Physical activity intensity but not sedentary activity is reduced in chronic fatigue syndrome and is associated with autonomic regulation

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a common debilitating condition associated with reduced function and impaired quality of life. The cause is unknown and treatments limited. Studies confirm that CFS is associated with impaired autonomic regulation and impaired muscle function.

AIM: Define the relationship between sedentary behaviour, physical activity and autonomic regulation in people with CFS.

DESIGN: Cohort study.

METHODS: Physical activity was assessed objectively in 107 CFS patients (Fukuda) and age, sex and body mass index (BMI)-matched sedentary controls (n= 107). Fatigue severity was determined using the Fatigue Impact Scale in all participants and heart rate variability performed in the CFS group.

RESULTS: The CFS group had levels and patterns of sedentary behaviour similar to non-fatigue controls (P > 0.05). Seventy-nine percent of the CFS group did not achieve the WHO recommended 10,000 steps per day. Active energy expenditure [time >3 METs (metabolic equivalents)] was reduced in CFS when compared with controls (P < 0.0001). Physical activity duration was inversely associated with resting heart rate (P = 0.04; r(2) = 0.03), with reduced activity significantly associating with reduced heart rate variability in CFS. There were no relationships between fatigue severity and any parameter of activity. Thirty-seven percent of the CFS group were overweight (BMI 25-29.9) and 20% obese (BMI ≥ 30).

CONCLUSION: Low levels of physical activity reported in CFS represent a significant and potentially modifiable perpetuating factor in CFS and are not attributable to high levels of sedentary activity, rather a decrease in physical activity intensity. The reduction in physical activity can in part be explained by autonomic dysfunction but not fatigue severity.

 

Source: Newton JL, Pairman J, Hallsworth K, Moore S, Plötz T, Trenell MI. Physical activity intensity but not sedentary activity is reduced in chronic fatigue syndrome and is associated with autonomic regulation. QJM. 2011 Aug;104(8):681-7. doi: 10.1093/qjmed/hcr029. Epub 2011 Mar 7. http://qjmed.oxfordjournals.org/content/104/8/681.long (Full article)

 

Migraine headaches in chronic fatigue syndrome (CFS): comparison of two prospective cross-sectional studies

Abstract:

BACKGROUND: Headaches are more frequent in Chronic Fatigue Syndrome (CFS) than healthy control (HC) subjects. The 2004 International Headache Society (IHS) criteria were used to define CFS headache phenotypes.

METHODS: Subjects in Cohort 1 (HC = 368; CFS = 203) completed questionnaires about many diverse symptoms by giving nominal (yes/no) answers. Cohort 2 (HC = 21; CFS = 67) had more focused evaluations. They scored symptom severities on 0 to 4 anchored ordinal scales, and had structured headache evaluations. All subjects had history and physical examinations; assessments for exclusion criteria; questionnaires about CFS related symptoms (0 to 4 scale), Multidimensional Fatigue Inventory (MFI) and Medical Outcome Survey Short Form 36 (MOS SF-36).

RESULTS: Demographics, trends for the number of diffuse “functional” symptoms present, and severity of CFS case designation criteria symptoms were equivalent between CFS subjects in Cohorts 1 and 2. HC had significantly fewer symptoms, lower MFI and higher SF-36 domain scores than CFS in both cohorts. Migraine headaches were found in 84%, and tension-type headaches in 81% of Cohort 2 CFS. This compared to 5% and 45%, respectively, in HC. The CFS group had migraine without aura (60%; MO; CFS+MO), with aura (24%; CFS+MA), tension headaches only (12%), or no headaches (4%). Co-morbid tension and migraine headaches were found in 67% of CFS. CFS+MA had higher severity scores than CFS+MO for the sum of scores for poor memory, dizziness, balance, and numbness (“Neuro-construct”, p = 0.002) and perceived heart rhythm disturbances, palpitations and noncardiac chest pain (“Cardio-construct”; p = 0.045, t-tests after Bonferroni corrections). CFS+MO subjects had lower pressure-induced pain thresholds (2.36 kg [1.95-2.78; 95% C.I.] n = 40) and a higher prevalence of fibromyalgia (47%; 1990 criteria) compared to HC (5.23 kg [3.95-6.52] n = 20; and 0%, respectively). Sumatriptan was beneficial for 13 out of 14 newly diagnosed CFS migraine subjects.

