Clinical improvement in chronic fatigue syndrome is not associated with lymphocyte subsets of function or activation

Abstract:

The relationship between markers of immune function and chronic fatigue syndrome (CFS) is controversial. To examine the relationship directly, 43 subjects with CFS entering a randomized controlled trial of a nonpharmacological treatment for CFS gave samples for immunological analysis before and after treatment. Percentage levels of total CD3+ T cells, CD4 T cells, CD8 T cells, and activated subsets did not differ between CFS subjects and controls. Naive (CD45RA+ RO-) and memory (CD45RA- RO+) T cells did not differ between subjects and controls.

Natural killer cells (CD16+/CD56+/CD3-) were significantly increased in CFS patients compared to controls, as was the percentage of CD11b+ CD8 cells.

There were no correlations between any immune variable and measures of clinical status, with the exception of a weak correlation between total CD4 T cells and fatigue. There was a positive correlation between memory CD4 and CD8 T cells and depression scores and a negative correlation between naive CD4 T cells and depression.

No immune measures changed during the course of the study, and there was no link between clinical improvement as a result of the treatment program and immune status. Immune measures did not predict response or lack of response to treatment.

In conclusion, we have been unable to replicate previous findings of immune activation in CFS and unable to find any important associations between clinical status, treatment response, and immunological status.

 

Source: Peakman M, Deale A, Field R, Mahalingam M, Wessely S. Clinical improvement in chronic fatigue syndrome is not associated with lymphocyte subsets of function or activation. Clin Immunol Immunopathol. 1997 Jan;82(1):83-91. http://www.ncbi.nlm.nih.gov/pubmed/9000046

 

Fatigue in the chronic fatigue syndrome: a cognitive phenomenon?

Abstract:

What is the source of the perception of excessive fatigue in the chronic fatigue syndrome (CFS)? Studies of physiological response to aerobic activity, of muscle pathology and muscle function in CFS, are reviewed, and suggest that the subjective report of fatigue is not due to any peripheral impairment. In addition, current technological methods such as electroencephalography have failed to uncover the nature of any abnormality in the central motor unit. A physiological model which proposes that patients with CFS possess a reduced threshold for sensory fatigue signals is rejected, because it fails to account for recent findings. Instead, it is suggested that the perception of fatigue in CFS is enhanced by idiosyncrasies in cognitive processing. The implications of this view to our understanding of the perpetuation of CFS as a whole are explored.

 

Source: Fry AM, Martin M. Fatigue in the chronic fatigue syndrome: a cognitive phenomenon? J Psychosom Res. 1996 Nov;41(5):415-26. http://www.ncbi.nlm.nih.gov/pubmed/9032706

 

Susceptibility to immunologically mediated fatigue in C57BL/6 versus Balb/c mice

Abstract:

Proinflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha have been proposed to play a role in the pathogenesis of fatigue. In the present study we compared the susceptibility of two mouse strains to immunologically induced fatigue.

Daily running of two strains of mice, Balb/c and C57BL/ 6, was assessed after a single injection of Corynebacterium parvum antigen (2 mg/mouse). Spontaneous running activity of each animal was compared to mean running distance prior to injection. To evaluate the involvement of cytokines in fatigue development, C57BL/6 mice were treated with antibodies to specific cytokines at the time of challenge with C. parvum antigen. Also, cytokine mRNA expression was analyzed in the brains of mice at different time periods after immunologic challenge.

A significant difference in running activity between the two mice strains was observed after C. parvum antigen inoculation: C57BL/6 mice showing a greater (P < 0.05) reduction in running activity (relative to preinjection levels) and slower recovery to baseline than Balb/c mice. Injection of antibodies specific to either IL-1beta or TNF-alpha did not alter immunologically induced fatigue, suggesting a lack of involvement of these cytokines produced outside of the central nervous system (CNS).

However, increased TNF-alpha and IL-1beta mRNA expression was found in the brains of C57BL/6 compared to that seen in Balb/c mice at 6, 10, and 15 days after C. parvum antigen injection. The elevated CNS cytokine mRNA expression corresponded to development of fatigue. These findings are consistent with the hypothesis that expression of proinflammatory cytokines within the CNS plays a role in the pathogenesis of immunologically mediated fatigue.

 

Source: Sheng WS, Hu S, Lamkin A, Peterson PK, Chao CC. Susceptibility to immunologically mediated fatigue in C57BL/6 versus Balb/c mice. Clin Immunol Immunopathol. 1996 Nov;81(2):161-7. http://www.ncbi.nlm.nih.gov/pubmed/8906747

 

Is perfectionism associated with fatigue?

