Chronic fatigue syndrome, the immune system and viral infection

Abstract:

The chronic fatigue syndrome (CFS), as defined by recent criteria, is a heterogeneous disorder with a common set of symptoms that often either follows a viral infection or a period of stress. Despite many years of intense investigation there is little consensus on the presence, nature and degree of immune dysfunction in this condition.

However, slightly increased parameters of inflammation and pro-inflammatory cytokines such as interleukin (IL) 1, IL6 and tumour necrosis factor (TNF) α are likely present. Additionally, impaired natural killer cell function appears evident. Alterations in T cell numbers have been described by some and not others.

While the prevalence of positive serology for the common herpes viruses appears no different from healthy controls, there is some evidence of viral persistence and inadequate containment of viral replication. The ability of certain herpes viruses to impair the development of T cell memory may explain this viral persistence and the continuation of symptoms. New therapies based on this understanding are more likely to produce benefit than current methods.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Bansal AS, Bradley AS, Bishop KN, Kiani-Alikhan S, Ford B. Chronic fatigue syndrome, the immune system and viral infection. Brain Behav Immun. 2012 Jan;26(1):24-31. doi: 10.1016/j.bbi.2011.06.016. Epub 2011 Jul 2. https://www.ncbi.nlm.nih.gov/pubmed/21756995

 

Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case-control study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) patients frequently describe difficulties with repeat exercise. Here, we explore muscle bioenergetic function in response to three bouts of exercise.

METHODS: A total of 18 CFS (CDC 1994) patients and 12 sedentary controls underwent assessment of maximal voluntary contraction (MVC), repeat exercise with magnetic resonance spectroscopy and cardio-respiratory fitness test to determine anaerobic threshold.

RESULT: Chronic fatigue syndrome patients undertaking MVC fell into two distinct groups: 8 (45%) showed normal PCr depletion in response to exercise at 35% of MVC (PCr depletion >33%; lower 95% CI for controls); 10 CFS patients had low PCr depletion (generating abnormally low MVC values). The CFS whole group exhibited significantly reduced anaerobic threshold, heart rate, VO(2) , VO(2) peak and peak work compared to controls. Resting muscle pH was similar in controls and both CFS patient groups. However, the CFS group achieving normal PCr depletion values showed increased intramuscular acidosis compared to controls after similar work after each of the three exercise periods with no apparent reduction in acidosis with repeat exercise of the type reported in normal subjects. This CFS group also exhibited significant prolongation (almost 4-fold) of the time taken for pH to recover to baseline.

CONCLUSION: When exercising to comparable levels to normal controls, CFS patients exhibit profound abnormality in bioenergetic function and response to it. Although exercise intervention is the logical treatment for patients showing acidosis, any trial must exclude subjects who do not initiate exercise as they will not benefit. This potentially explains previous mixed results in CFS exercise trials.

© 2011 The Authors. European Journal of Clinical Investigation

© 2011 Stichting European Society for Clinical Investigation Journal Foundation.

 

Source: Jones DE, Hollingsworth KG, Jakovljevic DG, Fattakhova G, Pairman J, Blamire AM, Trenell MI, Newton JL. Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case-control study. Eur J Clin Invest. 2012 Feb;42(2):186-94. doi: 10.1111/j.1365-2362.2011.02567.x. Epub 2011 Jul 12. https://www.ncbi.nlm.nih.gov/pubmed/21749371

 

Psycho-physiological impact on women with chronic fatigue syndrome in the context of their couple relationship

Abstract:

The quality of dyadic adjustment is likely to play an important role in patients’ relational problems and may also be associated with the clinical presentation of chronic fatigue syndrome (CFS) symptoms. The objective of this study was (1) to determine whether CFS patients and their partners have similar perceptions of their dyadic adjustment and (2) to evaluate whether the influence of dyadic satisfaction in women with CFS, as well as common psychological parameters such as anxiety, may correlate with physiological responses at rest and/or when performing very low intensity exercise.

Forty females with CFS and their partners completed the Dyadic Adjustment Scale, the State-Trait Anxiety Inventory, and the Hospital Anxiety and Depression scale. The cardiovascular adaptation of patients was evaluated during resting conditions and on a precalibrated cycle ergometer while performing very low intensity exercise. Patients and partners had similar perceptions of their marital relationship.

