Category: Treatment

Clinical Remission After Therapeutic Apheresis in a Patient Suffering from Long Term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case Report

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating multifactorial illness characterized by profound fatigue persisting for more than six months, post-exertional malaise, cognitive impairments, and a range of systemic symptoms. Until now, no accepted causal treatment regimens have been available; therapeutic options include different approaches, such as alleviation of symptoms and promotion of energy conservation.

In this study, we report the case of a 49-year-old female presented to our center suffering from ME/CFS for more than 15 years, characterised by a strong energy loss and neurological and systemic symptoms; previous therapies remained unsuccessful. Therefore, we decided to perform double-filtration apheresis.

After comprehensive laboratory evaluation, including investigation of persistent viral infections, the patient was treated eight times with double-filtration apheresis within a period of 2 years, which resulted in a remarkable sustained clinical remission and significant improvement in her quality of life. Therefore, we conclude that double-filtration apheresis could be an effective therapeutic tool for the treatment of ME/CFS.

Source: Burgard H. Clinical Remission After Therapeutic Apheresis in a Patient Suffering from Long Term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Case Report. Int Med Case Rep J. 2024 Dec 6;17:997-1002. doi: 10.2147/IMCRJ.S476044. PMID: 39660109; PMCID: PMC11629661. https://pmc.ncbi.nlm.nih.gov/articles/PMC11629661/ (Full text)

Chronic inflammatory response syndrome: a review of the evidence of clinical efficacy of treatment

Abstract:

Chronic Inflammatory Response Syndrome (CIRS) is an acquired medical condition characterized by innate immune dysregulation following respiratory exposure to water-damaged buildings (WDB). This chronic syndrome involves a range of symptoms that simultaneously affecting multiple organ systems. The purpose of this literature review was to search the published literature for successful treatments for chronic inflammatory response syndrome, an under-recognized, underdiagnosed, multisymptom multisystem illness that can affect up to 25% of the population, thus representing a silent epidemic.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a common misdiagnosis for CIRS, is an entity that has broader awareness within the medical community despite the absence of a defined etiology, biomarkers or a treatment protocol that reverses the underlying conditions. Therefore, the search also included treatments for ME/CFS and sick building syndrome (SBS). Thirteen articles referenced treatment for CIRS, and 22 articles referenced treatment for CFS.

The only treatment with documented clinical efficacy was the Shoemaker Protocol, which was described in 11 of the 13 articles. This treatment protocol exhibits superior outcomes compared with the treatment protocols for ME/CFS.

Source: Dooley M, Vukelic A, Jim L. Chronic inflammatory response syndrome: a review of the evidence of clinical efficacy of treatment. Ann Med Surg (Lond). 2024 Nov 8;86(12):7248-7254. doi: 10.1097/MS9.0000000000002718. PMID: 39649915; PMCID: PMC11623837. https://pmc.ncbi.nlm.nih.gov/articles/PMC11623837/ (Full text)

Patient-Reported Treatment Outcomes in ME/CFS and Long COVID

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID are persistent multi-system illnesses affecting many patients. With no known effective FDA-approved treatments for either condition, patient-reported outcomes of treatments are invaluable for guiding management strategies in patient care and generating new avenues for research. Here, we present the results of an ME/CFS and Long COVID treatment survey with responses from 3,925 patients.

We assessed the experiences of these patients with more than 150 treatments, as well as their demographics, symptoms, and comorbidities. Patients with each condition who participated in the study shared similar symptom profiles, including all the core symptoms of ME/CFS, e.g., 89.7% of ME/CFS and 79.4% of Long COVID reported post-exertional malaise (PEM). Treatments with the greatest perceived benefits were identified, which had varied effects on different core symptoms.

In addition, treatment responses were significantly correlated (R² = 0.68) between the two patient groups. Patient subgroups with distinct profiles of symptoms and comorbidities showed varied responses to treatments, e.g., a POTS-dominant cluster benefiting from autonomic modulators and a cognitive-dysfunction cluster from CNS stimulants.

This study underscores the symptomatic and therapeutic similarities between ME/CFS and Long COVID and highlights the commonalities and nuanced complexities of infection-associated chronic diseases and related conditions. Insights from patient-reported experiences, in the absence of approved treatments, provide urgently needed real-world evidence for targeted therapies in patient care and for developing future clinical trials.

