Tag: post-exertional malaise

Diagnosis of myalgic encephalomyelitis: where are we now?

Abstract:

INTRODUCTION: The World Health Organization has classified myalgic encephalomyelitis (ME) as a neurological disease since 1969 considering chronic fatigue syndrome (CFS) as a synonym used interchangeably for ME since 1969. ME and CFS are considered to be neuro-immune disorders, characterized by specific symptom profiles and a neuro-immune pathophysiology. However, there is controversy as to which criteria should be used to classify patients with “chronic fatigue syndrome.”

AREAS COVERED: The Centers for Disease Control and Prevention (CDC) criteria consider chronic fatigue (CF) to be distinctive for CFS, whereas the International Consensus Criteria (ICC) stresses the presence of post-exertion malaise (PEM) as the hallmark feature of ME. These case definitions have not been subjected to rigorous external validation methods, for example, pattern recognition analyses, instead being based on clinical insights and consensus.

EXPERT OPINION: Pattern recognition methods showed the existence of three qualitatively different categories: (a) CF, where CF evident, but not satisfying full CDC syndrome criteria. (b) CFS, satisfying CDC criteria but without PEM. (c) ME, where PEM is evident in CFS. Future research on this “chronic fatigue spectrum” should, therefore, use the above-mentioned validated categories and novel tailored algorithms to classify patients into ME, CFS, or CF.

Comment in: Comment and reply on: ME is a distinct diagnostic entity, not part of a chronic fatigue spectrum. [Expert Opin Med Diagn. 2013]

 

Source: Maes M, Anderson G, Morris G, Berk M. Diagnosis of myalgic encephalomyelitis: where are we now? Expert Opin Med Diagn. 2013 May;7(3):221-5. doi: 10.1517/17530059.2013.776039. Epub 2013 Feb 27. https://www.ncbi.nlm.nih.gov/pubmed/23480562

 

Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Frequency of active human herpesvirus-6, -7 (HHV-6, HHV-7) and parvovirus B19 (B19) infection/coinfection and its association with clinical course of ME/CFS was evaluated. 108 ME/CFS patients and 90 practically healthy persons were enrolled in the study. Viral genomic sequences were detected by PCR, virus-specific antibodies and cytokine levels-by ELISA, HHV-6 variants-by restriction analysis.

Active viral infection including concurrent infection was found in 64.8% (70/108) of patients and in 13.3% (12/90) of practically healthy persons. Increase in peripheral blood leukocyte DNA HHV-6 load as well as in proinflammatory cytokines’ levels was detected in patients during active viral infection. Definite relationship was observed between active betaherpesvirus infection and subfebrility, lymphadenopathy and malaise after exertion, and between active B19 infection and multijoint pain. Neuropsychological disturbances were detected in all patients. The manifestation of symptoms was of more frequent occurrence in patients with concurrent infection.

The high rate of active HHV-6, HHV-7 and B19 infection/coinfection with the simultaneous increase in plasma proinflammatory cytokines’ level as well as the association between active viral infection and distinctive types of clinical symptoms shows necessity of simultaneous study of these viral infections for identification of possible subsets of ME/CFS.

 

Source: Chapenko S, Krumina A, Logina I, Rasa S, Chistjakovs M, Sultanova A, Viksna L, Murovska M. Association of active human herpesvirus-6, -7 and parvovirus b19 infection with clinical outcomes in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Adv Virol. 2012;2012:205085. doi: 10.1155/2012/205085. Epub 2012 Aug 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426163/ (Full article)

 

A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome

Abstract:

This paper proposes a neuro-immune model for Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). A wide range of immunological and neurological abnormalities have been reported in people suffering from ME/CFS. They include abnormalities in proinflammatory cytokines, raised production of nuclear factor-κB, mitochondrial dysfunctions, autoimmune responses, autonomic disturbances and brain pathology. Raised levels of oxidative and nitrosative stress (O&NS), together with reduced levels of antioxidants are indicative of an immuno-inflammatory pathology. A number of different pathogens have been reported either as triggering or maintaining factors.

Our model proposes that initial infection and immune activation caused by a number of possible pathogens leads to a state of chronic peripheral immune activation driven by activated O&NS pathways that lead to progressive damage of self epitopes even when the initial infection has been cleared. Subsequent activation of autoreactive T cells conspiring with O&NS pathways cause further damage and provoke chronic activation of immuno-inflammatory pathways. The subsequent upregulation of proinflammatory compounds may activate microglia via the vagus nerve.

