Category: Symptoms

Evidence for generalized hyperalgesia in chronic fatigue syndrome: a case control study

Abstract:

Several studies provided evidence for generalized hyperalgesia in fibromyalgia or whiplash-associated disorders. In chronic fatigue syndrome, however, pain is a frequently reported complaint, but up to now, evidence for generalized hyperalgesia is lacking.

The aim of this study is to examine whether the pressure pain thresholds (PPTs) at both symptomatic and asymptomatic sites differ in chronic fatigue syndrome (CFS) patients with chronic pain, compared to healthy controls.

Therefore, 30 CFS patients with chronic pain and 30 age- and gender-matched healthy controls indicated on a Margolis Pain Diagram where they felt pain lasting longer than 24 h in the past 4 weeks. After completing a test battery of questionnaires evaluating pain cognitions, functional status and symptomatology, a blinded researcher assessed PPTs bilaterally at seven nonspecific sites on both trunk and extremities. PPTs were compared for the two complete groups.

In addition, PPTs of patients and controls who did not report pain in a respective zone were compared. PPTs of the patients were significantly lower (p<0.001) compared to those of the control group, also when pain-free samples per zone were compared (p<0.001). The mean PPT was 3.30 kg/cm2 in all CFS patients and 8.09 kg/cm2 in the controls. No confounding factors responsible for the observed differences, as, e.g., catastrophizing and depression, could be revealed.

These findings provide evidence for the existence of hyperalgesia even in asymptomatic areas (generalized secondary hyperalgesia). The generalized hyperalgesia may represent the involvement of a sensitized central nervous system.

 

Source: Meeus M, Nijs J, Huybrechts S, Truijen S. Evidence for generalized hyperalgesia in chronic fatigue syndrome: a case control study. Clin Rheumatol. 2010 Apr;29(4):393-8. doi: 10.1007/s10067-009-1339-0. https://www.ncbi.nlm.nih.gov/pubmed/20077123

 

Sleep is not disrupted by exercise in patients with chronic fatigue syndromes

Abstract:

PURPOSE: Patients with chronic fatigue syndrome (CFS) report that exertion produces dramatic symptom worsening. We hypothesized this might be due to the exacerbation of an underlying sleep disorder, which we have previously demonstrated to exist.

METHODS: Female patients with CFS and matched healthy controls with no evidence of major depressive disorder were studied with overnight polysomnography on a baseline night and on a night after their performance of a maximal exercise test.

RESULTS: CFS patients as a group had evidence for disturbed sleep compared with controls. Although exercise improved sleep for healthy subjects, it did not do this for the group as a whole. When we stratified the sample on the basis of self-reported sleepiness after a night’s sleep, the patient group with reduced morning sleepiness showed improvement in sleep structure, whereas those with increased morning sleepiness continued to show evidence for sleep disruption.

CONCLUSIONS: Sleep is disturbed in CFS patients as a group, but exercise does not exacerbate this sleep disturbance. Approximately half the patients studied actually sleep better after exercise. Therefore, activity-related symptom worsening is not caused by worsened sleep.

 

Source: Togo F, Natelson BH, Cherniack NS, Klapholz M, Rapoport DM, Cook DB. Sleep is not disrupted by exercise in patients with chronic fatigue syndromes. Med Sci Sports Exerc. 2010 Jan;42(1):16-22. doi: 10.1249/MSS.0b013e3181b11bc7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796587/ (Full article)

 

Sleep apnea and psychological functioning in chronic fatigue syndrome

Abstract:

Objectives were to explore: (1) whether sleep apnea/hypopnea syndrome (SAHS) should be considered a chronic fatigue syndrome (CFS) comorbidity, rather than a diagnostic exclusion criterion; and (2) to compare sleep/wake/ psychopathology in individuals with CFS, controls and another illness.

Participants (CFS, SAHS, controls) completed questionnaires and were evaluated for SAHS; 68 percent were subsequently diagnosed with SAHS. CFS participants with and without SAHS did not differ. Both clinical groups were less well adjusted than controls. We conclude that SAHS should not be an exclusion criterion for CFS and that psychological problems in CFS seem a consequence of coping with illness.

 

Source: Libman E, Creti L, Baltzan M, Rizzo D, Fichten CS, Bailes S. Sleep apnea and psychological functioning in chronic fatigue syndrome. J Health Psychol. 2009 Nov;14(8):1251-67. Doi: 10.1177/1359105309344895. https://www.ncbi.nlm.nih.gov/pubmed/19858344

 

Transcription profile analysis of vastus lateralis muscle from patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a disabling condition characterized by unexplained chronic fatigue that impairs normal activities. Many body systems are affected and etiology has not yet been identified. In addition to immunological and psychological aspects, skeletal muscle symptoms are prominent in CFS patients.

