Sleep Medicine Reviews

Published by Elsevier
Print ISSN: 1087-0792
Physical exercise is a modality of non-pharmacological treatment for sleep disorders. Contradicting results are still found in studies of the effect of exercise on sleep. Among the substances that have been described as sleep modulators, cytokines produced during the recovery period after an acute exercise session are very important. Various studies have verified that physical exercise may alter the plasma concentration of the many pro-inflammatory cytokines that may in turn modulate sleep. A number of factors seem to mediate this effect of exercise, including duration, intensity, and form of exercise, in addition to temperature and metabolic alterations. The mechanisms through which exercise promotes alterations in sleep architecture remain to be clarified. Researchers speculate that many hormones and substances produced by metabolism may affect sleep. Therefore, the object of this review is to discuss the effects of exercise and cytokines on sleep, and the relation between these two sleep-regulating components, raising the hypothesis that the alterations in sleep promoted by exercise are mediated by cytokines, which, by increasing the nREM sleep phase, would stimulate the regenerating characteristics of sleep.
The objective of this systematic review and content analysis was to identify and quantify the concepts contained in patient-administered health status measures in sleep medicine practice and research using the International Classification of Functioning, Disability and Health (ICF) as a reference. Both generic and condition-specific patient-administered measures/questionnaires used in sleep medicine practice and research were identified and selected. A comprehensive search strategy for reviews, National/International Guidelines and Standard References to ensure that all areas of functioning, disability and health were captured was used. The contents of the selected measures were examined and linked to the ICF using established linking rules. The frequencies of ICF categories covering the concepts contained in the 115 patient-administered measures were used for the descriptive analysis and content comparison. Of these, 35 were of a generic nature, 17 were symptom-related, and 63 condition-specific. The concepts identified in the questionnaires' items were predominantly linked to categories of the ICF component related to body functions (61.4%), followed by activities and participation (15.3%), and then environmental factors (9.8%). The measures vary greatly with regard to the number and specificity of the ICF categories covered, as indicated by the proportional indices of content density and content diversity. The ICF provides a useful reference to identify, quantify and compare the concepts contained in health status measures used in sleep medicine practice and research.
Patients with multiple sclerosis (MS) often have unrecognized sleep disorders at higher frequency than the general population. Sleep disorders such as sleep disordered breathing, insomnia, REM sleep behavior disorder, narcolepsy and restless legs syndrome have all been reported in the MS population. Notably, the most common symptom of MS is "fatigue," which itself has been correlated with sleep disturbances. Sleep disorders may impact the quality of life of the MS patient population. This paper reviews the association of sleep disorders with MS, and discusses the association of sleep disruption with MS fatigue.
Occidental medicine has a given definition for restless legs syndrome (RLS) and knowledge of RLS pathophysiology has led to the development of its therapeutic management. RLS has no cure. Many methods have been used for its treatment, among which traditional Chinese medicine (TCM) has been considered as a new approach. However, description and management of the disease symptoms can be found in Chinese ancient medical systems. The first mention of RLS may have been as early as the third century BC described as "leg uncomfortable". Nonetheless, the lack of a complete description encompassing all four modern cardinal features of RLS makes this uncertain. On the other hand, the first description of RLS encompassing three of the four major modern criteria occurs in the ancient book of Neike Zhaiyao (Internal summary), 1529 AD just about a century and a half prior to the description of RLS by Sir Thomas Willis in England. Here, we introduce the philosophical concepts of traditional Chinese medicine and the description, classification and understanding of RLS symptoms in traditional Chinese medicine. We have conducted an in-depth review of the literature reporting one part of TCM, Chinese herbal treatment efficacy for RLS, through both English and Chinese search engines. Eighty-five studies were included in the review and more than 40 formulas (including 176 different ingredients) were found in the literature. According to the literature, Chinese herbs have been demonstrated to be safe and hold great potential to be an effective treatment modality for RLS, but the evidence is limited by the quality of these studies. Of the eighty-five studies, only nine were clinical trials with a control group and only three of them were randomized. In cases where herbal preparations were compared to Western medications for RLS, the herbal preparations appear to be superior. However, uncertainty as to whether the diagnosis of RLS was made in accord with Western norms and the use of homemade non-validated rating scales create uncertainty as to the meaning of these results. High-quality randomized and double blinded clinical trials of Chinese herbs in treating RLS will be required in the future. This review highlights aspects of Chinese herbal treatment important to guide future research and clinical practice. To our knowledge, this is the first systematic English review of the role of Chinese herbs in the treatment of RLS.
Caffeine is one of the most widely consumed psychoactive substances and it has profound effects on sleep and wake function. Laboratory studies have documented its sleep-disruptive effects. It clearly enhances alertness and performance in studies with explicit sleep deprivation, restriction, or circadian sleep schedule reversals. But, under conditions of habitual sleep the evidence indicates that caffeine, rather then enhancing performance, is merely restoring performance degraded by sleepiness. The sleepiness and degraded function may be due to basal sleep insufficiency, circadian sleep schedule reversals, rebound sleepiness, and/or a withdrawal syndrome after the acute, over-night, caffeine discontinuation typical of most studies. Studies have shown that caffeine dependence develops at relatively low daily doses and after short periods of regular daily use. Large sample and population-based studies indicate that regular daily dietary caffeine intake is associated with disturbed sleep and associated daytime sleepiness. Further, children and adolescents, while reporting lower daily, weight-corrected caffeine intake, similarly experience sleep disturbance and daytime sleepiness associated with their caffeine use. The risks to sleep and alertness of regular caffeine use are greatly underestimated by both the general population and physicians.