CONCLUSIONS: CFS subjects had higher prevalences of MO and MA than HC, suggesting that mechanisms of migraine pathogenesis such as central sensitization may contribute to CFS pathophysiology.

CLINICAL TRIAL REGISTRATION: Georgetown University IRB # 2006-481

TRIAL REGISTRATION: ClinicalTrials.gov NCT00810329 NCT00810329.

 

Source: Ravindran MK, Zheng Y, Timbol C, Merck SJ, Baraniuk JN. Migraine headaches in chronic fatigue syndrome (CFS): comparison of two prospective cross-sectional studies. BMC Neurol. 2011 Mar 5;11:30. doi: 10.1186/1471-2377-11-30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058027/ (Full article)

 

Resveratrol improves hippocampal atrophy in chronic fatigue mice by enhancing neurogenesis and inhibiting apoptosis of granular cells

Abstract:

Neuroimaging evidence showed structural and/or functional abnormalities existing in the central nervous system, especially the hippocampus, in chronic fatigue syndrome (CFS) patients. However, its pathophysiologic mechanisms are unclear in part due to the lack of an applicable animal model. We established a chronic fatigue murine model by six repeated injections of Brucella abortus antigen to mice, which was manifested as reduced daily running activity and hippocampal atrophy. Thereafter, resveratrol, a polyphenolic activator of sirtuin 1, was used for treatment in this model. Daily running activity was increased by more than 20%, and the hippocampus was enlarged after 4-week resveratrol therapy.

Furthermore, resveratrol inhibited neuronal apoptosis and expression of hippocampal acetylated p53 in the fatigue mice. Resveratrol also improved neurogenesis and expression of brain-derived neurotrophic factor mRNA in the hippocampus. We concluded that repeated injection of B. abortus antigen could induce hypoactivity and hippocampal atrophy in mice. Resveratrol may be effective for improving fatigue symptoms and enlarging the atrophic hippocampus by repressing apoptosis and promoting neurogenesis.

 

Source: Moriya J, Chen R, Yamakawa J, Sasaki K, Ishigaki Y, Takahashi T. Resveratrol improves hippocampal atrophy in chronic fatigue mice by enhancing neurogenesis and inhibiting apoptosis of granular cells. Biol Pharm Bull. 2011;34(3):354-9. https://www.jstage.jst.go.jp/article/bpb/34/3/34_3_354/_article (Full article)

 

Serologic and PCR testing of persons with chronic fatigue syndrome in the United States shows no association with xenotropic or polytropic murine leukemia virus-related viruses

Abstract:

In 2009, a newly discovered human retrovirus, xenotropic murine leukemia virus (MuLV)-related virus (XMRV), was reported by Lombardi et al. in 67% of persons from the US with chronic fatigue syndrome (CFS) by PCR detection of gag sequences. Although six subsequent studies have been negative for XMRV, CFS was defined more broadly using only the CDC or Oxford criteria and samples from the US were limited in geographic diversity, both potentially reducing the chances of identifying XMRV positive CFS cases. A seventh study recently found polytropic MuLV sequences, but not XMRV, in a high proportion of persons with CFS. Here we tested blood specimens from 45 CFS cases and 42 persons without CFS from over 20 states in the United States for both XMRV and MuLV. The CFS patients all had a minimum of 6 months of post-exertional malaise and a high degree of disability, the same key symptoms described in the Lombardi et al. study. Using highly sensitive and generic DNA and RNA PCR tests, and a new Western blot assay employing purified whole XMRV as antigen, we found no evidence of XMRV or MuLV in all 45 CFS cases and in the 42 persons without CFS. Our findings, together with previous negative reports, do not suggest an association of XMRV or MuLV in the majority of CFS cases.

 

Source: Satterfield BC, Garcia RA, Jia H, Tang S, Zheng H, Switzer WM. Serologic and PCR testing of persons with chronic fatigue syndrome in the United States shows no association with xenotropic or polytropic murine leukemia virus-related viruses. Retrovirology. 2011 Feb 22;8:12. doi: 10.1186/1742-4690-8-12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050813/ (Full article)

 

Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial

Abstract:

BACKGROUND: Trial findings show cognitive behaviour therapy (CBT) and graded exercise therapy (GET) can be effective treatments for chronic fatigue syndrome, but patients’ organisations have reported that these treatments can be harmful and favour pacing and specialist health care. We aimed to assess effectiveness and safety of all four treatments.

