Chronic fatigue syndrome: an approach combining self-management with graded exercise to avoid exacerbations

Abstract:

Controversy regarding the aetiology and treatment of patients with chronic fatigue syndrome continues among the medical professions. The Cochrane Collaboration advises practitioners to implement graded exercise therapy for patients with chronic fatigue syndrome using cognitive behavioural principles. Conversely, there is evidence that exercise can exacerbate symptoms in chronic fatigue syndrome, if too-vigorous exercise/activity promotes immune dysfunction, which in turn increases symptoms.

When designing and implementing an exercise programme for chronic fatigue syndrome it is important to be aware of both of these seemingly opposing viewpoints in order to deliver a programme with no detrimental effects on the pathophysiology of the condition.

Using evidence from both the biological and clinical sciences, this paper explains that graded exercise therapy for people with chronic fatigue syndrome can be undertaken safely with no detrimental effects on the immune system. Exercise programmes should be designed to cater for individual physical capabilities and should take into account the fluctuating nature of symptoms.

In line with cognitive behaviourally and graded exercise-based strategies, self-management for people with chronic fatigue syndrome involves encouraging patients to pace their activities and respect their physical and mental limitations, with the ultimate aim of improving their everyday functioning.

Comment in: Chronic fatigue syndrome. [J Rehabil Med. 2008]

 

Source: Nijs J, Paul L, Wallman K. Chronic fatigue syndrome: an approach combining self-management with graded exercise to avoid exacerbations. J Rehabil Med. 2008 Apr;40(4):241-7. Doi: 10.2340/16501977-0185. https://www.ncbi.nlm.nih.gov/pubmed/18382818

 

Alterations in diurnal salivary cortisol rhythm in a population-based sample of cases with chronic fatigue syndrome

Abstract:

OBJECTIVE: To examine diurnal salivary cortisol rhythms and plasma IL-6 concentrations in persons with chronic fatigue syndrome (CFS), persons not fulfilling a diagnosis of CFS (we term them cases with insufficient symptoms or fatigue, ISF) and nonfatigued controls (NF). Previous studies of CFS patients have implicated the hypothalamic-pituitary-adrenal axis and the immune system in the pathophysiology of CFS, although results have been equivocal.

METHODS: Twenty-eight people with CFS, 35 persons with ISF, and 39 NF identified from the general population of Wichita, Kansas, were admitted to a research ward for 2 days. Saliva was collected immediately on awakening (6:30 AM), at 08:00 AM, 12 noon, 4:00 PM, 8:00 PM and at bedtime (10:00 PM) and plasma was obtained at 7:30 AM. Salivary cortisol concentrations were assessed using radioimmunoassay, and plasma IL-6 was measured using sandwich enzyme-linked immunosorbent assay.

RESULTS: People with CFS demonstrated lower salivary cortisol concentrations in the morning and higher salivary cortisol concentrations in the evening compared with both ISF and NF groups indicating a flattening of the diurnal cortisol profile. Mean plasma IL-6 concentrations were highest in CFS compared with the other groups, although these differences were no longer significant after controlling for BMI. Attenuated decline of salivary cortisol concentrations across the day and IL-6 concentration were associated with fatigue symptoms in CFS.

CONCLUSIONS: These results suggest an altered diurnal cortisol rhythm and IL-6 concentrations in CFS cases identified from a population-based sample.

 

Source: Nater UM, Youngblood LS, Jones JF, Unger ER, Miller AH, Reeves WC, Heim C. Alterations in diurnal salivary cortisol rhythm in a population-based sample of cases with chronic fatigue syndrome. Psychosom Med. 2008 Apr;70(3):298-305. doi: 10.1097/PSY.0b013e3181651025. Epub 2008 Mar 31. https://www.ncbi.nlm.nih.gov/pubmed/18378875

 

Etiology of chronic fatigue syndrome: testing popular hypotheses using a national birth cohort study

Abstract:

OBJECTIVE: To review the etiology of chronic fatigue syndrome (CFS) and test hypotheses relating to immune system dysfunction, physical deconditioning, exercise avoidance, and childhood illness experiences, using a large prospective birth cohort.

METHODS: A total of 4779 participants from the Medical Research Council’s National Survey of Health and Development were prospectively followed for the first 53 years of their life with >20 separate data collections. Information was collected on childhood and parental health, atopic illness, levels of physical activity, fatigue, and participant’s weight and height at multiple time points. CFS was identified through self-report during a semistructured interview at age 53 years with additional case notes review.

