Physical activity patterns among children and adolescents with mild-to-moderate chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

OBJECTIVE: Chronic fatigue syndromemyalgic encephalomyelitis (CFS/ME) is relatively common among children and adolescents; however, little is known about the physical activity levels and patterns of this population. The aim of this study was to examine the underlying patterns of physical activity among youth with mild-to-moderate CFS/ME. Cross-sectional associations between physical activity patterns with self-reported physical function, pain, fatigue, anxiety and depression were also examined.

DESIGN: Baseline cross-sectional data from the Managed Activity Graded Exercise iN Teenagers and pre-Adolescents randomised controlled trial.

PATIENTS: Children and adolescents (aged 8-17 years) diagnosed with mild-to-moderate CFS/ME who wore an accelerometer for at least three valid weekdays.

ANALYSES: Latent profile analysis was used to identify physical activity patterns. Linear regression models examined associations between physical activity classes and self-reported physical function, pain, fatigue, anxiety and depression.

RESULTS: 138 children and adolescents (72.5% females) had valid data. Overall, participants did less than half the government recommended level of physical activity for children and adolescents, but not all were inactive: three (2.2%) did more than 1 hour of physical activity every day, and 13 (9.4%) achieved an average of 60 min a day. Adolescents (≥12 years) were less active than younger children, but activity levels were similar between genders. Three latent classes emerged from the data: ‘active’, ‘light’ and ‘inactive’. Compared with being ‘inactive’, being in the ‘light’ class was associated with greater self-reported physical function (10.35, 95% CI 2.32 to 18.38) and lower fatigue (-1.60, 95% CI -3.13 to -0.06), while being ‘active’ was associated with greater physical function (15.26, 95% CI 0.12 to 30.40), but also greater anxiety (13.79, 95% CI 1.73 to 25.85).

CONCLUSIONS: Paediatricians need to be aware that physical activity patterns vary widely before recommending treatment.

Source: Solomon-Moore E, Jago R, Beasant L, Brigden A, Crawley E. Physical activity patterns among children and adolescents with mild-to-moderate chronic fatigue syndrome/myalgic encephalomyelitis. BMJ Paediatr Open. 2019 May 2;3(1):e000425. doi: 10.1136/bmjpo-2018-000425. eCollection 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542452/ (Full article)

Acupuncture for chronic fatigue syndrome: a systematic review and meta-analysis

Abstract:

OBJECTIVE: To evaluate evidence for the efficacy of acupuncture for chronic fatigue syndrome (CFS).

METHODS: Randomized controlled trials (RCTs) comparing acupuncture with sham acupuncture, other interventions that may have a therapeutic effect, or no intervention, for the treatment of CFS, were searched for in the following databases up to March 2018: Pubmed; Embase; the Cochrane Library; Web of Science; Wanfang database; China National Knowledge Infrastructure (CNKI); Chinese Biomedicine (CBM) database; and VIP database. Risk of bias was determined using the Cochrane tool. Meta-analyses were performed using RevMan V.5.3 software. The GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) was adopted for levels of evidence.

RESULTS: Sixteen studies with 1346 subjects were included. Most studies had low methodological quality. Meta-analyses showed a favourable effect of acupuncture on overall response rate compared with sham acupuncture (four studies, 281 participants, RR=2.08, 95% CI 1.4 to 3.1, I2=64%, low certainty) and Chinese herbal medicine (three studies, 290 participants, RR=1.17, 95% CI 1.07 to 1.29, I2=0%, low certainty). Acupuncture also appeared to significantly reduce fatigue severity measured by Chalder’s Fatigue Scale and the Fatigue Severity Scale compared with other types of control.

CONCLUSION: Our review indicated that acupuncture was more effective than sham acupuncture and other interventions (Chinese herbal medicine, mainly), but no firm conclusion could be reached owing to limited data, poor quality and potentially exaggerated effect size evaluation. Further large, rigorously designed and reported RCTs are required.

Source: Zhang Q, Gong J, Dong H, Xu S, Wang W, Huang G. Acupuncture for chronic fatigue syndrome: a systematic review and meta-analysis. Acupunct Med. 2019 Jun 17:acupmed2017011582. doi: 10.1136/acupmed-2017-011582. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31204859

Gut bacteria associated with chronic pain for first time

Press Release:

Scientists have found a correlation between a disease involving chronic pain and alterations in the gut microbiome.

