Category: Symptoms

Chronic fatigue syndrome (CFS) symptom-based phenotypes in two clinical cohorts of adult patients in the UK and The Netherlands

Abstract:

OBJECTIVE: Studies have provided evidence of heterogeneity within chronic fatigue syndrome (CFS), but few have used data from large cohorts of CFS patients or replication samples.

METHODS: 29 UK secondary-care CFS services recorded the presence/absence of 12 CFS-related symptoms; 8 of these symptoms were recorded by a Dutch tertiary service. Latent Class Analysis (LCA) was used to assign symptom profiles (phenotypes). Regression models were fitted with phenotype as outcome (in relation to age, sex, BMI, duration of illness) and exposure (in relation to comorbidities and patient-reported measures).

RESULTS: Data were available for 7041 UK and 1392 Dutch patients. Almost all patients in both cohorts presented with post-exertional malaise, cognitive dysfunction and disturbed/unrefreshing sleep, and these 3 symptoms were excluded from LCA. In UK patients, six phenotypes emerged: ‘full’ polysymptomatic (median 8, IQR 7-9 symptoms) 32.8%; ‘pain-only’ (muscle/joint) 20.3%; ‘sore throat/painful lymph node’ 4.5%; and ‘oligosymptomatic’ (median 1, IQR 0-2 symptoms) 4.7%. Two ‘partial’ polysymptomatic phenotypes were similar to the ‘full’ phenotype, bar absence of dizziness/nausea/palpitations (21.4%) or sore throat/painful lymph nodes (16.3%). Women and patients with longer duration of illness were more likely to be polysymptomatic. Polysymptomatic patients had more severe illness and more comorbidities. LCA restricted to 5 symptoms recorded in both cohorts indicated 3 classes (polysymptomatic, oligosymptomatic, pain-only), which were replicated in Dutch data.

CONCLUSIONS: Adults with CFS may have one of 6 symptom-based phenotypes associated with sex, duration and severity of illness, and comorbidity. Future research needs to determine whether phenotypes predict treatment outcomes, and require different treatments.

Copyright © 2015 Elsevier Inc. All rights reserved.

 

Source: Collin SM, Nikolaus S, Heron J, Knoop H, White PD, Crawley E. Chronic fatigue syndrome (CFS) symptom-based phenotypes in two clinical cohorts of adult patients in the UK and The Netherlands. J Psychosom Res. 2016 Feb;81:14-23. doi: 10.1016/j.jpsychores.2015.12.006. Epub 2015 Dec 23. https://www.ncbi.nlm.nih.gov/pubmed/26800634

 

Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

BACKGROUND: Mitochondrial dysfunction has been hypothesized to occur in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a disease characterized by fatigue, cognitive difficulties, pain, malaise, and exercise intolerance. We investigated whether haplogroup, single nucleotide polymorphisms (SNPs), or heteroplasmy of mitochondrial DNA (mtDNA) were associated with health status and/or symptoms.

METHODS: Illumina sequencing of PCR-amplified mtDNA was performed to analyze sequence and extent of heteroplasmy of mtDNAs of 193 cases and 196 age- and gender-matched controls from DNA samples collected by the Chronic Fatigue Initiative. Association testing was carried out to examine possible correlations of mitochondrial sequences with case/control status and symptom constellation and severity as reported by subjects on Short Form-36 and DePaul Symptom Questionnaires.

RESULTS: No ME/CFS subject exhibited known disease-causing mtDNA mutations. Extent of heteroplasmy was low in all subjects. Although no association between mtDNA SNPs and ME/CFS vs. healthy status was observed, haplogroups J, U and H as well as eight SNPs in ME/CFS cases were significantly associated with individual symptoms, symptom clusters, or symptom severity.

CONCLUSIONS: Analysis of mitochondrial genomes in ME/CFS cases indicates that individuals of a certain haplogroup or carrying specific SNPs are more likely to exhibit certain neurological, inflammatory, and/or gastrointestinal symptoms. No increase in susceptibility to ME/CFS of individuals carrying particular mitochondrial genomes or SNPs was observed.

