Disordered sleep in fibromyalgia and related myofascial facial pain conditions.

Myofascial pain and fibromyalgia have a recognized relationship to sleep disturbances. Understanding the comorbidity of these entities helps the practitioner, physician and dentist alike, be better prepared to manage the causative factors related to these conditions rather than treating only the symptoms. The increasing recognition of the coexistence of fibromyalgia, myofascial pain in the head and neck region, and the presence of temporomandibular disorders further increases the need for the dentist to be aware of sleep as a contributory factor from the diagnostic and the therapeutic aspects. This awareness results in more comprehensive management and an improved opportunity for optimal patient management as well as improved sleep and diminished pain levels.

Insomnia and health problems in Canadians.

STUDY OBJECTIVES: The objective of this study was to determine the prevalence of, and to identify the relative contribution of selected factors associated with insomnia in the Canadian population age 15 and older. DESIGN: Weighted analysis of cross-sectional data from the Canadian General Social Survey, Cycle 6, 1991. Prevalence estimates were calculated for the total and age-specific Canadian population age 15 and older. Multiple logistic regression techniques were employed to study the contribution of an array of sociodemographic, lifestyle, stress, and physical health factors to the experience of insomnia. SETTING: N/A. PARTICIPANTS: A representative sample of the Canadian household population age 15+ (n=11,924). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Twenty-four percent of the Canadian population age 15+ report insomnia. The following factors were associated with insomnia in multivariate logistic regression: female gender, being widowed or single, low education, low income, not being in the labor force, ever having smoked, life stress, specific chronic physical health problems (circulatory, digestive and respiratory disease, migraine, allergy and rheumatic disorders), pain, activity limitation and health dissatisfaction. Age was not significantly associated with insomnia. CONCLUSIONS: Insomnia was highly prevalent among the non-institutionalized Canadian population age 15 and older. A very stressful life, severe pain and dissatisfaction with one's health demonstrated the highest odds ratios associated with insomnia. Increasing age per se and lifestyle factors were not significantly associated with insomnia.

Seasonal symptom severity in patients with rheumatic diseases: a study of 1,424 patients.

OBJECTIVE: To examine the nature of seasonal symptoms, their prevalence, and differences among rheumatic disorders by examining longitudinal data over a period of up to 24 years. METHODS: We used a questionnaire assessment of seasonal symptoms using the Seasonal Pattern Assessment Questionnaire (SPAQ) in 1,424 patients with rheumatoid arthritis (RA), osteoarthritis (OA), and fibromyalgia (FM). Clinical status was evaluated with standard assessment measures, and reported symptoms were compared with actual seasonal differences measured for periods of up to 24 years. RESULTS: About 50% of patients with rheumatic disease reported exacerbation of rheumatic symptoms (pain, global severity, and fatigue) by seasonal changes. The presence of seasonal symptoms was not related to diagnosis or to seasonal affective disorder (SAD) symptoms, and symptoms were less common in older patients and in men. The number of symptoms and the severity of allied factors (depression, anxiety, pain, global severity, number of months with seasonal symptoms) were increased in persons with FM and/or complete SAD symptoms. Using circular statistics, the modal months for worse symptoms were December and January, and for best symptoms was July. Bimodal patterns of seasonality were identified for global severity, joint pain, fatigue, and socialization. Seasonal symptoms differed as to the degree at which they were dispersed around the 12 month circle. When pain and global severity measurements obtained over a 24 year period were analyzed, pain was slightly increased in the summer and global severity was not related to season at all. Even when patients who specifically reported worse symptoms in winter and best symptoms in summer were examined, no effect of season could be found. CONCLUSION: Seasonal rheumatic symptoms are commonly reported across all rheumatic diseases, but appear to reflect perception rather than reality since reported symptoms do not agree with measured clinical scores. In addition, regardless of seasonal complaints, measured pain and global severity scores are not worse in winter. Although patients with FM and Season (+) patients report more severe symptoms, their pattern of reporting and their actual scores do not differ according to season compared to persons without FM or positive seasonality.

Actigraphy and parental ratings of sleep in children with attention-deficit/hyperactivity disorder (ADHD).

