Category: Symptoms

A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior

Abstract:

It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation.

There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS. While sickness is an adaptive response induced by proinflammatory cytokines, ME/CFS is a chronic, disabling disorder, where the pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses.

While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acute response to infection/injury, the trigger factors in ME/CFS are less well defined and encompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions.

 

Source: Morris G, Anderson G, Galecki P, Berk M, Maes M. A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and sickness behavior. BMC Med. 2013 Mar 8;11:64. doi: 10.1186/1741-7015-11-64. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751187/ (Full article)

 

Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies

Abstract:

Chronic Fatigue Syndrome (CFS) subjects have many systemic complaints including shortness of breath. Dyspnea was compared in two CFS and control cohorts to characterize pathophysiology. Cohort 1 of 257 CFS and 456 control subjects were compared using the Medical Research Council chronic Dyspnea Scale (MRC Score; range 0-5). Cohort 2 of 106 CFS and 90 controls answered a Dyspnea Severity Score (range 0-20) adapted from the MRC Score. Subsets of both cohorts completed CFS Severity Scores, fatigue, and other questionnaires. A subset had pulmonary function and total lung capacity measurements.

Results show MRC Scores were equivalent between sexes in Cohort 1 CFS (1.92 [1.72-2.16]; mean [95% C.I.]) and controls (0.31 [0.23-0.39]; p<0.0001). Receiver-operator curves identified 2 as the threshold for positive MRC Scores in Cohort 1. This indicated 54% of CFS, but only 3% of controls, had significant dyspnea.

In Cohort 2, Dyspnea Score threshold of 4 indicated shortness of breath in 67% of CFS and 23% of controls. Cohort 2 Dyspnea Scores were higher for CFS (7.80 [6.60-9.00]) than controls (2.40 [1.60-3.20]; p<0.0001). CFS had significantly worse fatigue and other complaints compared to controls. Pulmonary function was normal in CFS, but Borg scores and sensations of chest pain and dizziness were significantly greater during testing than controls. General linear model of Cohort 2 CFS responses linked Dyspnea with rapid heart rate, chest pain and dizziness.

In conclusion, sensory hypersensitivity without airflow limitation contributed to dyspnea in CFS. Correlates of dyspnea in controls were distinct from CFS suggesting different mechanisms.

 

Source: Ravindran M, Adewuyi O, Zheng Y, Rayhan RU, Le U, Timbol C, Merck S, Esteitie R, Read C, Cooney M, Baraniuk J. Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies. Glob J Health Sci. 2012 Dec 12;5(2):94-110. doi: 10.5539/gjhs.v5n2p94. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209305/ (Full article)

 

Fatigue heralding multiple sclerosis

Abstract:

BACKGROUND: Fatigue is a common symptom in multiple sclerosis (MS) and is an important determinant of overall well-being and disability.

OBJECTIVE: To assess the frequency with which fatigue precedes the diagnosis of MS using a retrospective database analysis.

METHODS: Between January 1, 2003 and September 30, 2008, patients diagnosed with fatigue with and without fatigue-related medications within a 3-year period prior to newly diagnosed MS were identified from the MarketScan Databases. All statistical analysis was performed using SAS.

RESULTS: Of the 16,976 patients with MS in the overall population, 5305 (31.3%) were newly diagnosed with MS and had three years of continuous healthcare coverage prior to MS diagnosis. Of these patients, 1534 (28.9%) were labeled with chronic fatigue syndrome (ICD9-780.71) or malaise or fatigue (ICD9-780.79) prior to the diagnosis of MS. One-third of these patients were labeled with fatigue one to two years before the diagnosis; 30.8% were diagnosed only with fatigue and had no other MS symptoms prior to their MS diagnosis. Among the patients diagnosed with fatigue, 10.4% were also prescribed medication for fatigue.

CONCLUSION: This study demonstrates that fatigue may herald MS, often by years. A careful history for transient neurological symptoms and a physical examination is warranted in any patient presenting with fatigue.

