What is in a name? Comparing diagnostic criteria for chronic fatigue syndrome with or without fibromyalgia

Abstract:

The current study had two objectives. (1) to compare objective and self-report measures in patients with chronic fatigue syndrome (CFS) according to the 1994 Center for Disease Control (CDC) criteria, patients with multiple sclerosis (MS), and healthy controls, and (2) to contrast CFS patients who only fulfill CDC criteria to those who also fulfill the criteria for myalgic encephalomyelitis (ME), the 2003 Canadian criteria for ME/CFS, or the comorbid diagnosis of fibromyalgia (FM).

One hundred six participants (48 CFS patients diagnosed following the 1994 CDC criteria, 19 MS patients, and 39 healthy controls) completed questionnaires assessing symptom severity, quality of life, daily functioning, and psychological factors. Objective measures consisted of activity monitoring, evaluation of maximal voluntary contraction and muscle recovery, and cognitive performance. CFS patients were screened whether they also fulfilled ME criteria, the Canadian criteria, and the diagnosis of FM.

CFS patients scored higher on symptom severity, lower on quality of life, and higher on depression and kinesiophobia and worse on MVC, muscle recovery, and cognitive performance compared to the MS patients and the healthy subjects. Daily activity levels were also lower compared to healthy subjects. Only one difference was found between those fulfilling the ME criteria and those who did not regarding the degree of kinesiophobia (lower in ME), while comorbidity for FM significantly increased the symptom burden.

CFS patients report more severe symptoms and are more disabled compared to MS patients and healthy controls. Based on the present study, fulfillment of the ME or Canadian criteria did not seem to give a clinically different picture, whereas a diagnosis of comorbid FM selected symptomatically worse and more disabled patients.

 

Source: Meeus M, Ickmans K, Struyf F, Kos D, Lambrecht L, Willekens B, Cras P, Nijs J. What is in a name? Comparing diagnostic criteria for chronic fatigue syndrome with or without fibromyalgia. Clin Rheumatol. 2016 Jan;35(1):191-203. doi: 10.1007/s10067-014-2793-x. Epub 2014 Oct 14. https://www.ncbi.nlm.nih.gov/pubmed/25308475

 

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

 

A Chronic Fatigue Syndrome (CFS) severity score based on case designation criteria

Abstract:

BACKGROUND: Chronic Fatigue Syndrome case designation criteria are scored as physicians’ subjective, nominal interpretations of patient fatigue, pain (headaches, myalgia, arthralgia, sore throat and lymph nodes), cognitive dysfunction, sleep and exertional exhaustion.

METHODS: Subjects self-reported symptoms using an anchored ordinal scale of 0 (no symptom), 1 (trivial complaints), 2 (mild), 3 (moderate), and 4 (severe). Fatigue of 3 or 4 distinguished “Fatigued” from “Not Fatigued” subjects. The sum of the 8(Sum8) ancillary criteria was tested as a proxy for fatigue. All subjects had history and physical examinations to exclude medical fatigue, and ensure categorization as healthy or CFS subjects.

RESULTS: Fatigued subjects were divided into CFS with ≥4 symptoms or Chronic Idiopathic Fatigue (CIF) with ≤3 symptoms. ROC of Sum8 for CFS and Not Fatigued subjects generated a threshold of 14 (specificity=0.934; sensitivity=0.928). CFS (n=256) and CIF (n=55) criteria were refined to include Sum8≥14 and ≤13, respectively. Not Fatigued subjects had highly skewed Sum8 responses. Healthy Controls (HC; n=269) were defined by fatigue≤2 and Sum8≤13. Those with Sum8≥14 were defined as CFS-Like With Insufficient Fatigue Syndrome (CFSLWIFS; n=20). Sum8 and Fatigue were highly correlated (R(2)=0.977; Cronbach’s alpha=0.924) indicating an intimate relationship between symptom constructs. Cluster analysis suggested 4 clades each in CFS and HC. Translational utility was inferred from the clustering of proteomics from cerebrospinal fluid.

CONCLUSIONS: Plotting Fatigue severity versus Sum8 produced an internally consistent classifying system. This is a necessary step for translating symptom profiles into fatigue phenotypes and their pathophysiological mechanisms.

 

Source: Baraniuk JN, Adewuyi O, Merck SJ, Ali M, Ravindran MK, Timbol CR, Rayhan R, Zheng Y, Le U, Esteitie R, Petrie KN. A Chronic Fatigue Syndrome (CFS) severity score based on case designation criteria. Am J Transl Res. 2013;5(1):53-68. Epub 2013 Jan 21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560481/ (Full article)

 

Metacognitions and negative emotions as predictors of symptom severity in chronic fatigue syndrome

Abstract:

OBJECTIVE: Chronic fatigue syndrome (CFS) describes a condition that is primarily characterized by fatigue and flu-like symptoms that are not alleviated by rest. This study investigated the relationship among metacognitions, negative emotions, and symptom severity in CFS.

