Pediatric chronic fatigue syndrome: current perspectives

Abstract:

Pediatric chronic fatigue syndrome is an important illness as it is relatively common and also very disabling with a wide range of impacts on the child, the family, and health care systems. It is a complicated illness but the majority of children get better with specialist treatment. This literature review provides an update on the epidemiology of chronic fatigue syndrome/myalgic encephalomyelitis, including factors associated with it, and discusses the current evidence for treatment.

Source: Esther Crawley. Pediatric chronic fatigue syndrome: current perspectives. Dove Press. 29 March 2018 Volume 2018:9 Pages 27—33 https://www.dovepress.com/pediatric-chronic-fatigue-syndrome-current-perspectives-peer-reviewed-article-PHMT (You can download a PDF file of the full article.)

Negative Affectivity, Depression, and Resting Heart Rate Variability (HRV) as Possible Moderators of Endogenous Pain Modulation in Functional Somatic Syndromes

Abstract:

Background: Several studies have shown that patients with functional somatic syndromes (FSS) have, on average, deficient endogenous pain modulation (EPM), as well as elevated levels of negative affectivity (NA) and high comorbidity with depression and reduced resting heart rate variability (HRV) compared to healthy controls (HC). The goals of this study were (1) to replicate these findings and (2) to investigate the moderating role of NA, depression, and resting HRV in EPM efficiency within a patient group with fibromyalgia and/or chronic fatigue syndrome (CFS). Resting HRV was quantified as the root mean square of successive differences between inter-beat intervals (RMSSD) in rest, a vagally mediated time domain measure of HRV.

Methods: Seventy-eight patients with fibromyalgia and/or CFS and 33 HC completed a counter-irritation paradigm as a measure of EPM efficiency. Participants rated the painfulness of electrocutaneous stimuli (of individually calibrated intensity) on the ankle before (baseline phase), during (counter-irritation phase) and after (recovery phase) the application of a cold pain stimulus on the forearm. A larger reduction in pain in the counter-irritation phase compared to the baseline phase reflects a more efficient EPM.

Results: In contrast to our expectations, there was no difference between pain ratings in the baseline compared to counter-irritation phase for both patients and HC. Therefore, reliable conclusions on the moderating effect of NA, depression, and RMSSD could not be made. Surprisingly, patients reported more pain in the recovery compared to the counter-irritation and baseline phase, while HC did not. This latter effect was more pronounced in patients with comorbid depression, patients who rated the painfulness of the counter-irritation stimulus as high and patients who rated the painfulness of the electrocutaneous stimuli as low. We did not manage to successfully replicate the counter-irritation effect in HC or FSS patients. Therefore, no valid conclusions on the association between RMSSD, depression, NA and EPM efficiency can be drawn from this study. Possible reasons for the lack of the counter-irritation effect are discussed.

Source: Van Den Houte M, Van Oudenhove L, Van Diest I, Bogaerts K, Persoons P, De Bie J, Van den Bergh O. Negative Affectivity, Depression, and Resting Heart Rate Variability (HRV) as Possible Moderators of Endogenous Pain Modulation in Functional Somatic Syndromes. Front Psychol. 2018 Mar 6;9:275. doi: 10.3389/fpsyg.2018.00275. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845717/ (Full article)

Balance deficits in Chronic Fatigue Syndrome with and without fibromyalgia

Abstract:

OBJECTIVE: Chronic Fatigue Syndrome (CFS) is a disorder of unknown etiology associated with debilitating fatigue. One symptom commonly reported is disequilibrium. The goal of this study was to determine if CFS patients demonstrated verified balance deficits and if this was effected by comorbid fibromyalgia (FM).

METHODS: Twenty-seven patients with CFS (12 with comorbid FM) and 22 age and gender matched controls performed posturography.

RESULTS: Balance scores were significantly correlated with physical functional status in the CFS group (R2 = 0.43, P < 0.001), which was not found for mental functional status (R2 = 0.06, P > 0.5). CFS patients (regardless of FM) had significantly higher anxiety subscale of the vertigo symptom scale scores. CFS patients, regardless of FM status, demonstrated significantly lower overall composite balance scores (Controls – 78.8±1.5; CFS – 69.0±1.4, P < 0.005) even when controlling for anxiety and also had worse preference scores, indicating they relied on visual information preferentially even when visual information was incorrect. Interestingly, the CFS+FM group, not CFS only, demonstrated significantly worse vestibular scores (Controls – 70.2±2.4; CFS only – 67.9±3.8; CFS with FM – 55.4±4.6, P = 0.013).

