Tag: De Meirleir

Chronic musculoskeletal pain in chronic fatigue syndrome: recent developments and therapeutic implications

Abstract:

Patients with chronic fatigue syndrome (CFS) experience chronic musculoskeletal pain which is even more debilitating than fatigue. Scientific research data gathered around the world enables clinicians to understand, at least in part, chronic musculoskeletal pain in CFS patients. Generalized joint hypermobility and benign joint hypermobility syndrome appear to be highly prevalent among CFS sufferers, but they do not seem to be of any clinical importance.

On the other hand, pain catastrophizing accounts for a substantial portion of musculoskeletal pain and is a predictor of exercise performance in CFS patients. The evidence concerning pain catastrophizing is supportive of the indirect evidence of a dysfunctional pain processing system in CFS patients with musculoskeletal pain. CFS sufferers respond to incremental exercise with a lengthened and accentuated oxidative stress response, explaining muscle pain, postexertional malaise, and the decrease in pain threshold following graded exercise in CFS patients.

Applying the scientific evidence to the manual physiotherapy profession, pacing self-management techniques and pain neurophysiology education are indicated for the treatment of musculoskeletal pain in CFS patients. Studies examining the effectiveness of these strategies for CFS patients are warranted.

 

Source: Nijs J, Meeus M, De Meirleir K. Chronic musculoskeletal pain in chronic fatigue syndrome: recent developments and therapeutic implications. Man Ther. 2006 Aug;11(3):187-91. Epub 2006 Jun 14. https://www.ncbi.nlm.nih.gov/pubmed/16781183

 

Generalized joint hypermobility is more common in chronic fatigue syndrome than in healthy control subjects

Abstract:

OBJECTIVES: This study aimed at (1) comparing the prevalence of generalized hypermobility in patients with chronic fatigue syndrome (CFS) and healthy volunteers, (2) examining the clinical importance of generalized hypermobility in patients with CFS, and (3) examining whether knee proprioception is associated with hypermobility in patients with CFS.

METHODS: Sixty-eight patients with CFS filled out two self-reported measures (for the assessment of symptom severity and disability), were questioned about muscle and joint pain, and were screened for generalized hypermobility. Afterward, the patients performed a knee repositioning test (assessment of knee proprioception), and it was examined whether or not they fulfilled the criteria for benign joint hypermobility syndrome (BJHS). Sixty-nine age- and sex-matched healthy volunteers were screened for generalized joint hypermobility and performed the same knee repositioning test.

RESULTS: Compared with the healthy volunteers (4.3%, 3/68), significantly more patients with CFS (20.6%, 14/69) fulfilled the criteria for generalized joint hypermobility (Fisher exact test, P < .004). No associations were found between generalized joint hypermobility and the self-reported measures (including pain severity) or knee proprioception (Spearman correlation analysis). Knee proprioception was similar in both groups (Mann-Whitney U = 1961, z = -1.745, P = .81). Forty patients with CFS (58.8%) fulfilled the criteria for BJHS.

CONCLUSIONS: These data indicate that a subgroup of patients with CFS present with generalized joint hypermobility and most patients with of CFS fulfill the diagnostic criteria for BJHS. There appears to be no association between musculoskeletal pain and joint hypermobility in patients with CFS.

 

Source: Nijs J, Aerts A, De Meirleir K. Generalized joint hypermobility is more common in chronic fatigue syndrome than in healthy control subjects. J Manipulative Physiol Ther. 2006 Jan;29(1):32-9. http://www.ncbi.nlm.nih.gov/pubmed/16396727

 

Employment status in chronic fatigue syndrome. A cross-sectional study examining the value of exercise testing and self-reported measures for the assessment of employment status

Abstract:

OBJECTIVE: To examine the value of exercise testing and self-reported disability for the assessment of employment status in patients with chronic fatigue syndrome.

DESIGN: Cross-sectional observational study.

SETTING: A university-based chronic fatigue clinic.

SUBJECTS: Fifty-four consecutive, Flemish, employed (not self-employed) chronic fatigue syndrome patients (49/54 female).

INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURES: Participants were questioned about their current and premorbid employment status, filled in the Chronic Fatigue Syndrome Activities and Participation Questionnaire (CFS-APQ), the Medical Outcomes Short Form 36 Health Status Survey (SF-36), and performed a maximal exercise test on a bicycle ergometer with continuous monitoring of cardiorespiratory variables.

RESULTS: A significant association was observed between the current employment rate and two SF-36 subscales (i.e., role limitations due to physical functioning and social functioning; rho = 0.39 and 0.35 respectively) (n = 54). Analysing only the female chronic fatigue syndrome patients (n = 49), the current employment rate correlated significantly with the peak workload (rho = 0.38).

CONCLUSIONS: The associations between either exercise testing or self-reported disability and employment status are too weak to predict employment status.

 

Source: Nijs J, Van de Putte K, Louckx F, De Meirleir K. Employment status in chronic fatigue syndrome. A cross-sectional study examining the value of exercise testing and self-reported measures for the assessment of employment status. Clin Rehabil. 2005 Dec;19(8):895-9. http://www.ncbi.nlm.nih.gov/pubmed/16323389

 

Chronic fatigue syndrome: exercise performance related to immune dysfunction

Abstract:

PURPOSE: To date, the exact cause of abnormal exercise response in chronic fatigue syndrome (CFS) remains to be revealed, but evidence addressing intracellular immune deregulation in CFS is growing. Therefore, the aim of this cross-sectional study was to examine the interactions between several intracellular immune variables and exercise performance in CFS patients.

METHODS: After venous blood sampling, subjects (16 CFS patients) performed a maximal exercise stress test on a bicycle ergometer with continuous monitoring of cardiorespiratory variables. The following immune variables were assessed: the ratio of 37 kDa Ribonuclease (RNase) L to the 83 kDa native RNase L (using a radiolabeled ligand/receptor assay), RNase L enzymatic activity (enzymatic assay), protein kinase R activity assay (comparison Western blot), elastase activity (enzymatic-colorimetric assay), the percent of monocytes, and nitric oxide determination (for monocytes and lymphocytes; flow cytometry, live cell assay).

RESULTS: Forward stepwise multiple regression analysis revealed 1) that elastase activity was the only factor related to the reduction in oxygen uptake at a respiratory exchange ratio (RER) of 1.0 (regression model: R = 0.53, F (1,14) = 15.5, P < 0.002; elastase activity P < 0.002); 2) that the protein kinase R activity was the principle factor related to the reduction in workload at RER = 1.0; and 3) that elastase activity was the principle factor related to the reduction in percent of target heart rate achieved.

CONCLUSION: These data provide evidence for an association between intracellular immune deregulation and exercise performance in patients with CFS. To establish a causal relationship, further study of these interactions using a prospective longitudinal design is required.

 

Source: Nijs J, Meeus M, McGregor NR, Meeusen R, de Schutter G, van Hoof E, de Meirleir K. Chronic fatigue syndrome: exercise performance related to immune dysfunction. Med Sci Sports Exerc. 2005 Oct;37(10):1647-54. http://www.ncbi.nlm.nih.gov/pubmed/16260962

 

37-Kilodalton/83-kilodalton RNase L isoform ratio in peripheral blood mononuclear cells: analytical performance and relevance for chronic fatigue syndrome

Comment on: RNase L levels in peripheral blood mononuclear cells: 37-kilodalton/83-kilodalton isoform ratio is a potential test for chronic fatigue syndrome.[Clin Diagn Lab Immunol. 2003]

 

A French group has reported results (5) supporting the use of the RNase L 37-kDa/83-kDa ratio (37/83 R) in peripheral blood mononuclear cells (PBMC) as a diagnostic test for chronic fatigue syndrome (CFS). More recently (6), the same group cautioned about the diagnostic value of the 37/83 R, based on a small patient follow-up study which was likely to indicate analytical variability among duplicate assays, lack of reproducibility over time, and a weak correlation with the multidimensional fatigue inventory (MFI) score. Because of our long-term experience with this assay, we would like to offer some comments.