Historical timeline of Down syndrome sleep research in the context of general sleep research. AASM: American Academy of Sleep Medicine; DS: Down syndrome; EEG: electroencephalography; NEJM: New England Journal of Medicine; OSA: obstructive sleep apnea; PSG: polysomnography.  
Children with Down syndrome (DS) are at risk for sleep disturbances due to the anatomical features of the syndrome. Over the past 50 years research studies have measured sleep in children with DS to characterize sleep architecture and its relation to developmental delay. In the 1980s sleep disordered breathing (SDB) was recognized as a major cause of sleep disturbance in DS. The aim of this comprehensive review is to synthesize studies and present the historical context of evolving technologies, methodologies, and knowledge about SDB and DS. Future research opportunities and practice implications are discussed.
This review includes research findings from sleep-related studies on specific types of cancers, on specific types of treatment protocols, and on persons with end-stage cancer regardless of treatment protocol. Since treatment protocols have evolved in the past decade, literature since 1990 is emphasized. We conclude that researchers should design studies that attend to prior sleep history, gender, type of cancer and treatment modalities, and the specific type of sleep problems experienced over the course of diagnosis, treatment, and recovery. More research is also needed to understand sleep problems in children with cancer and sleep problems in family caregivers. Research is also needed on effective pharmacological and non-pharmacological interventions. Daytime functioning, daytime sleepiness, and altered circadian rhythms should be considered salient outcomes in addition to severity of cancer-related fatigue. Clinicians should consider whether a patient's sleep problem has been chronic and unrelated to cancer, or precipitated by diagnosis and treatment. The specific type of sleep problem should be ascertained so that appropriate interventions can be prescribed. Appropriate interventions can include either pharmacological medication or behavioral strategies, and each has the potential to promote restorative sleep and thereby improve the patient's quality of life, daytime functioning, and well-being.
This paper summarizes a group of presentations and panel discussions on chronic insomnia at the 2001 NCDEU meeting. The presentations and discussions focused on the twin issues of efficacy and concerns of abuse liability with long-term hypnotic therapy. The panel concluded that insomnia may be an epidemiological marker for a variety of difficulties including accidents, increased health care utilization and subsequent development of major depression. Whether or not treatment of insomnia will prevent these long-term problems has not yet been determined. Since the mid-1980s there has been a rapid rise in the off-label use of antidepressants, particularly trazodone, for treating insomnia. Some participants expressed concern at the lack of data for this practice, particularly the absence of dose-response and tolerance information, and noted that the small amount of efficacy data available is not encouraging. Similarly, there are minimal data to support the use of antihistamines as sleep aids; moreover, their side effect profile and interactions with other drugs may be under appreciated. The limited data available on nightly long-term usage of the newer non-benzodiazepine hypnotics, primarily of six-months' duration, suggest an absence of tolerance, but more data for both nightly and non-nightly administration are needed. Insomniacs tend to show therapy-seeking, rather than drug-seeking behavior, and patients without histories of drug abuse are unlikely to self-escalate dosage of currently available hypnotics. There is fairly good agreement on the characteristics of an ideal hypnotic. All currently available agents, while effective and safe, do not achieve this ideal. The next few years are likely to see the appearance of a variety of agents with new and promising mechanisms of action.
This paper presents a clinical review of delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake syndrome (non-24). These syndromes seem to be common and under-recognized in society, not only in the blind, but also typically emerging during adolescence. Both types of syndrome can appear alternatively or intermittently in an individual patient. Psychiatric problems are also common in both syndromes. DSPS and non-24 could share a common circadian rhythm pathology in terms of clinical process and biological evidence. The biological basis is characterized by a longer sleep period, a prolonged interval from the body temperature nadir-to-sleep offset, a relatively advanced temperature rhythm, lower sleep propensity after total sleep deprivation, and higher sensitivity to light than in normal controls. There are multiple lines of evidence suggesting dysfunctions at the behavioral, physiological and genetic levels. Treatment procedures and prevention of the syndromes require further attention using behavioral, environmental, and psychiatric approaches, since an increasing number of patients in modern society suffer from these disorders.
Cross-sectional adult studies.
Longitudinal adult studies.
Cross-sectional paediatric studies.
Longitudinal paediatric studies.
