Plasma Cytokine Levels in Fibromyalgia and Their Response to 15 Weeks of Progressive Resistance Exercise or Relaxation Therapy.

The aims of this study were to compare circulating cytokines between FM and healthy controls and to investigate the effect on cytokine levels by 15 weeks of progressive resistance exercise or relaxation therapy in FM. Baseline plasma cytokine levels and clinical data were analyzed in 125 women with FM and 130 age-matched healthy women. The FM women were then randomized to progressive resistance exercise (n = 49) or relaxation (n = 43). Baseline IL-2, IL-6, TNF-α, IP-10, and eotaxin were higher in FM than in healthy controls (P < 0.041), whereas IL-1ß was lower (P < 0.001). There were weak correlations between cytokine levels and clinical variables. After both interventions, IL-1ra had increased (P = 0.004), while IL-1ß had increased in the relaxation group (P = 0.002). Changes of IFN-γ, IL-2, IL-4, IL-6, IL-8, and IL-17A were weakly correlated with changes of PPT, but there were no significant correlations between changes of cytokine and changes in other clinical variables. The elevated plasma levels of several cytokines supports the hypothesis that chronic systemic inflammation may underlie the pathophysiology of FM even if the relation to clinical variables was weak. However, 15 weeks of resistance exercise, as performed in this study, did not show any anti-inflammatory effect on neither FM symptoms nor clinical and functional variables. This trial is registered with ClinicalTrials.gov NCT01226784, registered October 21, 2010. The first patient was recruited October 28, 2010.

The role of long-term physical exercise on performance and brain activation during the Stroop colour word task in fibromyalgia patients.

The Stroop colour word test (SCWT) has been widely used to assess changes in cognitive performance such as processing speed, selective attention and the degree of automaticity. Moreover, the SCWT has proven to be a valuable tool to assess neuronal plasticity that is coupled to improvement in performance in clinical populations. In a previous study, we showed impaired cognitive processing during SCWT along with reduced task-related activations in patients with fibromyalgia. In this study, we used SCWT and functional magnetic resonance imagingFMRI to investigate the effects of a 15-week physical exercise intervention on cognitive performance, task-related cortical activation and distraction-induced analgesia (DIA) in patients with fibromyalgia and healthy controls. The exercise intervention yielded reduced fibromyalgia symptoms, improved cognitive processing and increased task-related activation of amygdala, but no effect on DIA. Our results suggest beneficial effects of physical exercise on cognitive functioning in FM.

Normalization of aberrant resting state functional connectivity in fibromyalgia patients following a three month physical exercise therapy.

Physical exercise is one of the most efficient interventions to mitigate chronic pain symptoms in fibromyalgia (FM). However, little is known about the neurophysiological mechanisms mediating these effects. In this study we investigated resting-state connectivity using functional magnetic resonance imaging (fMRI) before and after a 15 week standardized exercise program supervised by physical therapists. Our aim was to gain an understanding of how physical exercise influences previously shown aberrant patterns of intrinsic brain activity in FM. Fourteen FM patients and eleven healthy controls successfully completed the physical exercise treatment. We investigated post- versus pre-treatment changes of brain connectivity, as well as changes in clinical symptoms in the patient group. FM patients reported improvements in symptom severity. Although several brain regions showed a treatment-related change in connectivity, only the connectivity between the right anterior insula and the left primary sensorimotor area was significantly more affected by the physical exercise among the fibromyalgia patients compared to healthy controls. Our results suggest that previously observed aberrant intrinsic brain connectivity patterns in FM are partly normalized by the physical exercise therapy. However, none of the observed normalizations in intrinsic brain connectivity were significantly correlated with symptom changes. Further studies conducted in larger cohorts are warranted to investigate the precise relationship between improvements in fibromyalgia symptoms and changes in intrinsic brain activity.