RESULTS: Of 2983 participants assessed at age 53 years, 34 (1.1%, 95% Confidence Interval 0.8-1.5) reported a diagnosis of CFS. Those who reported CFS were no more likely to have suffered from childhood illness or atopy. Increased levels of exercise throughout childhood and early adult life and a lower body mass index were associated with an increased risk of later CFS. Participants who later reported CFS continued to exercise more frequently even after they began to experience early symptoms of fatigue.

CONCLUSIONS: Individuals who exercise frequently are more likely to report a diagnosis of CFS in later life. This may be due to the direct effects of this behavior or associated personality factors. Continuing to be active despite increasing fatigue may be a crucial step in the development of CFS.

 

Source: Harvey SB, Wadsworth M, Wessely S, Hotopf M. Etiology of chronic fatigue syndrome: testing popular hypotheses using a national birth cohort study. Psychosom Med. 2008 May;70(4):488-95. doi: 10.1097/PSY.0b013e31816a8dbc. Epub 2008 Mar 31. https://www.ncbi.nlm.nih.gov/pubmed/18378866

 

The awareness of chronic fatigue syndrome: a comparative study in Brazil and the United Kingdom

Abstract:

OBJECTIVE: While in many Western affluent countries there is widespread awareness of chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), little is known about the awareness of CFS/ME in low- and middle-income countries. We compared the awareness of CFS in Brazil and the United Kingdom.

METHODS: Recognition and knowledge of CFS were assessed among 120 Brazilian specialist doctors in two major university hospitals using a typical case vignette of CFS. We also surveyed 3914 and 2435 consecutive attenders in Brazilian and British primary care clinics, respectively, concerning their awareness of CFS.

RESULTS: When given a typical case vignette of CFS, only 30.8% [95% confidence interval (CI), 22.7-39.9%] of Brazilian specialist doctors mentioned chronic fatigue or CFS as a possible diagnosis, a proportion substantially lower than that observed in Western affluent countries. Similarly, only 16.2% (95% CI, 15.1-17.4%) of Brazilian primary care attenders were aware of CFS, in contrast to 55.1% (95% CI, 53.1-57.1%) of their British counterparts (P<.001). This difference remained highly significant after controlling for patients’ sociodemographic and socioeconomic characteristics (P<.001).

CONCLUSIONS: The awareness of CFS was substantially lower in Brazil than the United Kingdom. The observed difference may influence patients’ help-seeking behavior and both doctors’ and patients’ beliefs and attitudes in relation to fatigue-related syndromes. Attempts to promote the awareness of CFS should be considered in Brazil, but careful plans are required to ensure the delivery of sound evidence-based information.

 

Source: Cho HJ, Menezes PR, Bhugra D, Wessely S. The awareness of chronic fatigue syndrome: a comparative study in Brazil and the United Kingdom. J Psychosom Res. 2008 Apr;64(4):351-5. doi: 10.1016/j.jpsychores.2007.12.006. https://www.ncbi.nlm.nih.gov/pubmed/18374733

 

Health-related quality of life in chronic fatigue syndrome: predictors of physical functioning and psychological distress

Abstract:

This study investigated health-related quality of life (HRQoL; physical functioning and psychological distress) in an Australian chronic fatigue syndrome (CFS) population. The aims of the study were to compare HRQoL in those with CFS to the normal population, and to investigate the extent to which sociodemographic (age, gender, partner status, education), illness-related (illness duration, symptom frequency), and fatigue severity (physical, mental) variables predicted HRQoL.

A total of 139 people meeting CFS criteria completed questionnaires. HRQoL was assessed using standardised measures of distress and physical functioning. Compared with norms, those with CFS obtained significantly lower scores on all physical functioning areas, whereas 63% of participants reported clinically significant psychological distress.

Hierarchical regression analyses indicated that physical fatigue severity and symptom frequency were the strongest predictors of deficits in physical domain HRQoL. Physical HRQoL outcomes were also predicted by mental fatigue severity, older age, and female gender. All predictors were unrelated to psychological distress apart from weak positive associations with physical fatigue and symptom frequency.

Results identify a potent set of predictors of HRQoL and show that CFS has a pervasive negative impact on quality of life, particularly physical and psychological functioning.

 

Source: Lowry TJ, Pakenham KI. Health-related quality of life in chronic fatigue syndrome: predictors of physical functioning and psychological distress. Psychol Health Med. 2008 Mar;13(2):222-38. Doi: 10.1080/13548500701335698. https://www.ncbi.nlm.nih.gov/pubmed/18350466

 

Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic Ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins

Abstract:

This study examined 328 CFS sera in a study with 17 CCFP, 8 Gulf War Veterans (GWV), 24 Prostate Cancer (PC), and 52 normal sera in the modified Membrane Immunobead Assay (MIA) procedure for CTX. Three hundred and twenty-eight CFS patients’ sera were examined by the modified MIA with purified MAb-CTX and 91.2% gave a titre > or =1:40. 76% of the 17 CCFP sera samples and 100% of the 8 GWV sera samples also had a titre > or =1:40. 92.3% of 52 normal sera showed titres of 1:20 or less, while 4 gave titres of > or =1:40.