1. Observational studies have implicated habitual sleep duration as a risk factor for mortality and morbidity. Part of this association might be mediated by obesity, which has also been associated with habitual sleep duration. These studies generate wide media attention because of the public's health concerns surrounding increasing obesity and the temporal association with the other modern "epidemic" of sleep loss. Some commentators have recommended public health interventions to control obesity via habitual sleep duration modification. We conducted a critical review of the available literature describing the relationship between habitual sleep duration and obesity in community-based studies in both adults and children, with particular emphasis on longitudinal studies and on studies with objective measures of habitual sleep duration. 2. Existing data have variable consistency. Only one study objectively measured sleep duration for more than one 24-h period. Cross-sectional and longitudinal studies in adults often demonstrated an association of short sleep duration with BMI. However, some of these studies also showed that long sleep duration was also associated with obesity. In contrast, other studies showed that neither long nor short sleep was associated with obesity. In paediatric populations there appeared to be a clear pattern where shorter sleep durations were associated with obesity. We did not locate any interventional studies where sleep duration had been manipulated in order to prevent or treat obesity. 3. We contend that the evidence base is not yet strong enough to give public health advice to the general population or specific groups about sleep duration being a modifiable risk factor for obesity. We need to experimentally clarify whether sleep duration variability is a risk factor for obesity, in what manner, and in which populations. If a reliable aetiological model could be found, we would ideally then need community-based randomised controlled trials that show that sleep duration can be changed and that sleep duration manipulation produces actual weight loss and/or prevents the development of obesity without undue side-effects.
Common symptoms associated with sleep fragmentation and sleep deprivation include increased objective sleepiness (as measured by the Multiple Sleep Latency Test); decreased psychomotor performance on a number of tasks including tasks involving short term memory, reaction time, or vigilance; and degraded mood. Differences in degree of sleepiness are more related to the degree of sleep loss or fragmentation rather than to the type of sleep disturbance. Both sleep fragmentation and sleep deprivation can exacerbate sleep pathology by increasing the length and pathophysiology of sleep apnea. The incidence of both fragmenting sleep disorders and chronic partial sleep deprivation is very high in our society, and clinicians must be able to recognize and treat Insufficient Sleep Syndrome even when present with other sleep disorders.
Based on 339 cases this review identifies, quantifies and compares 4 clinical forms of recurrent hypersomnia (1) Kleine-Levin syndrome (KLS) (239 cases), (2) Kleine-Levin syndrome without compulsive eating (KLS WOCE) (54 cases), (3) Menstrual related hypersomnia (MRH) (18 cases) and Recurrent hypersomnia with comorbidity (RHC) (28 cases). A second part of the review considers the main current issues on recurrent hypersomnia: the predisposing factors, including a window on family cases; the pathophysiology based on clinical patterns, neuroimaging data, neuropathological examinations and cerebrospinal fluid (CSF) hypocretin-1 measurements; the issues of recurrence and of a possible disruption of the circadian timing system; the relationships between recurrent hypersomnia and mood disorders; and a note on the atypical Kleine-Levin syndrome. The main outcomes of this study are a clear nosologic distinction of the different forms of recurrent hypersomnia, the finding that the prevalence of familial cases of KLS is in the same range as in narcolepsy, the suggestion of the possible involvement of a large set of cortical and subcortical structures in recurrent hypersomnia and some clues in favour of a relationship between recurrent hypersomnia and mood disorders.
The illicit recreational drugs cocaine, ecstasy and marijuana have pronounced effects upon sleep. Administration of cocaine increases wakefulness and suppresses REM sleep. Acute cocaine withdrawal is often associated with sleep disturbances and unpleasant dreams. Studies have revealed that polysomnographically assessed sleep parameters deteriorate even further during sustained abstinence, although patients report that sleep quality remains unchanged or improves. This deterioration of objective sleep measures is associated with a worsening in sleep-related cognitive performance. Like cocaine, 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") is a substance with arousing properties. Heavy MDMA consumption is often associated with persistent sleep disturbances. Polysomnography (PSG) studies have demonstrated altered sleep architecture in abstinent heavy MDMA users. Smoked marijuana and oral Delta-9-tetrahydrocannabinol (THC) reduce REM sleep. Moreover, acute administration of cannabis appears to facilitate falling asleep and to increase Stage 4 sleep. Difficulty sleeping and strange dreams are among the most consistently reported symptoms of acute and subacute cannabis withdrawal. Longer sleep onset latency, reduced slow wave sleep and a REM rebound can be observed. Prospective studies are needed in order to verify whether sleep disturbances during cocaine and cannabis withdrawal predict treatment outcome.
This paper reviews a novel hypothesis about the functions of slow wave sleep-the synaptic homeostasis hypothesis. According to the hypothesis, plastic processes occurring during wakefulness result in a net increase in synaptic strength in many brain circuits. The role of sleep is to downscale synaptic strength to a baseline level that is energetically sustainable, makes efficient use of gray matter space, and is beneficial for learning and memory. Thus, sleep is the price we have to pay for plasticity, and its goal is the homeostatic regulation of the total synaptic weight impinging on neurons. The hypothesis accounts for a large number of experimental facts, makes several specific predictions, and has implications for both sleep and mood disorders.
Non-rapid eye movement (NREM) sleep has recently garnered support for its role in consolidating hippocampus-based declarative memories in humans. We provide a brief review of the latest research on NREM sleep activity and its association with declarative memory consolidation. Utilizing empirical findings from sleep studies on schizophrenia, Alzheimer's disease, and fibromyalgia, we argue that a significant reduction of slow-wave sleep and sleep spindle activity contribute to the development of deficits in declarative memory consolidation along with concomitant sleep disturbances commonly experienced in the aforementioned disorders. A tentative model is introduced to describe the mediating role of the thalamocortical network in disruptions of both declarative memory consolidation and NREM sleep. The hope is to stimulate new research in further investigating the intimate link between these two very important functions.
