Sleep Medicine Reviews

Published by Elsevier BV

Print ISSN: 1087-0792


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  • Article

December 2011


54 Reads


Exercise, sleep and cytokines: Is there a relation? Sleep Medicine Reviews, 11, 231-239
  • Literature Review
  • Full-text available

July 2007


833 Reads

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.

Content comparison of 115 health status measures in sleep medicine using the International Classification of Functioning, Disability and Health (ICF) as a reference

February 2011


68 Reads

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.

Sleep disorders in patients with multiple sclerosis. Sleep Medicine Reviews, 14(2), 121-129

October 2009


67 Reads

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.

Traditional Chinese medicine herbal preparations in restless legs syndrome (RLS) treatment: A review and probable first description of RLS in 1529

March 2012


381 Reads

Xue Yan


Wei-Dong Wang


Arthur S Walters




Fu-Yong Chu
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: Sleep and daytime sleepiness. Sleep Med Rev 12: 153-162

May 2008


1,200 Reads

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.

Fig. 1. 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.  
Sleep measurement and monitoring in children with Down syndrome: A review of the literature, 1960-2010
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.

Impaired sleep and rhythms in persons with cancer. Sleep Medicine Reviews, 8(3), 199-212

July 2004


61 Reads

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.

The treatment of chronic insomnia: Drug indications, chronic use and abuse liability. Summary of a 2001 New Clinical Drug Evaluation unit Meeting Sympoium

March 2004


78 Reads

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.

Circadian rhythm sleep disorders: Characteristics and entrainment pathology in delayed sleep phase and non-24 sleep–wake syndrome

January 2008


127 Reads

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.

Table 1 Cross-sectional adult studies.
Table 2 Longitudinal adult studies.
Table 3 Cross-sectional paediatric studies.
Table 4 Longitudinal paediatric studies.
Marshall NS, Glozier N, Grunstein RR. Is sleep duration related to obesity? A critical review of the epidemiological evidence. Sleep Med Rev 12, 289-298

September 2008


1,752 Reads

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.

Bonnet MH, Arand DL. Clinical effects of sleep fragmentation versus sleep deprivation. Sleep Med Rev 7: 297-310

September 2003


5,263 Reads

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.

Recurrent hypersomnia: A review of 339 cases

October 2010


175 Reads

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.

Schierenbeck T, Riemann D, Berger M, Hornyak M. Effect of illicit recreational drugs upon sleep: cocaine, ecstasy, and marijuana. Sleep Med Rev 12: 381-389

March 2008


812 Reads

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.

Tononi G, Cirelli C. Sleep function and synaptic homeostasis. Sleep Med Rev 10: 49-62

March 2006


1,427 Reads

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.

Does abnormal non-rapid eye movement sleep impair declarative memory consolidation? Disturbed thalamic functions in sleep and memory processing

August 2011


231 Reads

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.

A visit to Absurdistan: A nightmare of a sleep specialist

September 2013


46 Reads

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.

Circadian Rhythms, Sleep, and Substance Abuse

May 2011


210 Reads

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.

Sleep, sleepiness, sleep disorders and alcohol use and abuse

September 2001


1,512 Reads

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

Sleep loss, Learning capacity and academic performance

November 2006


29,586 Reads

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.

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