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Concept: Excessive daytime sleepiness

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BACKGROUND: The recent SLEEMSA study that evaluated excessive daytime sleepiness (EDS) in Caucasian patients with multiple system atrophy (MSA) demonstrated that EDS was more frequent in patients (28%) than in healthy subjects (2%). However, the prevalence and determinants of EDS in other ethnic populations have not been reported to date. METHODS: We performed a single-hospital prospective study on patients with probable MSA. To ascertain the prevalence and determinants of EDS in Japanese MSA patients, we assessed the patients' degree of daytime sleepiness by using the Japanese version of the Epworth Sleepiness Scale (ESS). In addition, we investigated the effects of sleep-disordered breathing (SDB) and abnormal periodic leg movements in sleep (PLMS), which were measured by polysomnography, on the patients' ESS scores. RESULTS: A total of 25 patients with probable MSA (21 patients with cerebellar MSA and 4 patients with parkinsonian MSA) were included in this study. All patients underwent standard polysomnography. The mean ESS score was 6.2 +/- 0.9, and EDS was identified in 24% of the patients. SDB and abnormal PLMS were identified in 24 (96%) and 11 (44%) patients, respectively. The prevalences of EDS in patients with SDB and abnormal PLMS were 25% and 18%, respectively. No correlations were observed between ESS scores and the parameters of SDB or abnormal PLMS. CONCLUSIONS: The frequency of EDS in Japanese patients with MSA was similar to that in Caucasian MSA patients. SDB and abnormal PLMS were frequently observed in MSA patients, although the severities of these factors were not correlated with EDS. Further investigations using objective sleep tests need to be performed.

Concepts: Sleep, Sleep disorder, Parkinson's disease, Sleep apnea, Sleep medicine, Epworth Sleepiness Scale, Excessive daytime sleepiness, Sleep disorders

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The biology underlying excessive daytime sleepiness (hypersomnolence) is incompletely understood. After excluding known causes of sleepiness in 32 hypersomnolent patients, we showed that, in the presence of 10 μM γ-aminobutyric acid (GABA), cerebrospinal fluid (CSF) from these subjects stimulated GABA(A) receptor function in vitro by 84.0 ± 40.7% (SD) relative to the 35.8 ± 7.5% (SD) stimulation obtained with CSF from control subjects (Student’s t test, t = 6.47, P < 0.0001); CSF alone had no effect on GABA(A) signaling. The bioactive CSF component had a mass of 500 to 3000 daltons and was neutralized by trypsin. Enhancement was greater for α2 subunit- versus α1 subunit-containing GABA(A) receptors and negligible for α4 subunit-containing ones. CSF samples from hypersomnolent patients also modestly enhanced benzodiazepine (BZD)-insensitive GABA(A) receptors and did not competitively displace BZDs from human brain tissue. Flumazenil-a drug that is generally believed to antagonize the sedative-hypnotic actions of BZDs only at the classical BZD-binding domain in GABA(A) receptors and to lack intrinsic activity-nevertheless reversed enhancement of GABA(A) signaling by hypersomnolent CSF in vitro. Furthermore, flumazenil normalized vigilance in seven hypersomnolent patients. We conclude that a naturally occurring substance in CSF augments inhibitory GABA signaling, thus revealing a new pathophysiology associated with excessive daytime sleepiness.

Concepts: Brain, Receptor, Cerebrospinal fluid, Somnolence, Benzodiazepine, Excessive daytime sleepiness, Hypersomnia, GABAA receptor

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A 66-year-old man with hypertension presented with complaints of excessive daytime sleepiness (Epworth Sleepiness Score 14/24), dyspnea upon exertion, and episodes of noninjurious dream-enacting behavior. He reported tongue biting when sleeping in the right lateral decubitus position. Medications included atenolol 12.5 mg, lovastatin 20 mg, doxazosin 2 mg, amlodipine 5 mg, isosorbide mononitrate 60 mg, and aspirin 81 mg. He denied headaches, visual changes, dysarthria, dysphagia, or localized weakness. He denied use of alcohol, tobacco, or drugs.

