Tag: treatment

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)

Diagnosis and Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic neurologic disease often preceded by infection. There has been increased interest in ME/CFS recently because of its significant overlap with the post-COVID syndrome (long COVID or post-acute sequelae of COVID), with several studies estimating that half of patients with post-COVID syndrome fulfill ME/CFS criteria. Our concise review describes a generalist approach to ME/CFS, including diagnosis, evaluation, and management strategies.

Source: Grach SL, Seltzer J, Chon TY, Ganesh R. Diagnosis and Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Mayo Clin Proc. 2023 Oct;98(10):1544-1551. doi: 10.1016/j.mayocp.2023.07.032. PMID: 37793728. https://www.mayoclinicproceedings.org/article/S0025-6196(23)00402-0/fulltext (Full text)

Chronic inflammation, neuroglia dysfunction, and plasmalogen deficiency as a new pathobiological hypothesis addressing the overlap between post-COVID-19 symptoms and myalgic encephalomyelitis/chronic fatigue syndrome

Highlights:

  • Plasmalogens (Pls) are lipids containing a vinyl-ether bond in their glycerol backbone
  • Pls have antioxidant properties and are important for curved membrane assemblies
  • Post-COVID-19 symptoms are highly prevalent and share several features with ME/CFS
  • Pls depletion is a shared biological hallmark of ME/CFS and acute COVID-19 syndrome
  • Pls replacement is a promising tool against neuroinflammation in these two conditions

Abstract:

After five waves of COVID-19 outbreaks, it has been recognized that a significant portion of the affected individuals developed long-term debilitating symptoms marked by chronic fatigue, cognitive difficulties (“brain fog”), post-exertional malaise, and autonomic dysfunction. The onset, progression, and clinical presentation of this condition, generically named post-COVID-19 syndrome, overlap significantly with another enigmatic condition, referred to as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Several pathobiological mechanisms have been proposed for ME/CFS, including redox imbalance, systemic and central nervous system inflammation, and mitochondrial dysfunction. Chronic inflammation and glial pathological reactivity are common hallmarks of several neurodegenerative and neuropsychiatric disorders and have been consistently associated with reduced central and peripheral levels of plasmalogens, one of the major phospholipid components of cell membranes with several homeostatic functions.

Of great interest, recent evidence revealed a significant reduction of plasmalogens contents, biosynthesis, and metabolism in ME/CFS and acute COVID-19, with a strong association to symptom severity and other relevant clinical outcomes. These bioactive lipids have increasingly attracted attention due to their reduced levels representing a common pathophysiological manifestation between several disorders associated with aging and chronic inflammation. However, alterations in plasmalogen levels or their lipidic metabolism have not yet been examined in individuals suffering from post-COVID-19 symptoms.

Here, we proposed a pathobiological model for post-COVID-19 and ME/CFS based on their common inflammation and dysfunctional glial reactivity, and highlighted the emerging implications of plasmalogen deficiency in the underlying mechanisms. Along with the promising outcomes of plasmalogen replacement therapy (PRT) for various neurodegenerative/neuropsychiatric disorders, we sought to propose PRT as a simple, effective, and safe strategy for the potential relief of the debilitating symptoms associated with ME/CFS and post-COVID-19 syndrome.

Source: Chaves AM, Braniff O, Angelova A, Deng Y, Tremblay MÈ. Chronic inflammation, neuroglia dysfunction, and plasmalogen deficiency as a new pathobiological hypothesis addressing the overlap between post-COVID-19 symptoms and myalgic encephalomyelitis/chronic fatigue syndrome. Brain Res Bull. 2023 Jul 7:110702. doi: 10.1016/j.brainresbull.2023.110702. Epub ahead of print. PMID: 37423295. https://www.sciencedirect.com/science/article/pii/S0361923023001272?via%3Dihub (Full text)

Effects of whole-body cryotherapy and static stretching are maintained 4 weeks after treatment in most patients with chronic fatigue syndrome

Abstract

In the previous study, whole-body cryotherapy (WBC)+static stretching (SS) has been shown to reduce the severity of some symptoms in Chronic Fatigue Syndrome (CFS) noted just after the therapy. Here we consider the effects of treatment and explore the sustainability of symptom improvements at four weeks (one-month) follow-up.

Twenty-two CFS patients were assessed one month after WBC + SS programme. Parameters related to fatigue (Chalder Fatigue Questionnaire (CFQ), Fatigue Impact Scale (FIS), Fatigue Severity Scale (FSS)), cognitive function (Trial Making test part A and B (TMT A and TMT B and its difference (TMT B-A)), Coding) hemodynamic, aortic stiffness (aortic systolic blood pressure (sBP aortic)) and autonomic nervous system functioning were measured. TMT A, TMT B, TMT B-A and Coding improved at one month after the WBC + SS programme.

