Neural Consequences of Post-Exertion Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Post exertion malaise is one of the most debilitating aspects of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, yet the neurobiological consequences are largely unexplored. The objective of the study was to determine the neural consequences of acute exercise using functional brain imaging.

Fifteen female Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients and 15 healthy female controls completed 30 minutes of submaximal exercise (70% of peak heart rate) on a cycle ergometer. Symptom assessments (e.g. fatigue, pain, mood) and brain imaging data were collected one week prior to and 24 hours following exercise.

Functional brain images were obtained during performance of: 1) a fatiguing cognitive task – the Paced Auditory Serial Addition Task, 2) a non-fatiguing cognitive task – simple number recognition, and 3) a non-fatiguing motor task – finger tapping. Symptom and exercise data were analyzed using independent samples t-tests. Cognitive performance data were analyzed using mixed-model analysis of variance with repeated measures. Brain responses to fatiguing and non-fatiguing tasks were analyzed using linear mixed effects with cluster-wise (101-voxels) alpha of 0.05.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients reported large symptom changes compared to controls (effect size ≥0.8, p<0.05). Patients and controls had similar physiological responses to exercise (p>0.05). However, patients exercised at significantly lower Watts and reported greater exertion and leg muscle pain (p<0.05).

For cognitive performance, a significant Group by Time interaction (p<0.05), demonstrated pre- to post-exercise improvements for controls and worsening for patients. Brain responses to finger tapping did not differ between groups at either time point. During number recognition, controls exhibited greater brain activity (p<0.05) in the posterior cingulate cortex, but only for the pre-exercise scan. For the Paced Serial Auditory Addition Task, there was a significant Group by Time interaction (p<0.05) with patients exhibiting increased brain activity from pre- to post-exercise compared to controls bilaterally for inferior and superior parietal and cingulate cortices.

Changes in brain activity were significantly related to symptoms for patients (p<0.05). Acute exercise exacerbated symptoms, impaired cognitive performance and affected brain function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients.

These converging results, linking symptom exacerbation with brain function, provide objective evidence of the detrimental neurophysiological effects of post-exertion malaise.

Published by Elsevier Inc.

 

Source: Cook DB, Light AR, Light KC, Broderick G, Shields MR, Dougherty RJ, Meyer JD, VanRiper S, Stegner AJ, Ellingson LD, Vernon SD. Neural Consequences of Post-Exertion Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Brain Behav Immun. 2017 Feb 16. pii: S0889-1591(17)30051-X. doi: 10.1016/j.bbi.2017.02.009. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28216087

 

A systematic review of the association between fatigue and genetic polymorphisms

Abstract:

Fatigue is one of the most common and distressing symptoms, leading to markedly decreased quality of life among a large subset of patients with a variety of disorders. Susceptibility to fatigue may be influenced by genetic factors including single nucleotide polymorphisms (SNPs), especially in the regulatory regions, of relevant genes.

To further investigate the association of SNPs with fatigue in various patient populations, a systematic search was conducted on Pubmed, CINAHL, PsycINFO, and Sociological Abstracts Database for fatigue related-terms in combination with polymorphisms or genetic variation-related terms. Fifty papers in total met the inclusion and exclusion criteria for this analysis. These 50 papers were further classified into three subgroups for evaluation: chronic fatigue syndrome (CFS), cancer-related fatigue (CRF) and other disease-related fatigue.

SNPs in regulatory pathways of immune and neurotransmitter systems were found to play important roles in the etiologies of CFS, CRF and other disease-related fatigue. Evidence for associations between elevated fatigue and specific polymorphisms in TNFα, IL1b, IL4 and IL6 genes was revealed for all three subgroups of fatigue.

We also found CFS shared a series of polymorphisms in HLA, IFN-γ, 5-HT and NR3C1 genes with other disease-related fatigue, however these SNPs (excluding IFN-γ) were not found to be adequately investigated in CRF. Gaps in knowledge related to fatigue etiology and recommendations for future research are further discussed.

Copyright © 2017 Elsevier Inc. All rights reserved.