 

Source: Billing-Ross P, Germain A, Ye K, Keinan A, Gu Z, Hanson MR. Mitochondrial DNA variants correlate with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome. J Transl Med. 2016 Jan 20;14:19. doi: 10.1186/s12967-016-0771-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719218/ (Full article)

 

Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study

Abstract:

Chronic Fatigue Syndrome (CFS) is a multisystem illness, which may be associated with imbalances in gut microbiota. This study builds on recent evidence that sleep may be influenced by gut microbiota, by assessing whether changes to microbiota in a clinical population known to have both poor sleep and high rates of colonization with gram-positive faecal Streptococcus, can improve sleep.

Twenty-one CFS participants completed a 22- day open label trial. Faecal microbiota analysis was performed at baseline and at the end of the trial. Participants were administered erythromycin 400 mg b.d. for 6 days. Actigraphy and questionnaires were used to monitor sleep, symptoms and mood. Changes in patients who showed a clinically significant change in faecal Streptococcus after treatment (responders; defined as post-therapy distribution<6%) were compared to participants who did not respond to treatment.

In the seven responders, there was a significant increase in actigraphic total sleep time (p=0.028) from baseline to follow up, compared with non-responders. Improved vigour scores were associated with a lower Streptococcus count (ρ=-0.90, p=0.037). For both the responders and the whole group, poorer mood was associated with higher Lactobacillus.

Short term antibiotic treatment appears to be insufficient to effect sustainable changes in the gut ecosystem in most CFS participants. Some improvement in objective sleep parameters and mood were found in participants with reduced levels of gram-positive gut microbiota after antibiotic treatment, which is encouraging. Further study of possible links between gut microorganisms and sleep and mood disturbances is warranted.

 

Source: Jackson ML, Butt H, Ball M, Lewis DP, Bruck D. Sleep quality and the treatment of intestinal microbiota imbalance in Chronic Fatigue Syndrome: A pilot study. Sleep Sci. 2015 Nov;8(3):124-33. doi: 10.1016/j.slsci.2015.10.001. Epub 2015 Oct 23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688574/ (Full article)

 

Fatigue in adults with post-infectious fatigue syndrome: a qualitative content analysis

Abstract:

BACKGROUND: Fatigue is a major problem among individuals with post-infectious fatigue syndrome (PIFS), also known as chronic fatigue syndrome or myalgic encephalomyelitis. It is a complex phenomenon that varies across illnesses. From a nursing perspective, knowledge and understanding of fatigue in this illness is limited. Nurses lack confidence in caring for these patients and devalue their professional role. The aim of this study was to explore in-depth the experiences of fatigue among individuals with PIFS. A detailed description of the phenomenon of fatigue is presented. Increased knowledge would likely contribute to more confident nurses and improved nursing care.

METHODS: A qualitative study with open interviews was employed. In-depth interviews with patients were fully transcribed and underwent a qualitative content analysis. A maximum variation sample of 26 affected adults between 26-59 years old was recruited from a population diagnosed at a fatigue outpatient clinic.

RESULTS: The fatigue was a post-exertional, multidimensional, fluctuating phenomenon with varying degrees of severity and several distinct characteristics and was accompanied by concomitant symptoms. Fatigue was perceived to be an all-pervasive complex experience that substantially reduced the ability to function personally or professionally. A range of trigger mechanisms evoked or worsened the fatigue, but the affected were not always aware of what triggered it. There was an excessive increase in fatigue in response to even minor activities. An increase in fatigue resulted in the exacerbation of other concomitant symptoms. The term fatigue does not capture the participants’ experiences, which are accompanied by a considerable symptom burden that contributes to the illness experience and the severe disability.

CONCLUSIONS: Although some aspects of the fatigue experience have been reported previously, more were added in our study, such as the dimension of awakening fatigue and the characteristic beyond time, when time passes unnoticed. We also identified trigger mechanisms such as emotional, neurological, social, financial, and pressure on oneself or from others. This in-depth exploration of fatigue in PIFS provides an overview of the dimensions, characteristics, and trigger mechanisms of fatigue, thus making better clinical observations, early recognition, improved communication with patients and more appropriate nursing interventions possible.