Both at rest and during very low workload, various physiological parameters in the patient group showed statistical correlations with certain psychological parameters. Several psychological variables, such as anxiety and dyadic adjustment, were associated with the cardioventilatory response monitored at rest and during very low intensity exercise. Further studies are needed to determine the nature of this association.

 

Source: Blazquez A, Guillamó E, Alegre J, Ruiz E, Javierre C. Psycho-physiological impact on women with chronic fatigue syndrome in the context of their couple relationship. Psychol Health Med. 2012;17(2):150-63. doi: 10.1080/13548506.2011.582124. Epub 2011 Jul 11. https://www.ncbi.nlm.nih.gov/pubmed/21745025

 

Multi-source synthesis of data to inform health policy

Abstract:

OBJECTIVES: To propose a new method for comparing and integrating original qualitative data with systematic reviews of quantitative and qualitative studies, demonstrated by a study of the psychosocial needs of chronic fatigue syndrome (CFS) sufferers in Québec.

METHODS: A systematic literature review was performed across various databases for English and French language studies, on the psychosocial aspects of CFS. Qualitative, quantitative, and mixed method studies published between January 1994 and July 2008 were included. Unpublished literature and reference lists of included studies were also searched. Themes identified in the literature were used to guide semi-structured interviews with seventeen CFS-sufferers, mostly recruited from a large specialist practice in Montreal. Interviews were transcribed verbatim and validated by a research assistant. Transcripts were coded using the identified themes. New codes were created when new issues arose. All themes were subsequently synthesized into overall categories using a constant comparative method.

RESULTS: The literature search yielded thirty-one papers: twenty-eight primary studies and three systematic reviews. Twelve themes were identified and synthesized into four overall problem categories, such as “Lack of professional recognition.” Interviews confirmed findings from the literature, but also revealed unidentified needs specific to CFS-sufferers in Québec. Policy recommendations were provided to address these needs.

CONCLUSIONS: Multi-Source Synthesis provides a systematic method for synthesizing data from original studies with literature findings, thereby broadening the knowledge base and the local relevance of decisions concerning specific patient populations.

 

Source: Pedersen VH, Dagenais P, Lehoux P. Multi-source synthesis of data to inform health policy. Int J Technol Assess Health Care. 2011 Jul;27(3):238-46. doi: 10.1017/S0266462311000213. Epub 2011 Jul 8. https://www.ncbi.nlm.nih.gov/pubmed/21736858

 

Pervasive refusal syndrome

Abstract:

We report here on a case of severe pervasive refusal syndrome. This is of interest for three reasons. Firstly, most reported cases are adolescent girls; our case is regarding an adolescent boy. Secondly, he was successfully treated at home and thirdly, the serology showed an apparent infective pre-cursor to the illness with evidence of possible autoimmune serology. A 14-year old boy deteriorated from a picture where diagnosed CFS/ME developed into Pervasive Refusal Syndrome. This included the inability to move or speak, with closed eyes, multiple tics, facial grimacing, heightened sensitivity to noise (hyperacusis) and touch (hyperaesthesia), and inability or unwillingness to eat anything except small amounts of sloppy food. Successful rehabilitation is reported. Finally the issue of nomenclature is discussed, raising the question whether Pervasive Refusal Syndrome would be better renamed in a way that does not imply that the condition is always volitional and oppositional, as this can distract focus away from an alliance between family and clinicians.

 

Source: Wright B, Beverley D. Pervasive refusal syndrome. Clin Child Psychol Psychiatry. 2012 Apr;17(2):221-8. doi: 10.1177/1359104511403680. Epub 2011 Jul 6. https://www.ncbi.nlm.nih.gov/pubmed/21733931

 

EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients–a case control study

Abstract:

BACKGROUND: Previous studies suggest central nervous system involvement in chronic fatigue syndrome (CFS), yet there are no established diagnostic criteria. CFS may be difficult to differentiate from clinical depression. The study’s objective was to determine if spectral coherence, a computational derivative of spectral analysis of the electroencephalogram (EEG), could distinguish patients with CFS from healthy control subjects and not erroneously classify depressed patients as having CFS.

