Category: Treatment

The Role of Immunity and Inflammation in ME/ CFS and Post-COVID Syndrome: Implications for Treatment

Abstract:

Probably one in seven patients who have experienced acute COVID-19 continue having long-lasting complaints, called post-COVID syndrome or long-COVID, that are similar to those observed in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

There are good reasons to believe that common immunological, epigenetic and inflammatory mechanisms are involved in the pathogenesis both diseases.

To date, various therapeutic approaches have been recommended, but with moderate success. In the present opinion paper, the author weights his clinical experience against data from the literature, and suggests novel approaches.

In addition to general measures and paramedical approaches, food supplementation with a specific nutraceutical can be completed by oral administration of sodium dichloroacetate and Meldonium to optimize glucose metabolism and mitochondrial energy generation.

Alternatively, intravenous infusions with magnesium salt and multivitamins can be completed with glutathione, m-tranexamic acid, and cultured stem cells.

Preliminary results of an open-label, prospective, two-centre trial suggest more than four in five patients benefit from combined oral and infusion therapy with significantly diminished fatigue and improved well-being.

Monoclonal antibodies in “biologicals”, blocking the effects of cytokines, and “small molecules” with Janus kinase inhibiting activity may offer novel opportunities by focusing on both immunologic and inflammation targets. A pilot trial with, in particular, one of the Janus kinase inhibitors could be considered.

Source: Comhaire F. The Role of Immunity and Inflammation in ME/CFS and Post-COVID Syndrome: Implications for Treatment. MedLife Clinics 2022, Volume 4 (2), Article 1043 http://www.medtextpublications.com/open-access/the-role-of-immunity-and-inflammation-in-me-cfs-and-1254.pdf (Full text)

Paxlovid accelerates cartilage degeneration and senescence through activating endoplasmic reticulum stress and interfering redox homeostasis

Abstract:

Background: The COVID-19 pandemic has become a huge threat to human health, infecting millions of people worldwide and causing enormous economic losses. Many novel small molecule drugs have been developed to treat patients with COVID-19, including Paxlovid, which block the synthesis of virus-related proteins and replication of viral RNA, respectively. Despite satisfactory clinical trial results, attention is now being paid to the long-term side effects of these antiviral drugs on the musculoskeletal system. To date, no study has reported the possible side effects, such as osteoarthritis, of Paxlovid. This study explored the effects of antiviral drug, Paxlovid, on chondrocyte proliferation and differentiation.

Methods: In this study, both in vitro and in vivo studies were performed to determine the effect of Paxlovid on chondrocyte degeneration and senescence. Furthermore, we explored the possible mechanism behind Paxlovid-induced acceleration of cartilage degeneration using transcriptome sequencing and related inhibitors were adopted to verify the downstream pathways behind such phenomenon.

Results: Paxlovid significantly inhibited chondrocyte extracellular matrix protein secretion. Additionally, Paxlovid significantly induced endoplasmic reticulum stress, oxidative stress, and downstream ferroptosis, thus accelerating the senescence and degeneration of chondrocytes. In vivo experiments showed that intraperitoneal injection of Paxlovid for 1 week exacerbated cartilage abrasion and accelerated the development of osteoarthritis in a mouse model.

Conclusions: Paxlovid accelerated cartilage degeneration and osteoarthritis development, potentially by inducing endoplasmic reticulum stress and oxidative stress. Long-term follow-up is needed with special attention to the occurrence and development of osteoarthritis in patients treated with Paxlovid.

Source: Kong K, Chang Y, Qiao H, Zhao C, Chen X, Rong K, Zhang P, Jin M, Zhang J, Li H, Zhai Z. Paxlovid accelerates cartilage degeneration and senescence through activating endoplasmic reticulum stress and interfering redox homeostasis. J Transl Med. 2022 Nov 26;20(1):549. doi: 10.1186/s12967-022-03770-4. PMID: 36435786; PMCID: PMC9701426. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701426/ (Full text)

What Primary Care Practitioners Need to Know about the New NICE Guideline for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Adults

Abstract:

The new NICE guideline for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), published in October 2021, makes significant changes in treatment recommendations. It acknowledges the complexity of this chronic medical condition, which always impacts quality of life and can be profoundly disabling, recognising the prejudice and stigma that people with ME/CFS often experience in the absence of any specific diagnostic test.