Fibromyalgia affects 2-4 percent of the population and has no known cure. Symptoms include fatigue, impaired sleep and cognitive difficulties, but the disease is most clearly characterized by widespread chronic pain. In a paper published today in the journal Pain, a Montreal-based research team has shown, for the first time, that there are alterations in the bacteria in the gastrointestinal tracts of people with fibromyalgia. Approximately 20 different species of bacteria were found in either greater or are lesser quantities in the microbiomes of participants suffering from the disease than in the healthy control group.

Greater presence or absence of certain species of bacteria

“We used a range of techniques, including Artificial Intelligence, to confirm that the changes we saw in the microbiomes of fibromyalgia patients were not caused by factors such as diet, medication, physical activity, age, and so on, which are known to affect the microbiome,” says Dr. Amir Minerbi, from the Alan Edwards Pain Management Unit at the McGill University Health Centre (MUHC), and first author on the paper. The team also included researchers from McGill University and Université de Montréal as well as others from the Research Institute of the MUHC.

Dr. Minerbi adds, “We found that fibromyalgia and the symptoms of fibromyalgia – pain, fatigue and cognitive difficulties – contribute more than any of the other factors to the variations we see in the microbiomes of those with the disease. We also saw that the severity of a patient’s symptoms was directly correlated with an increased presence or a more pronounced absence of certain bacteria – something which has never been reported before.”

Are bacteria simply the markers of the disease?

At this point, it’s not clear whether the changes in gut bacteria seen in patients with fibromyalgia are simply markers of the disease or whether they play a role in causing it. Because the disease involves a cluster of symptoms, and not simply pain, the next step in the research will be to investigate whether there are similar changes in the gut microbiome in other conditions involving chronic pain, such as lower back pain, headaches and neuropathic pain.

The researchers are also interested in exploring whether bacteria play a causal role in the development of pain and fibromyalgia. And whether their presence could, eventually, help in finding a cure, as well as speed up the process of diagnosis.

Confirming a diagnosis and next steps towards finding a cure

Fibromyalgia is a disease that has proved difficult to diagnose. Patients can wait as long as 4 to 5 years to get a final diagnosis. But this may be about to change.

“We sorted through large amounts of data, identifying 19 species that were either increased or decreased in individuals with fibromyalgia,” says Emmanuel Gonzalez, from the Canadian Center for Computational Genomics and the Department of Human Genetics at McGill University. “By using machine learning, our computer was able to make a diagnosis of fibromyalgia, based only on the composition of the microbiome, with an accuracy of 87 per cent. As we build on this first discovery with more research, we hope to improve upon this accuracy, potentially creating a step-change in diagnosis.”

“People with fibromyalgia suffer not only from the symptoms of their disease but also from the difficulty of family, friends and medical teams to comprehend their symptoms,” says Yoram Shir, the senior author on the paper who is the Director of the Alan Edwards Pain Management Unit at the MUHC and an Associate Investigator from the BRaiN Program of the RI-MUHC. “As pain physicians, we are frustrated by our inability to help, and this frustration is a good fuel for research. This is the first evidence, at least in humans, that the microbiome could have an effect on diffuse pain, and we really need new ways to look at chronic pain.”

How the research was done

The research was based on a cohort of 156 individuals in the Montreal area, 77 of whom suffer from fibromyalgia. Participants in the study were interviewed and gave stool, blood, saliva and urine samples, which were then compared with those of healthy control subjects, some of whom lived in the same house as the fibromyalgia patients or were their parents, offspring or siblings.

The researchers’ next steps will be to see whether they get similar results in another cohort, perhaps in a different part of the world, and to do studies in animals to discover whether changes in bacteria play a role in the development of the disease.

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To read the article, “Altered microbiome composition in individuals with fibromyalgia” by Amir Minerbi et al in Pain: https://journals.lww.com/pain/Abstract/publishahead/Altered_microbiome_composition_in_individuals_with.98647.aspx

The research was funded by the Louise and Alan Edwards Foundation and the Israeli Society for Musculoskeletal Medicine.

Contact:

Julie Robert
Communications (Research)
McGill University Health Centre
T : 514 934-1934 ext. 71381
C : 514 971-4747
julie.robert@muhc.mcgill.ca
muhc.ca I rimuhc.ca

Altered microbiome composition in individuals with fibromyalgia

Abstract:

Fibromyalgia (FM) is a prevalent syndrome, characterised by chronic widespread pain, fatigue and impaired sleep, that is challenging to diagnose and difficult to treat. The microbiomes of 77 women with FM and that of 79 control participants were compared using 16S rRNA gene amplification and whole genome sequencing.

