Tag: chronic fatigue syndrome vs fibromyalgia

Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia?

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are complex and serious illnesses that affect approximately 2.5% and 5% of the general population worldwide, respectively. The etiology is unknown; however, recent studies suggest that mitochondrial dysfunction has been involved in the pathophysiology of both conditions. We have investigated the possible association between mitochondrial biogenesis and oxidative stress in patients with CFS and FM.

We studied 23 CFS patients, 20 FM patients, and 15 healthy controls. Peripheral blood mononuclear cell showed decreased levels of Coenzyme Q10 from CFS patients (p<0.001 compared with controls) and from FM subjects (p<0.001 compared with controls) and ATP levels for CFS patients (p<0.001 compared with controls) and for FM subjects (p<0.001 compared with controls).

On the contrary, CFS/FM patients had significantly increased levels of lipid peroxidation, respectively (p<0.001 for both CFS and FM patients with regard to controls) that were indicative of oxidative stress-induced damage. Mitochondrial citrate synthase activity was significantly lower in FM patients (p<0.001) and, however, in CFS, it resulted in similar levels than controls. Mitochondrial DNA content (mtDNA/gDNA ratio) was normal in CFS and reduced in FM patients versus healthy controls, respectively (p<0.001). Expression levels of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha and transcription factor A, mitochondrial by immunoblotting were significantly lower in FM patients (p<0.001) and were normal in CFS subjects compared with healthy controls.

These data lead to the hypothesis that mitochondrial dysfunction-dependent events could be a marker of differentiation between CFS and FM, indicating the mitochondria as a new potential therapeutic target for these conditions.

 

Source: Castro-Marrero J, Cordero MD, Sáez-Francas N, Jimenez-Gutierrez C, Aguilar-Montilla FJ, Aliste L, Alegre-Martin J. Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia? Antioxid Redox Signal. 2013 Nov 20;19(15):1855-60. doi: 10.1089/ars.2013.5346. Epub 2013 May 29. https://www.ncbi.nlm.nih.gov/pubmed/23600892

 

Is chronic fatigue syndrome the same illness as fibromyalgia: evaluating the ‘single syndrome’ hypothesis

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are medically unexplained syndromes that can and often do co-occur. For this reason, some have posited that the two are part of the same somatic syndrome–examples of symptom amplification. This hypothesis would suggest that few differences exist between the two syndromes. To evaluate this interpretation, we have searched the literature for articles comparing CFS to FM, reviewing only those articles which report differences between the two. This review presents data showing differences across a number of parameters–implying that the underlying pathophysiology in CFS may differ from that of FM. We hope that our review encourages other groups to look for additional differences between CFS and FM. By continuing to preserve the unique illness definitions of the two syndromes, clinicians will be able to better identify, understand and provide treatment for these individuals.

 

Source: Abbi B, Natelson BH. Is chronic fatigue syndrome the same illness as fibromyalgia: evaluating the ‘single syndrome’ hypothesis. QJM. 2013 Jan;106(1):3-9. doi: 10.1093/qjmed/hcs156. Epub 2012 Aug 26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527744/ (Full article)

 

Linking disease symptoms and subtypes with personalized systems-based phenotypes: a proof of concept study

Abstract:

A dynamic systems model was used to generate parameters describing a phenotype of Hypothalamic-Pituitary-Adrenal (HPA) behavior in a sample of 36 patients with chronic fatigue syndrome (CFS) and/or fibromyalgia (FM) and 36 case-matched healthy controls. Altered neuroendocrine function, particularly in relation to somatic symptoms and poor sleep quality, may contribute to the pathophysiology of these disorders.

Blood plasma was assayed for cortisol and ACTH every 10 min for 24h. The dynamic model was specified with an ordinary differential equation using three parameters: (1) ACTH-adrenal signaling, (2) inhibitory feedback, and (3) non-ACTH influences. The model was “personalized” by estimating an individualized set of parameters from each participant’s data. Day and nighttime parameters were assessed separately.

Two nocturnal parameters (ACTH-adrenal signaling and inhibitory feedback) significantly differentiated the two patient subgroups (“fatigue-predominant” patients with CFS only versus “pain-predominant” patients with FM and comorbid chronic fatigue) from controls (all p’s<.05), whereas daytime parameters and diurnal/nocturnal slopes did not. The same nocturnal parameters were significantly associated with somatic symptoms among patients (p’s<.05). There was a significantly different pattern of association between nocturnal non-ACTH influences and sleep quality among patients versus controls (p<.05).