 

Source: Stormorken E, Jason LA, Kirkevold M. Fatigue in adults with post-infectious fatigue syndrome: a qualitative content analysis. BMC Nurs. 2015 Nov 28;14:64. doi: 10.1186/s12912-015-0115-5. ECollection 2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4662830/ (Full article)

 

Increased Vulnerability to Pattern-Related Visual Stress in Myalgic Encephalomyelitis

Abstract:

The objective of this study was to determine vulnerability to pattern-related visual stress in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A total of 20 ME/CFS patients and 20 matched (age, gender) controls were recruited to the study.

Pattern-related visual stress was determined using the Pattern Glare Test. Participants viewed three patterns, the spatial frequencies (SF) of which were 0.3 (low-SF), 2.3 (mid-SF), and 9.4 (high-SF) cycles per degree (c/deg). They reported the number of distortions they experienced when viewing each pattern.

ME/CFS patients exhibited significantly higher pattern glare scores than controls for the mid-SF pattern. Mid-high SF differences were also significantly higher in patients than controls. These findings provide evidence of altered visual perception in ME/CFS.

Pattern-related visual stress may represent an identifiable clinical feature of ME/CFS that will prove useful in its diagnosis. However, further research is required to establish if these symptoms reflect ME/CFS-related changes in the functioning of sensory neural pathways.

© The Author(s) 2015.

 

Source: Wilson RL, Paterson KB, Hutchinson CV. Increased Vulnerability to Pattern-Related Visual Stress in Myalgic Encephalomyelitis. Perception. 2015 Dec;44(12):1422-6. doi: 10.1177/0301006615614467. Epub 2015 Nov 3. https://www.ncbi.nlm.nih.gov/pubmed/26562880

 

A systematic review of the comorbidity between Temporomandibular Disorders and Chronic Fatigue Syndrome

Abstract:

The most common cause of chronic oro-facial pain is a group of disorders collectively termed temporomandibular disorders (TMDs). Chronic painful TMD is thought to be a ‘central sensitivity syndrome’ related to hypersensitivity of the nervous system, but the cause is unknown. A similar understanding is proposed for other unexplained conditions, including chronic fatigue syndrome (CFS). Exploring the comorbidity of the two conditions is a valuable first step in identifying potential common aetiological mechanisms or treatment targets.

METHOD: Systematic literature review. Studies were included if they recruited community or control samples and identified how many reported having both TMD and CFS, or if they recruited a sample of patients with either TMD or CFS and measured the presence of the other condition.

RESULTS: Six papers met inclusion criteria. In studies of patients with CFS (n = 3), 21-32% reported having TMD. In a sample of people with CFS and fibromyalgia, 50% reported having TMD. Studies in people with TMD (n = 3) reported 0-43% having CFS. Studies in samples recruited from oro-facial pain clinics (n = 2) reported a lower comorbidity with CFS (0-10%) than a study that recruited individuals from a TMD self-help organisation (43%).

CONCLUSION: The review highlights the limited standard of evidence addressing the comorbidity between oro-facial pain and CFS. There is a valuable signal that the potential overlap in these two conditions could be high; however, studies employing more rigorous methodology including standardised clinical assessments rather than self-report of prior diagnosis are needed.

© 2015 John Wiley & Sons Ltd.

