Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: The insufficient metabolic adaptation to exercise in Chronic Fatigue Syndrome (CFS) is still being debated and poorly understood.

METHODS: We analysed the cardiopulmonary exercise tests of CFS patients, idiopathic chronic fatigue (CFI) patients and healthy visitors. Continuous non-invasive measurement of the cardiac output by Nexfin (BMEYE B.V. Amsterdam, the Netherlands) was added to the cardiopulmonary exercise tests. The peak oxygen extraction by muscle cells and the increase of cardiac output relative to the increase of oxygen uptake (ΔQ’/ΔV’O₂) were measured, calculated from the cardiac output and the oxygen uptake during incremental exercise.

RESULTS: The peak oxygen extraction by muscle cells was 10.83 ± 2.80 ml/100ml in 178 CFS women, 11.62 ± 2.90 ml/100 ml in 172 CFI, and 13.45 ± 2.72 ml/100 ml in 11 healthy women (ANOVA: P=0.001), 13.66 ± 3.31 ml/100 ml in 25 CFS men, 14.63 ± 4.38 ml/100 ml in 51 CFI, and 19.52 ± 6.53 ml/100 ml in 7 healthy men (ANOVA: P=0.008).The ΔQ’/ΔV’O₂ was > 6 L/L (normal ΔQ’/ΔV’O₂ ≈ 5 L/L) in 70% of the patients and in 22% of the healthy group.

CONCLUSION: Low oxygen uptake by muscle cells causes exercise intolerance in a majority of CFS patients, indicating insufficient metabolic adaptation to incremental exercise. The high increase of the cardiac output relative to the increase of oxygen uptake argues against deconditioning as a cause for physical impairment in these patients.

 

Source: Vermeulen RC, Vermeulen van Eck IW. Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome. J Transl Med. 2014 Jan 23;12:20. doi: 10.1186/1479-5876-12-20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903040/ (Full article)’

 

Deficient EBV-specific B- and T-cell response in patients with chronic fatigue syndrome

Abstract:

Epstein-Barr virus (EBV) has long been discussed as a possible cause or trigger of Chronic Fatigue Syndrome (CFS). In a subset of patients the disease starts with infectious mononucleosis and both enhanced and diminished EBV-specific antibody titers have been reported.

In this study, we comprehensively analyzed the EBV-specific memory B- and T-cell response in patients with CFS. While we observed no difference in viral capsid antigen (VCA)-IgG antibodies, EBV nuclear antigen (EBNA)-IgG titers were low or absent in 10% of CFS patients.

Remarkably, when analyzing the EBV-specific memory B-cell reservoir in vitro a diminished or absent number of EBNA-1- and VCA-antibody secreting cells was found in up to 76% of patients. Moreover, the ex vivo EBV-induced secretion of TNF-α and IFN-γ was significantly lower in patients. Multicolor flow cytometry revealed that the frequencies of EBNA-1-specific triple TNF-α/IFN-γ/IL-2 producing CD4(+) and CD8(+) T-cell subsets were significantly diminished whereas no difference could be detected for HCMV-specific T-cell responses. When comparing EBV load in blood immune cells, we found more frequently EBER-DNA but not BZLF-1 RNA in CFS patients compared to healthy controls suggesting more frequent latent replication.

Taken together, our findings give evidence for a deficient EBV-specific B- and T-cell memory response in CFS patients and suggest an impaired ability to control early steps of EBV reactivation. In addition the diminished EBV response might be suitable to develop diagnostic marker in CFS.