In an effort to establish which pathways might be involved in the onset and development of muscle symptoms, we used global transcriptome analysis to identify genes that were differentially expressed in the vastus lateralis muscle of female and male CFS patients.

We found that the expression of genes that play key roles in mitochondrial function and oxidative balance, including superoxide dismutase 2, were altered, as were genes involved in energy production, muscular trophism and fiber phenotype determination. Importantly, the expression of a gene encoding a component of the nicotinic cholinergic receptor binding site was reduced, suggesting impaired neuromuscular transmission. We argue that these major biological processes could be involved in and/or responsible for the muscle symptoms of CFS.

Source: Pietrangelo T, Mancinelli R, Toniolo L, Montanari G, Vecchiet J, Fanò G, Fulle S. Transcription profile analysis of vastus lateralis muscle from patients with chronic fatigue syndrome. Int J Immunopathol Pharmacol. 2009 Jul-Sep;22(3):795-807. https://www.ncbi.nlm.nih.gov/pubmed/19822097

 

Electroencephalographic correlates of Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Unremitting fatigue and unrefreshing sleep, hallmark traits of Chronic Fatigue Syndrome (CFS), are also pathognomonic of sleep disorders. Yet, no reproducible perturbations of sleep architecture, multiple sleep latency times or Epworth Sleepiness Scores are found to be associated consistently with CFS. This led us to hypothesize that sleep homeostasis, rather than sleep architecture, may be perturbed in CFS. To probe this hypothesis, we measured and compared EEG frequencies associated with restorative sleep between persons with CFS and matched controls, both derived from a population-based sample.

METHODS: We evaluated overnight polysomnography (PSG) in 35 CFS and 40 control subjects. PSG records were manually scored and epochs containing artifact removed. Fast Fourier Transformation was utilized to deconstruct individual EEG signals into primary frequency bands of alpha, delta, theta, sigma, and beta frequency domains. The spectral power of each frequency domain for each sleep state was compared between persons with CFS and matched controls.

RESULTS: In persons with CFS, delta power was diminished during slow wave sleep, but elevated during both stage 1 and REM. Alpha power was reduced during stage 2, slow wave, and REM sleep. Those with CFS also had significantly lower theta, sigma, and beta spectral power during stage 2, Slow Wave Sleep, and REM.

DISCUSSION: Employing quantitative EEG analysis we demonstrate reduced spectral power of cortical delta activity during SWS. We also establish reduced spectral power of cortical alpha activity, with the greatest reduction occurring during REM sleep. Reductions in theta, beta, and sigma spectral power were also apparent.

CONCLUSION: Unremitting fatigue and unrefreshing sleep, the waking manifestations of CFS, may be the consequence of impaired sleep homeostasis rather than a primary sleep disorder.

 

Source: Decker MJ, Tabassum H, Lin JM, Reeves WC. Electroencephalographic correlates of Chronic Fatigue Syndrome. Behav Brain Funct. 2009 Oct 6;5:43. doi: 10.1186/1744-9081-5-43. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2765956/ (Full article)

 

Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects

Abstract:

Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue, often accompanied by widespread muscle pain that meets criteria for fibromyalgia syndrome (FMS). Symptoms become markedly worse after exercise. Previous studies implicated dysregulation of the sympathetic nervous system (SNS), and immune system (IS) in CFS and FMS.

We recently demonstrated that acid sensing ion channel (probably ASIC3), purinergic type 2X receptors (probably P2X4 and P2X5) and the transient receptor potential vanilloid type 1 (TRPV1) are molecular receptors in mouse sensory neurons detecting metabolites that cause acute muscle pain and possibly muscle fatigue. These molecular receptors are found on human leukocytes along with SNS and IS genes.

Real-time, quantitative PCR showed that 19 CFS patients had lower expression of beta-2 adrenergic receptors but otherwise did not differ from 16 control subjects before exercise. After a sustained moderate exercise test, CFS patients showed greater increases than control subjects in gene expression for metabolite detecting receptors ASIC3, P2X4, and P2X5, for SNS receptors alpha-2A, beta-1, beta-2, and COMT and IS genes for IL10 and TLR4 lasting from 0.5 to 48 hours (P < .05). These increases were also seen in the CFS subgroup with comorbid FMS and were highly correlated with symptoms of physical fatigue, mental fatigue, and pain.

These new findings suggest dysregulation of metabolite detecting receptors as well as SNS and IS in CFS and CFS-FMS.

PERSPECTIVE: Muscle fatigue and pain are major symptoms of CFS. After moderate exercise, CFS and CFS-FMS patients show enhanced gene expression for receptors detecting muscle metabolites and for SNS and IS, which correlate with these symptoms. These findings suggest possible new causes, points for intervention, and objective biomarkers for these disorders.