Although speculative, the finding that patient somatic symptoms decreased when more cortisol was produced per unit ACTH, is consistent with cortisol’s anti-inflammatory and sleep-modulatory effects. Patients’ HPA systems may compensate by promoting more rapid or sustained cortisol production. Mapping “behavioral phenotypes” of stress-arousal systems onto symptom clusters may help disentangle the pathophysiology of complex disorders with frequent comorbidity.

Copyright © 2012 Elsevier Inc. All rights reserved.

Comment in: A moving target: taking aim at the regulatory dynamics of illness. [Brain Behav Immun. 2012]

 

Source: Aschbacher K, Adam EK, Crofford LJ, Kemeny ME, Demitrack MA, Ben-Zvi A. Linking disease symptoms and subtypes with personalized systems-based phenotypes: a proof of concept study. Brain Behav Immun. 2012 Oct;26(7):1047-56. doi: 10.1016/j.bbi.2012.06.002. Epub 2012 Jun 9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725324/ (Full article)

 

Responses to exercise differ for chronic fatigue syndrome patients with fibromyalgia

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are chronic multisymptom illnesses with substantial clinical and diagnostic overlap. We have previously shown that, when controlling for aerobic fitness and accounting for comorbid FM, CFS patients do not exhibit abnormal cardiorespiratory responses during maximal aerobic exercise compared with healthy controls, despite differences in pain and exertion.

PURPOSE: The purpose of the present study was to examine cardiac and perceptual responses to steady-state submaximal exercise in CFS patients and healthy controls.

METHODS: Twenty-one CFS patients (13 CFS with comorbid FM (CFS + FM)) and 14 controls completed 20 min of submaximal cycling exercise. Impedance cardiography was used to determine cardiac responses during exercise. Systolic blood pressure (SBP), RPE, and leg muscle pain were also measured. Data were analyzed using a doubly multivariate, repeated-measures MANOVA to model the exercise response.

RESULTS: There was a significant multivariate time-by-group interaction (P < 0.05). The CFS + FM group exhibited an exercise response characterized by higher stroke index, ventilatory equivalents for oxygen and carbon dioxide and RPE, lower SBP, and similar HR responses compared to controls.

CONCLUSIONS: The present results extend on our previous work with maximal exercise and show that CFS and CFS + FM differ in their responses to steady-state exercise. These results highlight the importance of accounting for comorbid conditions when conducting CFS research, particularly when examining psychophysiological responses to exercise.

 

Source: Cook DB, Stegner AJ, Nagelkirk PR, Meyer JD, Togo F, Natelson BH. Responses to exercise differ for chronic fatigue syndrome patients with fibromyalgia. Med Sci Sports Exerc. 2012 Jun;44(6):1186-93. doi: 10.1249/MSS.0b013e3182417b9a. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319493/ (Full article)

 

Fibromyalgia and chronic fatigue syndrome in children

Abstract:

BACKGROUND: Fibromyalgia (FM) is characterized by widespread persistent pain and the presence of multiple discrete tender points. Chronic fatigue syndrome (CFS) is a syndrome characterized by debilitating fatigue associated with a variable number of non-specific complaints. Because neither condition had necessarily been recognized in children until recently, those patients have been treated as having school refusal without being diagnosed as having either syndrome. There is a considerable overlap of clinical symptoms between these two syndromes. It is therefore controversial as to whether these syndromes have the same pathogenesis or not. The aim of the present study was to clarify the relationship between these syndromes in children.

METHODS: Fifteen patients with FM and 21 patients with CFS were investigated both clinically and immunologically. Immunological assessments included thorough analysis of autoantibodies using several techniques.

RESULTS: Anti-nuclear antibody titers were higher and the prevalence of anti-Sa antibody was far more frequent in CFS patients than in FM patients.

CONCLUSION: CFS and FM are different from each other at least in childhood, from an immunological aspect, although some patients could have both conditions.

© 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

 

Source: Itoh Y, Shigemori T, Igarashi T, Fukunaga Y. Fibromyalgia and chronic fatigue syndrome in children. Pediatr Int. 2012 Apr;54(2):266-71. doi: 10.1111/j.1442-200X.2011.03514.x. Epub 2012 Jan 12. https://www.ncbi.nlm.nih.gov/pubmed/22115414

 

Genetics and Gene Expression Involving Stress and Distress Pathways in Fibromyalgia with and without Comorbid Chronic Fatigue Syndrome

Abstract:

In complex multisymptom disorders like fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) that are defined primarily by subjective symptoms, genetic and gene expression profiles can provide very useful objective information.