WBC + SS had a significant effect on the increase in sympathetic nervous system activity in rest. WBC + SS had a significant, positive chronotropic effect on the cardiac muscle. Peripheral and aortic systolic blood pressure decreased one month after WBC + SS in comparison to before.

Effects of WBC + SS on reduction of fatigue, indicators of aortic stiffness and symptoms severity related to autonomic nervous system disturbance and improvement in cognitive function were maintained at one month.

However, improvement in all three fatigue scales (CFQ, FIS and FSS) was noted in 17 of 22 patients. In addition, ten patients were treated initially but they were not assessed at 4 weeks, and are thus not included in the 22 patients who were examined on follow-up. The overall effects of WBC + SS noted at one month post-treatment should be interpreted with caution.

Source: Kujawski S, Zalewski P, Godlewska BR, Cudnoch-Jędrzejewska A, Murovska M, Newton JL, Sokołowski Ł, Słomko J. Effects of whole-body cryotherapy and static stretching are maintained 4 weeks after treatment in most patients with chronic fatigue syndrome. Cryobiology. 2023 May 23:S0011-2240(23)00035-4. doi: 10.1016/j.cryobiol.2023.05.003. Epub ahead of print. PMID: 37230457. https://www.sciencedirect.com/science/article/pii/S0011224023000354?via%3Dihub (Full text)

Fighting Post-COVID and ME/CFS – development of curative therapies

Abstract:

The sequela of COVID-19 include a broad spectrum of symptoms that fall under the umbrella term post-COVID-19 condition or syndrome (PCS). Immune dysregulation, autoimmunity, endothelial dysfunction, viral persistence, and viral reactivation have been identified as potential mechanisms.

However, there is heterogeneity in expression of biomarkers, and it is unknown yet whether these distinguish different clinical subgroups of PCS. There is an overlap of symptoms and pathomechanisms of PCS with postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

No curative therapies are available for neither ME/CFS nor PCS. The mechanisms identified so far provide targets for therapeutic interventions.

To accelerate the development of therapies, we propose evaluating drugs targeting different mechanisms in clinical trial networks using harmonized diagnostic and outcome criteria and subgrouping patients based on a thorough clinical profiling including a comprehensive diagnostic and biomarker phenotyping.

Source: Carmen Scheibenbogen, Judith T. Bellmann-Strobl, Cornelia Heindrich, Kirsten Wittke, Elisa Stein, Christiana Franke, Harald Prüss, Hannah Preßler, Marie-Luise Machule, Heinrich Audebert, Carsten Finke, Hanna G. Zimmerman,  Birgit Sawitzki, Christian Meisel, Markus Tölle, Anne Krüger, Anna C. Aschenbrenner, Joachim L. Schultz, Marc D. Beyer, Markus Ralser, Michael Mülleder, Leif E. Sander, Frank Konietschke, Friedemann Paul, Silvia Stojanov, Lisa Bruckert, Dennis M. Hedderich, Franziska Knolle, Gabriela Riemekasten, Maria J. Vehreschild, Oliver A. Cornely, Uta Behrends and Susen Burock.  Fighting Post-COVID and ME/CFS – development of curative therapies. Frontiers in Medicine, Sec. Infectious Diseases: Pathogenesis and Therapy: Volume 10 – 2023. https://www.frontiersin.org/articles/10.3389/fmed.2023.1194754/abstract

 

Webinar: New Hope for Diagnosing and Treating Post-Infection Illnesses: Lessons Learned from HIV/AIDS

Webinar:

Drs. Steven Deeks and David Hardy (Solve M.E. Medical Advisor) — two long-time researchers, clinicians, and veterans of the battle against HIV/AIDS, discussed how current studies on Long Covid, informed by knowledge gained in other fields, could help develop improved ways to diagnose and treat the broader challenge of post-infection illnesses, such as ME/CFS. In their conversation, Drs. Deeks and Hardy discussed the emerging scientific and medical findings, reflected on their HIV/AIDS experience and the importance of patient engagement in research and advocacy, and discussed the prospects for treatments and therapies.

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Who Have Already Visited Some Medical Institutions: The Points of Diagnosis and Treatment

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a syndrome primarily presenting fatigue-based symptoms; however, the challenge is this syndrome has no diagnostic biomarkers. The diagnosis and treatment of ME/CFS require highly specialized knowledge and skills. There is no definitive therapy for ME/CFS, including Chinese herbal medicine, vitamins, and/or L-carnitine. We recognised ME/CFS-like symptom in some patients infected COVID-19 . This directed our attention towards the research progress on the new research on the mechanisms and treatment of ME/CFS.

