Acylated ghrelin: a potential marker for fibromyalgia?

BACKGROUND: Fibromyalgia is characterized by chronic widespread pain and sleep disturbances. Overweight and obesity, which lead to metabolic changes, are additional comorbidities that are rarely explored, although they are highly prevalent in patients with fibromyalgia. METHODS: We compared the plasma levels of leptin and acylated ghrelin in 17 women with fibromyalgia (patients) and 16 healthy women (controls) with similar age, anthropometric measurements and levels of physical activity. We also investigated the relationships between these two neuropeptides and sleep and various pain characteristics in patients with fibromyalgia. Anthropometric measurements were recorded, and physical activity levels were assessed using a questionnaire. Pain intensity was measured using visual analogue scales (weekly general and mean pain scores). Sleep was assessed using an accelerometry technique. RESULTS: Compared to the control group, the patient group had increased leptin levels (patients: 22.4 ± 10.6 vs. controls: 13.3 ± 17.9 ng/mL; p < 0.01) and decreased acylated ghrelin levels (patients: 126.7 ± 47.8 vs. controls: 183.3 ± 102.2 pg/mL; p = 0.048). The leptin level was not significantly correlated with any of the variables. Acylated ghrelin level was inversely correlated with the weekly mean pain score (r = -0.67, p < 0.01) and the weekly general pain score (r = -0.67, p < 0.01). Multiple regression analysis revealed that the variations in acylated ghrelin levels accounted for 35% of the weekly general pain and 29% of the weekly mean pain variability. CONCLUSIONS: These findings indicate that the decreased acylated ghrelin levels in women with fibromyalgia are related to pain intensity.

Pain-related diseases and sleep disorders

Pain and sleep share mutual relations under the influence of cognitive and neuroendocrine changes. Sleep is an important homeostatic feature and, when impaired, contributes to the development or worsening of pain-related diseases. The aim of the present review is to provide a panoramic view for the generalist physician on sleep disorders that occur in pain-related diseases within the field of Internal Medicine, such as rheumatic diseases, acute coronary syndrome, digestive diseases, cancer, and headache.

Pain-related diseases and sleep disorders.

Pain and sleep share mutual relations under the influence of cognitive and neuroendocrine changes. Sleep is an important homeostatic feature and, when impaired, contributes to the development or worsening of pain-related diseases. The aim of the present review is to provide a panoramic view for the generalist physician on sleep disorders that occur in pain-related diseases within the field of Internal Medicine, such as rheumatic diseases, acute coronary syndrome, digestive diseases, cancer, and headache.

Delta sleep instability in children with chronic arthritis.

The objective of the present study was to evaluate the expression of a cyclic alternating pattern (CAP) in slow wave sleep (SWS) in children with the well-defined chronic syndrome juvenile idiopathic arthritis (JIA). Twelve patients (9-17 years of age), 7 girls, with JIA were compared to matched controls by age, pubertal stage and gender. After one night of habituation in the sleep laboratory, sleep measurements were obtained by standard polysomnography with conventional sleep scoring and additional CAP analyses. The sleep parameters of the JIA and control groups were similar for sleep efficiency (91.1 +/- 6.7 vs 95.8 +/- 4.0), sleep stage in minutes: stage 1 (16.8 +/- 8.5 vs 17.8 +/- 4.0), stage 2 (251.9 +/- 41 vs 262.8 +/- 38.1), stage 3 (17.0 +/- 6.0 vs 15.1 +/- 5.7), stage 4 (61.0 +/- 21.7 vs 77.1 +/- 20.4), and rapid eye movement sleep (82.0 +/- 27.6 vs 99.0 +/- 23.9), respectively. JIA patients presented nocturnal disrupted sleep, with an increase in short awakenings, but CAP analyses showed that sleep disruption was present even during SWS, showing an increase in the overall CAP rate (P < 0.01). Overall CAP rate during non-rapid eye movement sleep was significantly higher in pediatric patients who were in chronic pain. This is the first study of CAP in pediatric patients with chronic arthritis showing that CAP analyses can be a powerful tool for the investigation of disturbance of SWS in children, based on sleep EEG visual analysis.