INTERPRETATION: The major findings are that poor balance may be associated with poorer self-reported physical health. In addition, CFS patients seemed to rely preferentially on visual inputs, regardless of whether it was correct. The finding that vestibular function may be impaired in patients with CFS+FM but not in those with CFS alone suggests that the pathophysiology of CFS+FM may differ as has been suggested by some.

Source: Serrador JM, Quigley K, Zhao C, Findley T, Natelson BH. Balance deficits in Chronic Fatigue Syndrome with and without fibromyalgia. NeuroRehabilitation. 2018;42(2):235-246. doi: 10.3233/NRE-172245.

Task related cerebral blood flow changes of patients with chronic fatigue syndrome: an arterial spin labeling study

Abstract:

Purpose: One hallmark of chronic fatigue syndrome (ME/CFS) is task related worsening of fatigue. Global brain hypoperfusion, abnormal regional activation, and altered functional connectivity of brain areas associated with cognition and memory have been reported but remain controversial.

Methods: We enrolled 17 female participants fulfilling the CDC Criteria for ME/CFS and 16 matched healthy controls (HC). Using a 3T-Phillips Achieva MRI-scanner, pseudo-continuous arterial spin-labeling (pCASL), was used to study the dynamics of regional cerebral blood flow (rCBF) and their relationship to mental fatigue in ME/CFS patients and HC during a demanding cognitive task, i.e. modified Paced-Auditory-Serial-Addition-Testing (PASAT).

Results: ME/CFS subjects reported more fatigue than HC at baseline (p < .01). Global brain perfusion of ME/CFS and HC subjects was similar at rest. The PASAT resulted in significantly increased fatigue in ME/CFS participants and HC. Although not different between groups, overall CBF significantly increased over the first 3 min of the PASAT and then decreased thereafter. Regional CBF (rCBF) changes were significantly different between groups during the post-task recovery period. Whereas improvement of fatigue of ME/CFS subjects was associated with decreased rCBF in both superior temporal gyri (STG), precuneus, and fusiform gyrus, it was associated with increased rCBF in the same areas in HC.

Conclusions: Our results suggest that ME/CFS is associated with normal global CBF at rest and during a strenuous task (PASAT); however rCBF of several brain regions associated with memory, goal-oriented attention, and visual function was differentially associated with recovery from fatigue in ME/CFS patients and HC.

Source: Roland Staud, Jeff Boissoneault, Jason G. Craggs, Song Lai & Michael E. Robinson (2018) Task related cerebral blood flow changes of patients with chronic fatigue syndrome: an arterial spin labeling study, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2018.1453919

Markers of non-coeliac wheat sensitivity in patients with myalgic encephalomyelitis/chronic fatigue syndrome

We recently reported in Gut that non-coeliac wheat sensitivity (NCWS) is associated with a state of systemic immune activation in conjunction with a compromised intestinal epithelium.1 Patients with NCWS experience GI symptoms, most commonly including abdominal pain and bloating, as well as extraintestinal symptoms, among which fatigue, headache and cognitive difficulties feature prominently.1 2 A principal component analysis of the generated data from our study, including markers of antibody reactivity to wheat gluten, intestinal cell damage and systemic innate and adaptive immune responses to microbial components, found clustering of the patients and controls into discernible groups and demonstrated the potential utility of the identified biomarkers for identifying patients with NCWS.1

Extreme fatigue, in particular one that does not improve with rest, is a hallmark of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).3 Immune system abnormalities have been found to be associated with symptoms in a substantial number of patients with ME/CFS.4 5 Furthermore, many patients complain of GI symptoms of unknown aetiology.6–8 We considered whether a subset of patients with ME/CFS may exhibit serologic markers associated with NCWS, which might explain some of the corresponding symptoms. We screened serum samples from 131 patients with ME/CFS and 86 healthy controls (table 1), recruited as previously described,9 for the same markers as those in the above-mentioned study on NCWS.1 Questionnaires were used to assess GI symptoms within the past 6 months, including abdominal pain, bloating and nausea. Severity of individual symptoms was scored from 1 to 5 (1=absent; 2=mild; 3=moderate; 4=severe; 5=very severe), and a total score, based on the sum of individual symptom scores, was calculated for each subject.

Read full article HERE.