When comparing FM patients to unrelated controls using differential abundance analysis, significant differences were revealed in several bacterial taxa. Variance in the composition of the microbiomes was explained by FM-related variables more than by any other innate or environmental variable and correlated with clinical indices of FM. In line with observed alteration in butyrate metabolising species, targeted serum metabolite analysis verified differences in the serum levels of butyrate and propionate in FM patients.

Using machine learning algorithms, the microbiome composition alone allowed for the classification of patients and controls (ROC AUC 87.8%). To the best of our knowledge, this is the first demonstration of gut microbiome alteration in non-visceral pain. This observation paves the way for further studies, elucidating the pathophysiology of FM, developing diagnostic aids and possibly allowing for new treatment modalities to be explored.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Source: Minerbi, Amir; Gonzalez, Emmanuel; Brereton, Nicholas J.B.; Anjarkouchian, Abraham; Dewar, Ken; Fitzcharles, Mary-Ann; Chevalier, Stéphanie; Shir, Yoram. Altered microbiome composition in individuals with fibromyalgia. PAIN: June 18, 2019 – Volume Articles in Press doi: 10.1097/j.pain.0000000000001640 https://journals.lww.com/pain/Abstract/publishahead/Altered_microbiome_composition_in_individuals_with.98647.aspx

From neurasthenia to post-exertion disease: Evolution of the diagnostic criteria of chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

Changes in the terminology and diagnostic criteria for chronic fatigue syndrome/myalgic encephalomyelitis are explained in this paper. This syndrome is a complex and controversial entity of unknown origins. It appears in the medical literature in 1988, although clinical pictures of chronic idiopathic fatigue have been identified since the nineteenth century with different names, from neurasthenia, epidemic neuromyasthenia, and benign myalgic encephalomyelitis up to the current proposal of disease of intolerance to effort (post-effort). All of them allude to a chronic state of generalised fatigue of unknown origin, with limitations to physical and mental effort, accompanied by a set of symptoms that compromise diverse organic systems.

The International Classification of Diseases (ICD-10) places this syndrome in the section on neurological disorders (G93.3), although histopathological findings have not yet been found to clarify it. Multiple organic alterations have been documented, but a common biology that clarifies the mechanisms underlying this disease has not been established. It is defined as a neuro-immune-endocrine dysfunction, with an exclusively clinical diagnosis and by exclusion.

Several authors have proposed to include CFS/ME within central sensitivity syndromes, alluding to central sensitisation as the common pathophysiological substrate for this, and other syndromes. The role of the family doctor is a key figure in the disease, from the detection of those patients who present a fatigue of unknown nature that is continuous or intermittent for more than 6 months, in order to make an early diagnosis and establish a plan of action against a chronic disease with high levels of morbidity in the physical and mental sphere.

OBJECTIVE: To carry out a bibliographic review of the terminology and diagnostic criteria of the chronic fatigue syndrome/myalgic encephalomyelitis, in order to clarify the pathology conceptually, as a usefulness in the diagnosis of Primary Care physicians.

Copyright © 2019. Publicado por Elsevier España, S.L.U.

Source: Murga Í, Lafuente JV. From neurasthenia to post-exertion disease: Evolution of the diagnostic criteria of chronic fatigue syndrome/myalgic encephalomyelitis. Aten Primaria. 2019 Jun 7. pii: S0212-6567(19)30191-X. doi: 10.1016/j.aprim.2019.04.004. [Epub ahead of print][Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/31182238

Genetic Predisposition for Immune System, Hormone, and Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study

Abstract:

Introduction: Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a multifactorial illness of unknown etiology with considerable social and economic impact. To investigate a putative genetic predisposition to ME/CFS we conducted genome-wide single-nucleotide polymorphism (SNP) analysis to identify possible variants.

Methods: 383 ME/CFS participants underwent DNA testing using the commercial company 23andMe. The deidentified genetic data was then filtered to include only non-synonymous and nonsense SNPs from exons and microRNAs, and SNPs close to splice sites. The frequencies of each SNP were calculated within our cohort and compared to frequencies from the Kaviar reference database. Functional annotation of pathway sets containing SNP genes with high frequency in ME/CFS was performed using over-representation analysis via ConsensusPathDB. Furthermore, these SNPs were also scored using the Combined Annotation Dependent Depletion (CADD) algorithm to gauge their deleteriousness.

Results: 5693 SNPs were found to have at least 10% frequency in at least one cohort (ME/CFS or reference) and at least two-fold absolute difference for ME/CFS. Functional analysis identified the majority of SNPs as related to immune system, hormone, metabolic, and extracellular matrix organization. CADD scoring identified 517 SNPs in these pathways that are among the 10% most deleteriousness substitutions to the human genome.