Source: Martha Eckey, Peng Li, Braxton Morrison, Ronald W Davis, Wenzhong Xiao. Patient-Reported Treatment Outcomes in ME/CFS and Long COVID. medRxiv 2024.11.27.24317656; doi: https://doi.org/10.1101/2024.11.27.24317656 https://www.medrxiv.org/content/10.1101/2024.11.27.24317656v1.full-text (Full text)

Confirmed: The Conclusion by NICE that CBT is not an Effective Treatment for ME/CFS; Re-Analysis of a Systematic Review

Abstract:

In this article, we analyzed the systematic review by Kuut et al. into the efficacy of cognitive behavioral therapy (CBT) for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disease that predominantly affects women, and the eight trials
in it. We found many issues with the studies in the review, but also with the review itself.

For example, the systematic review by Kuut et al. included a researcher who was involved in seven of the eight studies in their review, and another one who was involved in five of them. Moreover, at least one of them was involved in every study in the review. On top of that, the three professors who were involved in the systematic review, have all built their career on the CB model and the reversibility of ME/CFS through CBT and GET and two of the systematic reviewers have a potential financial conflict of interest. Yet they failed to inform the readers about these conflicts of interest. Conducting a review in this manner and not informing the readers, undermines the credibility of a systematic review and its conclusion.

Regarding outcome differences between treatment and control group, it’s highly likely that the combination of non-blinded
trials, subjective outcomes and poorly chosen control groups, alone or together with response shift bias and/or patients filling in questionnaires in a manner to please the investigators, allegiance bias, small study effect bias and other forms of bias,
produced the appearance of positive effects, despite the lack of any substantial benefit to the patients, leading to the erroneous inference of efficacy in its absence. That CBT is not an effective treatment is highlighted by the fact that patients remained
severely disabled after treatment with it.

The absence of objective improvement as shown by the actometer, employment status and objective cognitive measures, confirms the inefficacy of CBT for ME/CFS. The systematic review did not report on safety but research by the Oxford Brookes University shows that CBT, which contains an element of graded exercise therapy, is harmful for many patients. Finally, our reanalysis highlights the fact that researchers should not mark their own homework.

Source: Vink M, Vink-Niese A. Confirmed: The Conclusion by NICE that CBT is not an Effective Treatment for ME/CFS; Re-Analysis of a Systematic Review. SciBase Neurol. 2024; 2(3): 1022. https://www.scibasejournals.org/neurology/1022.pdf (Full text)

Assessment of the therapeutic potential of salubrinal for ME/CFS and long-COVID

Highlights:

  • Long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are enigmatic diseases sharing many characteristics.
  • The most debilitating aspects of these diseases are cognitive dysfunction, ‘brain fog’, and exercise intolerance, ‘post-exertional malaise’.
  • There is no cure for these diseases; treatment is palliative only.
  • Mitochondrial dysfunction with endoplasmic reticulum (ER) stress occurs in both diseases.
  • Salubrinal inhibits the phosphatase that dephosphorylates phospho-eukaryotic initiation factor-2α (peIF2α), a protective protein for cells undergoing ER stress when phosphorylated.
  • Salubrinal reduces the formation of Wiskott–Aldrich syndrome protein family member 3 (WASF3), a protein that causes mitochondrial dysfunction that is overexpressed in a cohort of ME/CFS patients.
  • Salubrinal reduces WASF3 expression, restoring mitochondrial function in fibroblasts of a patient with ME/CFS.

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic debilitating condition with no cure that shares commonality with long-COVID.

This review examines current understanding of long-COVID symptoms, characteristics of the affected population, the connection with ME/CFS, and the potential for salubrinal, an agent known for its influence on cellular stress pathways, to mitigate these disorders.

It also describes the historical development and mechanism of action of salubrinal, to mitigate endoplasmic reticulum (ER)/cellular stress responses, that could potentially contribute to symptom improvement in both ME/CFS and long-COVID patients.

Further research and clinical trials are warranted to advance our understanding of the potential role of salubrinal in improving the quality of life for individuals with long-COVID-related ME/CFS symptoms as well as ME/CFS patients.

Source: Aseel Warrayat, Ayah Ali, Joulin Waked, Darcy Tocci, Robert C. Speth. Assessment of the therapeutic potential of salubrinal for ME/CFS and long-COVID. Trends in Molecular Medicine, 2024. ISSN 1471-4914, https://doi.org/10.1016/j.molmed.2024.10.001. https://www.sciencedirect.com/science/article/abs/pii/S1471491424002685

Six-Week Supplementation with Creatine in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Magnetic Resonance Spectroscopy Feasibility Study at 3 Tesla

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic medical condition with no specific pharmacological treatment. Creatine, a nutrient essential for maintaining energy homeostasis in the cells, is a candidate for interventions in ME/CFS.