 

Source: Light AR, White AT, Hughen RW, Light KC. Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects. J Pain. 2009 Oct;10(10):1099-112. doi: 10.1016/j.jpain.2009.06.003. Epub 2009 Jul 31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757484/ (Full article)

 

Exploratory analysis of the relationships between aerobic capacity and self-reported fatigue in patients with rheumatoid arthritis, polymyositis, and chronic fatigue syndrome

Abstract:

OBJECTIVE: To determine if self-reported levels of physical activity and fatigue are related to peak oxygen uptake (VO(2peak)) and whether these relationships differ among the patient groups (rheumatoid arthritis [RA], polymyositis [PM], and chronic fatigue syndrome [CFS]).

DESIGN: Correlational investigation.

SETTING: Two ambulatory research clinics at the National Institutes of Health, Clinical Center, Bethesda, MD.

PARTICIPANTS: There were 9 patients with PM, 10 with RA, and 10 with CFS. All patients met case criteria for their respective diagnoses. METHODS/MAIN OUTCOME MEASUREMENTS: VO(2peak) during bicycle ergometry and self-reported fatigability, fatigue, and physical activity. VO(2peak) was used as the criterion measurement of physiological fatigue with which the self-reported variables were compared.

RESULTS: The Pearson r revealed that self-reported physical activity correlated with VO(2peak) (r = 61, P = .01). However, fatigability and fatigue did not correlate with VO(2peak). Linear regression analysis was performed to assess the effects of diagnosis group, self-reported activity level or fatigue, and their interaction. A trend in the data showed a distinctive relationship between fatigue/fatigability within the 3 groups. In addition, when controlling for group status, self-reported activity predicted aerobic capacity as measured by VO(2peak).

CONCLUSIONS: This study confirms that patients with chronic, but stable RA, PM, or CFS are fatigued and have significantly decreased aerobic capacity. Self-reports of physical activity predicted VO(2peak), and may be used as an indicator of activity-based aerobic capacity. Self-reports of fatigue, however, did not correlate with VO(2peak) and hence are assessing something other than an index of aerobic capacity, and provide additional information about patients’ perceptions, which will require further investigation.

 

Source: Weinstein AA, Drinkard BM, Diao G, Furst G, Dale JK, Straus SE, Gerber LH. Exploratory analysis of the relationships between aerobic capacity and self-reported fatigue in patients with rheumatoid arthritis, polymyositis, and chronic fatigue syndrome. PM R. 2009 Jul;1(7):620-8. doi: 10.1016/j.pmrj.2009.04.007. https://www.ncbi.nlm.nih.gov/pubmed/19627955

 

High slow-wave sleep and low-light sleep: chronic fatigue syndrome is not likely to be a primary sleep disorder

Abstract:

The status of chronic fatigue syndrome (CFS) is still under debate. Mainstream views still often consider it as an undetected primary sleep disorder or as the psychosomatic expression of a related anxiety or depression syndrome. Both primary sleep disorder and CFS are often related to unrefreshing sleep and affective daytime symptoms.

The present study compares nonrapid eye movement sleep distribution between patients with a primary sleep disorder and “pure” CFS patients without sleep or mood disorders. Intensity measures of affective symptoms are also analyzed. Sleep variables of 32 pure CFS (mean age, 41.9 +/- 8.7 years; 25 women), 30 Sleep Apnea Hypopnea Syndrome patients (mean age, 43.7 +/- 6.7 years; 13 women), and 14 healthy controls (mean age, 40.2 +/- 7.6 years; 9 women) were compared. Related affective symptoms were assessed using the self-reported Zung anxiety and depression scales.

The study confirms previous reports on increased slow-wave sleep in CFS patients. Both patient groups showed similar sleep duration and efficiency. Sleep efficiency was lower in both patient groups compared with controls. CFS patients showed a higher microarousal index than controls. Anxiety, but not depression symptoms were more intense in the CFS group. The distribution of nonrapid eye movement sleep in CFS differs sizeably from what can be observed in a primary sleep disorder.

 

Source: Neu D, Cappeliez B, Hoffmann G, Verbanck P, Linkowski P, Le Bon O. High slow-wave sleep and low-light sleep: chronic fatigue syndrome is not likely to be a primary sleep disorder. J Clin Neurophysiol. 2009 Jun;26(3):207-12. doi: 10.1097/WNP.0b013e3181a1841b. https://www.ncbi.nlm.nih.gov/pubmed/19424087

 

On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics

Abstract:

Close similarities in the courses of multiple sclerosis and schizophrenia laid the theoretical ground for attempting to find a common infectious aetiology for the two diseases. Chlamydia pneumoniae, which belongs to the rickettsial family of microorganisms has been linked to both diseases. It is postulated that since rickettsial microorganisms are ubiquitous in human populations they and the human species normally live in peaceful coexistence. In rare cases, for unknown reasons, varieties of them may become aggressive and pathogenic.