Source: Perez M, Jaundoo R, Hilton K, Del Alamo A, Gemayel K, Klimas NG, Craddock TJA, Nathanson L. Genetic Predisposition for Immune System, Hormone, and Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study. Front Pediatr. 2019 May 24;7:206. doi: 10.3389/fped.2019.00206. eCollection 2019. https://www.ncbi.nlm.nih.gov/pubmed/31179255

Endometriosis as a Comorbid Condition in Chronic Fatigue Syndrome (CFS): Secondary Analysis of Data From a CFS Case-Control Study

Abstract:

Background: Endometriosis (EM) is a recognized co-morbid condition in women with chronic fatigue syndrome (CFS). This analysis evaluates the impact of EM on the health of women with CFS by comparing selected health characteristics and laboratory parameters in women with CFS with and without EM (CFS+EM and CFS-only).

Methods: This secondary analysis included all 36 women with CFS from a cross-sectional study of CFS in Wichita, KS, conducted between 2002 and 2003. The health characteristics and laboratory parameters of interest included functioning, fatigue, CFS-related symptoms, gynecologic history, routine laboratory parameters, inflammatory markers, cortisol levels, allostatic load, and sleep parameters (overnight polysomnography). We used parametric or non-parametric tests to compare group differences in the selected health characteristics and laboratory parameters. For examining the association between EM and variables of interest, logistic regression models were performed and odds ratios (OR) with 95% confidence intervals (CI) were reported for the magnitude of associations. Statistical significance was set at 0.05 (two-sided).

Results: The mean age of this study sample was 50.9 years. Of women with CFS, 36.1% reported having EM. Age and body mass index (BMI) did not differ between CFS+EM and CFS-only groups. When examining the impact of EM, compared to women with CFS-only, women with both CFS and EM were more likely to report chronic pelvic pain [OR = 9.00 (95% CI, 1.47-55.25)] and hysterectomy [OR = 10.3 (1.82-58.39)], had more CFS symptoms (6.8 ± 0.3 vs. 5.5 ± 0.3, p = 0.02), younger mean age at menopause onset (36.4 ± 3.0 vs. 47.0 ± 2.7 years, p = 0.03), higher mean number of obstructive apnea episodes per hour (20.3 vs. 4.4, p = 0.05) and reported more negative life events (15.8 vs. 4.4, p = 0.05). Other parameters did not differ significantly between the two groups.

Conclusions: We found more than a third of women with CFS reported endometriosis as a comorbid condition. The endometriosis comorbidity was associated with chronic pelvic pain, earlier menopause, hysterectomy, and more CFS-related symptoms. However, endometriosis in women with CFS did not appear to further impact functioning, fatigue, inflammatory markers, or other laboratory parameters. Further investigations including younger women are warranted.

Source: Boneva RS, Lin JS, Wieser F, Nater UM, Ditzen B, Taylor RN, Unger ER. Endometriosis as a Comorbid Condition in Chronic Fatigue Syndrome (CFS): Secondary Analysis of Data From a CFS Case-Control Study. Front Pediatr. 2019 May 21;7:195. doi: 10.3389/fped.2019.00195. eCollection 2019. https://www.ncbi.nlm.nih.gov/pubmed/31179251

Patients with fibromyalgia and chronic fatigue syndrome show increased hsCRP compared to healthy controls

Abstract:

Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM) are both chronic disorders that have a devastating effect on the lives of the affected patients and their families. Both conditions have overlapping clinical features that partly resemble those of inflammatory disorders. The etiology is still not understood, and it is suggested that the immune system might be a contributing factor. So far, the results are inconclusive. The purpose of this study was to compare the two conditions and investigate the level of the inflammatory marker high-sensitivity CRP (hsCRP) in CFS and FM patients compared to healthy controls.

Female participants aged 18-60 years were enrolled in this study. The group consisted of 49 CFS patients, 57 FM patients, and 54 healthy controls. hsCRP levels were significantly higher for both the CFS and the FM groups compared to healthy controls when adjusting for age, smoking, and BMI (p < .001).

There was no difference between the two patient groups. The level of hsCRP was affected by BMI but not by age and smoking. Patients with CFS and FM have higher concentrations of hsCRP compared to healthy controls. This remains significant even after adjusting for BMI. CFS and FM cannot be distinguished from each other on the basis of hsCRP in our study.

Copyright © 2019. Published by Elsevier Inc.

