Tag: treatment

The gastrointestinal microbiota in the development of ME/CFS: a critical view and potential perspectives

Abstract:

Like other infections, a SARS-CoV-2 infection can also trigger Post-Acute Infection Syndromes (PAIS), which often progress into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS, characterized by post-exercise malaise (PEM), is a severe multisystemic disease for which specific diagnostic markers or therapeutic concepts have not been established.

Despite numerous indications of post-infectious neurological, immunological, endocrinal, and metabolic deviations, the exact causes and pathophysiology remain unclear. To date, there is a paucity of data, that changes in the composition and function of the gastrointestinal microbiota have emerged as a potential influencing variable associated with immunological and inflammatory pathways, shifts in ME/CFS. It is postulated that this dysbiosis may lead to intestinal barrier dysfunction, translocation of microbial components with increased oxidative stress, and the development or progression of ME/CFS.

In this review, we detailed discuss the findings regarding alterations in the gastrointestinal microbiota and its microbial mediators in ME/CFS. When viewed critically, there is currently no evidence indicating causality between changes in the microbiota and the development of ME/CFS. Most studies describe associations within poorly defined patient populations, often combining various clinical presentations, such as irritable bowel syndrome and fatigue associated with ME/CFS.

Nevertheless, drawing on analogies with other gastrointestinal diseases, there is potential to develop strategies aimed at modulating the gut microbiota and/or its metabolites as potential treatments for ME/CFS and other PAIS. These strategies should be further investigated in clinical trials.

Source: Andreas Stallmach, Stefanie Quickert, Christian Puta, Philipp A. Reuken. The gastrointestinal microbiota in the development of ME/CFS: a critical view and potential perspectives. Front. Immunol., 27 March 2024, Sec. Microbial Immunology, Volume 15 – 2024. https://doi.org/10.3389/fimmu.2024.1352744 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1352744/full (Full text)

A Case Report of Chronic Epipharyngitis With Chronic Fatigue Treated With Epipharyngeal Abrasive Therapy (EAT)

Abstract:

A case of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with chronic epipharyngitis was treated with epipharyngeal abrasive therapy (EAT). The symptoms of ME/CFS improved along with the improvement of chronic epipharyngitis. The patient was followed up with endocrine and autonomic function tests.

Endocrine function tests included salivary cortisol and salivary α-amylase activity. Salivary α-amylase activity was stimulated by EAT. EAT improved the diurnal variability of salivary cortisol secretion. Autonomic function tests included heart rate variability analysis by orthostatic stress test. EAT normalized parasympathetic and sympathetic reflexes over time and regulated autonomic balance.

Based on the improvement of symptoms and test results, EAT was considered effective for ME/CFS. A literature review was conducted on the mechanism of the therapeutic effect of EAT on ME/CFS.

Source: Hirobumi I. A Case Report of Chronic Epipharyngitis With Chronic Fatigue Treated With Epipharyngeal Abrasive Therapy (EAT). Cureus. 2024 Feb 23;16(2):e54742. doi: 10.7759/cureus.54742. PMID: 38405656; PMCID: PMC10884883. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10884883/ (Full text)

Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating, and multi-faceted illness. Heterogenous onset and clinical presentation with additional comorbidities make it difficult to diagnose, characterize, and successfully treat. Current treatment guidelines focus on symptom management, but with no clear target or causative mechanism, remission rates are low, and fewer than 5% of patients return to their pre-morbid activity levels. Therefore, there is an urgent need to undertake robust clinical trials to identify effective treatments.
This review synthesizes insights from clinical trials exploring pharmacological interventions and dietary supplements targeting immunological, metabolic, gastrointestinal, neurological, and neuroendocrine dysfunction in ME/CFS patients which require further exploration. Additionally, the trialling of alternative interventions in ME/CFS based on reported efficacy in the treatment of illnesses with overlapping symptomology is also discussed. Finally, we provide important considerations and make recommendations, focusing on outcome measures, to ensure the execution of future high-quality clinical trials to establish clinical efficacy of evidence-based interventions that are needed for adoption in clinical practice.
Source: Seton KA, Espejo-Oltra JA, Giménez-Orenga K, Haagmans R, Ramadan DJ, Mehlsen J on behalf of the European ME Research Group for Early Career Researchers (Young EMERG). Advancing Research and Treatment: An Overview of Clinical Trials in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Future Perspectives. Journal of Clinical Medicine. 2024; 13(2):325. https://doi.org/10.3390/jcm13020325 https://www.mdpi.com/2077-0383/13/2/325 (Full text)