METHODS: In our parallel-group randomised trial, patients meeting Oxford criteria for chronic fatigue syndrome were recruited from six secondary-care clinics in the UK and randomly allocated by computer-generated sequence to receive specialist medical care (SMC) alone or with adaptive pacing therapy (APT), CBT, or GET. Primary outcomes were fatigue (measured by Chalder fatigue questionnaire score) and physical function (measured by short form-36 subscale score) up to 52 weeks after randomisation, and safety was assessed primarily by recording all serious adverse events, including serious adverse reactions to trial treatments. Primary outcomes were rated by participants, who were necessarily unmasked to treatment assignment; the statistician was masked to treatment assignment for the analysis of primary outcomes. We used longitudinal regression models to compare SMC alone with other treatments, APT with CBT, and APT with GET. The final analysis included all participants for whom we had data for primary outcomes. This trial is registered at http://isrctn.org, number ISRCTN54285094.

FINDINGS: We recruited 641 eligible patients, of whom 160 were assigned to the APT group, 161 to the CBT group, 160 to the GET group, and 160 to the SMC-alone group. Compared with SMC alone, mean fatigue scores at 52 weeks were 3·4 (95% CI 1·8 to 5·0) points lower for CBT (p = 0·0001) and 3·2 (1·7 to 4·8) points lower for GET (p = 0·0003), but did not differ for APT (0·7 [-0·9 to 2·3] points lower; p = 0·38). Compared with SMC alone, mean physical function scores were 7·1 (2·0 to 12·1) points higher for CBT (p = 0·0068) and 9·4 (4·4 to 14·4) points higher for GET (p = 0·0005), but did not differ for APT (3·4 [-1·6 to 8·4] points lower; p=0·18). Compared with APT, CBT and GET were associated with less fatigue (CBT p = 0·0027; GET p = 0·0059) and better physical function (CBT p=0·0002; GET p<0·0001). Subgroup analysis of 427 participants meeting international criteria for chronic fatigue syndrome and 329 participants meeting London criteria for myalgic encephalomyelitis yielded equivalent results. Serious adverse reactions were recorded in two (1%) of 159 participants in the APT group, three (2%) of 161 in the CBT group, two (1%) of 160 in the GET group, and two (1%) of 160 in the SMC-alone group.

INTERPRETATION: CBT and GET can safely be added to SMC to moderately improve outcomes for chronic fatigue syndrome, but APT is not an effective addition.

FUNDING: UK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Comment in:

 

Source: White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, Baber HL, Burgess M, Clark LV, Cox DL, Bavinton J, Angus BJ, Murphy G, Murphy M, O’Dowd H, Wilks D, McCrone P, Chalder T, Sharpe M; PACE trial management group. Collaborators (19). Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011 Mar 5;377(9768):823-36. doi: 10.1016/S0140-6736(11)60096-2. Epub 2011 Feb 18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065633/ (Full article)

 

Fatigue In Teenagers on the interNET–the FITNET Trial. A randomized clinical trial of web-based cognitive behavioural therapy for adolescents with chronic fatigue syndrome: study protocol

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS) is increasingly recognized as a cause of disability and inactivity in adolescents in the Netherlands. CFS is characterized by unexplained fatigue lasting more than 6 months. Cognitive Behavioural Therapy (CBT) has proven to be effective. However, CBT availability for adolescents with CFS is limited and requires special therapeutic skills not always readily available. An alternative to the face-to-face CBT is FITNET, a web-based therapeutic program designed specifically for adolescents diagnosed with CFS, and their parents. This new CBT approach appeals to the modern youth, who grow up with internet as their main source of information. A web-based program offers the opportunity to lower thresholds for the acceptance and realization of healthcare. This treatment can be activated at any chosen time. The communication between patient and therapist can elapse asynchronously. If effective, this web-based program would greatly increase the therapeutic accessibility.