Source: Groven N, Fors EA, Klæbo Reitan S. Patients with fibromyalgia and chronic fatigue syndrome show increased hsCRP compared to healthy controls. Brain Behav Immun. 2019 Jun 6. pii: S0889-1591(19)30208-9. doi: 10.1016/j.bbi.2019.06.010. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31176728

Neuropsychological dysfunction in chronic fatigue syndrome and the relation between objective and subjective findings

Abstract:

OBJECTIVE: This study aimed to explore the relationship between self-reported cognitive difficulties, objective neuropsychological test performances, and subjective health complaints in chronic fatigue syndrome (CFS) and to examine the degree of impaired cognitive functions.

METHOD: A total of 236 consecutively recruited outpatients, 18-62 years of age, completed the tests. Self-administered questionnaires were used for assessing fatigue, pain, depression, anxiety and subjective cognitive complaints (Everyday Memory Questionnaire [EMQ]). Also, neuropsychological tests, that is, Stroop I-IV, California Verbal Learning Test-Second Edition (CVLT-II) learning and delay, Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) Letter Number (L-N) Sequencing, and the Paced Auditory Serial Addition Task were performed to examine whether these objective measures correlated with subjective complaints and were compared with normative data.

RESULTS: There was a trend of association (p < .05) between the unadjusted EMQ with Stroop IV (inhibition and shifting attention), the CVLT-II learning and delay (verbal learning and memory), and the WAIS-III L-N Sequencing (working memory), but none were statistically significant at the .001 level. The EMQ was positively associated with fatigue, pain, and depression (p < .001). The PASAT (working memory) was negatively associated with pain (p < .001). Between 21% and 38% of the patients performed below the 1.5-SD cutoff for clinically significant impairment on the Stroop tests.

CONCLUSION: The self-reported cognitive performance was not strongly associated with the objective cognitive performances on any domains in patients with CFS. Patients with higher fatigue, pain, and depression levels reported greater subjective cognitive difficulties, as well as higher pain related to lower objective working memory function. The CFS patients had problems mainly in the domains of psychomotor speed and attention measured by the objective neuropsychological tests. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

TRIAL REGISTRATION: ClinicalTrials.gov NCT00920777.

Source: Rasouli O, Gotaas ME, Stensdotter AK, Skovlund E, Landrø NI, Dåstøl P, Fors EA. Neuropsychological dysfunction in chronic fatigue syndrome and the relation between objective and subjective findings. Neuropsychology. 2019 Jun 6. doi: 10.1037/neu0000550. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31169386

Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Post-exertional malaise and delayed recovery are hallmark symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Studies on repeated cardiopulmonary exercise testing (CPET) show that previous exercise negatively affects oxygen uptake (VO2 ) and power output (PO) in ME/CFS. Whether this affects arterial lactate concentrations ([Laa ]) is unknown.

We studied 18 female patients (18-50 years) fulfilling the Canadian Consensus Criteria for ME/CFS and 15 healthy females (18-50 years) who underwent repeated CPETs 24 h apart (CPET1 and CPET2 ) with [Laa ] measured every 30th second. VO2 at peak exercise (VO2 peak) was lower in patients than in controls on CPET1 (P < 0.001) and decreased in patients on CPET2 (P < 0.001).

However, the difference in VO2peak between CPETs did not differ significantly between groups. [Laa ] per PO was higher in patients during both CPETs (Pinteraction < 0.001), but increased in patients and decreased in controls from CPET1 to CPET2 (Pinteraction < 0.001). Patients had lower VO2 (P = 0.02) and PO (P = 0.002) at the gas exchange threshold (GET, the point where CO2 production increases relative to VO2 ), but relative intensity (%VO2peak ) and [Laa ] at GET did not differ significantly from controls on CPET1 .

Patients had a reduction in VO2 (P = 0.02) and PO (P = 0.01) at GET on CPET2 , but no significant differences in %VO2peak and [Laa ] at GET between CPETs. Controls had no significant differences in VO2 , PO or %VO2peak at GET between CPETs, but [Laa ] at GET was reduced on CPET2 (P = 0.008).

In conclusion, previous exercise deteriorates physical performance and increases [Laa ] during exercise in patients with ME/CFS while it lowers [Laa ] in healthy subjects.

© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Source: Lien K, Johansen B, Veierød MB, Haslestad AS, Bøhn SK, Melsom MN, Kardel KR, Iversen PO. Abnormal blood lactate accumulation during repeated exercise testing in myalgic encephalomyelitis/chronic fatigue syndrome. Physiol Rep. 2019 Jun;7(11):e14138. doi: 10.14814/phy2.14138. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546966/ (Full article)