What causes chronic fatigue syndrome?

Comment in: Patients with chronic fatigue syndrome are being ignored. [BMJ. 2004]

Comment on: Childhood predictors of self reported chronic fatigue syndrome/myalgic encephalomyelitis in adults: national birth cohort study. [BMJ. 2004]

 

Chronic fatigue syndrome, also known as myalgic encephalomyelitis, is an illness of unknown nature and cause, but most medical authorities now accept its existence.1-3 Research about its cause has been hampered by the absence of a biological marker, the heterogeneous nature of the illness, and difficulties in differentiating cause from effect.2,3 Yet, some progress has been made, particularly when causes are divided into predisposing, triggering, and maintaining factors.

Women get chronic fatigue syndrome more commonly than men for unknown reasons, although increasing evidence suggests a genetic influence on the illness.1,3 Premorbid mood disorders are replicated risk markers for chronic fatigue syndrome;1,3 the risks may be inflated by shared symptoms or they may be markers for those patients with comorbid mood disorders.1,3-5 Another replicated premorbid risk marker is increased consulting of a doctor for minor illnesses up to 15 years before diagnosis,w1 w2 suggesting a general vulnerability for either ill health or seeking health care, the latter possibly being mediated by comorbid anxiety.4

You can read the rest of this comment here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524091/

 

Source: White PD. What causes chronic fatigue syndrome? BMJ. 2004 Oct 23;329(7472):928-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524091/ (Full article)

 

Differential-display PCR of peripheral blood for biomarker discovery in chronic fatigue syndrome

Abstract:

We used differential-display PCR of peripheral blood mononuclear cells (PBMCs) to search for candidate biomarkers for chronic fatigue syndrome(CFS). PBMCs were collected from a subject with CFS and an age- and sex-matched control before and 24 h after exercise. RNA expression profiles were generated using 46 primer combinations, and the similarity between the individuals was striking.

Differentially expressed bands were excised, reamplified, and sequenced, yielding 95 nonredundant sequences, of which 50 matched to known gene transcripts, 38 matched to genes with unknown functions, and 7 had no similarity to any database entry. Most (86%) of the differences between the two subjects were present at baseline.

Differential expression of ten genes was verified by real-time reverse-transcription PCR: five (cystatin F, MHC class II, platelet factor 4, fetal brain expressed sequence tag, and perforin) were downregulated, and the remaining five genes (cathepsin B, DNA polymerase epsilon4, novel EST PBMC191MSt, heparanase precursor, and ORF2/L1 element) were upregulated in the subject with CFS. Many of these genes have known functions in defense and immunity, thus supporting prior suggestions of immune dysregulation in the pathogenesis of CFS.

Differential-display PCR is a powerful tool for identification of candidate biomarkers. Investigation of these markers in samples from well-designed epidemiological studies of CFS will be required to determine the validity of these candidate biomarkers. The real-time reverse-transcription PCR assays that we developed for assay of these biomarkers will facilitate high-throughput testing of these additional samples.

 

Source: Steinau M, Unger ER, Vernon SD, Jones JF, Rajeevan MS. Differential-display PCR of peripheral blood for biomarker discovery in chronic fatigue syndrome. J Mol Med (Berl). 2004 Nov;82(11):750-5. Epub 2004 Oct 14. http://www.ncbi.nlm.nih.gov/pubmed/15490094

 

Effect of Hochu-ekki-to (TJ-41), a Japanese Herbal Medicine, on Daily Activity in a Murine Model of Chronic Fatigue Syndrome

Abstract:

We aimed to evaluate the effect of a Japanese herbal medicine, Hochu-ekki-to (TJ-41), on daily activity in a murine model of chronic fatigue syndrome (CFS).

CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. TJ-41 was orally administered to mice in a dose of 500 mg/kg/day for 1 week before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving TJ-41 as compared with that in untreated mice. Survival of both mouse groups was also monitored during the observation period. Body weight (BW), spleen weight (SW), SW/ BW ratio and expression levels of interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice.

The daily activity was significantly higher in the treated group than in the control. Two mice in the untreated group died 2 days after the second injection of BA, whereas no mice in the group treated with TJ-41 died. The SW and SW/BW ratio were significantly lower in the treated mice than in the control. Suppressed IL-10 mRNA levels were observed in the spleens of the mice treated with TJ-41. Our data suggest that Hochu-ekki-to might possess an inhibitory effect on the marked decrease in running activity following BA injection.

