Category: Treatment

The evidence base for physiotherapy in myalgic encephalomyelitis/chronic fatigue syndrome when considering post-exertional malaise: a systematic review and narrative synthesis

Abstract:

Background: Due to the inconsistent use of diagnostic criteria in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), it is unsure whether physiotherapeutic management regarded effective in ME/CFS is appropriate for patients diagnosed with criteria that consider post-exertional malaise (PEM) as a hallmark feature.

Purpose: To appraise current evidence of the effects of physiotherapy on symptoms and functioning in ME/CFS patients in view of the significance of PEM in the applied diagnostic criteria for inclusion.

Methods: A systematic review of randomized controlled trials published over the last two decades was conducted. Studies evaluating physiotherapeutic interventions for adult ME/CFS patients were included. The diagnostic criteria sets were classified into three groups according to the extent to which the importance of PEM was emphasized: chronic fatigue (CF; PEM not mentioned as a criterion), CFS (PEM included as an optional or minor criterion) or ME (PEM is a required symptom). The main results of included studies were synthesized in relation to the classification of the applied diagnostic criteria. In addition, special attention was given to the tolerability of the interventions.

Results: Eighteen RCTs were included in the systematic review: three RCTs with CF patients, 14 RCTs with CFS patients and one RCT covering ME patients with PEM. Intervention effects, if any, seemed to disappear with more narrow case definitions, increasing objectivity of the outcome measures and longer follow-up.

Conclusion: Currently, there is no scientific evidence when it comes to effective physiotherapy for ME patients. Applying treatment that seems effective for CF or CFS patients may have adverse consequences for ME patients and should be avoided.

Source: Wormgoor MEA, Rodenburg SC. The evidence base for physiotherapy in myalgic encephalomyelitis/chronic fatigue syndrome when considering post-exertional malaise: a systematic review and narrative synthesis. J Transl Med. 2021 Jan 4;19(1):1. doi: 10.1186/s12967-020-02683-4. PMID: 33397399; PMCID: PMC7780213. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780213/ (Full text)

Graded Exercise Therapy Doesn’t Restore the Ability to Work in ME/CFS. Rethinking of a Cochrane Review

Abstract:

Background: Cochrane recently amended its exercise review for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in response to an official complaint.

Objective: To determine if the amended review has addressed the concerns raised about the previous review and if exercise is an effective treatment that restores the ability to work in ME/CFS.

Method: The authors reviewed the amended Cochrane exercise review and the eight trials in it by paying particular interest to the objective outcomes. We also summarised the recently published review of work rehabilitation and medical retirement for ME/CFS.

Results: The Cochrane review concluded that graded exercise therapy (GET) improves fatigue at the end of treatment compared to no-treatment. However, the review did not consider the unreliability of subjective outcomes in non-blinded trials, the objective outcomes which showed that GET is not effective, or the serious flaws of the studies included in the review. These flaws included badly matched control groups, relying on an unreliable fatigue instrument as primary outcome, outcome switching, p-hacking, ignoring evidence of harms, etc. The review did also not take into account that GET does not restore the ability to work.

Conclusion: GET not only fails to objectively improve function significantly or to restore the ability to work, but it’s also detrimental to the health of≥50% of patients, according to a multitude of patient surveys. Consequently, it should not be recommended.

Source: Vink M, Vink-Niese F. Graded exercise therapy doesn’t restore the ability to work in ME/CFS. Rethinking of a Cochrane review [published online ahead of print, 2020 Jun 14]. Work. 2020;10.3233/WOR-203174. doi:10.3233/WOR-203174 https://pubmed.ncbi.nlm.nih.gov/32568149/

Researchers discover potential therapeutic approach to treat ME / CFS

Press Release:

Researchers have discovered the pharmacological drug, Naltrexone, significantly restored the function of faulty receptors associated with myalgic encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS).

Researchers from the National Centre for Neuroimmunology and Emerging Diseases (NCNED), Menzies Health Institute Queensland, Griffith University led the research, which has been published in Frontiers in Immunology.

NCNED is the peak research centre nationally and is internationally recognised for its world-leading research on the identification of the pathology, developing a screening test and pharmacotherapeutic intervention for ME/CFS.