 

Source: Loebel M, Strohschein K, Giannini C, Koelsch U, Bauer S, Doebis C, Thomas S, Unterwalder N, von Baehr V, Reinke P, Knops M, Hanitsch LG, Meisel C, Volk HD, Scheibenbogen C. Deficient EBV-specific B- and T-cell response in patients with chronic fatigue syndrome. PLoS One. 2014 Jan 15;9(1):e85387. doi: 10.1371/journal.pone.0085387. ECollection 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893202/ (Full article)

 

Chronic fatigue syndrome: a personalized integrative medicine approach

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a relatively common illness, yet despite considerable investigation, current treatments have modest benefits, and the prognosis remains poor. Because CFS/ME is a heterogeneous disorder with diverse etiological factors and pathological features, a patient-centered integrative framework based on modifiable physiological and environmental factors may offer hope for more effective management and better clinical outcomes. An individualized approach may also help target interventions for subgroups most likely to respond to specific treatments. This review summarizes a number of avenues for integrative management, including dietary modification, functional nutritional deficiencies, physical fitness, psychological and physical stress, environmental toxicity, gastrointestinal disturbances, immunological aberrations, inflammation, oxidative stress, and mitochondrial dysfunction. A personalized, integrative approach to CFS/ME deserves further consideration as a template for patient management and future research.

 

Source: Brown B. Chronic fatigue syndrome: a personalized integrative medicine approach. Altern Ther Health Med. 2014 Jan-Feb;20(1):29-40. https://www.ncbi.nlm.nih.gov/pubmed/24445354

 

Valacyclovir treatment of chronic fatigue in adolescents

Abstract:

Chronic fatigue syndrome (CFS) presents with fatigue, low motivation, diminished mood, and reduced activity, all symptoms having extensive diagnostic overlaps with depression. Studies have linked chronic viral infections with CFS, and antiviral therapy has effectively treated CFS in adult patients.

In a retrospective case series, 15 adolescents and preteens referred to the author for treatment-resistant depression or mood disorder were evaluated and found to have met the Fukuda diagnostic criteria for CFS. While a subset (4/15) had been diagnosed in the past with CFS, the majority had a current diagnosis of depression or a mood disorder. The Diagnostic and Statistical Manual-IV Text Revision (DSM-IV TR) criteria for depression were not met in all patients, although 3 cases of mood disorder not otherwise specified (MD-NOS) and 1 case of Tourette syndrome (TS) plus MD-NOS were diagnosed. Baseline scores on the Children’s Depression Inventory (CDI) were below the cutoff for depression in all but 1 patient. Baseline self-assessment scales for CFS or fatigue were obtained and sleep was evaluated with sleep logs.

All patients were treated subsequently with valacyclovir, with 93% having a positive response. At the end of treatment, scores on fatigue self-assessment scales improved significantly (P < .001). Vigor subscale scores also improved significantly (P < .001). Some patients experienced complete resolution of symptoms. Although not every patient was tested, available laboratory testing revealed increased counts of natural killer (NK) cells and decreased human herpesvirus 6 (HHV-6) antibody titers in all patients who responded to valacyclovir.

This article discusses the significance of infectious agents in the pathogenesis of psychiatric symptoms. The study’s data support an intriguing hypothesis that a portion of treatment-resistant depression in fact may be undiagnosed CFS or other chronic viral infection.

 

Source: Henderson TA. Valacyclovir treatment of chronic fatigue in adolescents. Adv Mind Body Med. 2014 Winter;28(1):4-14. https://www.ncbi.nlm.nih.gov/pubmed/24445302

 

Multivitamin mineral supplementation in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by medically unexplained persistent or reoccurring fatigue lasting at least 6 months. CFS has a multifactorial pathogenesis in which oxidative stress (OS) plays a prominent role. Treatment is with a vitamin and mineral supplement, but this therapeutic option so far has not been properly researched.

MATERIAL AND METHODS: This prospective study included 38 women of reproductive age consecutively diagnosed by CDC definition of CFS and treated with a multivitamin mineral supplement. Before and after the 2-month supplementation, SOD activity was determined and patients self-assessed their improvement in 2 questionnaires: the Fibro Fatigue Scale (FFS) and the Quality of Life Scale (SF36).

Results There was a significant improvement in SOD activity levels; and significant decreases in fatigue (p=0.0009), sleep disorders (p=0.008), autonomic nervous system symptoms (p=0.018), frequency and intensity of headaches (p=0.0001), and subjective feeling of infection (p=0.0002). No positive effect on quality of life was found.

CONCLUSIONS: Treatment with a vitamin and mineral supplement could be a safe and easy way to improve symptoms and quality of life in patients with CFS.