Concepts: Hypertension, Ibuprofen, Aspirin, Sleep apnea, Epworth Sleepiness Scale, Somnolence, Excessive daytime sleepiness, Isosorbide mononitrate

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BACKGROUND: Excessive daytime sleepiness (EDS) is a common condition worldwide that has many negative effects on people who were afflicted with it, especially on their health-related quality of life (HRQOL). The Epworth Sleepiness Scale (ESS) is a commonly used method for evaluating EDS in English-speaking countries. This paper reported the prevalence of subjective EDS in China as assessed by the Mandarin version of the ESS; tested the scale’s response rate, reliability and validity; and investigated the relationship between ESS scores and HRQOL. METHODS: A population-based sample of 3600 residents was selected randomly in five cities in China. The demographic information was collected, subjective EDS was assessed by the Mandarin version of the ESS (ESS scores >10), and HRQOL was evaluated by the Mandarin version of the 36-item Short Form Health Survey (SF-36). RESULTS: The Mandarin version of ESS had very few missing responses, and the average response rate of its eight items was 97.92 %. The split-half reliability coefficient and Cronbach’s alpha coefficient were 0.81 and 0.80, respectively. One factor was identified by factor analysis with an eigenvalue of 2.78. The ESS scores showed positive skewness in the selected sample, with a median (Q1, Q3) of 6 (3, 0). 644 (22.16 %) respondents reported subjective EDS, and all of the scores of the eight dimensions of the SF-36 were negatively correlated with ESS scores. CONCLUSIONS: The Mandarin version of ESS is an acceptable, reliable, and valid tool for measuring EDS. In addition, subjective EDS is common in China, based on the ESS results, and impairs HRQOL.

Concepts: Psychometrics, Factor analysis, Reliability, Skewness, Cronbach's alpha, Epworth Sleepiness Scale, Excessive daytime sleepiness, Internal consistency

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Narcolepsy is characterised by excessive daytime sleepiness (EDS) and cataplexy. Histamine neurons are crucial to maintain wakefulness. We assessed the safety and efficacy of pitolisant (previously called BF2.649), a selective histamine H3 receptor inverse agonist that activates these neurons, in patients with narcolepsy.

Concepts: Pharmacology, Histamine, Receptor antagonist, Agonist, Inverse agonist, Excessive daytime sleepiness, Narcolepsy, Histamine H3 receptor

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OBJECTIVES: Although sleep disorders have been reported to affect more than half of adults with attention-deficit/hyperactivity disorder (ADHD), the association between sleep and ADHD is poorly understood. The aims of our study were to investigate sleep-related variables in adults with ADHD and to assess if any differences exist between ADHD of the predominantly inattentive (ADHD-I) and combined (ADHD-C) subtypes. METHODS: We used the Epworth sleepiness scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and the fatigue severity scale (FSS) to collect data on daytime sleepiness, sleep quality, and fatigue in 126 subjects (45 ADHD-I and 81 ADHD-C subjects). RESULTS: Approximately 85% of subjects reported excessive daytime sleepiness or poor sleep quality. The most common sleep concerns were initial insomnia, interrupted sleep, and feeling too hot. When examining ADHD subtype differences, ADHD-I subtypes reported poorer sleep quality and more fatigue than ADHD-C subtypes. Partial correlation analyses revealed that interrelationships between sleep quality, daytime sleepiness, and fatigue differ between ADHD subtypes; in ADHD-I subtypes fatigue was associated with sleep quality, while in the ADHD-C subtypes fatigue was associated with both sleep quality and daytime sleepiness. There also appears to be a subtype×gender interaction that affects the perception of fatigue, as subjective fatigue was markedly higher in ADHD-I women than in ADHD-C women. CONCLUSION: Altogether our data indicate that the interplay of variables associated with daytime function and sleep varies between ADHD subtypes. This finding may have considerable relevance in the management and pathophysiologic understanding of ADHD, and thus lead to tailored treatments for ADHD subtypes.