This paper summarizes research on genes that may be linked to increased susceptibility in developing and maintaining these disorders, and research on resting and stressor-evoked changes in leukocyte gene expression, highlighting physiological pathways linked to stress and distress. These include the adrenergic nervous system, the hypothalamic-pituitary-adrenal axis and serotonergic pathways, and exercise responsive metabolite-detecting ion channels.

The findings to date provide some support for both inherited susceptibility and/or physiological dysregulation in all three systems, particularly for catechol-O-methyl transferase (COMT) genes, the glucocorticoid and the related mineralocorticoid receptors (NR3C1, NR3C2), and the purinergic 2X4 (P2X4) ion channel involved as a sensory receptor for muscle pain and fatigue and also in upregulation of spinal microglia in chronic pain models. Methodological concerns for future research, including potential influences of comorbid clinical depression and antidepressants and other medications, on gene expression are also addressed.

 

Source: Light KC, White AT, Tadler S, Iacob E, Light AR. Genetics and Gene Expression Involving Stress and Distress Pathways in Fibromyalgia with and without Comorbid Chronic Fatigue Syndrome. Pain Res Treat. 2012;2012:427869. doi: 10.1155/2012/427869. Epub 2011 Sep 29. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3200121/ (Full article)

 

Sleep-stage dynamics in patients with chronic fatigue syndrome with or without fibromyalgia

Abstract:

STUDY OBJECTIVES: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are medically unexplained conditions that often have overlapping symptoms, including sleep-related complaints. However, differences between the 2 conditions have been reported, and we hypothesized that dynamic aspects of sleep would be different in the 2 groups of patients.

PARTICIPANTS: Subjects were 26 healthy control subjects, 14 patients with CFS but without FM (CFS alone), and 12 patients with CFS and FM (CFS+FM)-all women.

MEASUREMENTS AND RESULTS: We studied transition probabilities and rates between sleep stages (waking, rapid eye movement [REM] sleep, stage 1 [S1], stage 2 [S2], and slow-wave sleep [SWS]) and duration distributions of each sleep stage. We found that the probability of transition from REM sleep to waking was significantly greater in subjects with CFS alone than in control subjects, which may be the specific sleep problem for people with CFS alone. Probabilities of (a) transitions from waking, REM sleep, and S1 to S2 and (b) those from SWS to waking and S1 were significantly greater in subjects with CFS+FM than in control subjects; in addition, rates of these transitions were also significantly increased in subjects with CFS+FM. Result (a) might indicate increased sleep pressure in subjects with CFS+FM whereas result (b) may be the specific sleep problem of subjects with CFS+FM. We also found that shorter durations of S2 sleep are specific to patients with CFS+FM, not to CFS alone.

CONCLUSIONS: These results suggest that CFS and FM may be different illnesses associated with different problems of sleep regulation.

 

Source: Kishi A, Natelson BH, Togo F, Struzik ZR, Rapoport DM, Yamamoto Y. Sleep-stage dynamics in patients with chronic fatigue syndrome with or without fibromyalgia. Sleep. 2011 Nov 1;34(11):1551-60. doi: 10.5665/sleep.1396. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198210/ (Full article)

 

Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome

Abstract:

OBJECTIVES: To determine mRNA expression differences in genes involved in signalling and modulating sensory fatigue, and muscle pain in patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FM) at baseline, and following moderate exercise.

DESIGN: Forty-eight patients with CFS only, or CFS with comorbid FM, 18 patients with FM that did not meet criteria for CFS, and 49 healthy controls underwent moderate exercise (25 min at 70% maximum age-predicted heart rate). Visual-analogue measures of fatigue and pain were taken before, during and after exercise. Blood samples were taken before and 0.5, 8, 24 and 48 h after exercise. Leucocytes were immediately isolated from blood, number coded for blind processing and analyses and flash frozen. Using real-time, quantitative PCR, the amount of mRNA for 13 genes (relative to control genes) involved in sensory, adrenergic and immune functions was compared between groups at baseline and following exercise. Changes in amounts of mRNA were correlated with behavioural measures and functional clinical assessments.

RESULTS: No gene expression changes occurred following exercise in controls. In 71% of patients with CFS, moderate exercise increased most sensory and adrenergic receptor’s and one cytokine gene’s transcription for 48 h. These postexercise increases correlated with behavioural measures of fatigue and pain. In contrast, for the other 29% of patients with CFS, adrenergic α-2A receptor’s transcription was decreased at all time-points after exercise; other genes were not altered. History of orthostatic intolerance was significantly more common in the α-2A decrease subgroup. FM-only patients showed no postexercise alterations in gene expression, but their pre-exercise baseline mRNA for two sensory ion channels and one cytokine were significantly higher than controls.