Source: Shimomura T. [Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Who Have Already Visited Some Medical Institutions: The Points of Diagnosis and Treatment]. Brain Nerve. 2022 May;74(5):660-667. Japanese. doi: 10.11477/mf.1416202094. PMID: 35589661. https://pubmed.ncbi.nlm.nih.gov/35589661/ [Article in Japanese]

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Who Have Already Visited Some Medical Institutions: Diagnosis, Treatment and Research

Abstract:

Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is an acquired intractable disease characterized by profound fatigue, post-exertional malaise, sleep disturbance, cognitive impairment, and orthostatic intolerance, among other features. The onset often follows an infectious episode. Importantly, the various types of autonomic dysfunctions, pain, and intolerance to various stimuli in ME/CFS patients are intrinsically different from the “fatigue” of healthy individuals. In this short essay, I summarize the current diagnostic and therapeutic strategies for ME/CFS, as well as the progress in the immunological and imaging research on this intractable disease.

Source: Sato W. [Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Who Have Already Visited Some Medical Institutions: Diagnosis, Treatment and Research]. Brain Nerve. 2022 May;74(5):652-659. Japanese. doi: 10.11477/mf.1416202093. PMID: 35589660. https://pubmed.ncbi.nlm.nih.gov/35589660/ [Article in Japanese]

A Natural History of Disease Framework for Improving the Prevention, Management, and Research on Post-viral Fatigue Syndrome and Other Forms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

We propose a framework for the treatment, rehabilitation, and research into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) using a natural history of disease approach to outline the distinct disease stages, with an emphasis on cases following infection to provide insights into prevention.

Moving away from the method of subtyping patients based on the various phenotypic presentations and instead reframing along the lines of disease progression could help with defining the distinct stages of disease, each of which would benefit from large prospective cohort studies to accurately describe the pathological mechanisms taking place therein. With a better understanding of these mechanisms, management and research can be tailored specifically for each disease stage.

Pre-disease and early disease stages call for management strategies that may decrease the risk of long-term morbidity, by focusing on avoidance of further insults, adequate rest to enable recovery, and pacing of activities.

Later disease stages require a more holistic and tailored management approach, with treatment—as this becomes available—targeting the alleviation of symptoms and multi-systemic dysfunction.

More stringent and standardised use of case definitions in research is critical to improve generalisability of results and to create the strong evidence-based policies for management that are currently lacking in ME/CFS.

Source: O’Boyle S, Nacul L, Nacul FE, Mudie K, Kingdon CC, Cliff JM, Clark TG, Dockrell HM and Lacerda EM. A Natural History of Disease Framework for Improving the Prevention, Management, and Research on Post-viral Fatigue Syndrome and Other Forms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front. Med. 8:688159. https://www.frontiersin.org/articles/10.3389/fmed.2021.688159/full (Full text)

A Comprehensive Update of the Current Understanding of Chronic Fatigue Syndrome

Abstract:

This is a comprehensive literature review of chronic fatigue syndrome (CFS). We provide a description of the background, etiology, pathogenesis, diagnosis, and management regarding CFS. CFS is a multifaceted illness that has many symptoms and a wide array of clinical presentations.

As of recent, CFS has been merged with myalgic encephalomyelitis (ME). Much of the difficulty in its management has stemmed from a lack of a concrete understanding of its etiology and pathogenesis. There is a potential association between dysfunction of the autoimmune, neuroendocrine, or autonomic nervous systems and the development of CFS. Possible triggering events, such as infections followed by an immune dysregulation resulting have also been proposed. In fact, ME/CFS was first described following Epstein Barr virus (EBV) infections, but it was later determined that it was not always preceded by EBV infection.

Patient diagnosed with CFS have shown a noticeably earlier activation of anaerobic metabolism as a source of energy, which is suggestive of impaired oxygen consumption. The differential diagnoses range from tick-borne illnesses to psychiatric disorders to thyroid gland dysfunction. Given the many overlapping symptoms of CFS with other illnesses makes diagnosing it far from an easy task.

The Centers for Disease Control and Prevention (CDC) considers it a diagnosing of exclusion, stating that self-reported fatigue for at minimum of six months and four of the following symptoms are necessary for a proper diagnosis: memory problems, sore throat, post-exertion malaise, tender cervical or axillary lymph nodes, myalgia, multi-joint pain, headaches, and troubled sleep. In turn, management of CFS is just as difficult.

Treatment ranges from conservative, such as cognitive behavioral therapy (CBT) and antidepressants, to minimally invasive management. Minimally invasive management involving ranscutaneous electrical acupoint stimulation of target points has demonstrated significant improvement in fatigue and associated symptoms in a 2017 randomized controlled study. The understanding of CFS is evolving before us as we continue to learn more about it. As further reliable studies are conducted, providing a better grasp of what the syndrome encompasses, we will be able to improve our diagnosis and management of it.

Source: Noor N, Urits I, Degueure A, Rando L, Kata V, Cornett EM, Kaye AD, Imani F, Narimani-Zamanabadi M, Varrassi G, Viswanath O. A Comprehensive Update of the Current Understanding of Chronic Fatigue Syndrome. Anesth Pain Med. 2021 Jun 26;11(3):e113629. doi: 10.5812/aapm.113629. PMID: 34540633; PMCID: PMC8438707. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438707/  (Full text)