An international survey of experiences and attitudes towards transcutaneous auricular vagus nerve stimulation for people with Myalgic Encephalomyelitis/chronic fatigue syndrome

Abstract:

Background and objectives: Myalgic encephalomyelitis (ME) is a complex, multi-system neurological condition. Dysfunction of the autonomic nervous system is a primary feature in diagnostic criteria, and management may include attempts to stimulate the parasympathetic nervous system. Transcutaneous auricular vagus nerve stimulation is an intervention that has been researched in neurological disorders, e.g. epilepsy, depression. While little evidence exists for its use in ME, this survey aims to explore the experiences and attitudes of people with ME to this intervention.

Methods: A 31-question online survey was devised and released on ME websites, Twitter and Facebook pages. People with ME read the information sheet and followed an online link to the survey. The survey was open for four weeks and all answers were anonymous.

Results: 116 responses were received. 56% of respondents reported favourable effects. Benefits of transcutaneous auricular vagus nerve stimulation were identified in relation to post exertional malaise, pain, gut problems, urinary problems, mental health, and the ability to leave the house. 67.2% of respondents would recommend the intervention to other people with ME. However, 4.3% would not recommend it and 6% reported it made them worse. 8.6% received support in setting up the device from healthcare workers.

Conclusion: The survey highlights that many people with ME experience significant benefits from using transcutaneous auricular vagus nerve stimulation; however due to potential negative effects there is the need for formal intervention studies to clearly identify safe parameters.

Source: Karen Leslie, Nicola Clague-Baker, Mohammad Abdelfattah Atallah Madi, Dawn Wiley, Andrea Parker, Michelle Bull & Natalie Hilliard. (2023) An international survey of experiences and attitudes towards transcutaneous auricular vagus nerve stimulation for people with Myalgic Encephalomyelitis/chronic fatigue syndrome, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2023.2286029 https://www.tandfonline.com/doi/abs/10.1080/21641846.2023.2286029

Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview

Abstract:

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown cause characterized by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and more recently post-COVID-19 condition (Long COVID).

To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders.

Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. Accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and Long COVID.

To address this issue, this article aimed to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS.

Source: Mantle, D.; Hargreaves, I.P.; Domingo, J.C.; Castro-Marrero, J. Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview. Preprints 2023, 2023111554. https://doi.org/10.20944/preprints202311.1554.v1 https://www.preprints.org/manuscript/202311.1554/v1 (Full text available as PDF file)

Senolytic drugs: from discovery to translation

Abstract:

Senolytics are a class of drugs that selectively clear senescent cells (SC). The first senolytic drugs Dasatinib, Quercetin, Fisetin and Navitoclax were discovered using a hypothesis-driven approach.

SC accumulate with ageing and at causal sites of multiple chronic disorders, including diseases accounting for the bulk of morbidity, mortality and health expenditures. The most deleterious SC are resistant to apoptosis and have up-regulation of anti-apoptotic pathways which defend SC against their own inflammatory senescence-associated secretory phenotype (SASP), allowing them to survive, despite killing neighbouring cells. Senolytics transiently disable these SCAPs, causing apoptosis of those SC with a tissue-destructive SASP.

Because SC take weeks to reaccumulate, senolytics can be administered intermittently – a ‘hit-and-run’ approach. In preclinical models, senolytics delay, prevent or alleviate frailty, cancers and cardiovascular, neuropsychiatric, liver, kidney, musculoskeletal, lung, eye, haematological, metabolic and skin disorders as well as complications of organ transplantation, radiation and cancer treatment.