METHODS/DESIGN: A randomized clinical trial is currently conducted. One-hundred-forty adolescents aged 12-18 years diagnosed with CFS will be recruited and randomized to one of two groups: FITNET or usual care. After 6 months, the usual care group will have access to the FITNET program. Outcomes will be assessed at baseline, post intervention, and at 6 months follow-up. Primary outcome measures are school presence, fatigue severity, and physical functioning.

DISCUSSION: The FITNET study is the first randomized clinical trial which evaluates the effect of web-based CBT versus usual care in adolescents with CFS. The intervention is based on a theoretical existing model of CBT for patients with CFS. The results of this study will provide information about the possibility and efficacy of web-based CBT for adolescents with CFS and will reveal predictors of efficacy.

TRIAL REGISTRATION: ISRCTN: ISRCTN59878666 and ClinicalTrials.gov: NCT00893438.

 

Source: Nijhof SL, Bleijenberg G, Uiterwaal CS, Kimpen JL, van de Putte EM. Fatigue In Teenagers on the interNET–the FITNET Trial. A randomized clinical trial of web-based cognitive behavioural therapy for adolescents with chronic fatigue syndrome: study protocol. [ISRCTN59878666]. BMC Neurol. 2011 Feb 19;11:23. doi: 10.1186/1471-2377-11-23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049137/ (Full article)

 

Characteristics of chronic fatigue syndrome in a Japanese community population : chronic fatigue syndrome in Japan

Abstract:

This study seeks to estimate the prevalence of chronic fatigue syndrome (CFS) and assess the characteristics of CFS in a community population in Japan using laboratory tests and questionnaires for lifestyle, fatigue states, and depression states. The design of this study is a cross-sectional observational study. The setting of this study is a medical health checkup program in a general hospital.

This study was conducted with 1,430 Japanese (867 men and 563 women), 20 to 78 years of age. We classified participants who complained of fatigue according to the case definition of CFS proposed by the Centers for Disease Control and Prevention in the USA in 1994. Alcohol, caffeine, catechin and total polyphenol consumption, smoking status, sleep duration, and physical activity were evaluated using questionnaires.

The prevalence of CFS was 1.0% (95% CI 0.5-1.6%) of a community population in Japan. Although various lifestyle factors of the participants with CFS were similar to those without chronic fatigue, average sleep duration was significantly shorter among the participants with CFS (5.5 ± 0.8 h) compared to those without chronic fatigue (6.3 ± 0.9 h, P < 0.001). Proportion at subjects having average sleep duration of less than 6 h was 64.3% among the participants with CFS in contrast to only 15.0% in those without chronic fatigue (P < 0.001).

Among the eight case-defining symptoms, “Unrefreshing sleep” had high sensitivity and high specificity for screening CFS in Japanese population (92.9% and 87.8%, respectively). The average sleep duration was notably shorter in Japanese suffering from CFS. Further longitudinal study is needed to evaluate the possibility of extreme short sleep duration as a major cause of CFS in Japan.

 

Source: Hamaguchi M, Kawahito Y, Takeda N, Kato T, Kojima T. Characteristics of chronic fatigue syndrome in a Japanese community population : chronic fatigue syndrome in Japan. Clin Rheumatol. 2011 Jul;30(7):895-906. doi: 10.1007/s10067-011-1702-9. Epub 2011 Feb 8. https://www.ncbi.nlm.nih.gov/pubmed/21302125

 

Cognitive deficits in patients with chronic fatigue syndrome compared to those with major depressive disorder and healthy controls

Abstract:

OBJECT: Chronic fatigue syndrome (CFS) patients report usually cognitive complaints. They also have frequently comorbid depression that can be considered a possible explanation for their cognitive dysfunction. We evaluated the cognitive performance of patients with CFS in comparison with a control group of healthy volunteers and a group of patients with MDD.

PATIENTS AND METHODS: Twenty-five patients with CFS, 25 patients with major depressive disorder (MDD), and 25 healthy control subjects were given standardized tests of attention, working memory, and verbal and visual episodic memory, and were also tested for effects related to lack of effort/simulation, suggestibility, and fatigue.