In addition, 41 sera were examined for Anti-Cardiolipin (aCL) by a commercial ELISA procedure with 87.8% demonstrating IgM, IgM+IgA, or IgM+IgG aCL antibodies. These results showed mostly the IgM aCL antibody alone in the sera samples. In addition, 41 serum samples were examined for aCL, with 37 showing positive for aCL, representing 90.2% positive for the three disease categories examined: CFS, CCFP and GWV. Examination for antiMitochondrial-M2 autoantibody (aM-M2) in 28 patients (CFS (18), CCFP (5), and GWV (5)) was negative for aM-M2.

Inhibition analysis with antigens, CTX, CFS “Acute Phase Lipids”, commercial Cardiolipin (CL) and 1,2-Dipalmitoyl-sn-Glycero-3-[Phospho-L-Serine] (PS) and antibodies, MAb-CTX and aCL from patients’ serum show that the phospholipids in CL and CTX are antigenically indistinguishable with antibodies MAb-CTX and CFS-aCL. Preliminary chemical analyses have shown the lipids to be phospholipids associated with CL of the mitochondria.

We designate this “Acute Phase Lipid” comparable to “Acute Phase Proteins” (C-reactive protein (CRP) and Serum Amyloid A (SAA)) in inflammatory conditions.

(Copyright ) 2008 Wiley-Liss, Inc.

 

Source: Hokama Y, Empey-Campora C, Hara C, Higa N, Siu N, Lau R, Kuribayashi T, Yabusaki K. Acute phase phospholipids related to the cardiolipin of mitochondria in the sera of patients with chronic fatigue syndrome (CFS), chronic Ciguatera fish poisoning (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins. J Clin Lab Anal. 2008;22(2):99-105. doi: 10.1002/jcla.20217. https://www.ncbi.nlm.nih.gov/pubmed/18348309

 

Dietary intervention in chronic fatigue syndrome

Abstract:

BACKGROUND: Anecdotal reports and books have been published linking an over growth of Candida Albicans with chronic fatigue syndrome (CFS), suggesting dietary change as a treatment option. Little scientific data has been published to validate this controversial theory. This study aims to determine the efficacy of dietary intervention on level of fatigue and quality of life (QoL) in individuals with CFS.

METHODS: A 24-week randomized intervention study was conducted with 52 individuals diagnosed with CFS. Patients were randomized to either a low sugar low yeast (LSLY) or healthy eating (HE) dietary interventions. Primary outcome measures were fatigue as measured by the Chalder Fatigue Score and QoL measured by Medical Outcomes Survey Short Form-36.

RESULTS: A high drop out rate occurred with 13 participants not completing the final evaluation (7HE/6LSLY). Intention to treat analysis showed no statistically significant differences on primary outcome measurements.

CONCLUSION: In this randomized control trial, a LSLY diet appeared to be no more efficacious on levels of fatigue or QoL compared to HE. Given the difficulty with dietary compliance experienced by participants, especially in the LSLY group, it would appear HE guidance is a more pragmatic approach than advocating a complicated dietary regime.

 

Source: Hobday RA, Thomas S, O’Donovan A, Murphy M, Pinching AJ. Dietary intervention in chronic fatigue syndrome. J Hum Nutr Diet. 2008 Apr;21(2):141-9. doi: 10.1111/j.1365-277X.2008.00857.x. https://www.ncbi.nlm.nih.gov/pubmed/18339054

 

Possible role for early-life immune insult including developmental immunotoxicity in chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME)

Abstract:

Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME) in some countries, is a debilitating disease with a constellation of multi-system dysfunctions primarily involving the neurological, endocrine and immune systems. While substantial information is available concerning the complex dysfunction-associated symptoms of CFS, environmental origins of the disease have yet to be determined.

Part of the dilemma in identifying the cause(s) has been the focus on biomarkers (hormones, neurotransmitters, cytokines, infectious agents) that are contemporary with later-life CFS episodes. Yet, recent investigations on the origins of environmental diseases of the neurological, endocrine, reproductive, respiratory and immune systems suggest that early life toxicologic and other insults are pivotal in producing later-life onset of symptoms. As with autism and childhood asthma, CFS can also occur in children where the causes are certainly early-life events.