As anticipated for agents targeting the fundamental ageing mechanisms that are ‘root cause’ contributors to multiple disorders, potential uses of senolytics are protean, potentially alleviating over 40 conditions in preclinical studies, opening a new route for treating age-related dysfunction and diseases. Early pilot trials of senolytics suggest they decrease senescent cells, reduce inflammation and alleviate frailty in humans.

Clinical trials for diabetes, idiopathic pulmonary fibrosis, Alzheimer’s disease, COVID-19, osteoarthritis, osteoporosis, eye diseases and bone marrow transplant and childhood cancer survivors are underway or beginning. Until such studies are done, it is too early for senolytics to be used outside of clinical trials.

Source: Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation. J Intern Med. 2020 Nov;288(5):518-536. doi: 10.1111/joim.13141. Epub 2020 Aug 4. PMID: 32686219; PMCID: PMC7405395. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405395/ (Full text)

Patient perspectives of recovery from myalgic encephalomyelitis/chronic fatigue syndrome: An interpretive description study

Abstract:

Aims and objectives: Myalgic encephalomyelitis (ME), also called chronic fatigue syndrome (CFS), is characterised by persistent fatigue, postexertional malaise, and cognitive dysfunction. It is a complex, long-term, and debilitating illness without widely effective treatments. This study describes the treatment choices and experiences of ME/CFS patients who have experienced variable levels of recovery.

Method: Interpretive description study consisting of semi-structured qualitative interviews with 33 people who met the US Centers for Disease Control (2015) diagnostic criteria for ME/CFS and report recovery or symptom improvement.

Results: Twenty-six participants endorsed partial recovery, and seven reported full recovery from ME/CFS. Participants reported expending significant time and energy to identify, implement, and adapt therapeutic interventions, often without the guidance of a medical practitioner. They formulated individualised treatment plans reflecting their understanding of their illness and personal resources. Most fully recovered participants attributed their success to mind-body approaches.

Conclusion: Patients with ME/CFS describe independently constructing and managing treatment plans, due to a lack of health system support. Stigmatised and dismissive responses from clinicians precipitated disengagement from the medical system and prompted use of other forms of treatment.

Source: Hasan Z, Kuyvenhoven C, Chowdhury M, Amoudi L, Zeraatkar D, Busse JW, Sadik M, Vanstone M. Patient perspectives of recovery from myalgic encephalomyelitis/chronic fatigue syndrome: An interpretive description study. J Eval Clin Pract. 2023 Nov 6. doi: 10.1111/jep.13938. Epub ahead of print. PMID: 37927138. https://onlinelibrary.wiley.com/doi/10.1111/jep.13938 (Full text)

Repetitive Transcranial Magnetic Stimulation Ameliorates Symptoms in Patients with Myalgic Encephalomyelitis (Chronic Fatigue Syndrome)

Highlights:

• Repetitive transcranial magnetic stimulation (rTMS) was applied to the brain in patients with myalgic encephalomyelitis.
• After therapy, the restriction of activity of daily living was ameliorated in most patients.
• rTMS alleviated various symptoms, especially orthostatic intolerance and disequilibrium.

Abstract:

Background: Central nervous system dysfunction has been postulated to cause debilitating symptoms in patients with myalgic encephalomyelitis (ME) (originally called “chronic fatigue syndrome”). Repetitive transcranial magnetic stimulation (rTMS) is a newly developed neuromodulatory procedure and has been suggested to facilitate the cortical neural activity.

Methods: This study enrolled 30 patients with ME (7 men and 23 women) with a mean age of 39±12 years, who received rTMS treatment of both the left dorsolateral prefrontal cortex and the left primary motor area in the brain. The performance status score (0–9) for restricting activities of daily living, orthostatic intolerance (OI) during a 10-min standing test, neurologic disequilibrium diagnosed as unstable standing with their feet together and eyes closed, neuropathic pain or fibromyalgia, and muscle weakness were compared before and after treatment.