STUDY OBJECTIVES: To assess various sleep parameters in latency-aged children with ADHD and their normally developing peers through the use of multiple sleep measures. DESIGN: Six sleep parameters were evaluated for two groups of children, ADHD and normal comparison. Each group consisted of 25 children (20 males, 5 females) who ranged in age from 7 to 11 years. All children underwent rigorous diagnostic procedures and the ADHD subjects were selected only if they displayed pervasiveness in their symptomatology and were medication naive. Parents completed a retrospective questionnaire which evaluated sleep problems over the past six months. Additionally, each child wore an actigraph for seven consecutive nights, and the child's parents completed a sleep diary during this time period. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. RESULTS: Based on the findings from the questionnaire, parents of children with ADHD reported significantly more sleep problems than parents of normally developing children. However, the majority of these sleep differences were not verified through actigraphy or sleep diary data, with the exception of longer sleep duration for children with ADHD and parent reports that describe increased bedtime resistence. It was also found that child-parent interactions during bedtime routines were more challenging in the ADHD group. CONCLUSIONS: Despite the possibility of intrinsic sleep problems such as longer sleep duration, results indicate that many of the sleep problems of children with ADHD may be due to challenging behaviours during bedtime routines. The reason for discrepancies among sleep studies employing objective measures as well as between retrospective and prospective measures are discussed.

Alpha sleep characteristics in fibromyalgia.

OBJECTIVE: To characterize the patterns of alpha electroencephalographic sleep and their associations with pain and sleep in patients with fibromyalgia. METHODS: Pain and sleep symptoms of 40 female patients with fibromyalgia and 43 healthy control subjects were studied before and after overnight polysomnography. Blinded analyses of alpha activity in non-rapid eye movement (non-REM) sleep were performed using time domain, frequency domain, and visual analysis techniques. RESULTS: Three distinct patterns of alpha sleep activity were detected in fibromyalgia: phasic alpha (simultaneous with delta activity) in 50% of patients, tonic alpha (continuous throughout non-REM sleep) in 20% of patients, and low alpha activity in the remaining 30% of patients. Low alpha activity was exhibited by 83.7% of control subjects (P < 0.01). All fibromyalgia patients who displayed phasic alpha sleep, activity reported worsening of pain after sleep, compared with 58.3% of patients with low alpha activity (P < 0.01) and 25.0% of patients with tonic alpha activity (P < 0.01). Postsleep increase in the number of tender points occurred in 90.0% of patients with phasic alpha activity, 41.7% of patients with low alpha activity, and 25.0% of patients with tonic alpha activity (P < 0.01). Self ratings of poor sleep were reported by all patients with phasic alpha activity, 58.3% of patients with low alpha activity (P < 0.01), and 12.5% of patients with tonic alpha activity (P < 0.01). Patients with phasic alpha activity reported longer duration of pain than patients in other subgroups (P < 0.01). Additionally, patients with phasic alpha sleep activity exhibited less total sleep time than patients in other subgroups (P < 0.05), as well as lower sleep efficiency (P < 0.05) and less slow wave sleep (P < 0.05) than patients with a tonic alpha sleep pattern. CONCLUSION: Alpha intrusion during sleep can be of different patterns. Phasic alpha sleep activity was the pattern that correlated better with clinical manifestations of fibromyalgia.

Brain-blood permeability: TNF-alpha promotes escape of protein tracer from CSF to blood.

The objective of this study was to determine the effect of tumor necrosis factor (TNF)-alpha on the efflux of protein from the central nervous system to blood based on assessing the clearance of radiolabeled albumin from the cerebrospinal fluid (CSF) to blood in rats. (125)I-labeled human serum albumin ((125)I-HSA) was injected into a lateral ventricle, and venous blood was sampled hourly to determine the basal CSF protein clearance into the blood. After this, rats were intraventricularly infused with 10 microliter TNF-alpha and 10 microliter (131)I-HSA (n = 6) or 10 microliter saline and 10 microliter (131)I-HSA (n = 6). Venous blood was sampled hourly for 3 h. (131)I-HSA tracer recovery increased threefold in the venous blood and was significantly higher in the spleen, muscles, and skin in animals treated with TNF-alpha. No significant changes were observed in control animals treated with saline. The data suggest that TNF-alpha promotes the clearance of protein macromolecules from the CSF to the venous blood.

Narcolepsy and the ability to resist sleep.

We describe five patients who presented with irresistible daytime sleepiness and who have the clinical and laboratory features of narcolepsy but differ from most patients with narcolepsy in their ability to resist falling asleep during the daytime. All of the patients described partial or complete remission of their symptoms. Using an HLA marker, the expected haplotypes for narcolepsy were found, but no specific genetic features were found associated with chromosome 6p that differentiated this group from patients with typical narcolepsy. Problems are discussed in the laboratory assessment of such patients using both the multiple sleep latency test and the maintenance of wakefulness test.

