Page 397 – American ME and CFS Society

How do women with chronic fatigue syndrome/myalgic encephalomyelitis rate quality and coordination of healthcare services? A cross-sectional study

Abstract:

OBJECTIVE: To test the association between self-rated health and self-rated degree of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), and CFS/ME patients’ assessment of quality of primary care, specialist care and coordination of care.

DESIGN: Cross-sectional study.

SETTING: Self-reported questionnaire data from women members of The Norwegian ME Association obtained in 2013.

PARTICIPANTS: 431 women with CFS/ME aged 16-73 years.

MAIN OUTCOME MEASURE: The participants’ assessment of quality in primary care, specialist care and in coordination of care (good/very good or poor/very poor). Main explanatory variables: self-rated health and self-rated degree of CFS/ME.

RESULTS: Quality of care was rated poor by 60.6% in primary care, by 47.7% in specialist care, and by 71.2% regarding coordination of care. Poorer self-rated health increased the probability of rating quality in primary care poor, particularly among women 40 years and over (OR 2.38, 95% CI 1.63 to 3.49), women with university education (OR 2.57, CI 1.68 to 3.94), and owing to less frequent general practitioner (GP) visits (OR 2.46, CI 1.60 to 3.78). Poorer self-rated health increased the probability of rating quality poor in specialist care (OR 1.38, CI 1.05 to 1.82), but not in coordination of care. A more severe CFS/ME was associated with a higher probability of rating quality in primary care poor (OR 0.61, CI 0.38 to 0.93). Frequent visitors and those with a long GP relationship were less likely to report primary care quality as poor.

CONCLUSIONS: A large proportion of women with CFS/ME rated quality of care poor/very poor in primary care, specialist care and in coordination of care. The dissatisfaction was higher for primary care than for specialist care. Overall, poorer self-rated health and a more severe CFS/ME were associated with lower quality scores in primary and specialist care, but not in coordination of care. Healthcare services, as assessed by women with CFS/ME, do have a large potential for improvement.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Source: Hansen AH, Lian OS. How do women with chronic fatigue syndrome/myalgic encephalomyelitis rate quality and coordination of healthcare services? A cross-sectional study. BMJ Open. 2016 Apr 4;6(4):e010277. doi: 10.1136/bmjopen-2015-010277. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823449/ (Full article)

Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence

Abstract:

Cognitive difficulties represent a common and debilitating feature of the enigmatic chronic fatigue syndrome (CFS). These difficulties manifest as self-reported problems with attention, memory, and concentration and present objectively as slowed information processing speed particularly on complex tasks requiring sustained attention. The mechanisms underlying cognitive dysfunction remain to be established; however, alterations in autonomic nervous system activity and cerebral blood flow have been proposed as possibilities.

Heterogeneity in the experience of cognitive impairment, as well as differences in the methods utilised to quantify dysfunction, may contribute to the difficulties in establishing plausible biological underpinnings. The development of a brief neurocognitive battery specifically tailored to CFS and adoption by the international research community would be beneficial in establishing a profile of cognitive dysfunction. This could also provide better insights into the underlying biological mechanisms of cognitive dysfunction in CFS and enhance the development of targeted treatments.

Source: Cvejic E, Birch RC, Vollmer-Conna U. Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence. Curr Rheumatol Rep. 2016 May;18(5):24. doi: 10.1007/s11926-016-0577-9. https://www.ncbi.nlm.nih.gov/pubmed/27032787

Treatment expectations influence the outcome of multidisciplinary rehabilitation treatment in patients with CFS

Abstract:

OBJECTIVE: To improve the effectiveness of treatment in patients with chronic fatigue syndrome it is worthwhile studying factors influencing outcomes. The aims of this study were (1) to assess the association of expectancy and credibility on treatment outcomes, and (2) to identify baseline variables associated with treatment expectancy and credibility.

METHODS: 122 patients were included in a randomized controlled trial of whom 60 received cognitive behavioural therapy (CBT) and 62 multidisciplinary rehabilitation treatment (MRT). Expectancy and credibility were measured with the credibility and expectancy questionnaire. Outcomes of treatment, fatigue, and quality of life (QoL), were measured at baseline and post-treatment. Multiple linear regressions were performed to analyse associations.

RESULTS: In explaining fatigue and the physical component of the QoL, the effect of expectancy was significant for MRT, whereas in CBT no such associations were found. The main effect of expectancy on the mental component of QoL was not significant. For credibility, the overall effect on fatigue and the physical component of QoL was not significant. In explaining the mental component of QoL, the interaction between treatment and credibility was significant. However, the effects within each group were not significant. In the regression model with expectancy as dependent variable, only treatment centre appeared significantly associated. In explaining credibility, treatment centre, treatment allocation and depression contributed significantly.