Results: After therapy, favorable effects were observed with a decrease in performance status score or index for restriction of activities of daily living of ≥2 points in 20 patients (67%). OI with the inability to complete the 10-min standing test was resolved in 10 (83%) out of 12 patients, and disequilibrium was resolved in 15 (88%) out of 17 patients. Neuropathic pain or fibromyalgia was attenuated in seven (70%) out of 10 patients. Muscle weakness with grip power of <10 kg was resolved in two (50%) out of four patients. No untoward effects were encountered in all the study patients.

Conclusion: The treatment with rTMS is effective in alleviating various symptoms, especially OI and disequilibrium, and in improving the activities of daily living in patients with ME.

Source: Kunihisa Miwa, Yukichi Inoue. Repetitive Transcranial Magnetic Stimulation Ameliorates Symptoms in Patients with Myalgic Encephalomyelitis (Chronic Fatigue Syndrome). Published: October 30, 2023 DOI:https://doi.org/10.1016/j.ibneur.2023.10.008 https://www.sciencedirect.com/science/article/pii/S2667242123022777 (Full text)

Case Report: Rapid and partially persistent, improvements of anorexia nervosa and probable myalgic encephalo-myelitis/chronic fatigue syndrome upon metreleptin treatment during two dosing episodes

Abstract

A comorbidity of anorexia nervosa (AN) and myalgic encephalomyelitis (ME/CSF) is uncommon. A 17-year-old male adolescent with possible onset of ME/CFS after an Epstein Barr Virus infection (EBV) and later onset of AN during a second period of weight loss was twice treated off-label with metreleptin for 15 and 11 days, respectively.

As in previous cases, eating disorder specific cognitions and mood improved. Interestingly, fatigue and post-exertional muscle pain (P-EMP) improved, too. We discuss potential mechanisms. Treatment with metreleptin may prove beneficial in AN and in ME/CSF associated with substantial weight loss.

Source: Jochen Antel, Johannes Hebebrand, Linda Von Piechowski, Cordula Kiewert, Burkhard Stüve, Gertraud Gradl-Dietsch. Rapid and partially persistent, improvements of anorexia nervosa and probable myalgic encephalo-myelitis/chronic fatigue syndrome upon metreleptin treatment during two dosing episodes. Front. Psychiatry, Sec. Adolescent and Young Adult Psychiatry, Volume 14 – 2023. https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1267495/abstract

A Systematic Analysis of the Effectiveness of Mitochondrial-Based Therapies for the Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Background: This study aimed to compile and analyze an assortment of research findings concerning potential therapeutic strategies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The understanding of the multifaceted nature of ME/CFS and the need for varied and personalized therapeutic approaches were central to this investigation.

Methods: A comprehensive review and analysis of various studies conducted on ME/CFS was undertaken. These studies covered a wide array of interventions, including pharmacological treatments, nutritional supplements, dietary changes, physical therapies, and lifestyle modifications. The analysis pertained to the effectiveness of these interventions, potential physiological and biochemical markers, and the response of ME/CFS patients to different treatment strategies.

Results: The 22 selected papers investigated demonstrated varied responses to the multitude of interventions. While some interventions showed significant improvement in fatigue and biochemical parameters, others found no significant differences between the treated and control groups. Potential physiological and biochemical markers for ME/CFS, such as impaired T cell metabolism, reduced flow-mediated dilation, and decreased work rate at the ventilatory threshold, were highlighted.

Conclusion: The findings underscored the complexity of ME/CFS and the need for personalized treatment strategies. Despite mixed results and several limitations, these studies collectively contributed to understanding ME/CFS’s complex pathophysiology and treatment, laying the groundwork for future research towards more effective therapeutic strategies for this debilitating disease.

Source: Keferstein, L.G. A Systematic Analysis of the Effectiveness of Mitochondrial-Based Therapies for the Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Preprints 2023, 2023100637. https://doi.org/10.20944/preprints202310.0637.v1 https://www.preprints.org/manuscript/202310.0637/v1 (Full text available as PDF)