 

Source: Wang T, Yin J, Miller AH, Xiao C. A systematic review of the association between fatigue and genetic polymorphisms. Brain Behav Immun. 2017 Jan 12. pii: S0889-1591(17)30007-7. doi: 10.1016/j.bbi.2017.01.007. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28089639

 

Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

Abstract:

It is unclear what key symptoms differentiate Myalgic Encephalomyelitis (ME) and Chronic Fatigue syndrome (CFS) from Multiple Sclerosis (MS). The current study compared self-report symptom data of patients with ME or CFS with those with MS. The self-report data is from the DePaul Symptom Questionnaire, and participants were recruited to take the questionnaire online.

Data were analyzed using a machine learning technique called decision trees. Five symptoms best differentiated the groups. The best discriminating symptoms were from the immune domain (i.e., flu-like symptoms and tender lymph nodes), and the trees correctly categorized MS from ME or CFS 81.2% of the time, with those with ME or CFS having more severe symptoms. Our findings support the use of machine learning to further explore the unique nature of these different chronic diseases

 

Source: Ohanian D, Brown A, Sunnquist M, Furst J, Nicholson L, Klebek L, Jason LA. Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis. Neurology (ECronicon). 2016;4(2):41-45. Epub 2016 Dec 19. https://www.ncbi.nlm.nih.gov/pubmed/28066845

 

Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women

Abstract:

OBJECTIVE: Poor sleep quality has been linked to inflammatory processes and worse disease outcomes in the context of many chronic illnesses, but less is known in conditions such as chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). This study examines the relationships between sleep quality, pro-inflammatory cytokines, and CFS/ME symptoms.

METHODS: Sixty women diagnosed with CFS/ME were assessed using the Pittsburgh Sleep Quality Index (PSQI), Fatigue Symptom Inventory (FSI) and Center for Disease Control and Prevention (CDC)-based CFS/ME symptom questionnaires. Circulating plasma pro-inflammatory cytokine levels were measured by ELISA. Multiple regression analyses examined associations between sleep, cytokines and symptoms, controlling for age, education, and body mass index.

RESULTS: Poor sleep quality (PSQI global score) was associated with greater pro-inflammatory cytokine levels: interleukin-1β (IL-1β) (β=0.258, p=0.043), IL-6 (β=0.281, p=0.033), and tumor necrosis factor-alpha (TNF-α) (β=0.263, p=0.044). Worse sleep quality related to greater fatigue severity (β=0.395, p=0.003) and fatigue-related interference with daily activities (β=0.464, p<0.001), and more severe and frequent CDC-defined core CFS/ME symptoms (β=0.499, p<0.001, and β=0.556, p<0.001, respectively).

CONCLUSIONS: Results underscore the importance of managing sleep-related difficulties in this patient population. Further research is needed to identify the etiology of sleep disruptions in CFS/ME and mechanistic factors linking sleep quality to symptom severity and inflammatory processes.

Copyright © 2016 Elsevier B.V. All rights reserved.

 

Source: Milrad SF, Hall DL, Jutagir DR, Lattie EG, Ironson GH, Wohlgemuth W, Nunez MV, Garcia L, Czaja SJ, Perdomo DM, Fletcher MA, Klimas N, Antoni MH. Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women. J Neuroimmunol. 2017 Feb 15;303:43-50. doi: 10.1016/j.jneuroim.2016.12.008. Epub 2016 Dec 14. https://www.ncbi.nlm.nih.gov/pubmed/28038892

 

Binocular Vision in Chronic Fatigue Syndrome

Abstract:

INTRODUCTION AND PURPOSE: To compare binocular vision measurements between Chronic Fatigue Syndrome (CFS) patients and healthy controls.

METHODS: Forty-one CFS patients referred by the Reference Centre for Chronic Fatigue Syndrome of the Antwerp University Hospital and forty-one healthy volunteers, matched for age and gender, underwent a complete orthoptic examination. Data of visual acuity, eye position, fusion amplitude, stereopsis, ocular motility, convergence, and accommodation were compared between both groups.

RESULTS: Patients with CFS showed highly significant smaller fusion amplitudes (P < 0.001), reduced convergence capacity (P < 0.001), and a smaller accommodation range (P < 0.001) compared to the control group.