A randomized trial of the long-term, continued efficacy and safety of modafinil in narcolepsy.

Objective: To assess the continued efficacy of modafinil in the treatment of excessive daytime somnolence (EDS) of narcolepsy.Background: Modafinil has been shown to be a safe and effective treatment for the EDS presented by patients with narcolepsy. However, the duration of treatment has been relatively brief, particularly considering the chronic nature of the disease.Methods: Sixty-nine patients with narcolepsy, who completed a 6-week crossover study of modafinil continued on modafinil for 16 weeks of open-label treatment (300+/-100 mg). This was followed by 2 weeks during which patients were randomly and blindly allocated to continue modafinil (M) at the same dose (n=30), or placebo (P; n=33).Results: A mean dose of 330 mg of modafinil continued to produce a significant decrease in EDS as measured by the Maintenance of Wakefulness Test (9.7+/-7.9 for P; 16.4+/-13.7 for M; P=0.009), the Epworth Sleepiness Scale (15.4+/-5.8 for P; 13.2+/-5.7 for M; P=0.023), and the number of episodes of severe somnolence and sleep reported in patient diaries (8.2+/-7.2 for P; 4.2+/-5.2 for M; P=0.017). Modafinil had no significant effects on nocturnal sleep, blood pressure, heart rate, the electrocardiogram (ECG), weight, or mood.Conclusion: Modafinil continues to be an effective and well-tolerated drug after 16 weeks of treatment.

The relationship of lymphocytes in blood and in lymph to sleep/wake states in sheep.

Based on evidence of a role for immune-associated cytokines in sleep induction, we investigated the possibility that lymphocyte distribution between blood and lymphatics could be altered as a function of sleep/wakefulness. Blood and lymph sample were obtained from 5 sheep during periods of slow-wave sleep and wake. Blood and lymph lymphocytes were phenotyped using monoclonal antibodies against CD4, CD8, gd T-cell receptors and a surface marker on ovine B cells. Lymph flow rates and efferent lymph cell output were measured. Lymph flow and prescapular efferent lymphocyte output were reduced during sleep compared to wakefulness (p<0.0005). There were no differences in lymphocyte subsets in the blood and in the lymph during sleep/wake brain states. These data indicate that migration of cells in the peripheral lymphatic system is altered during sleep compared to wakefulness.

The contribution of sleep medicine to the assessment of the tired patient.

Tiredness is one of the most common complaints that confront the clinician. Yet the nature of the symptom and its implications for sleep-related disorders is poorly understood. This review provides the clinician with an understanding of the difficulties inherent in assessing the tired patient. The complaint of tiredness is commonly an expression of sleepiness and fatigue that arises as the result of sleep-wake-related disorders. Behavioural and physiological procedures are described in the assessment and management of sleepiness and fatigue in primary sleep disorders and sleep-related medical and psychiatric disorders. Improvement in the diagnosis and management of the fatigued or sleepy patient requires that residents in psychiatry and neurology be exposed to the behavioural and physiological techniques of sleep medicine as part of their post-graduate training programs.

Sleep problems in children with attention-deficit/hyperactivity disorder: impact of subtype, comorbidity, and stimulant medication.

OBJECTIVE: To determine the relationship of sleep problems to attention-deficit/hyperactivity disorder (ADHD), diagnostic subtype, comorbid disorders, and the effects of stimulant treatment. METHOD: On the basis of clinical diagnostic interviews, children aged 6 to 12 years were assigned to 4 groups: unmedicated ADHD (n = 79), medicated ADHD (n = 22), clinical comparison (n = 35), and healthy nonclinical comparison (n = 36). These groups were compared on 2 sleep questionnaires completed by the parents that assessed current sleep problems and factors associated with sleep difficulties (i.e., sleep routines, sleep practices, child and family sleep history). RESULTS: Factor analysis revealed 3 sleep problem categories: dyssomnias, parasomnias, and sleep-related involuntary movements. Linear regression analyses showed that (1) dyssomnias were related to confounding factors (i.e., comorbid oppositional defiant disorder and stimulant medication) rather than ADHD; (2) parasomnias were similar in clinical and nonclinical children; and (3) the DSM-IV combined subtype of ADHD was associated with sleep-related involuntary movements. However, sleep-related involuntary movements were more highly associated with separation anxiety. CONCLUSIONS: The results suggest that the relationship between sleep problems and ADHD is complex and depends on the type of sleep problem assessed as well as confounding factors such as comorbid clinical disorders and treatment with stimulant medication.