During a nocturnal dream, the authors discover a strange and unknown country, Absurdistan. Absurdistanis main concern appears to be sleep, whether nocturnal or diurnal, rather than wakefulness. They are fond of sleeping in any form, and devote much time to this activity. The authors follow a guide that shows them all kinds of strange sleep habits and keeps explaining the complex as well as the obvious. As the journey evolves, the explanations turn more and more confusing, becoming also amazingly surrealistic. The dream ends with a welcome wakefulness leaving the authors unsure of which is the waking state and which the dream.
Substance abuse is linked to numerous mental and physical health problems, including disturbed sleep. The association between substance use and sleep appears to be bidirectional, in that substance use may directly cause sleep disturbances, and difficulty sleeping may be a risk factor for relapse to substance use. Growing evidence similarly links substance use to disturbances in circadian rhythms, although many gaps in knowledge persist, particularly regarding whether circadian disturbance leads to substance abuse or dependence. Given the integral role circadian rhythms play in regulating sleep, circadian mechanisms may account in part for sleep-substance abuse interactions. Furthermore, a burgeoning research base supports a role for the circadian system in regulating reward processing, indicating that circadian mechanisms may be directly linked to substance abuse independently of sleep pathways. More work in this area is needed, particularly in elucidating how sleep and circadian disturbance may contribute to initiation of, and/or relapse to, substance use. Sleep and circadian-based interventions could play a critical role in the prevention and treatment of substance use disorders.
The study of ethanol's effects on sleep has a long history dating back to the work of Nathaniel Kleitman. This paper reviews the extensive literature describing ethanol's effects on the sleep of healthy normals and alcoholics and the newer literature that describes its interactive effects on daytime sleepiness, physiological functions during sleep, and sleep disorders. Ethanol initially improves sleep in non-alcoholics at both low and high doses with disturbance in the second half of the night sleep at high doses. Tolerance develops to the initial beneficial effects. In alcoholics sleep is disturbed both while drinking and for months of abstinence and the nature of the abstinent sleep disturbance is predictive of relapse. Ethanol interacts to exacerbate daytime sleepiness and sleep-disordered breathing, even inducing apnea in persons at risk. Ethanol's effects on other physiological functions during sleep and other sleep disorders has yet to be documented. 2001 Harcourt Publishers Ltd
At a time when several studies have highlighted the relationship between sleep, learning and memory processes, an in-depth analysis of the effects of sleep deprivation on student learning ability and academic performance would appear to be essential. Most studies have been naturalistic correlative investigations, where sleep schedules were correlated with school and academic achievement. Nonetheless, some authors were able to actively manipulate sleep in order to observe neurocognitive and behavioral consequences, such as learning, memory capacity and school performance. The findings strongly suggest that: (a) students of different education levels (from school to university) are chronically sleep deprived or suffer from poor sleep quality and consequent daytime sleepiness; (b) sleep quality and quantity are closely related to student learning capacity and academic performance; (c) sleep loss is frequently associated with poor declarative and procedural learning in students; (d) studies in which sleep was actively restricted or optimized showed, respectively, a worsening and an improvement in neurocognitive and academic performance. These results may been related to the specific involvement of the prefrontal cortex (PFC) in vulnerability to sleep loss. Most methodological limitations are discussed and some future research goals are suggested.
Narcolepsy and idiopathic hypersomnia profoundly affect quality of life, education and work. Young patients are very handicapped by unexpected sleep episodes during lessons. Professionals frequently complain about sleepiness at work. Motor discomfort (i.e., cataplectic attacks) surprisingly is less handicapping in narcoleptics than sleepiness but only a few studies clearly assess the problem. Quality of life is also largely impaired in its physical and emotional dimensions. Sleepiness is the major factor explaining a decrease of quality of life and unexpectedly cataplectic attacks have little impact on patients. Another potential problem for these patients is the risk of accidents at work or when driving. Narcoleptic and hypersomniac patients have a higher risk of accidents than apneic or insomniac subjects. But, confounding factors such as duration of driving, number of cataplectic attacks or even objective level of alertness are not always entered in the analytic models mainly because of small samples of patients. Unlike in apneic patients, the effect of treatment on accidental risk has not been studied in narcoleptics or in hypersomniacs. Epidemiological data are needed to improve knowledge concerning these areas. Clinical trials assessing the impact of treatment on driving and work are also urgently needed. Finally, medical treatment does not seem to be completely efficient and physicians should pay more attention to the education, work, life and social environment of their patients.