Delta sleep instability in children with chronic arthritis

The objective of the present study was to evaluate the expression of a cyclic alternating pattern (CAP) in slow wave sleep (SWS) in children with the well-defined chronic syndrome juvenile idiopathic arthritis (JIA). Twelve patients (9-17 years of age), 7 girls, with JIA were compared to matched controls by age, pubertal stage and gender. After one night of habituation in the sleep laboratory, sleep measurements were obtained by standard polysomnography with conventional sleep scoring and additional CAP analyses. The sleep parameters of the JIA and control groups were similar for sleep efficiency (91.1 ± 6.7 vs 95.8 ± 4.0), sleep stage in minutes: stage 1 (16.8 ± 8.5 vs 17.8 ± 4.0), stage 2 (251.9 ± 41 vs 262.8 ± 38.1), stage 3 (17.0 ± 6.0 vs 15.1 ± 5.7), stage 4 (61.0 ± 21.7 vs 77.1 ± 20.4), and rapid eye movement sleep (82.0 ± 27.6 vs 99.0 ± 23.9), respectively. JIA patients presented nocturnal disrupted sleep, with an increase in short awakenings, but CAP analyses showed that sleep disruption was present even during SWS, showing an increase in the overall CAP rate (P < 0.01). Overall CAP rate during non-rapid eye movement sleep was significantly higher in pediatric patients who were in chronic pain. This is the first study of CAP in pediatric patients with chronic arthritis showing that CAP analyses can be a powerful tool for the investigation of disturbance of SWS in children, based on sleep EEG visual analysis.

Effect of smoking habits on sleep.

To evaluate the effect of smoking habits on sleep, data from 1492 adults referred to the Sleep Institute were accessed and divided into 3 categories of smoking status: current, former and non-smokers. Categories of pack-years (<15 and > or =15) defined smoking severity. The association of smoking status and smoking severity with sleep was analyzed for sleep parameters, especially apnea and hypopnea index (AHI) > or =5, more than 5% of total sleep time (TST) spent with oxyhemoglobin saturation (SaO2) <90%, and arousal index. The arousal index was higher among current (21 +/- 17) and former smokers (20 +/- 17) than non-smokers (17 +/- 15; P < 0.04). Former smokers had a higher percent of TST at SaO2 <90% than non-smokers (9 +/- 18 vs 6 +/- 13; P < 0.04). Former smokers with pack-years > or =15 compared to <15 exhibited higher AHI (22 +/- 24 vs 16 +/- 21; P < 0.05) and arousal index (22 +/- 19 vs 18 +/- 15; P < 0.05). Current smokers with pack-years > or =15 compared to <15 exhibited higher arousal index (23 +/- 18 vs 18 +/- 16; P < 0.05) and percent of TST at SaO2 <90% (11 +/- 17 vs 6 +/- 13; P < 0.05). Smoking status and pack-years were not associated with AHI > or =5 on logistic regression analysis, but current smokers with pack-years > or =15 were 1.9 times more likely to spend more than 5% of TST at SaO2 <90% than non-smokers (95%CI = 1.21-2.97; P = 0.005). The variability of arousal index was influenced by gender, AHI and current smokers with pack-years > or =15 (all P < 0.01). Smoking habits seem to be associated with arousal and oxyhemoglobin desaturation during sleep, but not with AHI. The effect was more pronounced in current than former smokers.

Effect of smoking habits on sleep

To evaluate the effect of smoking habits on sleep, data from 1492 adults referred to the Sleep Institute were accessed and divided into 3 categories of smoking status: current, former and non-smokers. Categories of pack-years (<15 and greater than or equal to 15) defined smoking severity. The association of smoking status and smoking severity with sleep was analyzed for sleep parameters, especially apnea and hypopnea index (AHI) greater than or equal to 5, more than 5 percent of total sleep time (TST) spent with oxyhemoglobin saturation (SaO2) <90 percent, and arousal index. The arousal index was higher among current (21 plus or minus 17) and former smokers (20 plus or minus 17) than non-smokers (17 plus or minus 15; P < 0.04). Former smokers had a higher percent of TST at SaO2 <90 percent than non-smokers (9 more less 18 vs 6 more less 13; P < 0.04). Former smokers with pack-years greater than or equal to 15 compared to <15 exhibited higher AHI (22 plus or minus 24 vs 16 plus or minus 21; P < 0.05) and arousal index (22 plus or minus 19 vs 18 plus or minus 15; P < 0.05). Current smokers with pack-years greater than or equal to 15 compared to <15 exhibited higher arousal index (23 plus or minus 18 vs 18 plus or minus 16; P < 0.05) and percent of TST at SaO2 <90 percent (11 plus or minus 17 vs 6 more less 13; P < 0.05). Smoking status and pack-years were not associated with AHI greater than or equal to 5 on logistic regression analysis, but current smokers with pack-years greater than or equal to 15 were 1.9 times more likely to spend more than 5 percent of TST at SaO2 <90 percent than non-smokers (95 percentCI = 1.21-2.97; P = 0.005). The variability of arousal index was influenced by gender, AHI and current smokers with pack-years greater than or equal to 15 (all P < 0.01). Smoking habits seem to be associated with arousal and oxyhemoglobin desaturation during sleep, but not with AHI. The effect was more pronounced in current than former smokers.