Source: Melanie Uhde, Alyssa C Indart, Xuechen B Yu, Sophie S Jang, Roberto De Giorgio, Peter H R Green, Umberto Volta, Suzanne D Vernon, Armin Alaedini. Markers of non-coeliac wheat sensitivity in patients with myalgic encephalomyelitis/chronic fatigue syndrome. http://dx.doi.org/10.1136/gutjnl-2018-316133

Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT

Abstract:

Background: The PACE trial was a well-powered randomised trial designed to examine the efficacy of graded exercise therapy (GET) and cognitive behavioural therapy (CBT) for chronic fatigue syndrome. Reports concluded that both treatments were moderately effective, each leading to recovery in over a fifth of patients. However, the reported analyses did not consistently follow the procedures set out in the published protocol, and it is unclear whether the conclusions are fully justified by the evidence.

Methods: Here, we present results based on the original protocol-specified procedures. Data from a recent Freedom of Information request enabled us to closely approximate these procedures. We also evaluate the conclusions from the trial as a whole.

Results: On the original protocol-specified primary outcome measure – overall improvement rates – there was a significant effect of treatment group. However, the groups receiving CBT or GET did not significantly outperform the Control group after correcting for the number of comparisons specified in the trial protocol. Also, rates of recovery were consistently low and not significantly different across treatment groups. Finally, on secondary measures, significant effects were almost entirely confined to self-report measures. These effects did not endure beyond two years.

Conclusions: These findings raise serious concerns about the robustness of the claims made about the efficacy of CBT and GET. The modest treatment effects obtained on self-report measures in the PACE trial do not exceed what could be reasonably accounted for by participant reporting biases.

Source: Carolyn E. Wilshire, Tom Kindlon, Robert Courtney, Alem Matthees, David Tuller, Keith Geraghty and Bruce Levin. Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC PsychologyBMC series. Received: 29 May 2017; Accepted: 22 February 2018; Published: 22 March 2018.  https://doi.org/10.1186/s40359-018-0218-3 (Full article) © The Author(s) 2018.

Help Desperate Patients Get Crisis Support!

 

AMMES’ Crowdrise campaign to raise funds for emergency aid for patients in financial crisis was successful! We raised $10,000 in online donations and in checks sent separately by donors. AMMES has already begun processing applications to the fund. A big THANK YOU to everyone who donated!

So any patients are disabled and unable to work. Assistance at the right time can go a long way. Our mission is to help patients and their families in practical ways. This is one of them.

This is the description that appeared on Crowdrise. The campaign ended on May 11, 2018. You can still donate to this fund HERE.

“Between 836,000 and 2.5 million Americans suffer from ME/CFS. One quarter of these patients are severely ill, and are either bedbound or housebound. Severely ill patients are unable to work, and many are denied disability. The financial crisis generated by a loss of income coupled with rising costs of medical care can force patients to forego necessary care and medication. In some cases, patients may even lose their homes and end up living in cars. In order to assist patients in need, AMMES is setting up a crisis fund to provide one-time grants to patients for specific needs. The funds can be used to purchase a wheelchair, pay a medical bill, hire home care, secure adequate housing, and other basic needs. All applicants will be required to provide written medical confirmation of their diagnosis, proof of financial need, and document the specific purpose of the grant. Where possible, a phone interview will be conducted. (Some severely ill patients cannot speak.) Any patient within the United States and its territories is eligible.”

 

UK Research Collaborative Adopts Biomedical Approach

The CMRC’s new biomedical focus and big ambitions

by Simon McGrath

In a dramatic move last week, the UK CFS/ME Research Collaborative (CMRC) committed itself to a new, biomedical direction. It has started taking concrete action to engage with patients and also announced ambitious plans to enable much more biomedical research in the UK. These changes are enshrined in a statement of purpose, objectives and values (PDF) that replaces the Collaborative’s former charter.

At the same time, Professor Esther Crawley, the CMRC’s controversial deputy chair, is stepping down from that role and from the board, due to a change in her role at her university. From this April, she will be replaced by Chris Ponting, Professor of Medical Bioinformatics at the University of Edinburgh. He heads the multi-million-pound Biomedical Genomics research programme at the Medical Research Council (MRC) Institute of Genetics and Molecular Medicine.

