Search

Purpose of Review: Recent studies have linked fibromyalgia (nociplastic pain) and depression to neuroinflammation. Restless legs syndrome (RLS) is highly prevalent in CWP (chronic widespread pain) and FMS (fibromyalgia syndrome) as well as in depression. This review focuses on evidence in the relationship between CWP and RLS and possible common pathophysiological mechanisms. Recent Findings: CWP is chronic pain spread over various locations of the body and is a cardinal sign of fibromyalgia. Poor sleep quality is a common symptom in fibromyalgia as well as high levels of fatigue, poor cognition, and other associated features which include depression, headache, and abdominal pain. Evidence for a bilateral relationship between pain and sleep deficit is robust. The latest research focus is not only on insomnia symptoms in chronic pain but also on other types of sleep disorders such as RLS which is characterized by complaints of an "urge to move" frequently associated with dysesthesias. These sensations can also have painful characteristics. Thus, there is a possible overlap between these two entities. The high prevalence of RLS (33-54%) in CWP has been shown in several studies. The pathophysiological mechanisms behind CWP and RLS are still not completely known, but there is a rising amount of evidence on proinflammatory and neuroinflammatory processes in CWP. In RLS, there are links to dopaminergic dysfunction and more generally to monoaminergic dysfunctional circuits, BID (brain iron deficiency), altered glutamatergic neurotransmission, and genetic traits. Depression is a common comorbidity as well in CWP as RLS, and proinflammatory mechanisms have also been demonstrated in this condition. Summary: The association between CWP and RLS is shown to be high and the pathogenesis of both conditions is still not completely understood. Recent research is focusing on proinflammatory and neuroinflammatory processes, not uniquely emerging in fibromyalgia/CWP, but inflammatory fe

Introduction: Recent studies suggest an increased prevalence of chronic pain conditions and restless legs syndrome (RLS) in patients with chronic pulmonary disease (CPD). We analyzed the prevalence and risk factors for pain and RLS in a population-based sample of females with comorbid CPD. Method: Questionnaire-based data from 2745 women aged 18–64 years were analyzed regarding comorbid CPD status (severe bronchitis, emphysema, asthma). Pain status was assessed according to symptoms reflecting severity (Visual Analogue Scale, VAS rating 0–10) and duration and spreading (limited spread or widespread) of pain. A diagnosis of RLS was defined by four validated diagnostic criteria. Anthropometrics and co-morbidities were assessed as covariates in univariate and multivariate analyses. Results: Widespread pain was overrepresented in women with CPD (44.6 vs. 24.6%, p < 0.001). The odds ratio for widespread pain in women with CPD was 1.6 (95% confidence interval (CI) 1.2–2.2, p < 0.001) in the fully adjusted model. Severe pain (VAS rating ≥ 7) was more prevalent in females with known CPD (28.8 vs. 15.4%, p < 0.001, odd ratio 1.4 (95% CI 1.0–1.9, p = 0.029)). The prevalence of RLS was 37.4 and 23.8% in subjects with or without CPD, respectively (p < 0.001). In multivariate analysis, CPD was associated with a 30% risk increase for RLS (odds ratio 1.3 (95% CI 1.0–1.7, p = 0.04)). Conclusion: This population-based study identified CPD as an independent risk factor for severe and widespread pain as well as for RLS. Further research addressing pathophysiological mechanisms linking CPD and chronic pain conditions/RLS is warranted.