METHODS: This is a study, conducted in an academic medical center electroencephalography laboratory, of 632 subjects: 390 healthy normal controls, 70 patients with carefully defined CFS, 24 with major depression, and 148 with general fatigue. Aside from fatigue, all patients were medically healthy by history and examination. EEGs were obtained and spectral coherences calculated after extensive artifact removal. Principal Components Analysis identified coherence factors and corresponding factor loading patterns. Discriminant analysis determined whether spectral coherence factors could reliably discriminate CFS patients from healthy control subjects without misclassifying depression as CFS.

RESULTS: Analysis of EEG coherence data from a large sample (n = 632) of patients and healthy controls identified 40 factors explaining 55.6% total variance. Factors showed highly significant group differentiation (p < .0004) identifying 89.5% of unmedicated female CFS patients and 92.4% of healthy female controls. Recursive jackknifing showed predictions were stable. A conservative 10-factor discriminant function model was subsequently applied, and also showed highly significant group discrimination (p < .001), accurately classifying 88.9% unmedicated males with CFS, and 82.4% unmedicated male healthy controls. No patient with depression was classified as having CFS. The model was less accurate (73.9%) in identifying CFS patients taking psychoactive medications. Factors involving the temporal lobes were of primary importance.

CONCLUSIONS: EEG spectral coherence analysis identified unmedicated patients with CFS and healthy control subjects without misclassifying depressed patients as CFS, providing evidence that CFS patients demonstrate brain physiology that is not observed in healthy normals or patients with major depression. Studies of new CFS patients and comparison groups are required to determine the possible clinical utility of this test. The results concur with other studies finding neurological abnormalities in CFS, and implicate temporal lobe involvement in CFS pathophysiology.

 

Source: Duffy FH, McAnulty GB, McCreary MC, Cuchural GJ, Komaroff AL. EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients–a case control study. BMC Neurol. 2011 Jul 1;11:82. doi: 10.1186/1471-2377-11-82. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146818/ (Full article)

 

Nitric oxide modulation in protective role of antidepressants against chronic fatigue syndrome in mice

Abstract:

BACKGROUND AND OBJECTIVE: The present study was designed to elucidate the possible nitric oxide (NO) mechanism in the protective effect of antidepressants using mice model of chronic fatigue syndrome (CFS).

MATERIALS AND METHODS: Male albino laca mice were forced to swim for each 6 min session for 7 days and immobility period was measured on every alternate day (1(st), 3(rd), 5(th), 7(th)). After 7 days various behavioral tests (locomotor, mirror chamber, and plus maze tests for anxiety) were performed and biochemical estimations (lipid peroxidation, nitrite levels, GSH (reduced glutathione), and catalase activity) in mice brain were performed. Animals were pretreated with citalopram (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) daily for 7 days.

RESULTS: The present study showed that continued forced swimming for 7 days caused chronic fatigue-induced anxiety-like behavior as assessed in mirror chamber, plus maze tests, and impairment in locomotor activity followed by oxidative damage (as evidenced by increased lipid peroxidation, nitrite levels, depleted reduced glutathione, and catalase activity) in animals. Seven days pretreatment with citalopram (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) significantly improved behavioral and biochemical alterations. Further, L-nitro-arginine methyl ester (L-NAME,5 mg/kg) and methylene blue (MB, 10 mg/kg) pretreatment with citalopram (5 mg/kg) or imipramine (10 mg/kg) potentiated their protective effect. However, l-arginine (100 mg/kg) pretreatment with citalopram (5 mg/kg) or imipramine (10 mg/kg) reversed their protective effect as compared with their effect per se (P < 0.05).

CONCLUSION: The present study suggests that protective effect of citalopram and imipramine might be due to its NO modulation against chronic fatigue induced behavioral and biochemical alterations.

 

Source: Kumar A, Garg R, Gaur V, Kumar P. Nitric oxide modulation in protective role of antidepressants against chronic fatigue syndrome in mice. Indian J Pharmacol. 2011 May;43(3):324-9. Doi: 10.4103/0253-7613.81506. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113388/ (Full article)

 

Reliability and validity of Short Form 36 Version 2 to measure health perceptions in a sub-group of individuals with fatigue

Abstract:

PURPOSE: To determine the validity and reliability of Short Form 36 Version 2 (SF36v2) in sub-groups of individuals with fatigue.