 

Source: Berger JR, Pocoski J, Preblick R, Boklage S. Fatigue heralding multiple sclerosis. Mult Scler. 2013 Oct;19(11):1526-32. doi: 10.1177/1352458513477924. Epub 2013 Feb 25. https://www.ncbi.nlm.nih.gov/pubmed/23439577

 

Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review

Abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a chronic, disabling illness that affects approximately 0.2% of the population. Non-restorative sleep despite sufficient or extended total sleep time is one of the major clinical diagnostic criteria; however, the underlying cause of this symptom is unknown.

This review aims to provide a comprehensive overview of the literature examining sleep in CFS/ME and the issues surrounding the current research findings. Polysomnographic and other objective measures of sleep have observed few differences in sleep parameters between CFS/ME patients and healthy controls, although some discrepancies do exist. This lack of significant objective differences contrasts with the common subjective complaints of disturbed and unrefreshed sleep by CFS/ME patients.

The emergence of new, more sensitive techniques that examine the microstructure of sleep are showing promise for detecting differences in sleep between patients and healthy individuals. There is preliminary evidence that alterations in sleep stage transitions and sleep instability, and other physiological mechanisms, such as heart rate variability and altered cortisol profiles, may be evident. Future research investigating the etiology of non-restorative sleep in CFS/ME may also help us to undercover the causes of non-restorative sleep and fatigue in other medical conditions.

 

Source: Jackson ML, Bruck D. Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review. J Clin Sleep Med. 2012 Dec 15;8(6):719-28. doi: 10.5664/jcsm.2276. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501671/ (Full article)

 

Modulation of the axon-reflex response to local heat by reactive oxygen species in subjects with chronic fatigue syndrome

Abstract:

Local cutaneous heating causes vasodilation as an initial first peak, a nadir, and increase to plateau. Reactive oxygen species (ROS) modulate the heat plateau in healthy controls. The initial peak, due to C-fiber nociceptor-mediated axon reflexes, is blunted with local anesthetics and may serve as a surrogate for the cutaneous response to peripheral heat. Chronic fatigue syndrome (CFS) subjects report increased perception of pain. To determine the role of ROS in this neurally mediated response, we evaluated changes in cutaneous blood flow from local heat in nine CFS subjects (16-22 yr) compared with eight healthy controls (18-26 yr).

We heated skin to 42°C and measured local blood flow as a percentage of maximum cutaneous vascular conductance (%CVC(max)). Although CFS subjects had significantly lower baseline flow [8.75 ± 0.56 vs. 12.27 ± 1.07 (%CVC(max), CFS vs. control)], there were no differences between groups to local heat. We then remeasured this with apocynin to inhibit NADPH oxidase, allopurinol to inhibit xanthine oxidase, tempol to inhibit superoxide, and ebselen to reduce H(2)O(2). Apocynin significantly increased baseline blood flow (before heat, 14.91 ± 2.21 vs. 8.75 ± 1.66) and the first heat peak (69.33 ± 3.36 vs. 59.75 ± 2.75). Allopurinol and ebselen only enhanced the first heat peaks (71.55 ± 2.48 vs. 61.72 ± 2.01 and 76.55 ± 5.21 vs. 58.56 ± 3.66, respectively). Tempol had no effect on local heating. None of these agents changed the response to local heat in control subjects. Thus the response to heat may be altered by local levels of ROS, particularly H(2)O(2) in CFS subjects, and may be related to their hyperesthesia/hyperalgesia.

 

Source: Medow MS, Aggarwal A, Baugham I, Messer Z, Stewart JM. Modulation of the axon-reflex response to local heat by reactive oxygen species in subjects with chronic fatigue syndrome. J Appl Physiol (1985). 2013 Jan 1;114(1):45-51. doi: 10.1152/japplphysiol.00821.2012. Epub 2012 Nov 8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3544512/ (Full article)

 

Sleep in the chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a disabling condition characterized by severe fatigue lasting for more than six months and the presence of at least four out of eight minor criteria. Sleep disturbance presenting as unrefreshing or nonrestorative sleep is one of these criteria and is very common in CFS patients. Biologically disturbed sleep is a known cause of fatigue and could play a role in the pathogenesis of CFS. However, the nature of presumed sleep impairment in CFS remains unclear. Whilst complaints of NRS persist over time, there is no demonstrable neurophysiological correlate to substantiate a basic deficit in sleep function in CFS. Polysomnographic findings have not shown to be significantly different between subjects with CFS and normal controls. Discrepancies between subjectively poor and objectively normal sleep suggest a role for psychosocial factors negatively affecting perception of sleep quality. Primary sleep disorders are often detected in patients who otherwise qualify for a CFS diagnosis. These disorders could contribute to the presence of daytime dysfunctioning. There is currently insufficient evidence to indicate that treatment of primary sleep disorders sufficiently improves the fatigue associated with CFS. Therefore, primary sleep disorders may be a comorbid rather than an exclusionary condition with respect to CFS.