We used meta-analysis to synthesize current evidence regarding the effect of nasal continuous positive airway pressure (nCPAP) on road traffic accidents in patients with obstructive sleep apnea (OSA) as well as on their performance in driving simulator. The primary outcomes were real accidents, near miss accidents, and accident-related events in the driving simulator. Pooled odds ratios (ORs), incidence rate ratios (IRRs) and standardized mean differences (SMDs) were appropriately calculated through fixed or random effects models after assessing between-study heterogeneity. Furthermore, risk differences (RDs) and numbers needed to treat (NNTs) were estimated for real and near miss accidents. Meta-regression analysis was performed to examine the effect of moderator variables and publication bias was also evaluated. Ten studies on real accidents (1221 patients), five studies on near miss accidents (769 patients) and six studies on the performance in driving simulator (110 patients) were included. A statistically significant reduction in real accidents (OR=0.21, 95% CI=0.12-0.35, random effects model; IRR=0.45, 95% CI=0.34-0.59, fixed effects model) and near miss accidents (OR=0.09, 95% CI=0.04-0.21, random effects model; IRR=0.23, 95% CI=0.08-0.67, random effects model) was observed. Likewise, a significant reduction in accident-related events was observed in the driving simulator (SMD=-1.20, 95% CI=-1.75 to -0.64, random effects). The RD for real accidents was -0.22 (95% CI=-0.32 to -0.13, random effects), with NNT equal to five patients (95% CI=3-8), whereas for near miss accidents the RD was -0.47 (95% CI=-0.69 to -0.25, random effects), with NNT equal to two patients (95% CI=1-4). For near miss accidents, meta-regression analysis suggested that nCPAP seemed more effective among patients entering the studies with higher baseline accident rates. In conclusion, all three meta-analyses demonstrated a sizeable protective effect of nCPAP on road traffic accidents, both in real life and virtual environment.
The vibration of the vocal folds produces a varying airflow which may be treated as a periodic signal (A) that produces a spectrum of equally-spaced frequency peaks or harmonics, starting with a fundamental frequency (F0). This source signal is input to the vocal tract. The tract behaves like a variable filter (B). Its response is different for different frequencies and the frequency response may be further adjusted by changing the position of the tongue, jaw etc. Resonance peaks R1 and R2 add gain to specific frequencies of the harmonic spectrum. The input signal and the vocal tract, together with the radiation properties of the mouth, face and external field, produce a sound output (C). The resonances R1 and R2 can be determined approximately from the peaks in the envelope of the sound spectrum. These peaks are called the formants (F1 and F2). Figure reproduced by courtesy of Joe Wolfe, BSc Qld, BA UNSW, PhD ANU, School of Physics, The University of New South Wales, Sydney 2052, Australia. 
Sound processing from source to clinical outcomes. The sound is captured with a suitable microphone. Before the analog signal is converted to a digital format, it is preamplified and filtered. Analog-to-digital conversion (ADC) means that the signal is sampled at a sufficiently high rate to enable adequate sound reproduction in the further process. The digitized record is stored as a computer file (e.g. wav-file), which may subsequently be used for several purposes. The sound may be replayed, graphically plotted or further analyzed and classified using different kinds of mathematical models. The ultimate goal is to identify individual snoring events and to discriminate them from non-snoring sounds. The true snoring events are then futher classified into different categories that are relevant for specific clinical outcomes, e.g. loudness and annoyance, anatomical site of snoring, apneic versus non-apneic snoring, and prediction models for efficacy of treatment.
Filtering or weighting the microphone signal reduces the influence of certain frequencies in the measured signal. Very common are the so-called A, B, C, or D- 
Four plots in the time domain, with time (sec) in the abscissa and sound amplitude ( w V) in the ordinate. Regular explosive peaks of sound at very low frequency can be seen during palatal snoring (top panel, left) but not during tongue base snoring (bottom panel, left). In order to quantify this aspect, a ratio of peak sound amplitude (99th centile measurement – gray bars) to effective average sound amplitude (rms – hatched bars) measurement was calculated during 0.2 s segments of a snore. This ratio is higher in palatal (4.2, top panel, right) than in nonpalatal snoring (2.6, bottom panel, right). [Reproduced with permission from 36 ]. 
Frequency analysis of a simulated mechanical palatal snoring model. A. Amplitude of the sound in the time domain. The first snore of a sequence of three. B. Frequency spectrum of the sound. The event in A is shown after Fourier analysis. Frequency (Hz) in the abscissa is plotted against power (SPL) in the ordinate. The first peak at about 40 Hz is called the fundamental frequency, the peaks at higher frequencies are called harmonics. Connecting the peaks yields the spectral envelope. Within a spectral plot different markers can be observed. The peak frequency describes the harmonic with greatest magnitude. The center frequency describes the average sound frequency for the range of frequencies over which sound occurs; it is the point at which the area under the graph is equal on both sides. The power ratio compares the
Snoring is a prevalent disorder affecting 20-40% of the general population. The mechanism of snoring is vibration of anatomical structures in the pharyngeal airway. Flutter of the soft palate accounts for the harsh aspect of the snoring sound. Natural or drug-induced sleep is required for its appearance. Snoring is subject to many influences such as body position, sleep stage, route of breathing and the presence or absence of sleep-disordered breathing. Its presentation may be variable within or between nights. While snoring is generally perceived as a social nuisance, rating of its noisiness is subjective and, therefore, inconsistent. Objective assessment of snoring is important to evaluate the effect of treatment interventions. Moreover, snoring carries information relating to the site and degree of obstruction of the upper airway. If evidence for monolevel snoring at the site of the soft palate is provided, the patient may benefit from palatal surgery. These considerations have inspired researchers to scrutinize the acoustic characteristics of snoring events. Similarly to speech, snoring is produced in the vocal tract. Because of this analogy, existing techniques for speech analysis have been applied to evaluate snoring sounds. It appears that the pitch of the snoring sound is in the low-frequency range (<500 Hz) and corresponds to a fundamental frequency with associated harmonics. The pitch of snoring is determined by vibration of the soft palate, while nonpalatal snoring is more 'noise-like', and has scattered energy content in the higher spectral sub-bands (>500 Hz). To evaluate acoustic properties of snoring, sleep nasendoscopy is often performed. Recent evidence suggests that the acoustic quality of snoring is markedly different in drug-induced sleep as compared with natural sleep. Most often, palatal surgery alters sound characteristics of snoring, but is no cure for this disorder. It is uncertain whether the perceived improvement after palatal surgery, as judged by the bed partner, is due to an altered sound spectrum. Whether some acoustic aspects of snoring, such as changes in pitch, have predictive value for the presence of obstructive sleep apnea is at present not sufficiently substantiated.