The guideline outlines steps for accurate diagnosis, recognising post-exertional malaise as a core symptom; importantly, ME/CFS can now be diagnosed after just 3 months in a bid to improve long-term health outcomes. It recommends the need for individual, tailored management by a multi-disciplinary team, ensuring that the wellbeing of the individual is paramount. The guideline makes clear that any programme based on fixed incremental increases in physical activity or exercise, for example graded exercise therapy (GET), should not be offered as a treatment for ME/CFS and emphasises that cognitive behavioural therapy (CBT) should only be offered as a supportive intervention.

Because of the rigorous methodology required by NICE Committee review and the inclusion of the testimony of people with lived experience as committee members, this guideline will influence the future diagnosis and management of ME/CFS in the UK and beyond.

Source:  Kingdon, C.C.; Lowe, A.; Shepherd, C.; Nacul, L. What Primary Care Practitioners Need to Know about the New NICE Guideline for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Adults . Preprints 2022, 2022110016 (doi: 10.20944/preprints202211.0016.v1).  https://www.preprints.org/manuscript/202211.0016/v1 (Full text available as PDF file)

Functional Vitamin B12 deficiency in Chronic Fatigue Syndrome

Abstract:

Chronic Fatigue Syndrome/Myalgic encephalomyelitis (CFS/ME) is a complex chronic condition, characterized by periods of extreme fatigue, for which an underlying medical condition has previously not been identified.

Many of the symptoms of CFS/ME, are, though, similar to those with vitamin B12 deficiency. In contrast to nutritional vitamin B12 deficiency, the majority of individuals with CFS have been shown to have functional vitamin B12 deficiency as well as functional vitamin B2 deficiency.

This functional B12 deficiency occurred despite elevated serum B12 being found, and hence presents as Paradoxical vitamin B12 deficiency. As such, CFS due to functional B2 deficiency presents as Paradoxical B12 deficiency.

Maintenance of vitamin B12 functional activity is critically dependent upon functional B2 sufficiency, and hence resolution of CFS there must first be resolution of functional B2 deficiency before treatment with vitamin B12 can be effective.

Disclosures: Gregory Russell-Jones is the director of B12 Oils Pty Ltd, a company that specializes in the manufacture and supply of vitamin B12 Oils.

Source: Gregory Russell-Jones.(2022). Functional Vitamin B12 deficiency in Chronic Fatigue Syndrome. Int J Psychiatry 7(3): 153-158. https://www.researchgate.net/publication/362644480_Functional_Vitamin_B12_deficiency_in_Chronic_Fatigue_Syndrome_International_Journal_of_Psychiatry_Corresponding_author (Full text available as PDF file)

Treatments Explored to Ease Post-Viral Symptoms of ME/CFS and Long COVID

August 5, 2022:

By Miriam Tucker

A variety of treatments, most already commercially available, are
under investigation for treating the constellation of overlapping
symptoms associated with myalgic encephalomyelitis/chronic fatigue
syndrome (ME/CFS), “long COVID,” and dysautonomia.

At the virtual annual meeting of the International Association for
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (IACFS/ME),
speakers presented data for a variety of approaches to ease symptoms
common across post-viral conditions, such as extreme fatigue,
post-exertional malaise (“crash”), cognitive dysfunction (“brain
fog”), orthostatic intolerance including postural orthostatic
tachycardia syndrome (POTS), and chronic pain. Most of the modalities
are already commercially available for other indications, although
some are costly and not covered by payers for these conditions.
—

Treatments discussed in the article are:

•Pyridostigmine (Mestinon, Others)
•Oxaloacetate (benaGene)
•Inspiritol
•Stellate Ganglion Block
•Transcutaneous Auricular Vagus Nerve Stimulation

Read the full article HERE.

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.

Animal Models for Neuroinflammation and Potential Treatment Methods

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown etiology and without effective treatment options. The onset of ME/CFS is often associated with neuroinflammation following bacterial or viral infection.

A positron emission tomography imaging study revealed that the degree of neuroinflammation was correlated with the severity of several symptoms in patients with ME/CFS. In animal studies, lipopolysaccharide- and polyinosinic-polycytidylic acid-induced models are thought to mimic the pathological features of ME/CFS and provoke neuroinflammation, characterized by increased levels of proinflammatory cytokines and activation of microglia.

In this review, we described the anti-inflammatory effects of three compounds on neuroinflammatory responses utilizing animal models. The findings of the included studies suggest that anti-inflammatory substances may be used as effective therapies to ameliorate disease symptoms in patients with ME/CFS.

Source: Tamura Y, Yamato M, Kataoka Y. Animal Models for Neuroinflammation and Potential Treatment Methods. Front Neurol. 2022 Jun 27;13:890217. doi: 10.3389/fneur.2022.890217. PMID: 35832182; PMCID: PMC9271866. https://pubmed.ncbi.nlm.nih.gov/35832182/  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271866/ (Full study)

Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle?