NCNED researchers were the first in the world to develop the gold standard in experimental research known as patch clamp technique in immune cells to measure TRP receptor function.

The immune cells are used as a model for assessing TRP receptor function and reflect physiological activity in all body tissues expressing these receptors.

NCNED researchers have paved the way for the identification of the pathology of ME/CFS and biomarker development by further reporting in several recent research papers that these receptors were faulty from ME/CFS patients when compared to healthy people.

These receptors are widely found in the body and implicated in symptoms and onset of this illness. Importantly, the current groundbreaking research has used Naltrexone to restore the function of these faulty receptors in the immune cells from ME/CFS patients.

“This world-first discovery suggests new potential pharmaco-therapeutic interventions in ME/CFS,” co-author and Stafford Fox Medical Research Professorial Fellow, Professor Sonya Marshall-Gradisnik said.

“We continue to confirm the pathology of these faulty receptors and now we are thrilled we are moving into possible treatments for ME/CFS.”

Dr Helene Cabanas, Post-Doctoral Research Fellow and first author, said: “We used the patch clamp technique to measure the faulty receptor function. Following Naltrexone treatment we found the faulty receptor function was significantly improved in immune cells from ME/CFS patients, suggesting beneficial effects for patients.”

Professor Paul Scuffham, Director of Menzies Health Institute Queensland, said NCNED continued to lead the world in the identification of the pathology of ME/CFS and this latest research signified possible ways forward for the treatment of ME/CFS patients.

“Our aim is to continue employ the gold standard technique to investigate the pathology and possible pharmacological inventions for the benefit of ME/CFs patients,” Professor Marshall-Gradisnik said.

“Our research aims to translate our research findings to benefit ME/CFS patients. The core of NCNED values is patients are our priority.

“We thank the Queensland Government, national granting organisations and our benefactors without whom this groundbreaking research would not be possible.”

Source: Griffith University News.

News and views in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): The role of co-morbidity and novel treatments

Abstract:

Though affecting many thousands of patients, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) should be considered an orphan disease, since the cause remains elusive and no treatment is available that can provide complete cure. There is reasonable insight into the pathogenesis of signs and symptoms, and treatments specifically directed to immunological, inflammatory and metabolic processes offer relief to an increasing number of patients. Particular attention is given to the importance of co-morbidity requiring appropriate therapy.

Promising results are obtained by treatment with Metformin, or possibly Momordica charantia extract, which will correct insulin resistance, with Meldonium improving the transportation of glucose into the mitochondria, with sodium dichloroacetate activating pyruvate dehydrogenase, and with nutraceutical support reducing oxidative and inflammatory impairment.

Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

Source: Comhaire F, Deslypere JP. News and views in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): The role of co-morbidity and novel treatments. Med Hypotheses. 2019 Oct 22;134:109444. doi: 10.1016/j.mehy.2019.109444. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31669858

Rethinking the Standard of Care for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

For over two decades, the standard of care for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has been cognitive behavior therapy (CBT) and graded exercise therapy (GET). Both interventions had been recommended by the US Centers for Disease Control and the UK NICE guidelines. Behavioral intervention as the clinical standard was given a considerable boost by the 5 million–pound PACE trial, a large multi-arm randomized trial of CBT and GET launched in 2007. This British government–funded trial was intended to definitively answer whether such interventions were beneficial in ME/CFS. In their 2011 and 2013 publications, the PACE trial authors announced with widespread publicity that 22% of their patients had “recovered” and 59–61% had clinically improved across the CBT and GET interventions., 

Read the rest of this article here.

Source: Friedberg, F., Sunnquist, M. & Nacul, L. J GEN INTERN MED (2019). https://doi.org/10.1007/s11606-019-05375-y https://link.springer.com/article/10.1007%2Fs11606-019-05375-y

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: From Pathophysiological Insights to Novel Therapeutic Opportunities

Abstract:

Myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) is a common and disabling condition with a paucity of effective and evidence-based therapies reflecting a major unmet need. Cognitive behavioural therapy and graded exercise are of modest benefit for only some ME/CFS patients, and many sufferers report aggravation of symptoms of fatigue with exercise.