This review investigates development in the durations of infants' capabilities for sustained sleep across their first year, a matter of interest to clinicians, parents and researchers. It describes three aspects of sleep development: longest sustained sleep period (sleep sustained without awakening), longest self-regulated sleep period (behavioural quietude including sleep and quiet awakenings), and sleeping through the night (a predetermined nocturnal period). Clear trends were evident despite methodological differences making comparison between studies difficult. The most marked changes were across the first 4 months, particularly ages 1 and 2 months. Minimal changes followed through to 9 months and a small increase in all but the longest sustained sleep period, until age 12 months. Moore and Ucko's early, yet influential definition for sleeping through the night (24:00-05:00 h) may have underestimated infants' capacities for uninterrupted sleep. Infants do meet more stringent criteria and most can sleep 8 h by age 6 months and 9 or more hours thereafter. These findings have implications for clinicians addressing parental concerns around developmentally appropriate expectations of infant sleep. Researchers now have sufficient evidence to identify developmentally sensitive timing for preventive interventions for infant sleep disturbance.
Pregabalin is approved for the treatment of a variety of clinical conditions and its analgesic, anxiolytic and anticonvulsant properties are well documented. Pregabalin's effects on sleep, however, are less well known. This review summarizes the published data on the effects of pregabalin on sleep disturbance associated with neuropathic pain, fibromyalgia, restless legs syndrome, partial onset seizures and general anxiety disorder. The data demonstrate that pregabalin has a positive benefit on sleep disturbance associated with several different clinical conditions. Polysomnographic data reveal that pregabalin primarily affects sleep maintenance. The evidence indicates that pregabalin has a direct effect on sleep that is distinct from its analgesic, anxiolytic and anticonvulsant effects.
Studies of sleep across the life cycle in women have utilized both survey and polysomnographic techniques, but have tended to be of small sample size with diverse methodology. As a result, definitive conclusions about the impact of the menstrual cycle and use of oral contraceptives on sleep parameters cannot yet be made. Sleep disruption during pregnancy and postpartum is nearly universal, but effective and practical countermeasures are still needed. Longitudinal studies of sleep in the postpartum period are also lacking. Menopause is associated with insomnia due to several factors including hot flashes, mood disorders and increased sleep-disordered breathing. The use of hormone replacement therapy to treat sleep and other variables is an active area of investigation. In summary, much research is required to fully elucidate the impact of the life cycle on sleep parameters in women.
Intervention components to promote CPAP * adherence: pediatric and older adult considerations. Add-on considerations (shaded diamonds, left side for children; right side for older adults and older adults with cognitive impairment) to promote CPAP use in children and older adults based on currently published studies. These suggestions extend the American Academy of Sleep Medicine ’ s Adult Obstructive Sleep Apnea Task Force recommendations. AASM e American Academy of Sleep Medicine; CBT e cognitive behavior therapy; CPAP e continuous positive airway pressure; OSA e obstructive sleep apnea; PAP e positive airway pressure. Flow diagram adapted with permission from. 10 
Continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA) but adherence to the treatment limits its overall effectiveness across all age groups of patients. Factors that influence adherence to CPAP include disease and patient characteristics, treatment titration procedures, technological device factors and side effects, and psychological and social factors. These influential factors have guided the development of interventions to promote CPAP adherence. Various intervention strategies have been described and include educational, technological, psychosocial, pharmacological, and multi-dimensional approaches. Though evidence to date has led to innovative strategies that address adherence in CPAP-treated children, adults, and older adults, significant opportunities exist to develop and test interventions that are clinically applicable, specific to sub-groups of patients likely to demonstrate poor adherence, and address the multi-factorial nature of CPAP adherence. The translation of CPAP adherence promotion interventions to clinical practice is imperative to improve health and functional outcomes in all persons with CPAP-treated OSA.