CONCLUSION: In patients with CFS binocular vision, convergence and accommodation should be routinely examined. CFS patients will benefit from reading glasses either with or without prism correction in an earlier stage compared to their healthy peers. Convergence exercises may be beneficial for CFS patients, despite the fact that they might be very tiring. Further research will be necessary to draw conclusions about the efficacy of treatment, especially regarding convergence exercises. To our knowledge, this is the first prospective study evaluating binocular vision in CFS patients.

© 2016 Board of regents of the University of Wisconsin System, American Orthoptic Journal, Volume 66, 2016, ISSN 0065-955X, E-ISSN 1553-4448.

 

Source: Godts D, Moorkens G, Mathysen DG. Binocular Vision in Chronic Fatigue Syndrome. Am Orthopt J. 2016 Jan;66(1):92-97. https://www.ncbi.nlm.nih.gov/pubmed/27799582

 

Deconstructing post-exertional malaise: An exploratory factor analysis

Abstract:

Post-exertional malaise is a cardinal symptom of myalgic encephalomyelitis and chronic fatigue syndrome. There are two differing focuses when defining post-exertional malaise: a generalized, full-body fatigue and a muscle-specific fatigue. This study aimed to discern whether post-exertional malaise is a unified construct or whether it is composed of two smaller constructs, muscle fatigue and generalized fatigue. An exploratory factor analysis was conducted on several symptoms that assess post-exertional malaise. The results suggest that post-exertional malaise is composed of two empirically different experiences, one for generalized fatigue and one for muscle-specific fatigue.

© The Author(s) 2016.

 

Source: McManimen SL, Sunnquist ML, Jason LA. Deconstructing post-exertional malaise: An exploratory factor analysis. J Health Psychol. 2016 Aug 24. pii: 1359105316664139. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27557649

 

Do evidence based interventions for chronic fatigue syndrome improve sleep? A systematic review and narrative synthesis

Abstract:

Cognitive behavioural therapy (CBT) and graded exercise therapy (GET) are recommended evidence based treatments for chronic fatigue syndrome (CFS), with research supporting their effectiveness in reducing fatigue and functional impairment. However, little research has focussed on the effect of these treatments on sleep, despite high reported sleep disturbance in CFS.

Using a narrative synthesis approach, we aimed to 1) systematically identify and summarise the current evidence for the effectiveness of CBT and GET in improving sleep; 2) consider factors influencing treatment effectiveness, including incorporation of sleep management techniques; and 3) consider the appropriateness of sleep outcome measures used within evaluations. Studies evaluating CBT and/or GET for CFS, and including a sleep outcome were eligible for inclusion. Eight studies were identified.

We found that GET interventions can improve sleep but this effect is inconsistent across studies. For CBT the evidence is limited with only one of two evaluations demonstrating sleep-related improvements.

We conclude from existing research that we know little about the effects of including sleep management components within CBT and GET interventions. We suggest that future research should explore the effectiveness of sleep components within interventions, and sleep specific interventions, using comprehensive outcome measures that fully capture the range of sleep difficulties experienced in CFS.

Copyright © 2016 Elsevier Ltd. All rights reserved.

 

Source: Russell C, Kyle SD, Wearden AJ. Do evidence based interventions for chronic fatigue syndrome improve sleep? A systematic review and narrative synthesis. Sleep Med Rev. 2016 May 13. pii: S1087-0792(16)30012-0. doi: 10.1016/j.smrv.2016.05.001. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27524207

 

TauG-guidance of dynamic balance control during gait initiation in patients with chronic fatigue syndrome and fibromyalgia

Abstract:

BACKGROUND: Impaired postural control has been reported in static conditions in chronic fatigue syndrome and fibromyalgia, but postural control in dynamic tasks have not yet been investigated. Thus, we investigated measurements from a force plate to evaluate dynamic balance control during gait initiation in patients with chronic fatigue syndrome and fibromyalgia compared to matched healthy controls.

METHODS: Thirty female participants (10 per group) performed five trials of gait initiation. Center of pressure (CoP) trajectory of the initial weight shift onto the supporting foot in the mediolateral direction (CoPX) was analyzed using General Tau Theory. We investigated the hypothesis that tau of the CoPX motion-gap (τCoPx) is coupled onto an intrinsic tauG-guide (τG) by keeping the relation τCoPx=KτG, where K is a scaling factor that determines the relevant kinematics of a movement.