METHODS: A total of 96 patients who had received a diagnosis of CFS according to the Oxford Criteria completed a battery of self-report measures that consisted of the Depression Anxiety Stress Scales, the 30-Item Metacognitions Questionnaire, the Chalder Fatigue Questionnaire (CFQ), and the RAND 36-Item Short-Form Health Survey-Physical Functioning.

RESULTS: Correlation analyses showed that negative emotions and metacognitions were positively correlated with measures of symptom severity and that metacognitions were a better predictor of symptom severity than anxiety and depression. Hierarchical regression analyses indicated that (1) lack of cognitive confidence predicted both mental and physical factors of the CFQ and physical functioning independently of negative emotions and (2) beliefs about the need to control thoughts predicted the mental factor of the CFQ independently of negative emotions and lack of cognitive confidence.

CONCLUSION: The data support the potential application of the metacognitive model of psychological disorder to understanding CFS.

Copyright © 2011 Elsevier Inc. All rights reserved.

 

Source: Maher-Edwards L, Fernie BA, Murphy G, Wells A, Spada MM. Metacognitions and negative emotions as predictors of symptom severity in chronic fatigue syndrome. J Psychosom Res. 2011 Apr;70(4):311-7. doi: 10.1016/j.jpsychores.2010.09.016. Epub 2010 Nov 18. https://www.ncbi.nlm.nih.gov/pubmed/21414450

 

Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a complex, multi-symptom illness with a multisystem pathogenesis involving alterations in the nervous, endocrine and immune systems.Abnormalities in stress responses have been identified as potential triggers or mediators of CFS symptoms. This study focused on the stress mediator neuropeptide Y (NPY). We hypothesized that NPY would be a useful biomarker for CFS.

METHODS: The CFS patients (n = 93) were from the Chronic Fatigue and Related Disorders Clinic at the University of Miami and met the 1994 case definition of Fukuda and colleagues. Healthy sedentary controls (n = 100)) were from NIH or VA funded studies. Another fatiguing, multi-symptom illness, Gulf War Illness (GWI), was also compared to CFS. We measured NPY in plasma using a radioimmunoassay (RIA). Psychometric measures, available for a subset of CFS patients included: Perceived Stress Scale, Profile of Mood States, ATQ Positive & Negative Self-Talk Scores, the COPE, the Beck Depression Inventory, Fatigue Symptom Inventory, Cognitive Capacity Screening Examination, Medical Outcomes Survey Short Form-36, and the Quality of Life Scale.

RESULTS: Plasma NPY was elevated in CFS subjects, compared to controls (p = .000) and to GWI cases (p = .000). Receiver operating characteristics (ROC) curve analyses indicated that the predictive ability of plasma NPY to distinguish CFS patients from healthy controls and from GWI was significantly better than chance alone. In 42 patients with CFS, plasma NPY had significant correlations (<0.05) with perceived stress, depression, anger/hostility, confusion, negative thoughts, positive thoughts, general health, and cognitive status. In each case the correlation (+ or -) was in the anticipated direction.

CONCLUSIONS: This study is the first in the CFS literature to report that plasma NPY is elevated compared to healthy controls and to a fatigued comparison group, GWI patients. The significant correlations of NPY with stress, negative mood, general health, depression and cognitive function strongly suggest that this peptide be considered as a biomarker to distinguish subsets of CFS.

 

Source: Fletcher MA, Rosenthal M, Antoni M, Ironson G, Zeng XR, Barnes Z, Harvey JM, Hurwitz B, Levis S, Broderick G, Klimas NG. Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome. Behav Brain Funct. 2010 Dec 29;6:76. doi: 10.1186/1744-9081-6-76. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024290/ (Full article)

 

Fluctuation of serum vitamin E (alpha-tocopherol) concentrations during exacerbation and remission phases in patients with chronic fatigue syndrome

Abstract:

The etiology of chronic fatigue syndrome remains unknown. Oxidative stress may be involved in its pathogenesis. Vitamin E is a major endogenous lipid-soluble antioxidative substance, and is consumed during the lipid peroxidation process.

We studied a population comprising 27 patients with chronic fatigue syndrome (10 men and 17 women, 29 +/- 6 years of age) and 27 age- and sex-matched control subjects. Serum vitamin E (alpha-tocopherol) concentrations were determined and expressed as mg/g total lipids (total cholesterol and triglyceride) to evaluate oxidative stress. Serum alpha-tocopherol concentrations (mg/g lipids) were significantly (P < 0.001) lower in the patients with chronic fatigue syndrome (2.81 +/- 0.73) than in the control subjects (3.88 +/- 0.65).