Hypersomnia is prevalent and persistent across mood disorders. This review has two aims: (1) to synthesize the research that has accrued on hypersomnia in mood disorders and (2) to identify an agenda for future research that advances knowledge on this critical, but understudied, feature of mood disorders. We begin by reviewing the state-of-the-science on the diagnosis, epidemiology and course of hypersomnia in Major Depressive Disorder, Bipolar Disorder, Dysthymic Disorder, and Seasonal Affective Disorder. We then address key measurement and assessment issues, particularly those arising from the use of objective methods. This section identifies a need to explore whether hypersomnia is a disorder of Time in Bed (TIB) rather than a disorder of Total Sleep Time (TST), or whether presentations of TIB vs. TST represent two subtypes of hypersomnia with differing etiologies. Established and proposed mechanisms contributing to hypersomnia are then highlighted, including the possibility that hypersomnia is an important mechanism contributing to the maintenance of mood disorder symptoms. We then move on to review the small body of literature on pharmacological interventions for hypersomnia in mood disorders. Though non-pharmacological treatments targeting hypersomnia have not yet been developed, we offer initial guidelines for such treatments and conclude with an agenda for future research.
The use of actigraphs, or ambulatory devices that estimate sleep-wake patterns from activity levels, has become common in pediatric research. Actigraphy provides a more objective measure than parent-report, and has gained popularity due to its ability to measure sleep-wake patterns for extended periods of time in the child's natural environment. The purpose of this review is: 1) to provide comprehensive information on the historic and current uses of actigraphy in pediatric sleep research; 2) to review how actigraphy has been validated among pediatric populations; and 3) offer recommendations for methodological areas that should be included in all studies that utilize actigraphy, including the definition and scoring of variables commonly reported. The poor specificity to detect wake after sleep onset was consistently noted across devices and age groups, thus raising concerns about what is an "acceptable" level of specificity for actigraphy. Other notable findings from this review include the lack of standard scoring rules or variable definitions. Suggestions for the use and reporting of actigraphy in pediatric research are provided.
During the last decade actigraphy (activity-based monitoring) has become an essential tool in sleep research and sleep medicine. The validity, reliability and limitations of actigraphy for documenting sleep-wake patterns have been addressed. Normative data on sleep-wake patterns across development have been collected. Multiple studies have documented the adequacy of actigraphy to distinguish between clinical groups and to identify certain sleep-wake disorders. Actigraphy has also been shown to be effective in documenting the effects of various behavioral and medical interventions on sleep-wake patterns. Actigraphy is less useful for documenting sleep-wake in individuals who have long motionless periods of wakefulness (e.g. insomnia patients) or who have disorders that involve altered motility patterns (e.g. sleep apnea). Potential users should be aware of a number of pitfalls of actigraphy: (1) validity has not been established for all scoring algorithms or devices, or for all clinical groups; (2) actigraphy is not sufficient for diagnosis of sleep disorders in individuals with motor disorders or high motility during sleep; (3) the use of computer scoring algorithms without controlling for potential artifacts can lead to inaccurate and misleading results.
Ever since the discovery of rapid eye movement sleep (REMS), studies have been undertaken to understand its necessity, function and mechanism of action on normal physiological processes as well as in pathological conditions. In this review, first, we briefly surveyed the literature which led us to hypothesise REMS maintains brain excitability. Thereafter, we present evidence from in vivo and in vitro studies tracing behavioural to cellular to molecular pathways showing REMS deprivation (REMSD) increases noradrenaline level in the brain, which stimulates neuronal Na-K ATPase, the key factor for maintaining neuronal excitability, the fundamental property of a neuron for executing brain functions; we also show for the first time the role of glia in maintaining ionic homeostasis in the brain. As REMSD exerts a global effect on most of the physiological processes regulated by the brain, we propose that REMS possibly serves a housekeeping function in the brain. Finally, subject to confirmation from clinical studies, based on the results reviewed here, it is being proposed that the subjects suffering from REMS loss may be effectively treated by reducing either noradrenaline level or Na-K ATPase activity in the brain.
This review considers recent evidence showing that cells in the reticular activating system (RAS) exhibit 1) electrical coupling mainly in GABAergic cells, and 2) gamma band activity in virtually all of the cells. Specifically, cells in the mesopontine pedunculopontine nucleus (PPN), intralaminar parafascicular nucleus (Pf), and pontine dorsal subcoeruleus nucleus dorsalis (SubCD) 1) show electrical coupling, and 2) all fire in the beta/gamma band range when maximally activated, but no higher. The mechanism behind electrical coupling is important because the stimulant modafinil was shown to increase electrical coupling. We also provide recent findings demonstrating that all cells in the PPN and Pf have high threshold, voltage-dependent P/Q-type calcium channels that are essential to gamma band activity. On the other hand, all SubCD, and some PPN, cells manifested sodium-dependent subthreshold oscillations. A novel mechanism for sleep-wake control based on transmitter interactions, electrical coupling, and gamma band activity is described. We speculate that continuous sensory input will modulate coupling and induce gamma band activity in the RAS that could participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions.