Adenosine: a mediator of interleukin-1beta-induced hippocampal synaptic inhibition.

Interleukin-1 (IL-1) is a pleotrophic cytokine implicated in a variety of central activities, including fever, sleep, ischemic injury, and neuromodulatory responses, such as neuroimmune, and neuroendocrine interactions. Although accumulating evidence is available regarding the expression pattern of this cytokine, its receptors in the CNS, and its mechanistic profile under pathological levels, it is unclear whether this substance modulates central neurons under physiological concentrations. Further, in light of the functional and spatial overlap between the adenosine and IL-1 systems, it is not known whether these two systems are coupled. We report here that, in rat brain slices, brief application of sub-femtomolar IL-1beta causes a profound decrease of glutamate transmission, but not GABAergic inhibition, in hippocampal CA1 pyramidal neurons. This decrease by IL-1beta is prevented by pharmacological blockade of adenosine A1 receptors. In addition, we show that IL-1beta failed to suppress glutamate transmission at room temperature. Because the production and release of adenosine in the CNS is thought to be metabolically dependent, this observation suggests that one of the functions of IL-1beta is to increase the endogenous production of adenosine. Together, these data suggest for the first time that sub-femtomolar levels of IL-1 can effectively modulate glutamate excitation in hippocampal neurons via an adenosine-dependent mechanism.

Intracerebroventricular injection of TNF-alpha promotes sleep and is recovered in cervical lymph.

Recent studies have shown that the central nervous system (CNS) communicates with the periphery by the drainage of cerebrospinal fluid and brain interstitial fluid into blood and lymph. We hypothesized that tumor necrosis factor (TNF)-alpha would not only influence the CNS by promoting sleep but also would be directly transmitted into the peripheral immune system. Five hundred nanograms of 125I-labeled TNF-alpha were injected into the lateral ventricles of the brain of six sheep and sampled in venous blood and cervical and prescapular lymph every 30 min for 6 h. 125I-TNF-alpha was measured in lymph nodes and control fat, skin, and muscle tissues 6 h postinjection. 125I-TNF-alpha was detected in the cervical lymphatics within the first 30 min and peaked within 2-3 h. 125I-TNF-alpha counts were elevated in the nodes of the head and neck region. Polysomnographic recordings of four animals showed that TNF-alpha induced a significant increase in slow-wave sleep at postinjection hours 4 and 5. CNS TNF-alpha and its direct drainage into the lymphatic system may influence both the sleeping/waking brain and peripheral immune functions.

Sleep, cytokines and immune function.

Bi-directional communication pathways exist between the brain and the cytokine-immune-endocrine systems. The hypothalamic-pituitary axis, the efferent neuronal hypothalamus-autonomic nervous system axis, and the direct drainage of macromolecules from the brain into the blood and the lymphatic system provide a network by which the sleeping/waking brain influence bodily functions. Similarly, changes in cytokine levels in the periphery modulate the central nervous system either directly or via the vagal nerve and influence the sleeping/waking brain. In humans, circadian nocturnal sleep-daytime wakefulness is associated with changes in peripheral cytokines, cellular immune functions, and endocrines. Progesterone levels influence sleep and cellular immune functions during the menstrual cycle. The interaction between the circadian sleeping/waking brain and the cytokine-immune-endocrine system are integral to preserving homeostasis. Disorganization or loss of sleep disrupts the harmonious integration of the circadian cytokine-immune-endocrine system. However, the mechanisms of circadian sleep/wakefulness-related cytokine-immune-endocrine functions in host defence against disease remain to be determined.

Determinants of disability after a work related musculetal injury.

OBJECTIVE: Musculoskeletal soft tissue injuries consume considerable resources in personal suffering, medical care, work absenteeism, and compensation benefits. Our aim was to determine specific clinical and behavioral factors that prognostically influence return to work following musculoskeletal work related injuries. METHODS: A longitudinal cohort study was conducted on 148 randomly selected workers who had not returned to work in 3 months following musculoskeletal soft tissue injury. The cohort was identified from the files of the Workers' Compensation Board of Ontario, Canada. The workers were interviewed and assessed at 3, 9, 15, and 21 months after injury. The WHO Classification of Impairment, Disabilities and Handicap was used as the conceptual framework. The analysis employed a proportional hazards regression model with allowance for time dependent covariates. RESULTS: The rate of return to work for men was 1.5 times that for women, and 20% less for every 10 year increase in age. Controlling for sex and age, psychological distress and functional disability were associated with a slower rate of return to work. The rate of return to work for workers who were provided with modified jobs was 2 times higher than for those with no such accommodation in employment. CONCLUSION: The negative effect of psychological distress and functional disability on return to work rates must be considered in the design and delivery of rehabilitation programming for workers with musculoskeletal soft tissue injuries. The employer's provision of a "modified job" is important in the prevention of continued disability.

Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder.

BACKGROUND: Sleep disturbances are common in major depressive disorder. In previous open-label trials, nefazodone improved sleep continuity and increased rapid eye movement (REM) sleep, while not affecting stage 3/4 sleep or REM latency: in contrast, fluoxetine suppressed REM sleep. This study compared the objective and subjective effects of nefazodone and fluoxetine on sleep. METHODS: This paper reports combined results of three identical, multisite, randomized, double-blind, 8-week, acute-phase trials comparing nefazodone (n = 64) with fluoxetine (n = 61) in outpatients with nonpsychotic major depressive disorder and insomnia. Sleep electroencephalographic (EEG) recordings were gathered at baseline and weeks 2, 4, and 8. Clinical ratings were obtained at weeks 1-4, 6, and 8. RESULTS: Nefazodone and fluoxetine were equally effective in reducing depressive symptoms; however, nefazodone differentially and progressively increased (while fluoxetine reduced) sleep efficiency and reduced (while fluoxetine increased) the number of awakenings in a linear fashion over the 8-week trial. Fluoxetine, but not nefazodone, prolonged REM latency and suppressed REM sleep. Nefazodone significantly increased total REM sleep time. Clinical evaluations of sleep quality were significantly improved with nefazodone compared with fluoxetine. CONCLUSIONS: Nefazodone and fluoxetine were equally effective antidepressants. Nefazodone was associated with normal objective, and clinician- and patient-rated assessments of sleep when compared with fluoxetine. These differential sleep EEG effects are consistent with the notion that nefazodone and fluoxetine may have somewhat different modes and spectra of action.

Sleep disturbances in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: To evaluate the relationship between sleep disturbances and attention-deficit/hyperactivity disorder (ADHD). METHOD: Empirical research published since 1970 on sleep disturbances in children with ADHD was systematically reviewed. A "box-score" approach was used to examine consistency of findings across the studies, which used different outcome measures. RESULTS: Although subjective accounts of sleep disturbances in ADHD were prevalent, objective verification of these disturbances was less robust. The only consistent objective findings were that children with ADHD displayed more movements during sleep but did not differ from normal controls in total sleep time. An additional finding was that stimulant medication led to changes in the children's sleep (e.g., prolonged sleep latency, increased length of onset to first rapid eye movement cycle), but these changes were believed to be nonpathological. CONCLUSIONS: The exact nature of the sleep problems in children with ADHD remains to be determined. Many of the relevant issues have not been adequately addressed. Factors such as poorly defined diagnostic groups, small sample sizes, few studies, and methodological and procedural limitations make it difficult to determine the relationship between ADHD and sleep problems.

Sleep, daytime symptoms, and cognitive performance in patients with fibromyalgia.

OBJECTIVE: To assess sleep, daytime symptoms, and cognitive performance in patients with fibromyalgia (FM). METHODS: Ten female patients with FM (mean age 32 yrs) and a matched, noncomplaintive comparison group (n = 9; mean age 30 yrs) spent 2 nights in the sleep laboratory. After the 2nd night, subjects completed a computerized 20 min battery of self-assessment and performance tests at hourly intervals from 07:00 to 20:00 h. RESULTS: Patients with FM spent more time in stage 1 sleep; however, there were no group differences on any other sleep measures. They reported greater sleepiness, more fatigue, more pain, more negative mood, and lower accuracy on performance tasks across a 14 h day. The FM group was slower in speed, but not impaired in accuracy, on performance of complex tasks, i.e., grammatical reasoning, serial addition/subtraction, and a simulated multi-task office procedure. CONCLUSION: Patients with FM have diurnal impairment in speed of performance on complex cognitive tasks, which accompany light stage 1 electroencephalographic (EEG) sleep and their experience of diffuse pain and nonrestorative sleep symptoms of sleepiness, fatigue, and negative mood.