Elevated proinflammatory cytokines together with raised O&NS conspire to produce mitochondrial damage. The subsequent ATP deficit together with inflammation and O&NS are responsible for the landmark symptoms of ME/CFS, including post-exertional malaise. Raised levels of O&NS subsequently cause progressive elevation of autoimmune activity facilitated by molecular mimicry, bystander activation or epitope spreading. These processes provoke central nervous system (CNS) activation in an attempt to restore immune homeostatsis.

This model proposes that the antagonistic activities of the CNS response to peripheral inflammation, O&NS and chronic immune activation are responsible for the remitting-relapsing nature of ME/CFS. Leads for future research are suggested based on this neuro-immune model.

 

Source: Morris G, Maes M. A neuro-immune model of Myalgic Encephalomyelitis/Chronic fatigue syndrome. Metab Brain Dis. 2013 Dec;28(4):523-40. doi: 10.1007/s11011-012-9324-8. Epub 2012 Jun 21. https://www.ncbi.nlm.nih.gov/pubmed/22718491

 

A natural history study of chronic fatigue syndrome

Abstract:

OBJECTIVE: There is a need for natural history chronic fatigue syndrome (CFS) studies from random, community-based, multi-ethnic populations.

DESIGN: The present study examined the course of CFS from Wave 1 to Wave 2, which spanned over a ten year period of time, and, assessed whether socio-environmental and symptomatology factors were associated with CFS status over the ten year period.

RESULTS: There was relative stability over time on critical measures of disability, fatigue, support, optimism and coping over time. One cardinal symptoms of CFS, post-exertional malaise, best differentiated the CFS group from the others. By Wave 2, of the original group of 32 individuals diagnosed with CFS, 4 had died, and 24 were found and agreed to be re-evaluated, and of this group, 16 continued to have CFS, 5 developed exclusionary illnesses, 2 were classified as Idiopathic chronic fatigue, and one had remitted.

CONCLUSIONS: The current study found that over time in a community-based sample, unbiased by help seeking behavior the CFS group remained rather ill with a variety of different conditions over time.

(c) 2011 APA, all rights reserved

 

Source: Jason LA, Porter N, Hunnell J, Brown A, Rademaker A, Richman JA. A natural history study of chronic fatigue syndrome. Rehabil Psychol. 2011 Feb;56(1):32-42. doi: 10.1037/a0022595. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171164/ (Full article)

 

Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta

Abstract:

OBJECTIVES: Too vigorous exercise or activity increase frequently triggers postexertional malaise in people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a primary characteristic evident in up to 95% of people with ME/CFS. The present study aimed at examining whether two different types of exercise results in changes in health status, circulating elastase activity, interleukin (IL)-1beta and complement C4a levels.

DESIGN: Comparative experimental design.

SETTING: University.

SUBJECTS: Twenty-two women with ME/CFS and 22 healthy sedentary controls.

INTERVENTIONS: participants were subjected to a submaximal exercise (day 8) and a self-paced, physiologically limited exercise (day 16). Each bout of exercise was preceded and followed by blood sampling, actigraphy and assessment of their health status.

RESULTS: Both submaximal exercise and self-paced, physiologically limited exercise resulted in postexertional malaise in people with ME/CFS. However, neither exercise bout altered elastase activity, IL-1beta or complement C4a split product levels in people with ME/CFS or healthy sedentary control subjects (P > 0.05). Postexercise complement C4a level was identified as a clinically important biomarker for postexertional malaise in people with ME/CFS.

CONCLUSIONS: Submaximal exercise as well as self-paced, physiologically limited exercise triggers postexertional malaise in people with ME/CFS, but neither types of exercise alter acute circulating levels of IL-1beta, complement C4a split product or elastase activity. Further studying of immune alterations in relation to postexertional malaise in people with ME/CFS using multiple measurement points postexercise is required.

 

Source: Nijs J, Van Oosterwijck J, Meeus M, Lambrecht L, Metzger K, Frémont M, Paul L. Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta. J Intern Med. 2010 Apr;267(4):418-35. doi: 10.1111/j.1365-2796.2009.02178.x. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2009.02178.x/full (Full article)

 

Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an experimental study

Abstract:

OBJECTIVES: To examine the efficacy of the pain inhibitory systems in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) during two different types of exercise and to examine whether the (mal)functioning of pain inhibitory systems is associated with symptom increases following exercise.

DESIGN: A controlled experimental study.