CONCLUSIONS: For clinical practice it seems important to check the expectations of the patient, since expectations influence the outcome after MRT.

Source: Vos-Vromans DC, Huijnen IP, Rijnders LJ, Winkens B, Knottnerus JA, Smeets RJ. Treatment expectations influence the outcome of multidisciplinary rehabilitation treatment in patients with CFS. J Psychosom Res. 2016 Apr;83:40-5. doi: 10.1016/j.jpsychores.2016.02.004. Epub 2016 Feb 17. https://www.ncbi.nlm.nih.gov/pubmed/27020075

Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison

Abstract:

BACKGROUND: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), and Multiple Sclerosis (MS) may share some similarities in relation to reduced NK cell activity. It is likely that other cells such as regulatory T (Tregs), invariant Natural Killer T (iNKT) and gamma delta T (γδ T) cells may also be dysregulated in CFS/ME and MS.

OBJECTIVE: To evaluate and compare specific immune regulatory cells of patients with CFS/ME, patients with MS and healthy controls.

METHOD: Sixty three volunteers were included in this study: 24 were CFS/ME patients, 11 were MS patients and 27 were healthy controls. Blood samples were obtained from all participants for flow cytometry analysis of iNKT cells, Tregs and γδ T cell phenotypes.

RESULTS: We observed a significant increase in Tregs in the CFS/ME group (p≤0.05) compared to the healthy control group. Total γδ and γδ2 T cells were significantly reduced in MS patients in comparison with the healthy control group. Conversely, CD4+iNKT percentage of iNKT, was significantly increased in the CFS/ME group compared with healthy controls and the double-negative iNKT percentage of iNKT significantly decreased compared with the healthy control group.

CONCLUSIONS: This study has not identified any immunological disturbances that are common in both MS and CFS/ME patients. However, the differential expression of cell types between the conditions investigated suggests different pathways of disease. These differences need to be explored in further studies.

Source: Ramos S, Brenu E, Broadley S, Kwiatek R, Ng J, Nguyen T, Freeman S, Staines D, Marshall-Gradisnik S. Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison. Asian Pac J Allergy Immunol. 2016 Dec;34(4):300-305. doi: 10.12932/AP0733. http://apjai-journal.org/wp-content/uploads/2016/12/8RegulatoryTnaturalkillerAPJAIVol34No4December2016P300.pdf (Full text as PDF)

Understanding Muscle Dysfunction in Chronic Fatigue Syndrome

Abstract:

Introduction. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown aetiology, characterised by severe disabling fatigue in the absence of alternative diagnosis. Historically, there has been a tendency to draw psychological explanations for the origin of fatigue; however, this model is at odds with findings that fatigue and accompanying symptoms may be explained by central and peripheral pathophysiological mechanisms, including effects of the immune, oxidative, mitochondrial, and neuronal pathways. For example, patient descriptions of their fatigue regularly cite difficulty in maintaining muscle activity due to perceived lack of energy. This narrative review examined the literature for evidence of biochemical dysfunction in CFS/ME at the skeletal muscle level.

Methods. Literature was examined following searches of PUB MED, MEDLINE, and Google Scholar, using key words such as CFS/ME, immune, autoimmune, mitochondria, muscle, and acidosis.

Results. Studies show evidence for skeletal muscle biochemical abnormality in CFS/ME patients, particularly in relation to bioenergetic dysfunction.

Discussion. Bioenergetic muscle dysfunction is evident in CFS/ME, with a tendency towards an overutilisation of the lactate dehydrogenase pathway following low-level exercise, in addition to slowed acid clearance after exercise. Potentially, these abnormalities may lead to the perception of severe fatigue in CFS/ME.

Source: Rutherford G, Manning P, Newton JL. Understanding Muscle Dysfunction in Chronic Fatigue Syndrome. J Aging Res. 2016;2016:2497348. doi: 10.1155/2016/2497348. Epub 2016 Feb 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779819/ (Full article)

Neurocognitive improvements after best-practice intervention for chronic fatigue syndrome: Preliminary evidence of divergence between objective indices and subjective perceptions

Abstract:

BACKGROUND: Neurocognitive difficulties are commonly reported by patients suffering from chronic fatigue syndrome (CFS). Moderate improvements from ‘best practice’ therapy are promising, but to date reported efficacy is based entirely on subjective measures. This is problematic, given the well-documented divergence between subjective perceptions and actual neurocognitive performance, including in this patient group.

MATERIAL AND METHODS: Subjective and objective measures of neurocognitive performance were obtained from 25 patients with well-characterized CFS before and after the completion of a 12-week graded-activity program incorporating a cognitive training component. Additionally, self-reported symptoms, cardiac autonomic activity (a relevant biomarker of stress responsivity), and their relation to neurocognitive improvements were examined.