 

Source: Wang XQ, Takahashi T, Zhu SJ, Moriya J, Saegusa S, Yamakawa J, Kusaka K, Itoh T, Kanda T. Effect of Hochu-ekki-to (TJ-41), a Japanese Herbal Medicine, on Daily Activity in a Murine Model of Chronic Fatigue Syndrome. Evid Based Complement Alternat Med. 2004 Sep 1;1(2):203-206. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC516453/ (Full article)

 

Neuropathology in rhinosinusitis

Abstract:

Pathophysiologic differences in neural responses to hypertonic saline (HTS) were investigated in subjects with acute sinusitis (n = 25), subjects with chronic fatigue syndrome (CFS) with nonallergic rhinitis (n = 14), subjects with active allergic rhinitis (AR; n = 17), and normal (n = 20) subjects. Increasing strengths of HTS were sprayed into their nostrils at 5-minute intervals. Sensations of nasal pain, blockage, and drip increased with concentration and were significantly elevated above normal. These parallels suggested activation of similar subsets of afferent neurons.

Urea and lysozyme secretion were dose dependent in all groups, suggesting that serous cell exocytosis was one source of urea after neural stimulation. Only AR and normal groups had mucin dose responses and correlations between symptoms and lysozyme secretion (R(2) = 0.12-0.23). The lysozyme dose responses may represent axon responses in these groups. The neurogenic stimulus did not alter albumin (vascular) exudation in any group. Albumin and mucin concentrations were correlated in sinusitis, suggesting that nonneurogenic factors predominated in sinusitis mucous hypersecretion. CFS had neural hypersensitivity (pain) but reduced serous cell secretion. HTS nasal provocations identified significant, unique patterns of neural and mucosal dysregulation in each rhinosinusitis syndrome.

 

Source: Baraniuk JN, Petrie KN, Le U, Tai CF, Park YJ, Yuta A, Ali M, Vandenbussche CJ, Nelson B. Neuropathology in rhinosinusitis. Am J Respir Crit Care Med. 2005 Jan 1;171(1):5-11. Epub 2004 Oct 11. http://www.ncbi.nlm.nih.gov/pubmed/15477496

 

Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome

Abstract:

OBJECTIVE: It has been suggested that a hypofunctional hypothalamic-pituitary-adrenal (HPA) axis in chronic fatigue syndrome could result in an exaggerated release of pro-inflammatory cytokines during stress. As pro-inflammatory cytokines are involved in the induction of sickness behavior and thus constitute a potential physiological correlate of stress-induced symptom exacerbation in chronic fatigue syndrome, we set out to evaluate the LPS-induced production of pro-inflammatory cytokines during psychosocial stress in CFS and healthy controls.

METHOD: Twenty-one CFS patients and 20 healthy controls matched for age and gender underwent a standardized psychosocial stress test (Trier social stress test, TSST). Adrenocorticotropine hormone (ACTH), salivary cortisol and plasma cortisol levels were measured before and repeatedly following exposure to the stressor. Lipopolysaccharide-stimulated production of interleukin-6 and tumor necrosis factor-alpha were assessed at baseline as well as 10 and 60 min after the stress test.

RESULTS: CFS patients showed an inverse stress-induced response pattern of LPS-stimulated cytokines responses in comparison to healthy controls, i.e. stimulated cytokine production decreased shortly after stress in CFS patients, while it increased in controls. Fatigue scores and basal LPS-induced cytokine levels were significantly associated for TNF-alpha in controls and for both cytokines in CFS patients. Stress-induced changes in stimulated cytokine production were not associated with general fatigue scores in the control group, whereas in the CFS group, fatigue scores were significantly correlated with integrated levels of LPS-induced cytokines. However, partial correlations revealed that these results were due to the high correlations with basal LPS-induced cytokine levels.

CONCLUSION: CFS patients do not show an exaggerated secretion of LPS-induced cytokines. Although cortisol responses to stress were normal, pro-inflammatory cytokine levels in CFS patients were significantly attenuated. Possible intracellular mechanisms, such as for example an enhanced sensitivity to inhibitory effects of glucocorticoids, a diminished responsivity to catecholaminergic stimulation, and a disruption of intracellular activation are discussed. Basal levels of stimulated pro-inflammatory Il-6 levels are generally related to fatigue scores. However, in CFS patients this association is of greater magnitude and can also be observed for TNF-alpha.

 

Source: Gaab J, Rohleder N, Heitz V, Engert V, Schad T, Schürmeyer TH, Ehlert U. Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome. Psychoneuroendocrinology. 2005 Feb;30(2):188-98. http://www.ncbi.nlm.nih.gov/pubmed/15471616

 

Manual-based cognitive behaviour therapy for chronic fatigue syndrome: therapists’ adherence and perceptions

Abstract:

Several randomized controlled trials have indicated that cognitive behaviour therapy is an effective treatment for chronic fatigue syndrome. In 1 of these studies 13 therapists applied cognitive behaviour therapy for chronic fatigue syndrome in 83 chronic fatigue syndrome patients.

In the present study therapists’ adherence and perceptions of the manual are studied. Following completion of the study the therapists were asked to complete a questionnaire. Audiotaped sessions were conducted to verify the therapists’ adherence. Analyses of the audiotapes showed that in 87% of the sessions this appeared to be the case.

The questionnaire revealed that the therapists found it more difficult to treat patients with chronic fatigue syndrome than to treat patients with psychological or other physical problems. Treatment aspects posing the most problems were integrating individual problems into the standardized treatment, dealing with the patients’ lack of confidence in the treatment and handling insufficient motivation.