Cerebrospinal Flt3 ligand correlates to tau protein levels in primary Sjögren's syndrome.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is an autoimmune disease affecting the exocrine glands and internal organs including the central nervous system (CNS). The fms-related tyrosine kinase 3 ligand (Flt3L) is a maturation factor essential for brain homeostasis. Blood levels of Flt3L are increased in inflammatory diseases including the inflamed salivary glands in pSS. The present study evaluated the role of Flt3L in the CNS of patients with pSS and in two non-autoimmune conditions, fibromyalgia (FM) and Alzheimer's disease (AD). METHOD: Levels of Flt3L were measured in cerebrospinal fluid (CSF) and serum of patients with pSS (n = 15), FM (n = 29), and AD (n = 39) and related to CNS symptoms and to markers of inflammation and degeneration. RESULTS: Levels of CSF Flt3L in pSS and AD were significantly lower than in FM (p = 0.005 and p = 0.0003, respectively). Flt3L in pSS correlated to tau proteins [total tau (T-tau), r = 0.679; phosphorylated tau (P-tau), r = 0.646] and to a marker for microglia activation, monocyte chemoattractant protein 1 (MCP-1). Similar correlations were present in FM and AD patients. One-third of pSS patients had low levels of CSF Flt3L. This group had decreased levels of amyloid precursor protein metabolites (Aß40 and Aß42) in CSF, which was not seen in FM patients. CONCLUSIONS: This study shows a strong correlation between CSF Flt3L and tau proteins in pSS patients suggesting ongoing degradation/remodelling in the CNS. In pSS patients, low levels of Flt3L were linked to changes in amyloid turnover and may represent processes similar to those in AD.

Fatigue and blood pressure in primary Sjogren's syndrome.

OBJECTIVE: Primary Sjogren's syndrome (SS) is an autoimmune disease characterized by fatigue. Little is known about the genesis of fatigue. Fatigue is thought to represent a multidimensional concept and it is important to be able to measure it confidently. The aims were to evaluate the reliability and validity of the 20-item Multidimensional Fatigue Inventory (MFI-20) in SS and to search for factors associated with this disabling symptom. METHODS: Forty-eight women with primary SS completed the MFI-20 questionnaire. The results were compared with age-matched women with fibromyalgia (FM) and healthy controls. Convergent construct validity was assessed by correlations to a Visual Analogue Scale (VAS) for global fatigue by Spearman's correlation (r(s)). Test-retest reliability was analysed by the intraclass correlation coefficient (ICC) in 28 women. Associations between clinical variables and subscales of the MFI-20 were analysed. RESULTS: The SS women scored significantly higher in all subscales of the MFI-20 compared to controls but similar to FM. The ICCs were satisfactory, ranging from 0.66 for general fatigue to 0.85 for the total score of MFI-20. All subscales correlated significantly to VAS for global fatigue, general fatigue showing the highest correlation (r(s) = 0.70). The estimated number of hours of sleep/day was significantly associated with many of the fatigue dimensions. All five subscales of the MFI-20 were inversely associated with diastolic blood pressure (BP) and two with systolic BP. CONCLUSIONS: The MFI-20 was found to be a reliable and valid tool for the measurement of fatigue in primary SS. High levels of fatigue were correlated with low BP, suggesting an associated involvement of the autonomic nervous system.

Pool exercise combined with an education program for patients with fibromyalgia syndrome. A prospective, randomized study.

OBJECTIVE: To evaluate the effects of 6 months of pool exercise combined with a 6 session education program for patients with fibromyalgia syndrome (FM). METHODS: The study population comprised 58 patients, randomized to a treatment or a control group. Patients were instructed to match the pool exercises to their threshold of pain and fatigue. The education focused on strategies for coping with symptoms and encouragement of physical activity. The primary outcome measurements were the total score of the Fibromyalgia Impact Questionnaire (FIQ) and the 6 min walk test, recorded at study start and after 6 mo. Several other tests and instruments assessing functional limitations, severity of symptoms, disabilities, and quality of life were also applied. RESULTS: Significant differences between the treatment group and the control group were found for the FIQ total score (p = 0.017) and the 6 min walk test (p < 0.0001). Significant differences were also found for physical function, grip strength, pain severity, social functioning, psychological distress, and quality of life. CONCLUSION: The results suggest that a 6 month program of exercises in a temperate pool combined with education will improve the consequences of FM.

Tests of functional limitations in fibromyalgia syndrome: a reliability study.

OBJECTIVE: To evaluate the reliability and discriminative ability of a test battery consisting of 7 tests designed for the assessment of functional limitations in patients with fibromyalgia syndrome (FMS). METHODS: The intrarater reliability of the test battery was evaluated for 15 women with FMS. Interrater reliability was calculated on 4 tests separately. Fifteen healthy women constituted a reference group. RESULTS: The intrarater coefficient of variation was < 8% for the shoulder range of motion tests, chair test, and 6-minute walk test, and < 21% for the shoulder endurance test, with correlation coefficients above 0.80 for all tests. Kappa was 0.70-0.80 for the hand-to-scapula tests. The interrater coefficient of variation was < 5% for shoulder range of motion. The performances of the FMS patients were significantly decreased in comparison with healthy subjects in all the tests except for the hand-to-scapula movement. CONCLUSIONS: All but 1 of the selected 7 tests were considered to possess acceptable intrarater reliability for use in FMS in clinical physical therapy practice.