The presence of a multiplicity of pathophysiological abnormalities, in at least the subgroup of people with ME/CFS diagnosed with the current international consensus “Fukuda” criteria, points to numerous potential therapeutic targets. Such abnormalities include extensive data showing that at least a subgroup has a pro-inflammatory state, increased oxidative and nitrosative stress, disruption of gut mucosal barriers and mitochondrial dysfunction together with dysregulated bioenergetics.

In this paper, these pathways are summarised, and data regarding promising therapeutic options that target these pathways are highlighted; they include coenzyme Q10, melatonin, curcumin, molecular hydrogen and N-acetylcysteine. These data are promising yet preliminary, suggesting hopeful avenues to address this major unmet burden of illness.

Copyright © 2019. Published by Elsevier Ltd.

Source: Morris G, Puri BK, Walker AJ, Maes M, Carvalho AF, Walder K, Mazza C, Berk M. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: From Pathophysiological Insights to Novel Therapeutic Opportunities. Pharmacol Res. 2019 Sep 8:104450. doi: 10.1016/j.phrs.2019.104450. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31509764

Monitoring treatment harm in myalgic encephalomyelitis/chronic fatigue syndrome: A freedom-of-information study of National Health Service specialist centres in England

Abstract:

The use of graded exercise therapy and cognitive behavioural therapy for myalgic encephalomyelitis/chronic fatigue syndrome has attracted considerable controversy. This controversy relates not only to the disputed evidence for treatment efficacy but also to widespread reports from patients that graded exercise therapy, in particular, has caused them harm. We surveyed the National Health Service-affiliated myalgic encephalomyelitis/chronic fatigue syndrome specialist clinics in England to assess how harms following treatment are detected and to examine how patients are warned about the potential for harms.

We sent 57 clinics standardised information requests under the United Kingdom’s Freedom of Information Act. Data were received from 38 clinics. Clinics were highly inconsistent in their approaches to the issue of treatment-related harm. They placed little or no focus on the potential for treatment-related harm in their written information for patients and for staff. Furthermore, no clinic reported any cases of treatment-related harm, despite acknowledging that many patients dropped out of treatment.

In light of these findings, we recommend that clinics develop standardised protocols for anticipating, recording, and remedying harms, and that these protocols allow for therapies to be discontinued immediately whenever harm is identified.

Source: McPhee G, Baldwin A, Kindlon T, Hughes BM. Monitoring treatment harm in myalgic encephalomyelitis/chronic fatigue syndrome: A freedom-of-information study of National Health Service specialist centres in England. J Health Psychol. 2019 Jun 24:1359105319854532. doi: 10.1177/1359105319854532. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31234662

Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and the Emerging Osteopathic Approach: A Narrative Review

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating syndrome of unknown origin, characterized by profound postexertional malaise and fatigue, unrefreshing sleep, cognitive impairments, immune dysfunction, pain, autonomic dysfunction, and neuroendocrine symptoms. Although ME/CFS is well documented within the medical literature, it remains difficult to diagnosis and manage.

Some of the current challenges include an absence of diagnostic markers, differing diagnostic criteria, and an overall lack of awareness within the medical community. As a result, patients are often frustrated by the difficulties in acquiring a diagnosis and from the overall lack of available treatments. In an effort to increase awareness, this review discusses disease pathophysiology, clinical presentation, and treatment options, while also highlighting the benefits of an osteopathic approach.

J Am Osteopath Assoc. 2019 Jul 1;119(7):446-455. doi: 10.7556/jaoa.2019.081.

Source: Larrimore C, Ramnot A, Jaghab A, Sarduy S, Guerrero G, Troccoli P, Hilton K, Bested A. Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and the Emerging Osteopathic Approach: A Narrative Review. J Am Osteopath Assoc. 2019 Jul 1;119(7):446-455. doi: 10.7556/jaoa.2019.081. https://www.ncbi.nlm.nih.gov/pubmed/31233110

Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients

Abstract:

BACKGROUND: Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME) is a complex multifactorial disorder of unknown cause having multi-system manifestations. Although the aetiology of CFS/ME remains elusive, immunological dysfunction and more particularly reduced cytotoxic activity in natural killer (NK) cells is the most consistent laboratory finding. The Transient Receptor Potential (TRP) superfamily of cation channels play a pivotal role in the pathophysiology of immune diseases and are therefore potential therapeutic targets. We have previously identified single nucleotide polymorphisms in TRP genes in peripheral NK cells from CFS/ME patients. We have also described biochemical pathway changes and calcium signaling perturbations in NK cells from CFS/ME patients. Notably, we have previously reported a decrease of TRP cation channel subfamily melastatin member 3 (TRPM3) function in NK cells isolated from CFS/ME patients compared with healthy controls after modulation with pregnenolone sulfate and ononetin using a patch-clamp technique. In the present study, we aim to confirm the previous results describing an impaired TRPM3 activity in a new cohort of CFS/ME patients using a whole cell patch-clamp technique after modulation with reversible TRPM3 agonists, pregnenolone sulfate and nifedipine, and an effective TRPM3 antagonist, ononetin. Indeed, no formal research has commented on using pregnenolone sulfate or nifedipine to treat CFS/ME patients while there is evidence that clinicians prescribe calcium channel blockers to improve different symptoms.

METHODS: Whole-cell patch-clamp technique was used to measure TRPM3 activity in isolated NK cells from twelve age- and sex-matched healthy controls and CFS/ME patients, after activation with pregnenolone sulfate and nifedipine and inhibition with ononetin.

RESULTS: We confirmed a significant reduction in amplitude of TRPM3 currents after pregnenolone sulfate stimulation in isolated NK cells from another cohort of CFS/ME patients compared with healthy controls. The pregnenolone sulfate-evoked ionic currents through TRPM3 channels were again significantly modulated by ononetin in isolated NK cells from healthy controls compared with CFS/ME patients. In addition, we used nifedipine, another reversible TRPM3 agonist to support the previous findings and found similar results confirming a significant loss of the TRPM3 channel activity in CFS/ME patients.

CONCLUSIONS: Impaired TRPM3 activity was validated in NK cells isolated from CFS/ME patients using different pharmacological tools and whole-cell patch-clamp technique as the gold standard for ion channel research. This investigation further helps to establish TRPM3 channels as a prognostic marker and/ or a potential therapeutic target for CFS/ME.

Source: Cabanas H, Muraki K, Balinas C, Eaton-Fitch N, Staines D, Marshall-Gradisnik S. Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in natural killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients. Mol Med. 2019 Apr 23;25(1):14. doi: 10.1186/s10020-019-0083-4. https://www.ncbi.nlm.nih.gov/pubmed/31014226

Chronic fatigue syndrome (CFS): Suggestions for a nutritional treatment in the therapeutic approach

Abstract:

Chronic fatigue syndrome (CFS) is known as a multi-systemic and complex illness, which induces fatigue and long-term disability in educational, occupational, social, or personal activities. The diagnosis of this disease is difficult, due to lacking a proper and suited diagnostic laboratory test, besides to its multifaceted symptoms. Numerous factors, including environmental and immunological issues, and a large spectrum of CFS symptoms, have recently been reported.

In this review, we focus on the nutritional intervention in CFS, discussing the many immunological, environmental, and nutritional aspects currently investigated about this disease. Changes in immunoglobulin levels, cytokine profiles and B- and T- cell phenotype and declined cytotoxicity of natural killer cells, are commonly reported features of immune dysregulation in CFS. Also, some nutrient deficiencies (vitamin C, vitamin B complex, sodium, magnesium, zinc, folic acid, l-carnitine, l-tryptophan, essential fatty acids, and coenzyme Q10) appear to be important in the severity and exacerbation of CFS symptoms. This review highlights a far-driven analysis of mineral and vitamin deficiencies among CFS patients.

Source: Bjørklund G, Dadar M, Pen JJ, Chirumbolo S, Aaseth J. Chronic fatigue syndrome (CFS): Suggestions for a nutritional treatment in the therapeutic approach. Biomed Pharmacother. 2019 Jan;109:1000-1007. doi: 10.1016/j.biopha.2018.10.076. Epub 2018 Nov 5.  https://www.sciencedirect.com/science/article/pii/S0753332218342987?via%3Dihub (Full article)