Copyright © 2012 Elsevier Ltd. All rights reserved.

 

Source: Mariman AN, Vogelaers DP, Tobback E, Delesie LM, Hanoulle IP, Pevernagie DA. Sleep in the chronic fatigue syndrome. Sleep Med Rev. 2013 Jun;17(3):193-9. doi: 10.1016/j.smrv.2012.06.003. Epub 2012 Oct 6. https://www.ncbi.nlm.nih.gov/pubmed/23046847

 

Pain in patients with chronic fatigue syndrome: time for specific pain treatment?

Abstract:

BACKGROUND: Besides chronic fatigue, patients with chronic fatigue syndrome (CFS) have debilitating widespread pain. Yet pain from CFS is often ignored by clinicians and researchers.

OBJECTIVES: To examine whether pain is a unique feature of CFS, or does it share the same underlying mechanisms as other CFS symptoms? Second, it is examined whether effective treatments for pain from CFS are currently available.

STUDY DESIGN: Narrative review covering the scientific literature up through December 2011.

SETTING: Several universities.

RESULTS: From the available literature, it is concluded that musculoskeletal factors are unlikely to account for pain from CFS. Pain seems to be one out of many symptoms related to central sensitization from CFS. This idea is supported by the findings of generalized hyperalgesia (including widespread increased responsiveness to painful stimuli) and dysfunctional endogenous analgesia in response to noxious thermal stimuli. Pain catastrophizing and depression partly account for pain from CFS. Pain increases during exercise is probably due to the lack of endogenous analgesia and activation of several genes in response to exercise in CFS. There is currently no evidence in support for the efficacy of complementary medicine in the treatment of pain from CFS. Intensive education about the biology of pain from CFS (within the framework of central sensitization) has positive short-term effects for patients with CFS, and fatigue-targeting cognitive behavioral therapy appears to be effective for pain from CFS as well.

LIMITATIONS: The role of the deficient hypothalamus-pituitary-adrenal axis in relation to pain from CFS, as well as the interactions with immune (dys)functioning require further study.

CONCLUSION: Recent research has increased our understanding of pain from CFS, including its treatment. It is advocated to optimize current CFS treatment protocols by targeting the underlying mechanism for those patients having severe pain.

 

Source: Nijs J, Crombez G, Meeus M, Knoop H, Damme SV, Cauwenbergh V, Bleijenberg G. Pain in patients with chronic fatigue syndrome: time for specific pain treatment? Pain Physician. 2012 Sep-Oct;15(5):E677-86. http://www.painphysicianjournal.com/linkout?issn=1533-3159&vol=15&page=E677 (Full article)

 

Sub-typing daily fatigue progression in chronic fatigue syndrome

Abstract:

BACKGROUND: Activity logs involve patients writing down their activities and symptoms over 1 or more days. Aims This study sought to classify daily fatigue patterns among patients with chronic fatigue syndrome (CFS) using activity logs.

METHOD: Fatigue intensity was self-reported every 30 min in a sample of 90 patients with CFS over 1 day. A cluster analysis using fatigue intensity, variability and slope was conducted.

RESULTS: Three clusters emerged involving patients with different trajectories. One group evidenced high fatigue intensity, low variability, and fatigue intensity stayed the same over time. A second group had moderate fatigue intensity, high variability, and fatigue intensity decreased over time. A third group had moderate fatigue intensity, high variability, but fatigue intensity increased over time. The three clusters of patients differed on measures of actigraphy, pain and immune functioning.

CONCLUSIONS: Activity logs can provide investigators and clinicians with valuable sources of data for understanding patterns of fatigue and activity among patients with CFS.