Concepts: Sleep, Sleep deprivation, Sleep disorder, Attention-deficit hyperactivity disorder, ADHD predominantly inattentive, Epworth Sleepiness Scale, Excessive daytime sleepiness, Sleep disorders

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One workweek of mild sleep restriction adversely impacts sleepiness, performance and pro-inflammatory cytokines. Many individuals try to overcome these adverse effects by extending their sleep on weekends. To assess whether extended recovery sleep reverses the effects of mild sleep restriction on sleepiness/alertness, inflammation and stress hormones, 30 healthy, young men and women (mean age ±SD, 24.7 ± 3.5; mean body mass index ±SD, 23.6 ± 2.4 kg/m2) participated in a sleep laboratory experiment of 13 nights [4 baseline nights (8h/night), followed by 6 sleep restriction nights (6h/night) and 3 recovery nights (10h /night)]. Twenty-four-hour profiles of circulating interleukin-6 (IL-6) and cortisol, objective and subjective daytime sleepiness (Multiple Sleep Latency Test and Stanford Sleepiness Scale), and performance (Psychomotor Vigilance Task) were assessed on days 4 (baseline), 10 (after one week of sleep restriction) and 13 (after 2 nights of recovery sleep). Serial 24-h IL-6 plasma levels increased significantly during sleep restriction and returned to baseline after recovery sleep. Serial 24-h cortisol levels during restriction did not change compared to baseline, but after recovery they were significantly lower. Subjective and objective sleepiness increased significantly after restriction and returned to baseline after recovery. In contrast, performance deteriorated significantly after restriction and did not improve after recovery. Extended recovery sleep over the weekend reverses the impact of one workweek of mild sleep restriction on daytime sleepiness, fatigue and IL-6 levels, reduces cortisol levels, but does not correct performance deficits. The long-term effects of a repeated sleep restriction/sleep recovery weekly cycle in humans remain unknown.

Concepts: Sleep, Sleep deprivation, Body mass index, Cortisol, Excessive daytime sleepiness, Weekend, Workweek, Multiple Sleep Latency Test

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Post-traumatic sleep-wake disturbances are common after acute traumatic brain injury. Increased sleep need per 24 h and excessive daytime sleepiness are among the most prevalent post-traumatic sleep disorders and impair quality of life of trauma patients. Nevertheless, the relation between traumatic brain injury and sleep outcome, but also the link between post-traumatic sleep problems and clinical measures in the acute phase after traumatic brain injury has so far not been addressed in a controlled and prospective approach. We therefore performed a prospective controlled clinical study to examine (i) sleep-wake outcome after traumatic brain injury; and (ii) to screen for clinical and laboratory predictors of poor sleep-wake outcome after acute traumatic brain injury. Forty-two of 60 included patients with first-ever traumatic brain injury were available for follow-up examinations. Six months after trauma, the average sleep need per 24 h as assessed by actigraphy was markedly increased in patients as compared to controls (8.3 ± 1.1 h versus 7.1 ± 0.8 h, P < 0.0001). Objective daytime sleepiness was found in 57% of trauma patients and 19% of healthy subjects, and the average sleep latency in patients was reduced to 8.7 ± 4.6 min (12.1 ± 4.7 min in controls, P = 0.0009). Patients, but not controls, markedly underestimated both excessive sleep need and excessive daytime sleepiness when assessed only by subjective means, emphasizing the unreliability of self-assessment of increased sleep propensity in traumatic brain injury patients. At polysomnography, slow wave sleep after traumatic brain injury was more consolidated. The most important risk factor for developing increased sleep need after traumatic brain injury was the presence of an intracranial haemorrhage. In conclusion, we provide controlled and objective evidence for a direct relation between sleep-wake disturbances and traumatic brain injury, and for clinically significant underestimation of post-traumatic sleep-wake disturbances by trauma patients.

Concepts: Epidemiology, Clinical trial, Traumatic brain injury, Intracranial pressure, Sleep, Sleep disorder, Sleep medicine, Excessive daytime sleepiness

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Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25-30% of adults worldwide. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586). We discover loci associated with insomnia symptoms (near MEIS1, TMEM132E, CYCL1 and TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR-OPHN1) and a composite sleep trait (near PATJ (INADL) and HCRTR2) and replicate a locus associated with sleep duration (at PAX8). We also observe genetic correlation between longer sleep duration and schizophrenia risk (rg = 0.29, P = 1.90 × 10(-13)) and between increased levels of excessive daytime sleepiness and increased measures for adiposity traits (body mass index (BMI): rg = 0.20, P = 3.12 × 10(-9); waist circumference: rg = 0.20, P = 2.12 × 10(-7)).

Concepts: Genetics, Sleep, Sleep disorder, Body mass index, Sleep medicine, Excessive daytime sleepiness, Narcolepsy, Insomnia