Background and aims: Chronic widespread pain (CWP) is associated with poor quality of sleep, but the detailed underlying mechanisms are still not fully understood. In this study we investigated the influence of CWP on morning cortisol and fasting glucose concentrations as well as sleep disordered breathing. Methods: In this case-control study, subjects with CWP (n=31) and a control group without CWP (n=23) were randomly selected from a population-based cohort of women. Current pain intensity, sleep quality, excessive daytime sleepiness [Epworth sleepiness scale (ESS)], psychiatric comorbidity and occurrence of restless legs syndrome (RLS) were assessed. Overnight polygraphy was applied to quantify sleep apnoea, airflow limitation and attenuations of finger pulse wave amplitude (>50%) as a surrogate marker for increased skin sympathetic activity. Morning cortisol and fasting glucose concentrations were determined. Generalised linear models were used for multivariate analyses. Results: CWP was associated with higher cortisol (464±141 vs. 366±111 nmol/L, p=0.011) and fasting glucose (6.0±0.8 vs. 5.4±0.7 mmol/L, p=0.007) compared with controls. The significance remained after adjustment for age, body mass index, RLS and anxiety status (β=122±47 nmol/L and 0.89±0.28 mmol/L, p=0.009 and 0.001, respectively). The duration of flow limitation in sleep was longer (35±22 vs. 21±34 min, p=0.022), and pulse wave attenuation was more frequent (11±8 vs. 6±2 events/h, p=0.048) in CWP subjects compared with controls. RLS was associated with higher ESS independent of CWP (β=3.1±1.3, p=0.018). Conclusions: Elevated morning cortisol, impaired fasting glucose concentration and increased skin sympathetic activity during sleep suggested an activated adrenal medullary system in subjects with CWP, which was not influenced by comorbid RLS. Implications: CWP is associated with activated stress markers that may deteriorate sleep.

Background: Chronic pain conditions as well as Restless Legs Syndrome (RLS) are known to be associated with subjectively and objectively disturbed sleep. RLS has been recently described as highly prevalent in multisite pain and the role of sleep as a modifying factor in this RLS phenotype is unknown. This study aimed to investigate if perceived sleep deficit and other sleep related parameters predict RLS in subjects with multisite pain. Current knowledge/study rationale: We have recently demonstrated a strong association between Restless Legs Syndrome (RLS) and number of pain locations. In the current analysis we hypothesized that impaired sleep predicts RLS in subjects with multisite pain. Method: Questionnaire-based data from 2727 randomly selected women aged 18-64 years were used to analyze RLS symptoms, self-reported sleep quality, and the degree of daytime sleepiness (Epworth Sleepiness Scale (ESS)) in relation to type, degree and localization of body pain. Potential confounders including anthropometrics, pain localization, co-morbidities, and medication were adjusted for in the Generalized Linear Models (GLM). Results: Perceived sleep deficit >= 90 min (OR 2.4 (1.5-3.8), p < 0.001) and frequent nocturnal awakenings (OR 2.3 (1.4-3.6), p < 0.001) were the strongest sleep related predictors for RLS in subjects with multisite pain. Additional factors include prolonged sleep latency (>= 30 min, OR 1.8 (1.1-2.8), p = 0.01) and daytime symptoms like elevated daytime sleepiness (ESS score = 9, OR 1.8 (1.2-2.7), p = 0.005). Accordingly, RLS diagnosis was associated with impaired sleep quality (TST (Total Sleep Time) -8.2 min, sleep latency + 8.0 min, and number of awakenings from sleep + 0.4, p < 0.01). ESS score increased with RLS diagnosis (+0.74, p < 0.01) and number of pain locations (0.5, 1.7, and 1.8 for 1, 3, and 5 pain areas, p < 0.001). In addition, confounders like pain severity, the history of psychiatric disease, and current smoking wer

Study Objectives: Vascular disturbances leading to tissue hypoxia have been named as a possible cause for RLS/WED. Vibration to the whole body (WBV) in subjects with RLS/WED results in increased skin blood flow (SBF). The aims of this investigation were to (1) determine if a two-week treatment with WBV will decrease symptoms associated with RLS/WED and, (2) if so, determine if the mechanism for improvement in symptoms is related to an increase in SBF, as measured in flux. Methods: Eleven subjects with RLS/WED underwent 2 weeks of 14-minute intermittent WBV and a 2-week sham treatment in randomized order. Pre and post intervention RLS symptom severity were compared. Baseline SBF was compared between subjects with RLS/WED and an age-and sex-matched control group. A crossover design (aim 1) and a matched case-control design and repeated measures design (aim 2) were used. The data analyses consisted of 2-sample and paired t-tests; where applicable we used a standard crossover design adjustment. Results: WBV did significantly decrease symptoms associated with RLS/WED compared to baseline data and compared to sham treatment. The baseline flux was significantly lower in RLS/WED subjects than matched controls, but this deficit was negated with WBV. There was no increase in resting SBF over the 2 weeks of treatment. Conclusions: Subjects with RLS/WED have decreased SBF but are able to increase flux to the same level as normal subjects with WBV. A 2-week intervention with WBV decreases symptoms associated with RLS/WED, but this does not seem to be related to an increase in resting SBF.