 

Source: Robinson LJ, Durham J, Newton JL. A systematic review of the comorbidity between Temporomandibular Disorders and Chronic Fatigue Syndrome. J Oral Rehabil. 2016 Apr;43(4):306-16. doi: 10.1111/joor.12367. Epub 2015 Nov 9. https://www.ncbi.nlm.nih.gov/pubmed/26549386

 

Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts

Abstract:

OBJECTIVE: To investigate differences between young children, adolescents and adults with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

STUDY DESIGN: Comparison of clinical cohorts from 8 paediatric and 27 adult CFS/ME services in the UK and a paediatric randomised controlled trial from the Netherlands. Outcome measures include: fatigue (the UK-Chalder Fatigue Scale); Disability (the UK-SF-36 physical function subscale; the Netherlands-CHQ-CF87); school attendance, pain, anxiety and depression (the UK-Hospital Anxiety & Depression Scale, Spence Children’s Anxiety Scale; the Netherlands-Spielberger State-Trait Anxiety Inventory for Children, Children’s Depression Inventory); symptoms; time-to-assessment; and body mass index. We used multinomial regression to compare younger (aged <12 years) and older (aged 12-18 years) children with adults, and logistic regression to compare UK and Dutch adolescents.

RESULTS: Younger children had a more equal gender balance compared to adolescents and adults. Adults had more disability and fatigue, and had been ill for longer. Younger children were less likely to have cognitive symptoms (OR 0.18 (95% CI 0.13 to 0.25)) and more likely to present with a sore throat (OR 1.42 (1.07 to 1.90). Adolescents were more likely to have headaches (81.1%, OR 1.56 (1.36% to 1.80%)) and less likely to have tender lymph nodes, palpitations, dizziness, general malaise and pain, compared to adults. Adolescents were more likely to have comorbid depression (OR 1.51 (1.33 to 1.72)) and less likely to have anxiety (OR 0.46 (0.41 to 0.53)) compared to adults.

CONCLUSIONS: Paediatricians need to recognise that children with CFS/ME present differently from adults. Whether these differences reflect an underlying aetiopathology requires further investigation.

TRIAL REGISTRATION NUMBERS: FITNET trial registration numbers are ISRCTN59878666 and NCT00893438. This paper includes secondary (post-results) analysis of data from this trial, but are unrelated to trial outcomes.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

 

Source: Collin SM, Nuevo R, van de Putte EM, Nijhof SL, Crawley E. Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is different in children compared to in adults: a study of UK and Dutch clinical cohorts. BMJ Open. 2015 Oct 28;5(10):e008830. doi: 10.1136/bmjopen-2015-008830. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636651/ (Full article)

 

A Cross Cultural Comparison of Disability and Symptomatology Associated with CFS

Abstract:

Few studies have compared symptomatology and functional differences experienced by patients with chronic fatigue syndrome (CFS) across cultures. The current study compared patients with CFS from the United States (US) to those from the United Kingdom (UK) across areas of functioning, symptomatology, and illness onset characteristics.

Individuals in each sample met criteria for CFS as defined by Fukuda et al. (1994). These samples were compared on two measures of disability and impairment, the DePaul Symptom Questionnarie (DSQ) and the Medical outcomes study 36-item short-form health survey (SF-36).

Results revealed that the UK sample was significantly more impaired in terms of mental health and role emotional functioning, as well as specific symptoms of pain, neurocognitive difficulties, and immune manifestations. In addition, the UK sample was more likely to be working rather than on disability.

Individuals in the US sample reported more difficulties falling asleep, more frequently reported experiencing a sudden illness onset (within 24 hours), and more often reported that the cause of illness was primarily due to physical causes. These findings suggest that there may be important differences in illness characteristics across individuals with CFS in the US and the UK, and this has implications for the comparability of research findings across these two countries.

 

Source: Zdunek M, Jason LA, Evans M, Jantke R, Newton JL. A Cross Cultural Comparison of Disability and Symptomatology Associated with CFS. Int J Psychol Behav Sci. 2015;5(2):98-107. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605442/ (Full article)

 

Associations Between Cognitive Performance and Pain in Chronic Fatigue Syndrome: Comorbidity with Fibromyalgia Does Matter

Abstract:

BACKGROUND: In addition to the frequently reported pain complaints, performance-based cognitive capabilities in patients with chronic fatigue syndrome (CFS) with and without comorbid fibromyalgia (FM) are significantly worse than those of healthy controls. In various chronic pain populations, cognitive impairments are known to be related to pain severity. However, to the best of our knowledge, the association between cognitive performance and experimental pain measurements has never been examined in CFS patients.