 

Source: Jason LA, Brown MM. Sub-typing daily fatigue progression in chronic fatigue syndrome. J Ment Health. 2013 Feb;22(1):4-11. doi: 10.3109/09638237.2012.670879. Epub 2012 May 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889482/ (Full article)

 

Subjective sleep quality and daytime sleepiness in a large sample of patients with chronic fatigue syndrome (CFS)

Abstract:

Chronic fatigue syndrome (CFS) is characterised by incapacitating fatigue in combination with a number of minor criteria, including unrefreshing sleep without further specifications, in the absence of psychiatric and internal disease. As little data exist on subjective sleep quality and daytime sleepiness, these parameters were assessed in a large sample of CFS patients.

Consecutive patients with a diagnosis of CFS in a tertiary referral centre filled out the Fatigue Questionnaire (FQ), Medical Outcomes Study 36-Item Short Form Health Survey (MOS SF-36), Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Inclusion comprised 415 individuals (mean age 40.5 yr, SD 7.9, range 18-64; 86% female). Mean FQ (26.90; SD 4.04), mean Global Physical Health from the MOS SF-36 (29.30; SD 12.25) and Global Mental Health from the MOS SF-36 (49.62; SD 18.31) scores corresponded with literature data for similar CFS samples. High mean ESS (10.51; SD 5.52) and global PSQI (10.17; SD 4.02) were observed. No significant relationship was found between ESS and global PSQI.

In contrast, regression analysis demonstrated a significant cubic relation between ESS and ‘PSQI without daytime dysfunction’. A subgroup (n=69) with an insomnia-like phenotype low ESS (<5), high PSQI (mean 11.51; SD 3.86) was observed. The assessment of subjective sleep quality and daytime sleepiness in a large sample of CFS patients indicated high mean PSQI and ESS values. ESS and ‘PSQI without daytime dysfunction’ were inversely related at the spectral ends of ESS. A distinct subgroup with clinical features of insomnia was identified.

 

Source: Mariman A, Vogelaers D, Hanoulle I, Delesie L, Pevernagie D. Subjective sleep quality and daytime sleepiness in a large sample of patients with chronic fatigue syndrome (CFS). Acta Clin Belg. 2012 Jan-Feb;67(1):19-24. https://www.ncbi.nlm.nih.gov/pubmed/22480034

 

Small heart with low cardiac output for orthostatic intolerance in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: The etiology of chronic fatigue syndrome (CFS) is unknown. Orthostatic intolerance (OI) is common in CFS patients. Recently, small heart with low cardiac output has been postulated to be related to the genesis of both CFS and OI.

HYPOTHESIS: Small heart is associated with OI in patients with CFS.

METHODS: Study CFS patients were divided into groups of 26 (57%) CFSOI(+) and 20 (43%) CFSOI(-) according to the presence or absence of OI. In addition, 11 OI patients and 27 age- and sex-matched control subjects were studied. Left ventricular (LV) dimensions and function were determined echocardiographically.

RESULTS: The mean values of cardiothoracic ratio, systemic systolic and diastolic pressures, LV end-diastolic dimension, LV end-systolic dimension, stroke volume index, cardiac index, and LV mass index were all significantly smaller in CFSOI(+) patients than in CFSOI(-) patients and healthy controls, and also in OI patients than in controls. A smaller LV end-diastolic dimension (<40 mm) was significantly (P<0.05) more prevalently noted in CFSOI(+) (54%) and OI (45%) than in CFSOI(-) (5%) and controls (4%). A lower cardiac index (<2 L/min/mm(2)) was more prevalent in CFSOI(+) (65%) than in CFSOI(-) (5%, P<0.01), OI (27%), and controls (11%, P<0.01).

CONCLUSIONS: A small size of LV with low cardiac output was noted in OI, and its degree was more pronounced in CFSOI(+). A small heart appears to be related to the genesis of OI and CFS via both cerebral and systemic hypoperfusion. CFSOI(+) seems to constitute a well-defined and predominant subgroup of CFS.

© 2011 Wiley Periodicals, Inc.

 

Source: Miwa K, Fujita M. Small heart with low cardiac output for orthostatic intolerance in patients with chronic fatigue syndrome. Clin Cardiol. 2011 Dec;34(12):782-6. doi: 10.1002/clc.20962. Epub 2011 Nov 28. http://onlinelibrary.wiley.com/doi/10.1002/clc.20962/full (Full article)