RESULTS: Substantive post-intervention improvements in subjective (p=0.006) and objective (including faster responses speeds and greater accuracy, p’s<0.001) neurocognitive performance were documented. Participants also demonstrated reduced autonomic reactivity to the cognitive challenge at follow-up (p’s≤0.01). These improvements were accompanied by improvements in symptom ratings (p’s≤0.01). However, subjective ratings of neurocognitive difficulties, and CFS-related symptoms were not linked to objective performance improvements.

CONCLUSIONS: These initial data provide the first evidence of objective neurocognitive performance improvements accompanied by a significant reduction in responsiveness in stress-related neural pathways consequent to cognitive-behavioral/graded exercise therapy programs. These findings provide support for the effectiveness of such programs in remediating clinical status. These promising findings warrant further investigation, including replication in a larger sample utilizing more controlled study designs.

Source: Cvejic E, Lloyd AR, Vollmer-Conna U. Neurocognitive improvements after best-practice intervention for chronic fatigue syndrome: Preliminary evidence of divergence between objective indices and subjective perceptions. Compr Psychiatry. 2016 Apr;66:166-75. doi: 10.1016/j.comppsych.2016.02.002. Epub 2016 Feb 9. https://www.ncbi.nlm.nih.gov/pubmed/26995250

Chronic fatigue syndrome and experience with the Lightning Process

The cause of chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) is not well understood and is disputed, and therapeutic options are limited. Many patients who attended the Lightning Process course reported positive effects. This should lead to a randomised controlled intervention trial.

Since 2008 several thousand patients with CFS/ME have attended the Lightning Process (LP) course in Norway (1). The course is a three-day intensive brain rehearsal programme with the option for follow-up. Although what triggers CFS/ME in the individual case may vary, it is assumed that symptoms maintenance and chronification can be attributed to a stress response with elevated state of alertness and persisting activation of the sympathetic nervous system, driven by classic and operant conditioning mechanisms. The Lightning Process is based on these theories of stress.

You can read the rest of this article here: http://tidsskriftet.no/en/2016/03/chronic-fatigue-syndrome-and-experience-lightning-process

Source: Landmark L, Lindgren RM, Sivertsen B, Magnus P, Conradi S, Thorvaldsen SN, Stanghelle JK. Chronic fatigue syndrome and experience with the Lightning Process. Tidsskr Nor Laegeforen. 2016 Mar 15;136(5):396. doi: 10.4045/tidsskr.15.1214. ECollection 2016. [Article in English, Norwegian] http://tidsskriftet.no/en/2016/03/chronic-fatigue-syndrome-and-experience-lightning-process (Full article)

Methods of applying the 1994 case definition of chronic fatigue syndrome – impact on classification and observed illness characteristics

Abstract:

BACKGROUND: Multiple case definitions are in use to identify chronic fatigue syndrome (CFS). Even when using the same definition, methods used to apply definitional criteria may affect results. The Centers for Disease Control and Prevention (CDC) conducted two population-based studies estimating CFS prevalence using the 1994 case definition; one relied on direct questions for criteria of fatigue, functional impairment and symptoms (1997 Wichita; Method 1), and the other used subscale score thresholds of standardized questionnaires for criteria (2004 Georgia; Method 2). Compared to previous reports the 2004 CFS prevalence estimate was higher, raising questions about whether changes in the method of operationalizing affected this and illness characteristics.

METHODS: The follow-up of the Georgia cohort allowed direct comparison of both methods of applying the 1994 case definition. Of 1961 participants (53 % of eligible) who completed the detailed telephone interview, 919 (47 %) were eligible for and 751 (81 %) underwent clinical evaluation including medical/psychiatric evaluations. Data from the 499 individuals with complete data and without exclusionary conditions was available for this analysis.

RESULTS: A total of 86 participants were classified as CFS by one or both methods; 44 cases identified by both methods, 15 only identified by Method 1, and 27 only identified by Method 2 (Kappa 0.63; 95 % confidence interval [CI]: 0.53, 0.73 and concordance 91.59 %). The CFS group identified by both methods were more fatigued, had worse functioning, and more symptoms than those identified by only one method. Moderate to severe depression was noted in only one individual who was classified as CFS by both methods. When comparing the CFS groups identified by only one method, those only identified by Method 2 were either similar to or more severely affected in fatigue, function, and symptoms than those only identified by Method 1.

CONCLUSIONS: The two methods demonstrated substantial concordance. While Method 2 classified more participants as CFS, there was no indication that they were less severely ill or more depressed. The classification differences do not fully explain the prevalence increase noted in the 2004 Georgia study. Use of standardized instruments for the major CFS domains provides advantages for disease stratification and comparing CFS patients to other illnesses.

