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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 (ß = 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 (ß = 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. [ABSTRACT FROM AUTHOR]

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 were associated with impaired sleep quality in this group of females. Conclusions Perceived sleep deficit and sleep fragmentation are the strongest sleep related predictors of RLS in multisite pain. Potential implication of our results are that clinical management programmes of RLS in subjects with multisite pain need to consider both sleep quality and sleep quantity for individually tailored treatment regimes. Study impact RLS, pain, and sleep disorders are highly interrelated. Our study strongly suggests that clinical management of RLS in patients with multisite pain needs to consider sleep quality as an independent risk factor. [ABSTRACT FROM AUTHOR]

Summary: 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. [Copyright &y& Elsevier]

Sleep disturbances are commonly reported in patients with chronic liver disease (CLD). Changes in quality of sleep in patients with CLD could be related to multiple factors viz., elevated levels of tryptophan, histamine, and increased turnover of dopamine in caudate-putamen and cingulate cortex. Also, iron metabolism disturbances are reported in patients with CLD. These changes may result in restless legs syndrome (RLS) that worsens sleep-quality. There have been reports suggesting an increased prevalence of RLS among patients with CLD. Literature was searched in PubMed, EMBASE, and Google Scholar. A total of twenty-two relevant articles were found. Out of these, nine studies have assessed the prevalence of RLS among patients with chronic liver disease or cirrhosis in the clinical population. Population prevalence reported from various studies was used to calculate odds ratio. Having included studies using various methods for diagnosis (clinical as well as questionnaires) pooled odds-ratio for the RLS was 8.62. It remains unaffected by study-method, gender, age, and geographical-area. However, studies using clinical diagnosis for RLS had lower odds compared to questionnaire based diagnosis. Studies varied with regards to diagnostic methods, age, gender, etiology, and severity of liver dysfunction. The severity and etiology of CLD and biochemical correlate of CLD were not found to be associated with RLS. Possible pathophysiological mechanisms are discussed for the occurrence of RLS in this population. In conclusion, the prevalence of RLS is higher among patients with CLD, however, the correlates are unknown. [ABSTRACT FROM AUTHOR]