First, we tested the analytical performance of the 37/83 R assay according to CLSI (formerly NCCLS) procedure EP5-A (4), with control samples at three different levels made of extracts of the monocytic U937 cell line spiked with various concentrations of recombinant RNase L. The guideline protocol involves assaying the samples in duplicate twice daily over a total period of 20 days. The results summarized in Table Table11 indicate that both within- and between-run variation does not exceed 13%. In another series of experiments, we assayed eight patient samples in duplicate (average 37/83 R ranging from 0.5 to 245). Although in accordance with the NCCLS protocol results, the variation did not exceed 12% for samples with 37/83 R levels up to 20, and it rose significantly to 30% and more for samples with 37/83 R levels above 20. This should be expected, because beyond this level, more than 70% of the 83-kDa isoform is cleaved, and consequently, the faint 83-kDa band is difficult to scan with accuracy. Thus, in our opinion, the lower level of correlation between the duplicate assay results observed with the CFS group versus those with the controls (6) reflects the prevalence of high 37/83 R levels in the CFS group rather than a low test reproducibility as claimed by these authors. This is further supported by the good correlation found for the control group (r = 0.95). During validation, the lowest detectable ratio measured with a sample containing the 83-kDa isoform only was estimated (3 independent experiments with 26 replicates each) to be 0.13 ± 0.06 (average ± three standard deviations). Thus, the clinical cutoff ratio of 0.4 found by the authors (5, 6) to best discriminate CFS patients from controls falls within the measurable range.

You can read the rest of this comment here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1247842/

 

Source: Frémont M, Vaeyens F, Herst CV, De Meirleir K, Englebienne P. 37-Kilodalton/83-kilodalton RNase L isoform ratio in peripheral blood mononuclear cells: analytical performance and relevance for chronic fatigue syndrome. Clin Diagn Lab Immunol. 2005 Oct;12(10):1259-60; author reply 1260. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1247842/ (Full article)

 

The Chronic Fatigue Syndrome Activities and Participation Questionnaire (CFS-APQ): an overview

Abstract:

Chronic fatigue syndrome (CFS) is characterized by severe fatigue and a reduction in activity levels. The purpose of this study was to provide an overview of design, reliability, and validity of the CFS Activities and Participation Questionnaire (CFS-APQ).

The CFS-APQ was constructed based on a retrospective analysis of the Karnofsky Performance Status Questionnaire and the Activities of Daily Living Questionnaire (n = 141). In a reliability study of 34 participants the test-retest reliability coefficient of the CFS-APQ was 0.95. In two different studies, the Cronbach alpha coefficient for internal consistency varied between 0.87 (n = 88) and 0.94 (n = 47). The CFS-APQ was administered to 47 patients who listed 183 activities that had become difficult due to their chronic symptoms, and 157 (85.8%) answers matched the content of the CFS-APQ.

The outcome of a cross-sectional study (n = 88) studying the correlations between the Medical Outcomes Short Form 36 Health Status Survey subscale scores and the CFS-APQ supported the validity of the CFS-APQ. The CFS-APQ scores correlated with a behavioural assessment of the patients’ performance of activities encompassed by the questionnaire (r = 0.29-0.55; n = 63), and correlated with exercise capacity parameters (r = 0.26-0.39; n = 77) obtained during a maximal exercise capacity stress test. Finally, the CFS-APQ correlated with visual analogue scales for pain (r = 0.51) and fatigue (r = 0.50; n = 47).

It is concluded that the CFS-APQ generates reliable and valid data, and can be used as a clinical measure of disease severity in patients with CFS. Future studies should aim at examining the sensitivity of the CFS-APQ.

 

Source: Nijs J, Vaes P, De Meirleir K. The Chronic Fatigue Syndrome Activities and Participation Questionnaire (CFS-APQ): an overview. Occup Ther Int. 2005;12(2):107-21. http://www.ncbi.nlm.nih.gov/pubmed/16136868

 

Prediction of peak oxygen uptake in patients fulfilling the 1994 CDC criteria for chronic fatigue syndrome

Abstract:

PURPOSE: To establish an inexpensive, simple method of predicting peak oxygen uptake (VO2peak) in patients fulfilling the 1994 Centers for Disease Control and Prevention (CDC) criteria for chronic fatigue syndrome (CFS).

DESIGN: A retrospective observational study.