The CMRC has set out its new purpose as promoting the discovery of the biological mechanisms and causal pathways that underpin ME/CFS, in order to develop targeted new treatments…

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Chronic fatigue syndrome possibly explained by lower levels of key thyroid hormones

Press Release: New research demonstrates a link between chronic fatigue syndrome (CFS) symptoms and lower thyroid hormone levels. Published in Frontiers in Endocrinology, the study indicates that CFS, a condition with unknown causes, can be explained by lower thyroid hormones — but may be distinct from thyroidal disease. This finding can be seen as a first step to finding treatment for a debilitating illness for which there is no recognized treatment.

Chronic fatigue syndrome is a common disease marked by lengthy spells of weakness, fatigue and depression. Its diagnosis is predominantly based on symptoms and on ruling out any underlying medical condition, rather than on laboratory tests and physical examination.

Interestingly, several symptoms resemble those of hypothyroidism — a condition where the thyroid gland does not produce enough thyroid hormone. In hypothyroidism, the body tries to encourage thyroid hormone activity by releasing more thyroid-stimulating hormone — however, this does not happen in patients with chronic fatigue syndrome.

This contrast in thyroid-stimulating activity led the study’s authors to hypothesize that chronic fatigue syndrome is caused by low activity of thyroid hormones in the absence of thyroidal disease.

Led by Dr. Begoña Ruiz-Núñez at the University Medical Center Groningen, The Netherlands, the researchers compared thyroid function and markers of inflammation between 98 CFS patients and 99 healthy controls. Remarkably, the CFS patients had lower serum levels of certain key thyroid hormones such as triiodothyronine (T3) and thyroxine (T4), but normal levels of thyroid-stimulating hormone.

Additional analyses indicated that CFS patients had a lower urinary iodine status and low-grade inflammation, which possibly mirrored the symptoms of patients with hypothyroidism. These CFS patients, however, had relatively higher levels of another thyroid hormone called “reverse T3” or rT3. This appeared to be due to a shift in hormone production, where the body preferred to convert T4 to rT3 instead of producing T3. The low T3 levels found in CFS patients coupled with this switchover to rT3 could mean that T3 levels are severely reduced in tissue.

“One of the key elements of our study is that our observations persisted in the face of two sensitivity analyses to check the strength of the association between CFS and thyroid parameters and low-grade inflammation,” says Dr. Ruiz-Núñez. “This strengthens our test results considerably.”

The researchers believe inclusion of patient information, such as duration of illness, would enable a correlation with their biochemical profiles. Further, even though the study demonstrates a link between chronic fatigue syndrome symptoms and low levels of key thyroid hormones, a definitive cause for CFS remains unknown.

If the study findings are confirmed by additional research, it may pave the way for a treatment for chronic fatigue syndrome.

Source: Eurekalert

Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME

Abstract:

Introduction: Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) point to an autoimmune disease directed against neurotransmitter receptors. We had observed elevated autoantibodies against ß2 adrenergic receptors, and muscarinic 3 and 4 acetylcholine receptors in a subset of patients. Immunoadsorption (IA) was shown to be effective in removing autoantibodies and improve outcome in various autoimmune diseases.

Methods: 10 patients with post-infectious CFS/ME and elevated ß2 autoantibodies were treated with IA with an IgG-binding column for 5 days. We assessed severity of symptoms as outcome parameter by disease specific scores. Antibodies were determined by ELISA and B cell phenotype by flow cytometry.

Results: IgG levels dropped to median 0.73 g/l (normal 7–16 g/l) after the 4th cycle of IA, while IgA and IgM levels remained unchanged. Similarly, elevated ß2 IgG antibodies rapidly decreased during IA in 9 of 10 patients. Also 6 months later ß2 autoantibodies were significantly lower compared to pretreatment. Frequency of memory B cells significantly decreased and frequency of plasma cells increased after the 4th IA cycle. A rapid improvement of symptoms was reported by 7 patients during the IA. 3 of these patients had long lasting moderate to marked improvement for 6–12+ months, 2 patients had short improvement only and 2 patients improved for several months following initial worsening.

Conclusions: IA can remove autoantibodies against ß2 adrenergic receptor and lead to clinical improvement. B cell phenotyping provides evidence for an effect of IA on memory B cell development. Data from our pilot trial warrants further studies in CFS/ME.

Source: Carmen Scheibenbogen, Madlen Loebel, Helma Freitag, Anne Krueger, Sandra Bauer, Michaela Antelmann, Wolfram Doehner, Nadja Scherbakov, Harald Heidecke, Petra Reinke, Hans-Dieter Volk, Patricia Grabowski. Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME. PLOS ONE. Published: March 15, 2018 https://doi.org/10.1371/journal.pone.0193672 (Full article)