Abstract:

Perfectionism has been implicated as a vulnerability factor in the development of chronic unexplained fatigue. In the present study, different components of fatigue and perfectionism were studied in 121 female nurses. They completed a postal questionnaire assessing current (state) and usual (trait) fatigue, and dimensions of personality including six components of perfectionism. Night-shift work was associated with state, but not trait, fatigue. Negative, but not positive, components of perfectionism were associated with mental trait fatigue in particular, but also with physical trait fatigue. In contrast, the associations with positive perfectionism tended to be inverse. Multiple regression modeling indicated that neuroticism as well as negative perfectionism were separately associated with trait fatigue. We suggest that negative aspects of perfectionism may cause maladaptive coping strategies which predispose individuals to fatigue.

 

Source: Magnusson AE, Nias DK, White PD. Is perfectionism associated with fatigue? J Psychosom Res. 1996 Oct;41(4):377-83. http://www.ncbi.nlm.nih.gov/pubmed/8971668

 

The measurement of fatigue in patients with multiple sclerosis. A multidimensional comparison with patients with chronic fatigue syndrome and healthy subjects

Abstract:

OBJECTIVE: To provide a multidimensional characterization of fatigue in patients with multiple sclerosis (MS).

DESIGN: Cross-sectional design. Fifty patients with clinically definite MS were compared on the dimensions of fatigue with 51 patients with chronic fatigue syndrome (CFS) and 53 healthy subjects.

RESULTS: Fourty-six percent of the patients with MS reported fatigue to be present at least once a week. Patients with MS and patients with CFS had significantly higher subjective fatigue severity scores than healthy subjects. Patients with MS and patients with CFS had significantly higher scores on measures of psychological well-being than healthy subjects. Patients with MS had scores similar to those of patients with CFS, except that patients with CFS had significantly higher somatization scores. High somatization scores reflect strong focusing on bodily sensations. Both groups of patients were significantly less active than the healthy subjects. The Kurtzke Expanded Disability Status Scale (EDSS) and the Beck Depression Inventory scores were not related to subjective fatigue severity. In patients with MS and in patients with CFS, subjective fatigue severity was related to impairment in daily life, low sense of control over symptoms, and strong focusing on bodily sensations. In CFS, but not in MS, evidence was found for a relationship between low levels of physical activity and attributing symptoms to a physical cause and between subjective fatigue severity and physical activity.

CONCLUSIONS: Patients with MS experienced significant fatigue, which had a significant impact on daily functioning and was not related to depression on Expanded Disability Status Scale score. Psychological factors, such as focusing on bodily sensations and low sense of control play a role in the experience of fatigue in MS and CFS.

 

Source: Vercoulen JH, Hommes OR, Swanink CM, Jongen PJ, Fennis JF, Galama JM, van der Meer JW, Bleijenberg G. The measurement of fatigue in patients with multiple sclerosis. A multidimensional comparison with patients with chronic fatigue syndrome and healthy subjects. Arch Neurol. 1996 Jul;53(7):642-9. http://www.ncbi.nlm.nih.gov/pubmed/8929171

 

Postinfectious fatigue: prospective cohort study in primary care

Abstract:

The idea that chronic fatigue has an infectious origin has become popular, but the main evidence for such an association has come from retrospective case-control studies, which are subject to ascertainment bias. We report a prospective study of the outcome of clinically diagnosed infections in patients presenting to UK general practitioners.

Questionnaires assessing fatigue and psychiatric morbidity were sent to all patients aged 18-45 years in the study practices. The prevalence of chronic fatigue and chronic fatigue syndrome was then ascertained among 1199 people aged 18-45 who presented to the general practitioners with symptomatic infections and in 1167 people who attended the surgeries for other reasons. 84% were followed up at 6 months. 9.9% of cases and 11.7% of controls reported chronic fatigue (odds ratio 1.0 [95% CI 0.6-1.1]). There were no differences in the proportions who met various criteria for chronic fatigue syndrome. No effect of infection was noted when we excluded subjects who reported fatigue or psychological morbidity at the baseline screening.

The strongest independent predictors of postinfectious fatigue were fatigue assessed before presentation with clinical infection (3.0 [1.9-4.7]) and psychological distress before presentation (1.8 [1.2-2.9]) and at presentation with the acute infection (1.8 [1.1-2.8]). There was no effect of sex or social class. Our study shows no evidence that common infective episodes in primary care are related to the onset of chronic fatigue or chronic fatigue syndrome.