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.

Juvenile fibromyalgia: clinical and polysomnographic aspects.

OBJECTIVE: To identify the child-mother diagnostic correlation in fibromyalgia (FM), to study sleep disturbance in juvenile FM, and to compare clinical aspects and sleep disorders between these groups. METHODS: We studied 34 children with confirmed FM aged 11 +/- 1 years, 10 children with diffuse pain, and 17 age and sex matched asymptomatic controls. The respective 61 mothers were included: 34 asymptomatic and 27 with FM. All participants were subjected to clinical evaluation, a sleep questionnaire, and nocturnal polysomnography, preceded by a night of adaptation. Sleep scoring was done visually and a computerized analysis was performed for alpha, theta, and delta waves in slow wave sleep (SWS). RESULTS: A significant predominance of mothers with FM was observed in the group of children with FM (71%) compared to children with diffuse pain (30%) and asymptomatic children (0%). According to the sleep questionnaire, the complaints of superficial sleep and nonrestorative sleep were more prominent in mothers with FM than in children with FM, whereas motor agitation during sleep was more frequent in the children with FM. Polysomnographic anomalies were also more prominent in mothers with FM than in children with FM in terms of decrease in sleep efficiency, increase of number of arousals during sleep, and alpha intrusion in SWS. Both FM groups presented an increased alpha + theta time/delta time index during SWS compared to respective controls, and mothers with FM also showed an increase in alpha time/delta time index during SWS, compared to asymptomatic mothers. A correlation was found between alpha + theta time/delta time index during SWS and intensity of clinical manifestations of pain and sleep anomalies in children and their mothers. CONCLUSION: Significant concordance was observed regarding FM diagnosis in children and their mothers. Sleep complaints and polysomnography findings were less prominent in affected children compared to mothers with FM. In addition, we observed a significant correlation between polysomnographic indexes, sleep anomalies, and pain manifestations in children and their mothers.

7S IgG rheumatoid factor and hidden 19S IgM rheumatoid factor in juvenile chronic arthritis.

Hidden 19S IgM rheumatoid factor (RF) and 7S IgG RF were assayed in 24 children with juvenile chronic arthritis (JCA) and 26 controls, in whole sera and in the IgM and IgG containing fractions of the serum after separation by acid gel filtration. When non-fractioned serum was used, IgM RF detection was positive in 4.2% by latex fixation test and 4.2% by ELISA. IgG RF was positive in 91.7% by ELISA. In the IgM containing fraction of the serum, the positivity for IgM RF was 41.7% by LFT and 54.2% by ELISA. In the IgG containing fraction the positivity for IgG RF was 100%. These results suggest toward the need of previous serum dissociation before hidden 19S IgM RF is assayed and demonstrate high prevalence of 7S IgG RF.

Radioisotopic assessment of peripheral and cardiac muscle involvement and dysfunction in polymyositis/dermatomyositis.

99mTc-pyrophosphate musculoskeletal imaging and 99mTc-red blood cell gated blood pool imaging were performed on 10 patients with documented polymyositis/dermatomyositis. Abnormal 99mTc-pyrophosphate uptake by peripheral muscles was found in 8 patients (6 mild, 2 marked). Cardiac uptake occurred in 5 patients and was 3+ in 2 with cardiovascular symptoms. These 2 patients also had abnormal EF on gated blood pool imaging. Patients without myocardial 99mTc-pyrophosphate uptake had normal EF. Patients with myocardial 99mTc-pyrophosphate uptake had abnormal wall motion, in proportion to the degree of uptake. Response to therapy and outcome were poorer in patients with marked scintigraphic changes. These findings suggest that the magnitude of 99mTc-pyrophosphate myocardial uptake may have prognostic implications in these patients.

Cardiac tamponade in juvenile chronic arthritis: report of two cases and review of publications.

Two cases of systemic juvenile chronic arthritis, complicated by cardiac tamponade and eight previously reported cases are described. The clinical features and radiological, electrocardiographic, and echocardiographic findings were similar for all cases. One patient in this series was treated with corticosteroids and underwent pericardiectomy, dying of sepsis 30 days after surgery. The other patient was also treated with corticosteroids, underwent pericardiocentesis and developed fatal ventricular tachycardia. Of the 10 cases, only six were successfully treated. Early diagnosis and appropriate treatment are essential for a favourable outcome.