 

Source: Maric D, Brkic S, Tomic S, Novakov Mikic A, Cebovic T, Turkulov V. Multivitamin mineral supplementation in patients with chronic fatigue syndrome. Med Sci Monit. 2014 Jan 14;20:47-53. doi: 10.12659/MSM.889333. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907507/ (Full article)

 

A role for homeostatic drive in the perpetuation of complex chronic illness: Gulf War Illness and chronic fatigue syndrome

Erratum in

  • PLoS One. 2014;9(4):e94161.
  • PLoS One. 2014;9(6):e100355.

Abstract:

A key component in the body’s stress response, the hypothalamic-pituitary-adrenal (HPA) axis orchestrates changes across a broad range of major biological systems. Its dysfunction has been associated with numerous chronic diseases including Gulf War Illness (GWI) and chronic fatigue syndrome (CFS). Though tightly coupled with other components of endocrine and immune function, few models of HPA function account for these interactions.

Here we extend conventional models of HPA function by including feed-forward and feedback interaction with sex hormone regulation and immune response. We use this multi-axis model to explore the role of homeostatic regulation in perpetuating chronic conditions, specifically GWI and CFS. An important obstacle in building these models across regulatory systems remains the scarcity of detailed human in vivo kinetic data as its collection can present significant health risks to subjects. We circumvented this using a discrete logic representation based solely on literature of physiological and biochemical connectivity to provide a qualitative description of system behavior. This connectivity model linked molecular variables across the HPA axis, hypothalamic-pituitary-gonadal (HPG) axis in men and women, as well as a simple immune network. Inclusion of these interactions produced multiple alternate homeostatic states and sexually dimorphic responses.

Experimental data for endocrine-immune markers measured in male GWI subjects showed the greatest alignment with predictions of a naturally occurring alternate steady state presenting with hypercortisolism, low testosterone and a shift towards a Th1 immune response. In female CFS subjects, expression of these markers aligned with an alternate homeostatic state displaying hypocortisolism, high estradiol, and a shift towards an anti-inflammatory Th2 activation. These results support a role for homeostatic drive in perpetuating dysfunctional cortisol levels through persistent interaction with the immune system and HPG axis. Though coarse, these models may nonetheless support the design of robust treatments that might exploit these regulatory regimes.

 

Source: Craddock TJ, Fritsch P, Rice MA Jr, del Rosario RM, Miller DB, Fletcher MA, Klimas NG, Broderick G. A role for homeostatic drive in the perpetuation of complex chronic illness: Gulf War Illness and chronic fatigue syndrome. PLoS One. 2014 Jan 8;9(1):e84839. doi: 10.1371/journal.pone.0084839. ECollection 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885655/ (Full article)

 

Impact of the fibromyalgia in the chronic fatigue syndrome

Abstract:

BACKGROUND AND OBJECTIVE: Different studies have showed association of the chronic fatigue syndrome (CFS) with other pathologies, including fibromyalgia (FM). The objective of this study is to analyze whether there are differences in the clinic and in the assessment of fatigue in CFS patients associated or not with FM.

PATIENTS AND METHODS: A cross-sectional, single-site observational study was undertaken on a consecutive cases of a register of CFS patients at CFS Unit in Vall d’Hebron Hospital, Barcelona, from January 2008 until March 2011. The variables analyzed were FM comorbidity, sleep and fatigue characteristics and cognitive, neurological and autonomic symptoms. Questionnaires of fatigue impact scale, fatigue strength and impact on quality of life SF-36 were evaluated.

RESULTS: We included 980 CFS patients (mean age: 48±9 years; 91% women). Fibromyalgia was present in 528 patients (54%). The level of fatigue (P=.001) and pain (P<.001) was higher in FM patients. Patients with CFS and FM had more prevalence of sleep-related phenomena. The percentage of patients and the degree of severity of cognitive symptoms, neurological and autonomic dysfunction was higher in FM patients (P<.001). FM patients scored higher on the fatigue impact scale (P<.001) and showed worse results in the quality of life questionnaire (P<.001).