Immune dysfunction is recognized as part of the CFS phenotype but has received comparatively less attention than aberrant neurological or endocrine function. However, recent research results suggest that early life immune insults (ELII) including developmental immunotoxicity (DIT), which is induced by xenobiotics, may offer an important clue to the origin(s) of CFS.

The developing immune system is a sensitive and novel target for environmental insult (xenobiotic, infectious agents, stress) with major ramifications for postnatal health risks. Additionally, many prenatal and early postnatal neurological lesions associated with postnatal neurobehavioral diseases are now recognized as linked to prenatal immune insult and inflammatory dysregulation. This review considers the potential role of ELII including DIT as an early-life component of later-life CFS.

 

Source: Dietert RR, Dietert JM. Possible role for early-life immune insult including developmental immunotoxicity in chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME). Toxicology. 2008 May 2;247(1):61-72. doi: 10.1016/j.tox.2008.01.022. Epub 2008 Feb 8. https://www.ncbi.nlm.nih.gov/pubmed/18336982

 

Brain atrophy in a murine model of chronic fatigue syndrome and beneficial effect of Hochu-ekki-to (TJ-41)

Abstract:

Brain-derived neurotrophic factor (BDNF) is associated with the main symptoms of chronic fatigue syndrome (CFS) and neuron apoptosis. Nevertheless, no study has been performed directly to explore the relationship between CFS, BDNF and neuron apoptosis.

We induced a CFS model by six injections of killed Brucella abortus antigen in BALB/c mice and treated them with Hochu-ekki-to (TJ-41). Daily running activity, body weight (BW), ratio of cerebral weight to BW (CW/BW) and expression levels of BDNF and Bcl-2 mRNA in the hippocampus were determined. The daily activity and CW/BW decreased significantly in the CFS model. BDNF and Bcl-2 mRNA expression levels in the hippocampus were suppressed in the CFS model and TJ-41 treated mice, while no significant difference was found between them.

We improved a murine model to investigate the relationship between CFS and brain dysfunction. In this model, reduced daily activity might have been associated with decreased hippocampal BDNF mRNA expression, hippocampal apoptosis and brain atrophy. TJ-41 increased the daily running activity of the model, which was independent of brain recovery.

 

Source: Chen R, Moriya J, Yamakawa J, Takahashi T, Li Q, Morimoto S, Iwai K, Sumino H, Yamaguchi N, Kanda T. Brain atrophy in a murine model of chronic fatigue syndrome and beneficial effect of Hochu-ekki-to (TJ-41). Neurochem Res. 2008 Sep;33(9):1759-67. doi: 10.1007/s11064-008-9620-1. Epub 2008 Mar 4. https://www.ncbi.nlm.nih.gov/pubmed/18317925

 

Cognitive-behavioural therapy v. mirtazapine for chronic fatigue and neurasthenia: randomised placebo-controlled trial

Abstract:

BACKGROUND: Single interventions in chronic fatigue syndrome have shown only limited effectiveness, with few studies of comprehensive treatment programmes.

AIMS: To examine the effect of a comprehensive cognitive-behavioural treatment (CCBT) programme compared with placebo-controlled mirtazapine medication in patients with chronic fatigue, and to study the effect of combined medication and CCBT.

METHOD: A three-armed randomised clinical trial of mirtazapine, placebo and a CCBT programme was conducted to investigate treatment effect in a patient group (n=72) with chronic fatigue referred to a specialist clinic. The CCBT programme was compared with mirtazapine or placebo therapy for 12 weeks, followed by 12 weeks treatment with a mixed crossover-combination design. Assessments were done at 12 weeks and 24 weeks.

RESULTS: By 12 weeks the treatment effect was significantly better in the group initially receiving CCBT, as assessed with the Fatigue Scale (P=0.014) and the Clinical Global Impression Scale (P=0.001). By 24 weeks the treatment group initially receiving CCBT for 12 weeks followed by mirtazapine for 12 weeks showed significant improvement compared with the other treatment groups on the Fatigue Scale (P<0.001) and the Clinical Global Impression Scale (P=0.002). Secondary outcome measures showed overall improvement with no significant difference between treatment groups.

CONCLUSIONS: Multimodal interventions may have positive treatment effects in chronic fatigue syndrome. Sequence of interventions seem to be of importance.

 

Source: Stubhaug B, Lie SA, Ursin H, Eriksen HR. Cognitive-behavioural therapy v. mirtazapine for chronic fatigue and neurasthenia: randomised placebo-controlled trial. Br J Psychiatry. 2008 Mar;192(3):217-23. doi: 10.1192/bjp.bp.106.031815. http://bjp.rcpsych.org/content/192/3/217.long (Full article)