 

Source: Bazelmans E, Prins JB, Hoogveld S, Bleijenberg G. Manual-based cognitive behaviour therapy for chronic fatigue syndrome: therapists’ adherence and perceptions. Cogn Behav Ther. 2004;33(3):143-50. http://www.ncbi.nlm.nih.gov/pubmed/15471384

 

Childhood predictors of self reported chronic fatigue syndrome/myalgic encephalomyelitis in adults: national birth cohort study

Abstract:

OBJECTIVE: To study childhood risk factors for chronic fatigue syndrome in adult life.

DESIGN: Examination of data from the 1970 British birth cohort.

PARTICIPANTS: 16,567 babies born 5-11 April 1970, followed up at 5, 10, 16, and 29-30 years.

MAIN OUTCOME MEASURES: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) identified by self report at age 30 years. Data from childhood from questionnaires given to parents and teachers. Maternal mental health assessed with the malaise inventory.

RESULTS: 93 (0.8%, 95% confidence interval 0.7 to 1.0) of 11 261 participants reported ever having CFS/ME, and 48 (0.4%, 0.3 to 0.6) had the condition currently. Higher risk of CFS/ME was associated with having a limiting longstanding condition in childhood (odds ratio 2.3, 1.4 to 3.9), female sex (2.3, 1.4 to 2.6), and high social class in childhood (2.2, 1.4 to 3.5). Higher levels of exercise in childhood were associated with lower risk (0.5, 0.2 to 0.9). Maternal psychological disorder, psychological problems in childhood, birth weight, birth order, atopy, obesity, school absence, academic ability, and parental illness were not associated with risk of CFS/ME.

CONCLUSIONS: We identified no association between maternal or child psychological distress, academic ability, parental illness, atopy, or birth order and increasing risk of lifetime CFS/ME. Sedentary behaviour increased the risk.

Comment in: What causes chronic fatigue syndrome? [BMJ. 2004]

 

Source: Viner R, Hotopf M. Childhood predictors of self reported chronic fatigue syndrome/myalgic encephalomyelitis in adults: national birth cohort study. BMJ. 2004 Oct 23;329(7472):941. Epub 2004 Oct 6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524102/ (Full article)

 

 

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/post-viral fatigue syndrome

Chronic / post-viral fatigue syndrome is the diagnosis term Rikstrygdeverket opted for the ICD-10 called “benign myalgic encephalomyelitis / post-viral fatigue syndrome.” Benign myalgic encephalomyelitis has since 1956 designated the epidemic form of this disease picture.”Chronic Fatigue Syndrome” is the Norwegian translation of “chronic fatigue syndrome” which has different meanings according to how it is defined.

Methodological differences from evaluation and diagnosis of chronic / post-viral fatigue syndrome from a study of chronic fatigue syndrome, and states have different therapeutic implications. Rikstrygdeverket bases its diagnosis in the original research definition of “chronic fatigue syndrome” from the Centers for Disease Control in 1988, an illness which later was recognized as benign myalgic encephalomyelitis.

You can read the rest of this article here: http://tidsskriftet.no/article/1072526

 

Source: Kreyberg S. Chronic/post-viral fatigue syndrome. Tidsskr Nor Laegeforen. 2004 Sep 23;124(18):2382-3. [Article in Norwegian] http://tidsskriftet.no/article/1072526  (Full article)

 

Immunologic aspects of chronic fatigue syndrome. Report on a Research Symposium convened by The CFIDS Association of America and co-sponsored by the US Centers for Disease Control and Prevention and the National Institutes of Health

Abstract:

Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800,000 Americans of all ages, races, socioeconomic groups and genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the immune system.

A symposium was organized in October 2001 to explore the possibility of an association between immune dysfunction and CFS, with special emphasis on the interactions between immune dysfunction and other abnormalities noted in the neuroendocrine and autonomic nervous systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting.

Data suggest that persons with CFS manifest changes in immune responses that fall outside normative ranges, but current research does not provide definitive evidence on whether these immune abnormalities are a cause or result of the illness. It has become clear that CFS cannot be understood based on single measurements of immune, endocrine, cardiovascular, or autonomic nervous system dysfunction. This panel encourages a new emphasis on multidisciplinary research into CFS.

 

Source: Gerrity TR, Papanicolaou DA, Amsterdam JD, Bingham S, Grossman A, Hedrick T, Herberman RB, Krueger G, Levine S, Mohagheghpour N, Moore RC,Oleske J, Snell CR; CFIDS Association of America. Immunologic aspects of chronic fatigue syndrome. Report on a Research Symposium convened by The CFIDS Association of America and co-sponsored by the US Centers for Disease Control and Prevention and the National Institutes of Health. Neuroimmunomodulation. 2004;11(6):351-7. http://www.ncbi.nlm.nih.gov/pubmed/15467349