CONCLUSIONS: FM co-morbidity worse clinical parameters, fatigue and the perception of quality of life in CFS patients.

Copyright © 2013 Elsevier España, S.L. All rights reserved.

 

Source: Faro M, Sáez-Francàs N, Castro-Marrero J, Aliste L, Collado A, Alegre J. Impact of the fibromyalgia in the chronic fatigue syndrome. Med Clin (Barc). 2014 Jun 16;142(12):519-25. doi: 10.1016/j.medcli.2013.06.030. Epub 2014 Jan 2. [Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/24387955

 

Chronic Fatigue Syndrome: Case Definitions and Diagnostic Assessment

Abstract:

Chronic fatigue syndrome (CFS) is a chronic, debilitating illness that has posed considerable challenges for both patients and health care providers. Individuals with CFS often deal with considerable stigma and difficulties accessing appropriate care. Many medical professionals are increasingly recognizing the devastating nature of this illness, but at this time, few health care workers are knowledgeable and experienced enough to provide adequate patient care. There is a need for further efforts to educate health care workers on CFS diagnostic, assessment, and treatment issues. The present article reviews controversies regarding CFS case definitions, diagnostic criteria, the name of the illness, and epidemiological and treatment studies. We conclude that an imprecise case definition underlies many of the problems with diagnostic and treatment issues.

 

Source: Williams YJ, Jantke RL, Jason LA. Chronic Fatigue Syndrome: Case Definitions and Diagnostic Assessment. N Y State Psychol. 2014 Winter;26(4):41-45. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008849/ (Full article)

 

Validating a measure of myalgic encephalomyelitis/chronic fatigue syndrome symptomatology

Abstract:

OBJECTIVES: The present study sought to validate a comprehensive self-report measure of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptomatology to aid in clinical and research assessment.

METHOD: Exploratory factor analysis (EFA) was used to establish the underlying factor structure of the DePaul Symptom Questionnaire (DSQ) (Jason, Evans, et al., 2010) using a well-characterized sample of individuals (92.6% met the Fukuda et al. criteria (1994) and/or the Clinical Canadian Criteria (Carruthers et al., 2003)), and this structure was then tested on a less stringently recruited sample of individuals utilizing a confirmatory factor analysis (CFA). Convergent and discriminant validity of the DSQ were also examined utilizing alternative measures of symptomatology and functioning.

RESULTS: A 3-factor solution was found using EFA (Neuroendocrine, Autonomic & Immune Dysfunction; Neurological/Cognitive Dysfunction; Post-Exertional Malaise) and the fit of this factor structure was adequate for the second sample.

DISCUSSION: The DSQ is a valid measure of ME/CFS symptomatology. The emergent factors were consistent with previous literature on symptom clusters, and convergent and discriminant validity were established.

 

Source: Brown AA, Jason LA. Validating a measure of myalgic encephalomyelitis/chronic fatigue syndrome symptomatology. Fatigue. 2014;2(3):132-152. Epub 2014 Jul 23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4871625/ (Full article)

 

The effect of fatigue and fibromyalgia on sexual dysfunction in women with chronic fatigue syndrome

Abstract:

Sexual dysfunction in patients with chronic fatigue syndrome is attracting growing interest but, to date, few studies have analyzed it. For this reason, the authors evaluated sexual dysfunction in women with chronic fatigue syndrome (using the Golombok Rust Inventory of Sexual Satisfaction) and explore correlations with fatigue and other symptoms. Sexual dysfunction was greater in patients with chronic fatigue syndrome (n = 615) with a higher number of cognitive, neurological, and neurovegetative symptoms, concomitant fibromyalgia, Sjögren’s syndrome, or myofascial pain syndrome, and more intense fatigue (p <.05).

 

Source: Blazquez A, Ruiz E, Aliste L, García-Quintana A, Alegre J. The effect of fatigue and fibromyalgia on sexual dysfunction in women with chronic fatigue syndrome. J Sex Marital Ther. 2015;41(1):1-10. doi: 10.1080/0092623X.2013.864370. Epub 2014 Mar 11. https://www.ncbi.nlm.nih.gov/pubmed/24274008