Wakefulness is a functional brain state that allows the performance of several "high brain functions", such as diverse behavioural, cognitive and emotional activities. Present knowledge at the whole animal or cellular level suggests that the maintenance of the cerebral cortex in this highly complex state necessitates the convergent and divergent activity of an ascending network within a large reticular zone, extending from the medulla to the forebrain and involving four major subcortical structures (the thalamus, basal forebrain, posterior hypothalamus and brainstem monoaminergic nuclei), their integral interconnections and several neurotransmitters, such as glutamate, acetylcholine, histamine and noradrenaline. In this mini-review, the importance of the thalamus, basal forebrain and brainstem monoaminergic neurons in wake control is briefly summarized, before turning our attention to the posterior hypothalamus and histaminergic neurons, which have been far less studied. Classical and recent experimental data are summarized, supporting the hypothesis that (1) the posterior hypothalamus constitutes one of the brain ascending activating systems and plays an important role in waking; (2) this function is mediated, in part, by histaminergic neurons, which constitute one of the excitatory sources for cortical activation during waking; (3) the mechanisms of histaminergic arousal involve both the ascending and descending projections of histaminergic neurons and their interactions with diverse neuronal populations, such as neurons in the pre-optic area and cholinergic neurons; and (4) other widespread-projecting neurons in the posterior hypothalamus also contribute to the tonic cortical activation during wakefulness and/or paradoxical sleep.
Background: The use of benzodiazepine receptor agonists can significantly impair driving performance. The aim of this review was to determine if there is a relation between blood concentrations of these drugs and the degree of driving impairment. Methods: A literature search was conducted to identify driving studies that examined the effects of benzodiazepine receptor agonists. Studies were included if the on-the-road driving test was employed, using the standard deviation of lateral position (SDLP), i.e., the weaving of the car, as primary outcome measure. Results: A total of 24 studies were identified that employed the on-the-road driving test to examine driving performance after administration of benzodiazepine receptor agonists. Eleven of these studies (45.8%) measured blood drug concentrations after the on-the-road driving test was performed. Technical reports of some of these studies provided individual data on blood drug concentrations and ΔSDLP (the ΔSDLP difference between drug and placebo). While group differences in concentrations were found as evidenced by significant effects of dose and time of driving since time of drug ingestion, no significant relationship between individual blood drug concentrations and ΔSDLP was found in any of the studies. Conclusion: While group mean average ΔSDLP and blood drug concentration sometimes correlate, individual differences in blood drug concentrations of benzodiazepine receptor agonists correlate poorly with driving impairment. From the currently available data, it must be concluded that there are no significant relationships between individual blood drug concentration and ΔSDLP. Future driving studies should assess blood drug levels as a standard procedure, to enable further research into the relationship between blood drug concentration and performance impairment.
To examine the extent to which research supports the use of acupuncture in treating insomnia, a systematic review was conducted that included not only clinical trials, but also case series in both English and Chinese literature. Thirty studies were included in the review, 93% of which showed positive treatment effects of acupuncture in improving various aspects of sleep. Although acupuncture has been demonstrated to be safe and holds great potential to be an effective treatment modality for insomnia, the evidence is limited by the quality of these studies and mixed results from those with sham (or unreal treatment) controls. Of the thirty studies, twelve were clinical trials with only three double-blinded. Only five used sham controls, and of these, four showed statistically significant differences favoring real treatments; however, none evaluated the adequacy of sham assignment. Three studies used actigraphy or polysomnography as objective outcome measures. The considerable heterogeneity of acupuncture techniques and acupoint selections among all studies made the results difficult to compare and integrate. High-quality randomized clinical trials of acupuncture in treating insomnia, with proper sham and blinding procedures will be required in the future. This review highlights aspects of acupuncture treatments important to guide future research and clinical practice.
The circadian rhythms of shift workers do not usually phase shift to adapt to working at night and sleeping during the day. This misalignment results in a multitude of negative symptoms including poor performance and reduced alertness during night work and poor daytime sleep at home. After an introduction to circadian principles, we discuss the efficacy of appropriately timed bright light exposure (natural and artificial) and exogenous melatonin administration for producing circadian adaptation to night work. Interventions that generate alternative 24h light/dark patterns that facilitate appropriate circadian phase shifting are discussed. Such interventions include minimizing night workers' exposure to the external light/dark cycle, and the use of intermittent and moving patterns of bright light at work. The efficacy of melatonin in phase shifting circadian rhythms in the field is also addressed and compared to that of bright light. We present sleep/light exposure schedules that could produce circadian adaptation in permanent night workers. We conclude this review by discussing the impact of individual differences on possible circadian interventions and issues associated with the use of bright light interventions in the field.
Several aspects of behaviour relating to sleep in monkeys and apes are reviewed, including sleeping site selection, approach to and departure from sleeping sites, social behaviour at the sites, and nocturnal activities. Illustrative examples are given for each topic. Good sleeping sites for primates give protection from predators and/or some physical comfort from the elements and other sources of disturbance. Availability of sleeping sites may determine ranging patterns and whether an area is exploited or not. Times of retiring and resumption of daytime activities are influenced by foraging and ranging requirements. Social relationships and their influencing factors continue during the night, including dominance, kinship, affiliation and sex. Social partners may be used for thermoregulation and for increasing postural stability. Primates show a range of solutions to the problems surrounding sleep, and similarities and differences between monkeys and the large-bodied, nest-building great apes are described. Knowledge of natural sleep-related phenomena in non-human primates can provide valuable insights for human sleep research, and vice-versa.
Top-cited authors
Maurice Moyses Ohayon
  • Stanford University
Luigi De Gennaro
  • Sapienza University of Rome
Michele Ferrara
  • University of L'Aquila
Daniel Buysse
  • University of Pittsburgh
Eve Van Cauter
  • University of Chicago