How patients with fibromyalgia experience their symptoms in everyday life.

BACKGROUND AND PURPOSE: Fibromyalgia syndrome (FMS) is characterized by diffuse widespread pain and fatigue. The purpose of this study was to search for a deeper knowledge of the way patients with FMS experience their symptoms in everyday life. METHOD: Qualitative interviews, applying the phenomenological method, were used. The respondents were interviewed twice and asked to describe a typical day. Eleven Swedish women, aged 24-54 years, fulfilling the ACR criteria for FMS participated in the study. The duration of pain ranged from three to 20 years. Three patients worked full-time, six worked part-time and two did not work outside the home. RESULTS: The effect of perceived symptoms on everyday life was considerable. Four different patterns of perceiving and managing symptoms were identified: Struggling: respondents who perceived that they managed their everyday life by mobilizing their physical and psychological strength to fight their pain and fatigue; Adapting: respondents who perceived that they managed their everyday life by planning their activities on the basis of their assumptions of limitations; In despair: respondents who were in despair as they could no longer cope with their pain and life situation; Giving up: respondents who had given up many activities of everyday life and felt that their symptoms dominated their life. CONCLUSIONS: The study illuminates qualitative differences in FMS patients' experience and management of their symptoms in their everyday life. These differences ought to be considered when planning physiotherapy treatment.

Assessment of functional limitation and disability in patients with fibromyalgia.

Fibromyalgia syndrome (FMS) is characterized by diffuse widespread musculoskeletal pain. The aims of this literature study were to review measures and instruments used to assess functional limitations and disability in patients with FMS. A 10-year search was done on Medline, CATS, and CINAHL. Of the 73 articles found, only standardized instruments and tests permitting quantification were included. Reviews, trials of medication therapy, epidemiological studies, and measures of the psychological and impairment level were excluded. The articles were divided into cross-sectional and longitudinal studies. No studies evaluating the reliability, validity or sensitivity of the functional tests applied to the FMS were found. Of the disability instruments reviewed, only the Arthritis Impact Measurement Scales and Fibromyalgia Impact Questionnaire were evaluated for reliability and validity for the FMS population. The Arthritis Self-Efficacy Scales and Quality of Life Scale proved their sensitivity, detecting change in a controlled longitudinal study.

Physical performance characteristics of women with fibromyalgia.

OBJECTIVE: The aim of this study was to examine physical performance in women with fibromyalgia (FM) using methods that are easy to use in clinical settings and to compare our findings with published norms or a healthy comparison group. METHODS: Measures of shoulder pain and range-of-motion, isometric shoulder endurance, neck rotation, leg strength, hand grip strength, back flexibility, 6-minute walk distance, and symptom duration were completed on 97 subjects with FM. The comparison group was 30 age-matched healthy women. RESULTS: The FM group had significantly lower physical functioning scores on all variables when compared to the healthy group or published norms. When pain at rest was controlled, pain on motion was the most significant predictor of variance in shoulder range of motion, whereas range of motion was the most significant predictor of right shoulder endurance and grip strength of both hands. CONCLUSIONS: Women with FM are markedly below average in physical performance abilities when measured by clinical tests.

A randomized, controlled clinical trial of education and physical training for women with fibromyalgia.

OBJECTIVE: To determine the effectiveness of self-management education and physical training in decreasing fibromyalgia (FMS) symptoms and increasing physical and psychological well being. METHODS: A pretest-posttest control group design was used. Ninety-nine women with FMS were randomly assigned to 1 of 3 groups; 86 completed the study. The education only group received a 6-week self-management course. The education plus physical training group received the course and 6 h of training designed to assist them to exercise independently. The control group got treatment after 3 months. RESULTS: The experimental programs had a significant positive impact on quality of life and self-efficacy. Helplessness, number of days feeling bad, physical dysfunction, and pain in the tender points decreased significantly in one or both of the treated groups when retested 6 weeks after the end of the program. Longterm followup of 67 treated subjects showed significant positive changes on the Fibromyalgia Impact Questionnaire primarily in the physical training group. Among all subjects, 87% were exercising at least 3 times/week for 20 min or more; 46% said they had increased their exercise level since participating in the program; 70% were practicing relaxation strategies as needed; 46% were working at least half time as opposed to 37% at pretest. CONCLUSION: Self-efficacy of the treated groups was enhanced significantly by the program. Other changes were smaller and more delayed than had been expected. Recommendations for future trials include a longer education program, more vigorous physical training, and longterm followup.