Comment in:

Viral illness and chronic fatigue (syndrome). [Lancet. 1995]

Viral illness and chronic fatigue (syndrome) [Lancet. 1995]

Viral illness and chronic fatigue (syndrome). [Lancet. 1995]

Viral illness and chronic fatigue (syndrome) [Lancet. 1995]

Viral illness and chronic fatigue (syndrome). [Lancet. 1995]

 

Source: Wessely S, Chalder T, Hirsch S, Pawlikowska T, Wallace P, Wright DJ. Postinfectious fatigue: prospective cohort study in primary care. Lancet. 1995 May 27;345(8961):1333-8. http://www.ncbi.nlm.nih.gov/pubmed/7752755

 

The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue

Abstract:

The Multidimensional Fatigue Inventory (MFI) is a 20-item self-report instrument designed to measure fatigue. It covers the following dimensions: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity. This new instrument was tested for its psychometric properties in cancer patients receiving radiotherapy, patients with the chronic fatigue syndrome, psychology students, medical students, army recruits and junior physicians. We determined the dimensional structure using confirmatory factor analyses (LISREL’s unweighted least squares method). The hypothesized five-factor model appeared to fit the data in all samples tested (AGFIs > 0.93). The instrument was found to have good internal consistency, with an average Cronbach’s alpha coefficient of 0.84. Construct validity was established after comparisons between and within groups, assuming differences in fatigue based on differences in circumstances and/or activity level. Convergent validity was investigated by correlating the MFI-scales with a Visual Analogue Scale measuring fatigue (0.22 < r < 0.78). Results, by and large, support the validity of the MFI.

 

Source: Smets EM, Garssen B, Bonke B, De Haes JC. The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res. 1995 Apr;39(3):315-25. http://www.ncbi.nlm.nih.gov/pubmed/7636775

 

Sleep disturbances and fatigue in women with fibromyalgia and chronic fatigue syndrome

Abstract:

OBJECTIVE: To determine the relationship between sleep disturbances and fatigue in women with fibromyalgia (FM) and those with chronic fatigue syndrome (CFS) and to assess whether any differences existed between the two groups.

DESIGN: Descriptive comparative.

SETTING: Community program on chronic fatigue syndrome and related disorders.

PARTICIPANTS: Sixty-three women who attended the program; 13 had CFS, and 50 had FM.

MAIN OUTCOME MEASURES: A moderately strong relationship between fatigue and sleepiness was found (r = .63, p < .01). Trouble staying asleep was the highest rated sleep disturbance, and fatigue was the most common subjective feeling reported. Women with CFS reported significantly more trouble staying asleep than women with FM, t(61) = 1.81, p < .03.

CONCLUSIONS: Data from this study support that women with FM and CFS encounter problems sleeping. Clinicians are encouraged to assess women with FM and CFS for their quality of sleep rather than amount of sleep. Researchers are encouraged to continue study of sleep disturbances in women with FM and CFS to improve understanding of the disturbances and to test the effectiveness of sleep interventions.

 

Source: Schaefer KM. Sleep disturbances and fatigue in women with fibromyalgia and chronic fatigue syndrome. J Obstet Gynecol Neonatal Nurs. 1995 Mar-Apr;24(3):229-33. http://www.ncbi.nlm.nih.gov/pubmed/7782955

 

Frequency of deviant immunological test values in chronic fatigue syndrome patients

Abstract:

Of 11 immunological tests done on chronic fatigue syndrome patients and on fatigued controls, 3 tests (protein A binding, Raji cell, or C3 or C4 [deviant values in either complement component were counted as positive]) with deviant results discriminated best among the groups. Other tests, including immunoglobulin G subclasses, complement component CH50, interleukin-2, and anticardiolipin antibodies, did not discriminate well among the groups.

 

Source: Natelson BH, Ellis SP, Braonáin PJ, DeLuca J, Tapp WN. Frequency of deviant immunological test values in chronic fatigue syndrome patients. Clin Diagn Lab Immunol. 1995 Mar;2(2):238-40. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC170136/

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC170136/pdf/020238.pdf

 

Fatigue brought on by malfunction of the central and peripheral nervous systems

Abstract:

Increased fatigability necessarily occurs in every patient with muscle weakness, regardless of whether the latter is due to a central or peripheral neurological disorder. The tendency for disuse to increase fatigability, as a secondary phenomenon, must also be considered; disuse affects both motoneuron recruitment and the biochemical and physiological properties of the muscle fibers. In recent studies impaired recruitment has been observed in postpolio patients, while patients with multiple sclerosis or spinal cord injury have shown, in addition, altered neuromuscular function. Findings are also presented in ALS and the chronic fatigue syndrome. In general, the most dramatic increases in fatigability take place in disorders of the peripheral nervous system and almost any cell component can be incriminated. There is a need to study fatigability systematically in neurology and rehabilitation.

 

Source: McComas AJ, Miller RG, Gandevia SC. Fatigue brought on by malfunction of the central and peripheral nervous systems. Adv Exp Med Biol. 1995;384:495-512. http://www.ncbi.nlm.nih.gov/pubmed/8585475