SETTING AND SUBJECTS: Twenty-two women with ME/CFS and 22 healthy sedentary controls were studied at the Department of Human Physiology, Vrije Universiteit Brussel.

INTERVENTIONS: All subjects performed a submaximal exercise test and a self-paced, physiologically limited exercise test on a cycle ergometer. The exercise tests were undertaken with continuous cardiorespiratory monitoring. Before and after the exercise bouts, subjects filled out questionnaires to assess health status, and underwent pressure pain threshold measurements. Throughout the study, subjects’ activity levels were assessed using accelerometry.

RESULTS: In patients with ME/CFS, pain thresholds decreased following both types of exercise, whereas they increased in healthy subjects. This was accompanied by a worsening of the ME/CFS symptom complex post-exercise. Decreased pressure thresholds during submaximal exercise were associated with postexertional fatigue in the ME/CFS group (r = 0.454; P = 0.034).

CONCLUSIONS:These observations indicate the presence of abnormal central pain processing during exercise in patients with ME/CFS and demonstrate that both submaximal exercise and self-paced, physiologically limited exercise trigger postexertional malaise in these patients. Further study is required to identify specific modes and intensity of exercise that can be performed in people with ME/CFS without exacerbating symptoms.

Comment in: Chronic fatigue syndrome reflects loss of adaptability. [J Intern Med. 2010]

 

Source: Van Oosterwijck J, Nijs J, Meeus M, Lefever I, Huybrechts L, Lambrecht L, Paul L. Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an experimental study. J Intern Med. 2010 Sep;268(3):265-78. doi: 10.1111/j.1365-2796.2010.02228.x. Epub 2010 Mar 3. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2010.02228.x/full (Full article)

 

Postexertional malaise in women with chronic fatigue syndrome

Abstract:

OBJECTIVE: Postexertional malaise (PEM) is a defining characteristic of chronic fatigue syndrome (CFS) that remains a source of some controversy. The purpose of this study was to explore the effects of an exercise challenge on CFS symptoms from a patient perspective.

METHODS: This study included 25 female CFS patients and 23 age-matched sedentary controls. All participants underwent a maximal cardiopulmonary exercise test. Subjects completed a health and well-being survey (SF-36) 7 days postexercise. Subjects also provided, approximately 7 days after testing, written answers to open-ended questions pertaining to physical and cognitive responses to the test and length of recovery. SF-36 data were compared using multivariate analyses. Written questionnaire responses were used to determine recovery time as well as number and type of symptoms experienced.

RESULTS: Written questionnaires revealed that within 24 hours of the test, 85% of controls indicated full recovery, in contrast to 0 CFS patients. The remaining 15% of controls recovered within 48 hours of the test. In contrast, only 1 CFS patient recovered within 48 hours. Symptoms reported after the exercise test included fatigue, light-headedness, muscular/joint pain, cognitive dysfunction, headache, nausea, physical weakness, trembling/instability, insomnia, and sore throat/glands. A significant multivariate effect for the SF-36 responses (p < 0.001) indicated lower functioning among the CFS patients, which was most pronounced for items measuring physiological function.

CONCLUSIONS: The results of this study suggest that PEM is both a real and an incapacitating condition for women with CFS and that their responses to exercise are distinctively different from those of sedentary controls.

Source: VanNess JM, Stevens SR, Bateman L, Stiles TL, Snell CR. Postexertional malaise in women with chronic fatigue syndrome. J Womens Health (Larchmt). 2010 Feb;19(2):239-44. doi: 10.1089/jwh.2009.1507. https://www.ncbi.nlm.nih.gov/pubmed/20095909

 

Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome

Abstract:

Complement activation resulting in significant increases of C4a split product may be a marker of postexertional malaise in individuals with chronic fatigue syndrome (CFS). This study focused on identification of the transcriptional control that may contribute to the increased C4a in CFS subjects after exercise.

We used quantitative reverse-transcription polymerase chain reaction to evaluate differential expression of genes in the classical and lectin pathways in peripheral blood mononuclear cells (PBMCs). Calibrated expression values were normalized to the internal reference gene peptidylpropyl isomerase B (PPIB), the external reference gene ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL), or the geometric mean (GM) of the genes ribosomal protein, large, P0 (RPLP0) and phosphoglycerate kinase 1 (PGK1). All nine genes tested, except mannose-binding lectin 2 (MBL2), were expressed in PBMCs.