Study objectives: Periodic limb movements (PLMs) are characterized by involuntary movements of the lower extremity during sleep. The etiology of PLM has been suggested to involve the dopaminergic system which, in turn, can be modulated by estrogen. It is currently unknown whether PLMs are associated with the menopausal transition and/or concomitant vasomotor symptoms. The aim of the present study was to examine if objectively-diagnosed PLMs (with and without arousals) are more common in postmenopausal women or in women with vasomotor symptoms. Another aim was to analyze the influence of PLMs on self-reported HRQoL. Methods: A community-based sample of 348 women underwent full-night polysomnography. PLMs (index > 15) and associated arousals (PLM arousal index > 5) were evaluated according to AASM scoring rules. Health related quality of life was measured using the SF-36 questionnaire. The occurrence of peri- and postmenopausal symptoms were evaluated by a questionnaire and plasma levels of follicle stimulating hormone (FSH) were measured. Results: After adjusting for confounding factors, vasomotor symptoms remained a significant explanatory factor for the occurrence of PLMs (adj. OR 1.86, 95% CI 1.03 - 3.37). In women with PLM arousals, adjusted OR for vasomotor symptoms was 1.61, 95% CI 0.76 – 3.42. PLMs did not seem to affect HRQoL. Conclusion: We found that clinically-significant PLMs, but not PLM with arousals, were more common among women with vasomotor symptoms, even after controlling for confounding factors. Menopausal status per se, as evidenced by FSH in the postmenopausal range, was not associated with PLMs.

Sleep is an essential human behavior that shows prominent gender differences. Disturbed sleep, in particular, is much more prevalent in females than males. Restless legs syndrome (RLS) as one cause of disturbed sleep was observed to be somewhat more common among women than men in Ekbom's 1945 seminal series of clinical cases with the disease. He, however, reported this gender difference mainly for those with more severe symptoms. Since then numerous studies have reported that women are affected by RLS about twice as often as males for mild as well as moderate to severe RLS. The present review focuses on RLS in females from the perspectives of both epidemiology and pathophysiology. RLS will generally become worse or might appear for the first time during pregnancy. Parity increases the risk of RLS later in life suggesting that pregnancy is a specific behavioral risk factor for developing RLS. Some evidence suggests that dysfunction in iron metabolism and high estrogen levels might contribute to RLS during pregnancy. But, menopause does not lower the incidence of RLS nor does hormone replacement therapy lead to an increase, suggesting a quite complex uncertain role of hormones in the pathophysiology of RLS. Therefore, further, preferably longitudinal studies are needed to unravel the factors causing RLS in women. These studies should include genetic, clinical and polysomnographic variables, as well as hormonal measures and variables assessing iron metabolism.

Objective. To investigate the effects of bright light treatment for secondary outcome measures and to explore and validate empirically derived subgroups and treatment effects in subgroups. Methods. A descriptive design. A sample of forty-nine persons (mean age of 45.8) with clinically assessed seasonal affective disorder (SAD) or subsyndromal SAD (S-SAD) participated in a two-group clinical trial evaluating the effects of treatment with bright light therapy. A person-oriented cluster analysis was applied to study treatment effects in subgroups. Results. For the merged group, sleepiness (Epworth Sleepiness Scale), fatigue (fatigue questionnaire), and health-related quality of life (SF-36) were improved at posttreatment, and results were maintained at the one-month followup. Three distinct subgroups had a high level of fatigue in common, while the level of excessive daytime sleepiness and depressed mood differed between the subgroups. Over time, all subgroups improved following ten days treatment in a light room. Conclusion. Fatigue, excessive daytime sleepiness, and health-related quality of life improve in a similar way as depressed mood following treatment with bright light. The treatment was effective irrespective of the severity of the disorder, that is, for persons with SAD and subsyndromal SAD.