SETTING: An outpatient tertiary care chronic fatigue clinic.

SUBJECTS: Two hundred and forty consecutive patients fulfilling the 1994 CDC criteria for CFS.

INTERVENTIONS: Heart rate, metabolic and ventilatory parameters were measured continuously during a maximal exercise stress test on a bicycle ergometer. Using the equation peak oxygen uptake = 13.1 x peak workload +284 (used by Mullis et al., Br J Sports Med 1999; 33: 352-56), VO2peak was predicted from the peak workload of a maximal exercise capacity test. Pearson correlation coefficient and linear regression analysis were used to establish the most accurate way to predict VO2peak.

RESULTS: Percentage error encountered when comparing actual measured VO2peak with predicted value was 17.3% (+/-10.0). A strong correlation between VO2peak and peak workload was observed (r= 0.89, p < 0.001). A regression analysis established the relation as VO2peak = 10.47 x peak workload +284.1, where VO2peak is given in ml/min and peak workload in W (error in prediction = 11.0+/-9.5%).

CONCLUSIONS: Monitoring of the peak workload during a maximal, graded bicycle ergometric test suffices to predict the VO2peak. When predicting VO2peak the used operational definition for the diagnosis of CFS could be taken into account. Compared with the equation used by Mullis et al., peak workload is multiplied by 10.47 in order to predict peak oxygen uptake in CDC-defined CFS patients.

 

Source: Nijs J, De Meirleir K. Prediction of peak oxygen uptake in patients fulfilling the 1994 CDC criteria for chronic fatigue syndrome. Clin Rehabil. 2004 Nov;18(7):785-92. http://www.ncbi.nlm.nih.gov/pubmed/15573835

 

Kinesiophobia in chronic fatigue syndrome: assessment and associations with disability

Abstract:

OBJECTIVES: To investigate aspects of the validity of the total scores of the Tampa Scale for Kinesiophobia (TSK), Dutch Version, which was modified to make it an appropriate questionnaire for the assessment of kinesiophobia (fear of movement) in chronic fatigue syndrome (CFS) patients (the Dutch TSK-CFS), and, using this assessment tool, to examine the associations between kinesiophobia, exercise capacity, and activity limitations and participation restrictions in patients with CFS.

DESIGN: Prospective observational studies.

SETTING: An outpatient fatigue clinic.

PARTICIPANTS: In the first study, 40 patients fulfilling the 1994 US Centers for Disease Control and Prevention (CDC) criteria for CFS were enrolled. The sample of the second study consisted of 51 CDC-defined patients with CSF.

INTERVENTIONS: Not applicable. Main outcome measures Study 1: Subjects completed a set of questionnaires; the Utrechtse Coping List (UCL), the Dutch TSK-CFS, and the Dutch Baecke Questionnaire of Habitual Physical Activity. Study 2: All patients completed 2 questionnaires (Chronic Fatigue Syndrome Activities and Participation Questionnaire [CFS-APQ], Dutch TSK-CFS) and performed a maximal exercise stress test on a bicycle ergometer. The heart rate was monitored continuously by use of an electrocardiograph. Metabolic and ventilatory parameters were measured through spirometry.

RESULTS: Study 1: The Cronbach alpha coefficient for the individual item scores on the TSK-CFS was .80. The total scores on the Dutch TSK-CFS showed a statistically significant correlation with both the avoidance/abide subscale of the UCL (Spearman rho=.35, P=.029) and the total score of the Baecke Questionnaire (rho=-.45, P=.004). Study 2: The total scores on the Dutch TSK-CFS showed a statistically significant correlation with the total scores on the CFS-APQ (rho=.39, P=.004). No statistically significant associations were observed between the exercise capacity parameters and the total scores on the Dutch TSK-CFS.

CONCLUSIONS: These results provide evidence for the internal consistency and the convergent and congruent validity of the scores obtained by use of the Dutch TSK-CFS. Kinesiophobia appears to be associated with activity limitations/participation restrictions but not with exercise capacity in patients with CFS.