FINDINGS: Mean K values were 0.57, 0.55, and 0.50 in fibromyalgia, chronic fatigue syndrome, and healthy controls, respectively. Both patient groups showed K values significantly higher than 0.50 (P<0.05), indicating that patients showed poorer dynamic balance control, CoPX colliding with the boundaries of the base of support (K>0.5).

INTERPRETATION: The findings revealed a lower level of dynamic postural control in both fibromyalgia and chronic fatigue syndrome compared to controls.

Copyright © 2016 Elsevier Ltd. All rights reserved.

 

Source: Rasouli O, Stensdotter AK, Van der Meer AL. TauG-guidance of dynamic balance control during gait initiation in patients with chronic fatigue syndrome and fibromyalgia. Clin Biomech (Bristol, Avon). 2016 Aug;37:147-52. doi: 10.1016/j.clinbiomech.2016.07.008. Epub 2016 Jul 22. https://www.ncbi.nlm.nih.gov/pubmed/27474799

 

Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a complex, multisystem disorder that can be disabling. CFS symptoms can be provoked by increased physical or cognitive activity, and by orthostatic stress. In preliminary work, we noted that CFS symptoms also could be provoked by application of longitudinal neural and soft tissue strain to the limbs and spine of affected individuals.

In this study we measured the responses to a straight leg raise neuromuscular strain maneuver in individuals with CFS and healthy controls. We randomly assigned 60 individuals with CFS and 20 healthy controls to either a 15 minute period of passive supine straight leg raise (true neuromuscular strain) or a sham straight leg raise. The primary outcome measure was the symptom intensity difference between the scores during and 24 hours after the study maneuver compared to baseline.

Fatigue, body pain, lightheadedness, concentration difficulties, and headache scores were measured individually on a 0-10 scale, and summed to create a composite symptom score. Compared to individuals with CFS in the sham strain group, those with CFS in the true strain group reported significantly increased body pain (P = 0.04) and concentration difficulties (P = 0.02) as well as increased composite symptom scores (all P = 0.03) during the maneuver.

After 24 hours, the symptom intensity differences were significantly greater for the CFS true strain group for the individual symptom of lightheadedness (P = 0.001) and for the composite symptom score (P = 0.005). During and 24 hours after the exposure to the true strain maneuver, those with CFS had significantly higher individual and composite symptom intensity changes compared to the healthy controls.

We conclude that a longitudinal strain applied to the nerves and soft tissues of the lower limb is capable of increasing symptom intensity in individuals with CFS for up to 24 hours. These findings support our preliminary observations that increased mechanical sensitivity may be a contributor to the provocation of symptoms in this disorder.

 

Source: Rowe PC, Fontaine KR, Lauver M, Jasion SE, Marden CL, Moni M, Thompson CB, Violand RL. Neuromuscular Strain Increases Symptom Intensity in Chronic Fatigue Syndrome. PLoS One. 2016 Jul 18;11(7):e0159386. doi: 10.1371/journal.pone.0159386. ECollection 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4948885/ (Full article)

 

Factor Analysis of the DePaul Symptom Questionnaire: Identifying Core Domains

Abstract:

The present study attempted to identify critical symptom domains of individuals with Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Using patient and control samples collected in the United States, Great Britain, and Norway, exploratory factor analysis (EFA) was used to establish the underlying factor structure of ME and CFS symptoms.

The EFA suggested a four-factor solution: post-exertional malaise, cognitive dysfunction, sleep difficulties, and a combined factor consisting of neuroendocrine, autonomic, and immune dysfunction symptoms. The use of empirical methods could help better understand the fundamental symptom domains of this illness.

 

Source: Jason LA, Sunnquist M, Brown A, Furst J, Cid M, Farietta J, Kot B, Bloomer C, Nicholson L, Williams Y, Jantke R, Newton JL, Strand EB. Factor Analysis of the DePaul Symptom Questionnaire: Identifying Core Domains. J Neurol Neurobiol. 2015 Sep;1(4). doi: 10.16966/2379-7150.114. Epub 2015 Sep 17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4830389/ (Full article)