An increased capillary network has been observed in the skeletal muscle in patients with Restless Legs Syndrome (RLS) and Obstructive sleep apnea syndrome (OSAS). These changes could be due to upregulation of growth factors responsible for angiogenesis. The aim of the study was to examine the occurrence and localization of VEGF and capillary proliferation in skeletal muscle of RLS (n=12), OSAS (n=12) and controls (n=11). Double-immunofluorescence staining for capillaries (CD31) and VEGF, and proliferating cells (Ki-67), was carried out on biopsies taken from the tibialis anterior. The percentage of capillaries expressing VEGF (CD31,VEGF+) was significantly higher in OSAS and RLS compared to controls. The percentage of proliferating capillaries (CD31,Ki-67+) was significantly higher in OSAS compared with controls. In conclusion our study shows the occurrence of proliferation of endothelial cells in skeletal muscle in RLS and OSAS, supporting an upregulation of VEGF located in capillaries probably due to local hypoxia.

BACKGROUND: The most common way to provide bright light therapy to Swedish patients with Seasonal Affective Disorder (SAD), is treatment in a light therapy room. Since few studies have evaluated treatment provided in this setting and few have evaluated the effect of bright light in sub-clinical SAD (S-SAD), such a study including a one-month follow-up was designed. METHODS: Fifty adults recruited from a previous prevalence study and clinically assessed as having SAD or S-SAD, were randomised to treatment in a light room or to a three-week waiting-list control group. The Hamilton Depression Rating Scale-Seasonal Affective Disorders Self-rating 29-items Version (SIGH-SAD/SR) was used to measure depressive mood at baseline, directly following treatment and at the one-month follow-up. RESULTS: ANCOVA with adjustment for baseline depression score, showed a significant main effect for the light room therapy group (p<0.001). Fifty-four percent (n=13/24) improved > or = 50% while no such improvement was seen in the control condition (n=0/24). After merging the two groups, repeated measures ANOVA confirmed the experimental analysis (p<0.001). At the one-month follow-up, 83.0% (n=39/47) had improved > or = 50% and 63.8% (n=30/47) had normal depression scores, i.e. < or = 8. CONCLUSIONS: Light room therapy was effective in reducing depressive symptoms in subjects with winter depressive mood. Results were maintained over a period of one month.

Background: Despite the fact that patients with obstructive sleep apnoea syndrome (OSAS) often have symptoms at the level of skeletal muscle such as fatigue, the question of whether the structural, cellular and functional properties of limb skeletal muscles are affected has not been fully examined. Objective: The aim was to examine physiological and muscular parameters in patients with OSAS and to assess the relationship between these parameters and the clinical symptoms. Method: Eighteen patients with OSAS and 16 controls participated. Aerobic capacity was assessed using a submaximal test. Fibre type distribution and fibre area were analyzed on muscle biopsies taken from the tibialis anterior. The microvascularization was assessed using the following parameters: (1) the number of capillaries per fibre (CAF), (2) CAF per fibre area (CAFA), (3) capillary to fibre perimeter exchange (CFPE) index, which represents the interface between muscle fibre and capillaries, and (4) length of capillary/perimeter of the fibre (LC/PF) index or capillary tortuosity, which represents the percent of muscle fibre perimeter in contact with the wall of the microvessel. Results: The OSAS group had significantly lower predicted relative maximal oxygen uptake (p = 0.0047) which was inversely correlated to the apnoea/hypopnoea index (AHI; r = –0.6, p = 0.017). There was a significantly higher CFPE index for slow type I fibres (p = 0.007) and fast type II fibres (p = 0.0126) and a significantly higher LC/PF index for type I fibres (p = 0.0003) and type II fibres (p = 0.0285) in OSAS patients compared to controls. Conclusion: OSAS patients have a higher muscle microvascularization and a lower aerobic capacity than controls. Furthermore the aerobic capacity was inversely correlated to AHI.