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and debilitating disease with a substantial social and economic impact on individuals and their community. Despite its importance and deteriorating impact, progresses in diagnosis and treatment of ME/CFS is limited. This is due to the unclear pathophysiology of the disease and consequently lack of prognostic biomarkers.

To investigate pathophysiology of ME/CFS, several potential pathologic hallmarks have been investigated; however, these studies have failed to report a consistent result. These failures in introducing the underlying reason for ME/CFS have stimulated considering other possible contributing mechanisms such as tryptophan (TRP) metabolism and in particular kynurenine pathway (KP).

KP plays a central role in cellular energy production through the production of nicotinamide adenine dinucleotide (NADH). In addition, this pathway has been shown to mediate immune response and neuroinflammation through its metabolites. This review, we will discuss the pathology and management of ME/CFS and provide evidence pertaining KP abnormalities and symptoms that are classic characteristics of ME/CFS. Targeting the KP regulation may provide innovative approaches to the management of ME/CFS.

Source: Kavyani B, Lidbury BA, Schloeffel R, Fisher PR, Missailidis D, Annesley SJ, Dehhaghi M, Heng B, Guillemin GJ. Could the kynurenine pathway be the key missing piece of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) complex puzzle? Cell Mol Life Sci. 2022 Jul 11;79(8):412. doi: 10.1007/s00018-022-04380-5. PMID: 35821534. https://link.springer.com/article/10.1007/s00018-022-04380-5  (Full text)

Evidence-Based Care for People with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis

Letter to the Editor:

Sharpe et al. suggest that “the available evidence from randomized trials supports the use of the rehabilitative therapies of CBT and GET for patients with CFS/ME”.1 However, the current NICE guideline on the diagnosis and management of ME/CFS (which replaced the out-of-date guideline CG53 cited by Sharpe et al.) recommends that CBT and GET should not be prescribed as treatments for ME/CFS, due to the lack of evidence of efficacy and concerns about safety.2 As part of the process of updating its guidance, NICE reviewed all the relevant evidence from trials of these therapies. It concluded that none was better than low quality and that most was very low quality.3

It is notable that such therapies were first promoted and prescribed for ME/CFS before any clinical trials had been conducted to assess their efficacy or safety. In 1989, Wessely et al. acknowledged that it “may be correct in some cases” that physical and mental exertion should be avoided by people with ME/CFS, but they went on to recommend behavioural and cognitive therapies which encouraged patients to ignore their symptoms and gradually increase exercise, as there was “as yet no way” to identify the cases where such approaches may be harmful. Furthermore, the authors suggested that “it is reasonable to expect a patient to cooperate with treatment before being labelled as chronically disabled” for the purposes of receiving sickness benefits.4

Sharpe et al. acknowledge that since then CBT and GET have been “the most researched approaches” to treating what they refer to as CFS/ME. However, despite this, they conclude that “more research is needed into these approaches” and that “it would be a disservice to our patients to tell them we have nothing to offer them”.

It is deeply regrettable that, as NICE has concluded, there are currently no proven effective treatments for ME/CFS. However, it would be a far greater disservice to patients to prescribe ineffective and potentially harmful therapies than to tell them the truth. Given the history of how these therapies have been promoted, prescribed and researched, it is perhaps not surprising if some are reluctant to accept the evidence that they do not work and may be harmful. However, as Wilshire et al. concluded in their 2018 reanalysis of the PACE trial data: “The time has come to look elsewhere for effective treatments.”5

Read this article HERE.

Source: Saunders R. Evidence-Based Care for People with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis. J Gen Intern Med. 2022 Jul 5. doi: 10.1007/s11606-022-07715-x. Epub ahead of print. PMID: 35790668. https://link.springer.com/article/10.1007/s11606-022-07715-x (Full text)

Challenges of memory enhancers

Abstract:

40 per cent of people over the age of 65 experience some form of memory loss, called as the age related memory impairment. This might be due to hormone and proteins (Growth factors) which repair the brain cells decline with age. Certain conditions such as age, stress, disease and excessive emotional response may lead to loss of memory, loss of learning ability and altered mood and behaviour. These conditions may be treated by using nootropic agents which can help to improve learning abilities and memory.

Source: Chaudhry, Sunil. Challenges of memory enhancers. Annals of Geriatric Education and Medical Sciences; 2020/08/22. https://www.agems.in/article-details/11990 (Full text)