The patients with chronic fatigue syndrome were re-examined during a follow-up interval. After 8 +/- 2 months, 16 patients exhibited a status that warranted re-examination during remission of the symptoms at a regular visit to our hospital (Group 1), while the remaining 11 did not (Group 2). The serum alpha-tocopherol levels were significantly elevated during remission as compared with those at baseline in Group 1 (2.71 +/- 0.62 –> 3.24 +/- 0.83, P < 0.001). The levels did not significantly change after the interval in Group 2 (2.97 +/- 0.86 –> 2.85 +/- 0.73, not significant).

In conclusion, serum alpha-tocopherol concentrations were significantly lower in the patients with chronic fatigue syndrome as compared with the control subjects, suggesting increased oxidative stress in the former. The low level of serum alpha-tocopherol was ameliorated during the remission phase as compared with the exacerbation phase in the patients with chronic fatigue syndrome, suggesting that increased oxidative stress may be involved in the pathogenesis of chronic fatigue syndrome and might also be directly related to the severity of the symptoms of chronic fatigue syndrome.

 

Source: Miwa K, Fujita M. Fluctuation of serum vitamin E (alpha-tocopherol) concentrations during exacerbation and remission phases in patients with chronic fatigue syndrome. Heart Vessels. 2010 Jul;25(4):319-23. doi: 10.1007/s00380-009-1206-6. Epub 2010 Jul 31. https://www.ncbi.nlm.nih.gov/pubmed/20676841

 

Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) patients often report symptom flare (SF) for >24 h after moderate exercise (post-ex). We hypothesized that SF is linked to increases in circulating cytokines and CD40 Ligand (CD40L). In 19 CFS patients and 17 controls, mental and physical fatigue and pain symptom ratings were obtained together with serum for 11 cytokines and CD40L before and at 0.5, 8, 24, and 48 h post-ex.

Before exercise, CFS had lower CD40L (p<.05) but similar cytokines versus controls. In subgroups based on SF at 48 h, high SF patients (n=11) increased in IL-1beta, IL-12, IL-6, IL-8, IL-10, and IL-13 (p<.05) 8 h post-ex. Low SF patients (n=8) showed post-ex decreases in IL-10, IL-13, and CD40L, and controls decreased in IL-10, CD40L, and TNFalpha (p<.05). Thus, in CFS, cytokine activity may vary directly with SF, which may explain prior inconsistent findings.

 

Source: White AT, Light AR, Hughen RW, Bateman L, Martins TB, Hill HR, Light KC. Severity of symptom flare after moderate exercise is linked to cytokine activity in chronic fatigue syndrome. Psychophysiology. 2010 Jul 1;47(4):615-24. doi: 10.1111/j.1469-8986.2010.00978.x. Epub 2010 Mar 4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378647/ (Full article)

 

Evidence for T-helper 2 shift and association with illness parameters in chronic fatigue syndrome (CFS)

Abstract:

Few immunological markers have been consistently reported in CFS. However, a shift to a T-helper 2 (Th2) type immune response has been hypothesized for individuals with CFS. The current study investigated whether individuals with CFS who exhibited a stronger shift towards a Th2 type of immune response would also exhibit more severe symptoms, poorer neurocognitive functioning, and poorer physical and psychosocial functioning.

The current investigation measured the percentage of Th1-like and Th2-like memory cells using cell surface flow cytometry in 114 individuals with CFS. The associations between the ratio of Th1 and Th2 memory cells and various illness parameters measures were then examined, including symptom severity, psychiatric functioning, neurocognitive functioning, salivary cortisol levels, and chronic pain status.

Results indicated that individuals who exhibited a more extreme shift towards a Th2 immune response also exhibited poorer sleep and high levels of basal salivary cortisol. The implications of these findings are discussed.

 

Source: Torres-Harding S, Sorenson M, Jason LA, Maher K, Fletcher MA. Evidence for T-helper 2 shift and association with illness parameters in chronic fatigue syndrome (CFS). Bull IACFS ME. 2008 Fall;16(3):19-33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018761/ (Full article)

 

Differential diagnosis of chronic fatigue syndrome and major depressive disorder

Abstract:

The goal of this study was to identify variables that successfully differentiated patients with chronic fatigue syndrome, major depressive disorder, and controls. Fifteen participants were recruited for each of these three groups, and discriminant function analyses were conducted.

Using symptom occurrence and severity data from the Fukuda et al. (1994) definitional criteria, the best predictors were postexertional malaise, unrefreshing sleep, and impaired memory-concentration. Symptom occurrence variables only correctly classified 84.4% of cases, whereas 91.1% were correctly classified when using symptom severity ratings. Finally, when using percentage of time fatigue reported, postexertional malaise severity, unrefreshing sleep severity, confusion-disorientation severity, shortness of breath severity, and self-reproach to predict group membership, 100% were classified correctly.

 

Source: Hawk C, Jason LA, Torres-Harding S. Differential diagnosis of chronic fatigue syndrome and major depressive disorder. Int J Behav Med. 2006;13(3):244-51. https://www.ncbi.nlm.nih.gov/pubmed/17078775