AIM: The aim of the study was to assess the cellular and structural properties of skeletal muscle in restless legs syndrome (RLS). METHOD: Twenty patients and 16 controls were included. Aerobic performance was assessed using a submaximal test. On muscle biopsies taken from the tibialis anterior, fiber distribution and fiber area were analyzed together with parameters surveying the microvascularization, especially the tortuosity, which is expressed as a percent of muscle fiber perimeter in contact with the wall of the microvessel, length of capillary/perimeter of fiber (LC/PF) index. RESULTS: The RLS group had significantly lower predicted maximal oxygen uptake (p = 0.01) and significantly higher LC/PF index (p = 0.01) compared to the controls. CONCLUSION: The higher capillary tortuosity in RLS patients indicates the occurrence of significant remodeling in capillary geometry in RLS.

OBJECTIVE: There are few studies regarding the prevalence of seasonal variation in mood among children and adolescents. The main objective of this study was to estimate the prevalence of self-reported depressive mood during the winter season among Swedish adolescents and to investigate gender differences. Another aim was to analyze the factor structure and internal consistency of the Kiddie SPAQ (K-SPAQ), a pediatric version of the Seasonal Pattern Questionnaire (SPAQ). METHOD: All students 17 to 18 years old, registered in the second year of senior high school in Falun, a district in central Sweden, were screened with the K-SPAQ in January 2003 (response rate 87.3%, n = 756). RESULTS: The prevalence of self-reported depressive mood during the winter season was estimated at 20.1% (n = 151/751) and was higher among girls (25.5%) than boys (13.8%). Approximately 8% reported more severe depressive symptoms. Depressive mood during the summer was rare (0.1%, n = 1/751). Factor analysis of the General Seasonal Score items in the K-SPAQ revealed a two-factor structure. A Cronbach's alpha of 0.87 demonstrated a good internal consistency. CONCLUSIONS: Depressive symptoms during autumn and winter were common among Swedish senior high school students, especially among girls. This is probably an underdiagnosed condition among adolescents that ought to receive more attention from the health and school authorities.

BACKGROUND: Sleep apnea syndrome (SAS) is a common condition and a risk factor of cardiovascular and cerebrovascular diseases. The purpose of this pilot study was to investigate the effect of a gestagen (trimegeston) and estradiol hormone combination on perimenopausal and postmenopausal women with SAS. METHODS: Four postmenopausal and one perimenopausal women were studied by polysomnography before and after treatment with hormone replacement therapy (HRT). RESULTS: The subjects had a mean reduction of the severity of their sleep apnea by 75% measured by apnea/hypopnea index. CONCLUSIONS: HRT might be an alternative in the treatment of SAS.

The recent discovery of obstructive sleep apnea syndrome (OSAS) as a prevalent disorder has highlightedthe fact that snoring is not just a harmless noise. Snoring and OSAS in the work milieu has hardly beeninvestigated, which makes it important to identify both risk factors and consequences in the work place. Two different studies were undertaken to investigate whether occupational exposure to organicsolvents might be an independent risk factor in causing both snoring and OSAS. In two other studies theeffects on subjective work performance from snoring and OSAS, and the occurence of occupationalaccidents of traumatic origin among patients with sleep disordered breathing (SDB) were investigated. Among 66 male patients from Dalacarlia county, occupationally exposed to solvents and referred tothe Department of Occupational and Environmental Medicine, University Hospital, Uppsala, between1984 and 1988, a prevalence of 19.7% of OSAS was conservatively estimated, giving a relative riskestimate of 15.2 (95% CI 10.4-27.7). A questionnaire was used to investigate whether patients with OSAS and snoring are more frequentlyexposed to organic solvents during work than the general population. Men with OSAS or snoring, andwomen with snoring had more often been occupationally exposed to organic solvents than the samplefrom the general population, showing an almost twofold increase in risk for those exposed during wholeworking days. For men, the risk of OSAS or snoring increased with increasing exposure. The same questionnaire was used to evaluate the frequency of subjective excessive daytime sleepinessat work and self perceived work performance among males suffering from heavy snoring and OSAS. Theodds ratios for reporting sleepiness at work were thirtyfold for OSAS patients and tenfold for heavysnorers as compared to the referents. Patients with OSAS and snoring also both showed an increased oddsratios on measures of difficulties with concentration, learning new tasks and performi

RLS, OSAS, inflammation