METHOD: Thirty subjects participated in this study, including n = 16 subjects who met case definition criteria for chronic fatigue syndrome (CFS) and n = 14 non-disabled sedentary matched control subjects. SF36v2 and Multidimensional Fatigue Inventory (MFI-20) were administered before two maximal cardiopulmonary exercise tests (CPETs) administered 24 h apart and an open-ended recovery questionnaire was administered 7 days after CPET challenge. The main outcome measures were self-reported time to recover to pre-challenge functional and symptom status, frequency of post-exertional symptoms and SF36v2 sub-scale scores.

RESULTS: Individuals with CFS demonstrated significantly lower SF36v2 and MFI-20 sub-scale scores prior to CPET. Between-group differences remained significant post-CPET, however, there were no significant group by test interaction effects. Subjects with CFS reported significantly more total symptoms (p < 0.001), as well as reports of fatigue (p < 0.001), neuroendocrine (p < 0.001), immune (p < 0.01), pain (p < 0.01) and sleep disturbance (p < 0.01) symptoms than control subjects as a result of CPET. Many symptom counts demonstrated significant relationships with SF36v2 sub-scale scores (p < 0.05). SF36v2 and MFI-20 sub-scale scores demonstrated significant correlations (p < 0.05). Various SF36v2 sub-scale scores demonstrated significant predictive validity to identify subjects who recovered from CPET challenge within 1 day and 7 days (p < 0.05). Potential floor effects were observed for both questionnaires for individuals with CFS.

CONCLUSION: Various sub-scales of SF36v2 demonstrated adequate reliability and validity for clinical and research applications. Adequacy of sensitivity to change of SF36v2 as a result of a fatiguing stressor should be the subject of additional study.

 

Source: Davenport TE, Stevens SR, Baroni K, Van Ness JM, Snell CR. Reliability and validity of Short Form 36 Version 2 to measure health perceptions in a sub-group of individuals with fatigue. Disabil Rehabil. 2011;33(25-26):2596-604. doi: 10.3109/09638288.2011.582925. Epub 2011 Jun 20. https://www.ncbi.nlm.nih.gov/pubmed/21682669

 

Increased tenderness in the left third intercostal space in adult patients with myalgic encephalomyelitis: a controlled study

Abstract:

A clinical sign has not thus far been associated with myalgic encephalomyelitis (ME). The present study involved systematic clinical examination that included inspection, palpation, percussion and auscultation of the thorax of 42 ME patients and 20 age-matched healthy controls while sitting. Left lateral third intercostal space tenderness was noted in 34 (81%) of the patients and in none of the controls, a difference that was highly statistically significant. This finding may be related to changes in lymphatic function and to the descending course of the thoracic duct. Further studies, preferably blinded and combined with appropriate imaging, are required.

 

Source: Puri BK, Gunatilake KD, Fernando KA, Gurusinghe AI, Agour M, Treasaden IH. Increased tenderness in the left third intercostal space in adult patients with myalgic encephalomyelitis: a controlled study. J Int Med Res. 2011;39(1):212-4. https://www.ncbi.nlm.nih.gov/pubmed/21672323

 

Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome

Abstract:

We studied the extent of mitochondrial involvement in chronic fatigue syndrome (CFS) and investigated whether measurement of mitochondrial respiratory chain complex (RCC) activities discriminates between CFS and mitochondrial disorders.

Mitochondrial content was decreased in CFS compared to healthy controls, whereas RCC activities corrected for mitochondrial content were not. Conversely, mitochondrial content did not discriminate between CFS and two groups of mitochondrial disorders, whereas ATP production rate and complex I, III and IV activity did, all with higher activities in CFS. We conclude that the ATP production rate and RCC activities can reliably discriminate between mitochondrial disorders and CFS.

Copyright © 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

 

Source: Smits B, van den Heuvel L, Knoop H, Küsters B, Janssen A, Borm G, Bleijenberg G, Rodenburg R, van Engelen B. Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome. Mitochondrion. 2011 Sep;11(5):735-8. doi: 10.1016/j.mito.2011.05.005. Epub 2011 Jun 2. https://www.ncbi.nlm.nih.gov/pubmed/21664495