 3 hours. Phenindamine did not significantly differ from placebo or terfenadine. In the second trial, diphenhydramine produced significant impairment relative to placebo (p < 0.05) in CRT, divided attention, HS, and VAS, and SSS, also peaking at 3 hours. Stanford Sleepiness Scale scores after phenindamine were greater than placebo at 3 hours (p < 0.05) but significantly less than diphenhydramine (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Evaluation of antihistamine-related daytime sleepiness. A double-blind, placebo-controlled study with terfenadine.

The daytime sleepiness potentially associated with antihistamines was evaluated by the multiple sleep latency test (MSLT) in a study comparing terfenadine with placebo. According to a double-blind, randomized, cross-over design, 12 healthy men were given either 120 mg terfenadine or placebo once daily in the morning, for 3 consecutive days with a 5-day interval. EEG-polygraphic recordings were made each study day at 9:30 and 11:30 a.m., and 1:30, 3:30, and 5:30 p.m., and the tendency to fall asleep was measured. All mean stage-1 sleep latencies throughout the study failed to show any significant difference between terfenadine and placebo. Accordingly, psychomotor performance assessed by visual and auditory reaction time did not change after treatment. The results of this study confirmed that terfenadine does not induce daytime sleepiness as objectively measured by MSLT.

Adult

From obstructive sleep apnea syndrome to upper airway resistance syndrome: consistency of daytime sleepiness.

Some patients with excessive daytime sleepiness who do not present the features of obstructive sleep apnea syndrome (OSAS) present a sleep fragmentation due to transient alpha EEG arousals lasting between three and 14 seconds. These transient EEG arousals are related to an abnormal amount of breathing effort, indicated by peak inspiratory esophageal pressure (Pes) nadir. In the studied population, these increased efforts were associated with snoring. Usage of nasal CPAP, titrated on Pes nadir values, for several weeks eliminated subjective daytime sleepiness and improved Multiple Sleep Latency Test scores from baseline evaluations. Patients suspected of CNS hypersomnia should be asked about continuous snoring, and their clinical evaluation should include a good review of maxillo-mandibular and upper airway anatomy.

Airway Obstruction