The kynurenic acid hypothesis of schizophrenia has attracted much attention. It also seems to have initiated a paradigmatic shift from the hitherto prevailing serological research approach to one which focuses on immunological factors.

An open clinical pilot study in which, during 2006, eight female and five male patients with psychotic symptoms were treated with a combination of antibiotics is presented, to which, in the beginning of 2007 two female patients suffering from severe and long standing chronic fatigue syndrome were added. On one year follow-up, six out of the eight female patients showed stable excellent treatment results, whereas two were rated as showing significant treatment results. Four of the five men who entered the study were suffering from chronic schizophrenia, whereas the fifth, was a case of severe acute catatonic schizophrenia.

Two of the male patients showed significant treatment results, whereas three of them were rated as having had a slight to moderate improvement. No less than three of the women had suffered their first episode of psychosis after giving birth to their first (and only) child. This finding, as these women all responded excellently to treatment with antibiotics, indicates that post partum psychosis could be regarded as an infectious complication of childbirth of, as to the causative agent, unknown aetiology. High priority ought therefore be given to initiate controlled clinical trials with antibiotic treatment of this serious condition. The otherwise promising results of the pilot study seem to warrant further and controlled clinical trials with treatment with antibiotics of patients with psychotic symptoms.

As the second patient with psychotic symptoms to enter the study, had a long standing history of chronic fatigue, where an initial treatment with the antidepressant fluoxetine had only worsened her condition, whereas ninety days of treatment with antibiotics, combined with vitamin B injections, effected a complete recovery, the author decided, when two patients with long standing and incapacitating chronic fatigue syndromes sought the clinic in February and March 2007, to include them in the study. The first of them, after sixty days of treatment with antibiotics showed excellent treatment results on follow-up one year later, whereas the second, who also took the combination of antibiotics for sixty days, was rated as having shown a significant improvement.

Comment in: Hypotheses concerning rickettsial microorganisms, autoimmune diseases and new treatment strategies. [Med Hypotheses. 2010]

 

Source: Frykholm BO. On the question of infectious aetiologies for multiple sclerosis, schizophrenia and the chronic fatigue syndrome and their treatment with antibiotics. Med Hypotheses. 2009 Jun;72(6):736-9. doi: 10.1016/j.mehy.2008.11.045. Epub 2009 Mar 6. https://www.ncbi.nlm.nih.gov/pubmed/19269110

 

Exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing

Abstract:

OBJECTIVES: This study aimed to examine the associations between bodily pain, pain catastrophizing, depression, activity limitations/participation restrictions, employment status, and exercise performance in female patients with chronic fatigue syndrome (CFS) who experience widespread pain.

DESIGN: Cross-sectional observational study.

SETTING: A university-based clinic.

PATIENTS: Thirty-six female CFS patients who experienced widespread pain.

OUTCOME MEASURES: Patients filled in the Medical Outcomes Short-Form 36 Health Status Survey, the Chronic Fatigue Syndrome Activities and Participation Questionnaire, the Beck Depression Inventory, and the Pain Catastrophizing Scale, and underwent a maximal exercise stress test with continuous monitoring of electrocardiographic and ventilatory parameters.

RESULTS: Pain catastrophizing was related to bodily pain (r = -0.70), depression (r = 0.55), activity limitations/participation restrictions (r = 0.68), various aspects of quality of life ( r varied between -0.51 and -0.64), and exercise capacity (r varied between -0.41 and -0.61). Based on hierarchical multiple regression analysis, pain catastrophizing accounted for 41% of the variance in bodily pain in female CFS patients who experience chronic widespread musculoskeletal pain. Among the three subscale scores of the Pain Catastrophizing Scale, helplessness and rumination rather than magnification were strongly related to bodily pain. Neither pain catastrophizing nor depression was related to employment status.

CONCLUSIONS: These data provide evidence favoring a significant association between pain catastrophizing, bodily pain, exercise performance, and self-reported disability in female patients with CFS who experience widespread pain. Further prospective longitudinal studying of these variables is required.

Comment in: Response to: exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing. [Pain Med. 2009]

 

Source: Nijs J, Van de Putte K, Louckx F, Truijen S, De Meirleir K. Exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing. Pain Med. 2008 Nov;9(8):1164-72. Epub 2007 Oct 3. http://painmedicine.oxfordjournals.org/content/9/8/1164.long (Full article)