CONCLUSIONS: At least two subgroups of patients with CFS can be identified by gene expression changes following exercise. The larger subgroup showed increases in mRNA for sensory and adrenergic receptors and a cytokine. The smaller subgroup contained most of the patients with CFS with orthostatic intolerance, showed no postexercise increases in any gene and was defined by decreases in mRNA for α-2A. FM-only patients can be identified by baseline increases in three genes. Postexercise increases for four genes meet published criteria as an objective biomarker for CFS and could be useful in guiding treatment selection for different subgroups.

© 2011 The Association for the Publication of the Journal of Internal Medicine.

 

Source: Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, Light KC. Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome. J Intern Med. 2012 Jan;271(1):64-81. doi: 10.1111/j.1365-2796.2011.02405.x. Epub 2011 Jul 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175315/ (Full article)

 

Sleep stage transitions in chronic fatigue syndrome patients with or without fibromyalgia

Abstract:

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are medically unexplained conditions that share considerable overlapping symptoms, including sleep-related complaints. However, differences between the two conditions have been reported, and we hypothesized that dynamic aspects of sleep, recently attracting scientific interests, would be different in the two groups of patients. We thus study transition probabilities between sleep stages of CFS patients with or without FM. Subjects were 26 healthy controls, 14 CFS patients without FM (CFS alone) and 12 CFS patients with FM (CFS+FM) – all women.

We studied transition probabilities between sleep stages (waking, REM sleep and Stage I, Stage II and slow-wave sleep (Stage III+IV)). We found that probabilities of transition from REM sleep to waking were significantly greater in CFS alone than in controls; we have reported previously this sleep disruption as the specific sleep problem for CFS alone [Kishi et al., 2008]. Probabilities of transitions from waking, REM sleep and Stage I to Stage II, and those from slow-wave sleep to Stage I, were significantly greater in CFS+FM than in controls; the former might indicate increased sleep pressure in CFS+FM and the latter may be the specific sleep problem of CFS+FM. These results suggest that CFS and FM are different illnesses associated with different problems of sleep regulation.

 

Source: Kishi A, Natelson BH, Togo F, Struzik ZR, Rapoport DM, Yamamoto Y. Sleep stage transitions in chronic fatigue syndrome patients with or without fibromyalgia. Conf Proc IEEE Eng Med Biol Soc. 2010;2010:5391-4. doi: 10.1109/IEMBS.2010.5626478. https://www.ncbi.nlm.nih.gov/pubmed/21096267

 

Fibromyalgia and related conditions: electromyogram profile during isometric muscle contraction

Abstract:

OBJECTIVES: To evaluate electromyogram (EMG) profiles in patients with three related conditions: fibromyalgia, chronic fatigue syndrome, and depression.

METHODS: We studied 44 healthy volunteers, 22 patients with fibromyalgia, 11 patients with chronic fatigue syndrome, and 10 patients admitted for depression. The trapezius electromyogram was recorded during maximally sustained, bilateral, 90 degrees abduction of the shoulders. EMG signal frequency and amplitude were measured throughout the test.

RESULTS: In the fibromyalgia group, isometric contraction duration was significantly shorter than in the other two patient groups (P<0.001) and the EMG frequency and amplitude pattern indicated premature discontinuation of the muscle contraction. Findings in the chronic fatigue patients were similar to those in the healthy controls. The patients with depression had a distinctive EMG profile characterized by excessive initial motor-unit recruitment with a shift in the frequency spectrum.

CONCLUSIONS: Fibromyalgia was associated with a specific EMG pattern indicating premature discontinuation of the muscle contraction. Therefore, maximal voluntary muscle contraction tests may be of limited value for assessing function in fibromyalgia patients. Chronic fatigue syndrome patients had similar EMG findings to those in the healthy controls. The EMG alterations in the patients with depression were consistent with manifestations of psychomotor retardation.

Copyright 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

 

Source: Maquet D, Croisier JL, Dupont C, Moutschen M, Ansseau M, Zeevaert B, Crielaard JM. Fibromyalgia and related conditions: electromyogram profile during isometric muscle contraction. Joint Bone Spine. 2010 May;77(3):264-7. doi: 10.1016/j.jbspin.2010.02.003. Epub 2010 Apr 22. https://www.ncbi.nlm.nih.gov/pubmed/20417143