 

Source: Nijs J, De Meirleir K, Duquet W. Kinesiophobia in chronic fatigue syndrome: assessment and associations with disability. Arch Phys Med Rehabil. 2004 Oct;85(10):1586-92. http://www.ncbi.nlm.nih.gov/pubmed/15468015

 

Chronic fatigue syndrome: lack of association between pain-related fear of movement and exercise capacity and disability

Abstract:

BACKGROUND AND PURPOSE: Patients who experience pain, a symptom of chronic fatigue syndrome (CFS), often exhibit kinesiophobia (irrational fear of movement). The purpose of this study was to examine whether pain-related fear of movement is associated with exercise capacity, activity limitations, or participation restrictions in patients with CFS who experience widespread pain.

SUBJECTS AND METHODS: Sixty-four subjects met the inclusion criteria. All subjects fulfilled the 1994 Centers for Disease Control and Prevention case definition for CFS and experienced widespread myalgias or arthralgias. The subjects completed the Tampa Scale for Kinesiophobia-Dutch Version (TSK-DV) and the Dutch Chronic Fatigue Syndrome-Activities and Participation Questionnaire (CFS-APQ). They then performed a maximal exercise test on a bicycle ergometer. Heart rate was monitored continuously by use of an electrocardiograph. Ventilatory factors were measured through spirometry. Correlations between the TSK-DV scores and both the exercise capacity data and the CFS-APQ scores were assessed using the Spearman rank correlation coefficient. Using the Mann-Whitney U test, the TSK-DV scores were compared between subjects who performed a maximal exercise stress test and those who did not perform the test.

RESULTS: Forty-seven subjects (73.4%) attained a total score of greater than 37 on the TSK-DV, indicating high fear of movement. Neither the exercise capacity data nor the CFS-APQ scores indicated a correlation with the TSK-DV scores (n=64). Subjects who did not perform a maximal exercise capacity test had more fear of movement (median TSK-DV score=43.0, interquartile range=10.3) compared with those who did perform a maximal exercise capacity test (median TSK-DV score=38.0, interquartile range=13.2; Mann-Whitney U-test score=322.5, z=-1.974, P=.048), but the correlation analysis was unable to reveal an association between exercise capacity and kinesiophobia in either subgroup.

DISCUSSION AND CONCLUSION: These results indicate a lack of correlation between kinesiophobia and exercise capacity, activity limitations, or participation restrictions, at least in patients with CFS who are experiencing widespread muscle or joint pain.

 

Source: Nijs J, Vanherberghen K, Duquet W, De Meirleir K. Chronic fatigue syndrome: lack of association between pain-related fear of movement and exercise capacity and disability. Phys Ther. 2004 Aug;84(8):696-705. http://ptjournal.apta.org/content/84/8/696.long (Full article)

 

Chronic fatigue syndrome: intracellular immune deregulations as a possible etiology for abnormal exercise response

Abstract:

The exacerbation of symptoms after exercise differentiates Chronic fatigue syndrome (CFS) from several other fatigue-associated disorders. Research data point to an abnormal response to exercise in patients with CFS compared to healthy sedentary controls, and to an increasing amount of evidence pointing to severe intracellular immune deregulations in CFS patients. This manuscript explores the hypothetical interactions between these two separately reported observations.

First, it is explained that the deregulation of the 2-5A synthetase/RNase L pathway may be related to a channelopathy, capable of initiating both intracellular hypomagnesaemia in skeletal muscles and transient hypoglycemia. This might explain muscle weakness and the reduction of maximal oxygen uptake, as typically seen in CFS patients.

Second, the activation of the protein kinase R enzyme, a characteristic feature in at least subsets of CFS patients, might account for the observed excessive nitric oxide (NO) production in patients with CFS. Elevated NO is known to induce vasodilation, which may limit CFS patients to increase blood flow during exercise, and may even cause and enhanced postexercise hypotension.

Finally, it is explored how several types of infections, frequently identified in CFS patients, fit into these hypothetical pathophysiological interactions.

 

Source: Nijs J, De Meirleir K, Meeus M, McGregor NR, Englebienne P. Chronic fatigue syndrome: intracellular immune deregulations as a possible etiology for abnormal exercise response. Med Hypotheses. 2004;62(5):759-65. http://www.ncbi.nlm.nih.gov/pubmed/15082102