RESULTS: Patients with CFS had slower phasic alertness, and also had impaired working, visual and verbal episodic memory compared to controls. They were, however, no more sensitive than the other groups to suggestibility or to fatigue induced during the cognitive session. Cognitive impairments in MDD patients were strongly associated with depression and subjective fatigue; in patients with CFS, there was a weaker correlation between cognition and depression (and no correlation with fatigue).

CONCLUSIONS: This study confirms the presence of an objective impairment in attention and memory in patients with CFS but with good mobilization of effort and without exaggerated suggestibility.

Copyright © 2011 Elsevier B.V. All rights reserved.

 

Source: Constant EL, Adam S, Gillain B, Lambert M, Masquelier E, Seron X. Cognitive deficits in patients with chronic fatigue syndrome compared to those with major depressive disorder and healthy controls. Clin Neurol Neurosurg. 2011 May;113(4):295-302. doi: 10.1016/j.clineuro.2010.12.002. Epub 2011 Jan 20. https://www.ncbi.nlm.nih.gov/pubmed/21255911

 

The role of changes in activity as a function of perceived available and expended energy in nonpharmacological treatment outcomes for ME/CFS

Abstract:

Nonpharmacological interventions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often emphasize gradual increases in activity to promote improvement in physical functioning and fatigue. The energy envelope theory may provide a framework for understanding the relationship between changes in activity level and outcomes for patients with ME/CFS. This study examined the relationship between energy envelope and changes in activity after nonpharmacological interventions in a sample of 44 adults with ME/CFS.

Results showed that those who were within their energy envelope before treatment showed more improvement in physical functioning and fatigue compared with those outside of their energy envelope. These findings suggest that an assessment of perceived available and expended energy could help guide the development of individualized nonpharmacological interventions for people with ME/CFS.

© 2010 Wiley Periodicals, Inc.

 

Source: Brown M, Khorana N, Jason LA. The role of changes in activity as a function of perceived available and expended energy in nonpharmacological treatment outcomes for ME/CFS. J Clin Psychol. 2011 Mar;67(3):253-60. doi: 10.1002/jclp.20744. Epub 2010 Oct 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164291/ (Full article)

 

The economic impact of chronic fatigue syndrome in Georgia: direct and indirect costs

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating chronic illness affecting at least 4 million people in the United States. Understanding its cost improves decisions regarding resource allocation that may be directed towards treatment and cure, and guides the evaluation of clinical and community interventions designed to reduce the burden of disease.

METHODS: This research estimated direct and indirect costs of CFS and the impact on educational attainment using a population-based, case-control study between September 2004 and July 2005, Georgia, USA. Participants completed a clinical evaluation to confirm CFS, identify other illnesses, and report on socioeconomic factors. We estimated the effect of CFS on direct medical costs (inpatient hospitalizations, provider visits, prescription medication spending, other medical supplies and services) and loss in productivity (employment and earnings) with a stratified sample (n = 500) from metropolitan, urban, and rural Georgia. We adjusted medical costs and earnings for confounders (age, sex, race/ethnicity, education, and geographic strata) using econometric models and weighted estimates to reflect response-rate adjusted sampling rates.

RESULTS: Individuals with CFS had mean annual direct medical costs of $5,683. After adjusting for confounding factors, CFS accounted for $3,286 of these costs (p < 0.01), which were driven by increased provider visits and prescription medication use. Nearly one-quarter of these expenses were paid directly out-of pocket by those with CFS. Individuals with CFS reported mean annual household income of $23,076. After adjustment, CFS accounted for $8,554 annually in lost household earnings (p < 0.01). Lower educational attainment accounted for 19% of the reduction in earnings associated with CFS.

CONCLUSIONS: Study results indicate that chronic fatigue syndrome may lead to substantial increases in healthcare costs and decreases in individual earnings. Studies have estimated up to 2.5% of non-elderly adults may suffer from CFS. In Georgia, a state with roughly 5.5 million people age 18-59, illness could account for $452 million in total healthcare expenditures and $1.2 billion of lost productivity.

 

Source: Lin JM, Resch SC, Brimmer DJ, Johnson A, Kennedy S, Burstein N, Simon CJ. The economic impact of chronic fatigue syndrome in Georgia: direct and indirect costs. Cost Eff Resour Alloc. 2011 Jan 21;9(1):1. doi: 10.1186/1478-7547-9-1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033815/ (Full article)