At 1 hour postexercise, C4, mannan-binding lectin serine protease 2 (MASP2) and ficolin 1 (FCN1) transcripts were detected at higher levels (> or = 2-fold) in at least 50% (4 of 8) of CFS subjects and were detected in 88% (7 of 8) CFS subjects when subjects with overexpression of either C4 or MASP2 were combined. Only an increase in the MASP2 transcript was statistically significant (PPIB, P = 0.001; GM, P = 0.047; rbcL, P = 0.045). This result may be due to the significant but transient downregulation of MASP2 in control subjects (PPIB, P = 0.023; rbcL, P = 0.027). By 6 hours postexercise, MASP2 expression was similar in both groups.

In conclusion, lectin pathway responded to exercise differentially in CFS than in control subjects. MASP2 down-regulation may act as an antiinflammatory acute-phase response in healthy subjects, whereas its elevated level may account for increased C4a and inflammation-mediated postexertional malaise in CFS subjects.

 

Source: Sorensen B, Jones JF, Vernon SD, Rajeevan MS. Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome. Mol Med. 2009 Jan-Feb;15(1-2):34-42. doi: 10.2119/molmed.2008.00098. Epub 2008 Nov 10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583111/ (Full article)

 

Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial

Abstract:

OBJECTIVE: It was hypothesized that the use of exercise limits prevents symptom increases and worsening of their health status following a walking exercise in people with chronic fatigue syndrome.

DESIGN: An uncontrolled clinical trial (semi-experimental design).

SETTING: Outpatient clinic of a university department.

SUBJECTS: Twenty-four patients with chronic fatigue syndrome.

INTERVENTIONS: Subjects undertook a walking test with the two concurrent exercise limits. Each subject walked at an intensity where the maximum heart rate was determined by heart rate corresponding to the respiratory exchange ratio = 1.0 derived from a previous submaximal exercise test and for a duration calculated from how long each patient felt they were able to walk.

MAIN OUTCOME MEASURES: The Short Form 36 Health Survey or SF-36, the Chronic Fatigue Syndrome Symptom List, and the Chronic Fatigue Syndrome -Activities and Participation Questionnaire were filled in prior to, immediately after and 24 hours after exercise.

RESULTS: The fatigue increase observed immediately post-exercise (P= 0.006) returned to pre-exercise levels 24 hours post-exercise. The increase in pain observed immediately post-exercise was retained at 24 hours post-exercise (P=0.03). Fourteen of the 24 subjects experienced a clinically meaningful change in bodily pain (change of SF-36 bodily pain score > or =10); 6 indicated that the exercise bout had slightly worsened their health status, and 2 had a clinically meaningful decrease in vitality (change of SF-36 vitality score > or =20). There was no change in activity limitations/participation restrictions.

CONCLUSION: It was shown that the use of exercise limits (limiting both the intensity and duration of exercise) prevents important health status changes following a walking exercise in people with chronic fatigue syndrome, but was unable to prevent short-term symptom increases.

 

Source: Nijs J, Almond F, De Becker P, Truijen S, Paul L. Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial. Clin Rehabil. 2008 May;22(5):426-35. Doi: 10.1177/0269215507084410. https://www.ncbi.nlm.nih.gov/pubmed/18441039

 

A real-time assessment of the effect of exercise in chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) report substantial symptom worsening after exercise. However, the time course over which this develops has not been explored. Therefore, the objective of this study was to investigate the influence of exercise on subjective symptoms and on cognitive function in CFS patients in natural settings using a computerized ecological momentary assessment method, which allowed us to track the effects of exercise within and across days.

Subjects were 9 female patients with CFS and 9 healthy women. A watch-type computer was used to collect real-time data on physical and psychological symptoms and cognitive function for 1 week before and 2 weeks after a maximal exercise test. For each variable, we investigated temporal changes after exercise using multilevel modeling.

Following exercise, physical symptoms did get worse but not until a five-day delay in CFS patients. Despite this, there was no difference in the temporal pattern of changes in psychological symptoms or in cognitive function after exercise between CFS patients and controls. In conclusion, physical symptoms worsened after several days delay in patients with CFS following exercise while psychological symptoms or cognitive function did not change after exercise.

 

Source: Yoshiuchi K, Cook DB, Ohashi K, Kumano H, Kuboki T, Yamamoto Y, Natelson BH. A real-time assessment of the effect of exercise in chronic fatigue syndrome. Physiol Behav. 2007 Dec 5;92(5):963-8. Epub 2007 Jul 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170105/ (Full article)