Source: Unger ER, Lin JM, Tian H, Gurbaxani BM, Boneva RS, Jones JF. Methods of applying the 1994 case definition of chronic fatigue syndrome – impact on classification and observed illness characteristics. Popul Health Metr. 2016 Mar 12;14:5. doi: 10.1186/s12963-016-0077-1. eCollection 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788915/ (Full article)

MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c: Potential Diagnostic Biomarkers in Natural Killer (NK) Cells of Patients with Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS/ME) is a complex multisystem disease of unknown aetiology which causes debilitating symptoms in up to 1% of the global population. Although a large cohort of genes have been shown to exhibit altered expression in CFS/ME patients, it is currently unknown whether microRNA (miRNA) molecules which regulate gene translation contribute to disease pathogenesis. We hypothesized that changes in microRNA expression in patient leukocytes contribute to CFS/ME pathology, and may therefore represent useful diagnostic biomarkers that can be detected in the peripheral blood of CFS/ME patients.

METHODS: miRNA expression in peripheral blood mononuclear cells (PBMC) from CFS/ME patients and healthy controls was analysed using the Ambion Bioarray V1. miRNA demonstrating differential expression were validated by qRT-PCR and then replicated in fractionated blood leukocyte subsets from an independent patient cohort. The CFS/ME associated miRNA identified by these experiments were then transfected into primary NK cells and gene expression analyses conducted to identify their gene targets.

RESULTS: Microarray analysis identified differential expression of 34 miRNA, all of which were up-regulated. Four of the 34 miRNA had confirmed expression changes by qRT-PCR. Fractionating PBMC samples by cell type from an independent patient cohort identified changes in miRNA expression in NK-cells, B-cells and monocytes with the most significant abnormalities occurring in NK cells. Transfecting primary NK cells with hsa-miR-99b or hsa-miR-330-3p, resulted in gene expression changes consistent with NK cell activation but diminished cytotoxicity, suggesting that defective NK cell function contributes to CFS/ME pathology.

CONCLUSION: This study demonstrates altered microRNA expression in the peripheral blood mononuclear cells of CFS/ME patients, which are potential diagnostic biomarkers. The greatest degree of miRNA deregulation was identified in NK cells with targets consistent with cellular activation and altered effector function.

Source: Petty RD, McCarthy NE, Le Dieu R, Kerr JR. MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c: Potential Diagnostic Biomarkers in Natural Killer (NK) Cells of Patients with Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME). PLoS One. 2016 Mar 11;11(3):e0150904. doi: 10.1371/journal.pone.0150904. ECollection 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788442/ (Full article)

Illness progression in chronic fatigue syndrome: a shifting immune baseline

Abstract:

BACKGROUND: Validation of biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) across data sets has proven disappointing. As immune signature may be affected by many factors, our objective was to explore the shift in discriminatory cytokines across ME/CFS subjects separated by duration of illness.

METHODS: Cytokine expression collected at rest across multiple studies for female ME/CFS subjects (i) 18 years or younger, ill for 2 years or less (n = 18), (ii) 18-50 years of age, ill for 7 years (n = 22), and (iii) age 50 years or older (n = 28), ill for 11 years on average. Control subjects were matched for age and body mass index (BMI). Data describing the levels of 16 cytokines using a chemiluminescent assay was used to support the identification of separate linear classification models for each subgroup. In order to isolate the effects of duration of illness alone, cytokines that changed significantly with age in the healthy control subjects were excluded a priori.

RESULTS: Optimal selection of cytokines in each group resulted in subsets of IL-1α, 6, 8, 15 and TNFα. Common to any 2 of 3 groups were IL-1α, 6 and 8. Setting these 3 markers as a triple screen and adjusting their contribution according to illness duration sub-groups produced ME/CFS classification accuracies of 75-88 %. The contribution of IL-1α, higher in recently ill adolescent ME/CFS subjects was progressively less important with duration. While high levels of IL-8 screened positive for ME/CFS in the recently afflicted, the opposite was true for subjects ill for more than 2 years. Similarly, while low levels of IL-6 suggested early ME/CFS, the reverse was true in subjects over 18 years of age ill for more than 2 years.

CONCLUSIONS: These preliminary results suggest that IL-1α, 6 and 8 adjusted for illness duration may serve as robust biomarkers, independent of age, in screening for ME/CFS.

Source: Russell L, Broderick G, Taylor R, Fernandes H, Harvey J, Barnes Z, Smylie A, Collado F, Balbin EG, Katz BZ, Klimas NG, Fletcher MA. Illness progression in chronic fatigue syndrome: a shifting immune baseline. BMC Immunol. 2016 Mar 10;17:3. doi: 10.1186/s12865-016-0142-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785654/ (Full article)