OBJECTIVES: This study aimed to examine the association between cognitive performance and self-reported as well as experimental pain measurements in CFS patients with and without FM.

STUDY DESIGN: Observational study.

SETTING: The present study took place at the Vrije Universiteit Brussel and the University of Antwerp.

METHODS: Forty-eight (18 CFS-only and 30 CFS+FM) patients and 30 healthy controls were studied. Participants first completed 3 performance-based cognitive tests designed to assess selective and sustained attention, cognitive inhibition, and working memory capacity. Seven days later, experimental pain measurements (pressure pain thresholds [PPT], temporal summation [TS], and conditioned pain modulation [CPM]) took place and participants were asked to fill out 3 questionnaires to assess self-reported pain, fatigue, and depressive symptoms.

RESULTS: In the CFS+FM group, the capacity of pain inhibition was significantly associated with cognitive inhibition. Self-reported pain was significantly associated with simple reaction time in CFS-only patients. The CFS+FM but not the CFS-only group showed a significantly lower PPT and enhanced TS compared with controls.

LIMITATIONS: The cross-sectional nature of this study does not allow for inferences of causation.

CONCLUSIONS: The results underline disease heterogeneity in CFS by indicating that a measure of endogenous pain inhibition might be a significant predictor of cognitive functioning in CFS patients with FM, while self-reported pain appears more appropriate to predict cognitive functioning in CFS patients without FM.

 

Source: Ickmans K, Meeus M, De Kooning M, Lambrecht L, Pattyn N, Nijs J. Associations Between Cognitive Performance and Pain in Chronic Fatigue Syndrome: Comorbidity with Fibromyalgia Does Matter. Pain Physician. 2015 Sep-Oct;18(5):E841-52. http://www.painphysicianjournal.com/current/pdf?article=MjQxOA%3D%3D&journal=91 (Full article as PDF file)

 

Variability of postural orthostatic tachycardia in patients with myalgic encephalomyelitis and orthostatic intolerance

Abstract:

Central nervous system dysfunction with myalgic encephalomyelitis (ME) has been suggested as the main cause of chronic fatigue syndrome. Fluctuation of the symptom severity and hierarchy is a characteristic feature in ME patients. The characteristics of the sympathetic activation may differ between the “good days” and “bad days” in them.

Twenty-four ME patients with orthostatic intolerance underwent a conventional 10-min active standing test and echocardiography both on a “good day” and a “bad day”, defined according to the severity of their symptoms. The mean heart rate at rest was significantly higher on the “bad days” than on the “good days”. During the standing test on a “bad day”, 5 patients (21 %) failed to maintain an upright posture for 10 min, whereas on a “good day” all the 24 patients maintained it.

Postural orthostatic tachycardia (POT) (increase in heart rate ≥30 beats/min) or severe POT (heart rate ≥120 beats/min) was observed on the “bad days” in 10 patients (43 %) who did not suffer from the severe tachycardia on the “good days”, suggesting the exaggerated sympathetic nervous activation.

In contrast, POT did not occur or severe POT was attenuated on the “bad days” in 5 patients (21 %) who developed POT or severe POT on the “good days”, suggesting the impaired sympathetic activation. Echocardiography revealed significantly lower mean values of both the left ventricular end-diastolic diameter and stroke volume index on the “bad days” compared with the “good days”.

In conclusion, in ME patients with orthostatic intolerance, the exaggerated activation of the sympathetic nervous system while standing appears to switch to the impaired sympathetic activation after the system is loaded with the additional accentuated stimuli associated with the preload reduction.

 

Source: Miwa K. Variability of postural orthostatic tachycardia in patients with myalgic encephalomyelitis and orthostatic intolerance. Heart Vessels. 2016 Sep;31(9):1522-8. doi: 10.1007/s00380-015-0744-3. Epub 2015 Sep 15. https://www.ncbi.nlm.nih.gov/pubmed/26374335