Methods: Fourteen participants with ME/CFS received supplementation with 16 g creatine monohydrate for 6 weeks. Before starting creatine and on the last day of treatment, participants underwent brain magnetic resonance spectroscopy (MRS) scanning of the pregenual anterior cingulate cortex (pgACC) and dorsolateral prefrontal cortex (DLPFC), followed by symptom, cognition, and hand-grip strength assessments.

Results: Eleven participants completed the study. Creatine treatment increased creatine concentration in both the pgACC and DLPFC (p = 0.004 and 0.012, respectively), decreased fatigue and reaction time (RT) on congruent and incongruent trials of the Stroop test (p = 0.036 and 0.014, respectively), and increased hand-grip strength (p = 0.0004). There was a positive correlation between increases in pgACC creatine and changes in RT on Stroop congruent and incongruent trials (p = 0.048 and p = 0.022, respectively). Creatine was well tolerated, and none of the participants stopped treatment.

Conclusion: Creatine supplementation over six weeks in ME/CFS patients increased brain creatine and improved fatigue and some aspects of cognition. Despite its methodological limitations, this study encourages placebo-controlled investigations of creatine treatment in ME/CFS.

Source: Godlewska BR, Sylvester AL, Emir UE, Sharpley AL, Clarke WT, Martens MAG, Cowen PJ. Six-Week Supplementation with Creatine in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Magnetic Resonance Spectroscopy Feasibility Study at 3 Tesla. Nutrients. 2024 Sep 30;16(19):3308. doi: 10.3390/nu16193308. PMID: 39408275. https://www.mdpi.com/2072-6643/16/19/3308 (Full text)

A review of intravenous immunoglobulin in the treatment of neuroimmune conditions, acute COVID-19 infection, and post-acute sequelae of COVID-19 Syndrome

Abstract:

Intravenous immunoglobulin (IVIG) is an immunomodulatory therapy that has been studied in several neuroimmune conditions, such as Guillain-Barré Syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and multiple sclerosis. It has also been proposed as a potential treatment option for acute COVID-19 infection and post-acute sequelae of SARS-CoV-2 infection (PASC). IVIG is thought to function by providing the recipient with a pool of antibodies, which can, in turn, modulate immune responses through multiple mechanisms including neutralization of cytokines and autoantibodies, saturation of neonatal fragment crystallizable receptors, inhibition of complement activation, and regulation of T and B cell mediated inflammation.

In acute COVID-19, studies have shown that early administration of IVIG and plasmapheresis in severe cases can reduce the need for mechanical ventilation, shorten ICU and hospital stays, and lower mortality. Similarly, in PASC, while research is still in early stages, IVIG has been shown to alleviate persistent symptoms in small patient cohorts.

Furthermore, IVIG has shown benefits in another condition which has symptomatic overlap with PASC, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), though studies have yielded mixed results. It is important to note that IVIG can be associated with several potential adverse effects, such as anaphylaxis, headaches, thrombosis, liver enzyme elevations and renal complications. In addition, the high cost of IVIG can be a deterrent for payers and patients.

This review provides a comprehensive update on the use of IVIG in multiple neuroimmune conditions, ME/CFS, acute COVID-19, and PASC, as well as covers its history, production, pricing, and mechanisms of action. We also identify key areas of future research, including the need to optimize the use of Ig product dosing, timing, and patient selection across conditions, particularly in the context of COVID-19 and PASC.

Source: Morse BA, Motovilov K, Michael Brode W, Michael Tee F, Melamed E. A review of intravenous immunoglobulin in the treatment of neuroimmune conditions, acute COVID-19 infection, and post-acute sequelae of COVID-19 Syndrome. Brain Behav Immun. 2024 Oct 8:S0889-1591(24)00648-2. doi: 10.1016/j.bbi.2024.10.006. Epub ahead of print. PMID: 39389388. https://www.sciencedirect.com/science/article/abs/pii/S0889159124006482

Inspiratory muscle training improves autonomic function in myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of SARS-CoV-2: a pilot study

Abstract:

Post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are debilitating post-viral conditions with many symptomatic overlaps, including exercise intolerance and autonomic dysfunction. Both conditions are growing in prevalence, and effective safe treatment strategies must be investigated. We hypothesized that inspiratory muscle training (IMT) could be used in PASC and mild to moderate ME/CFS to mitigate symptoms, improve exercise capacity, and improve autonomic function.

We recruited healthy controls (n=12; 10 women), people with PASC (n=9; 8 women), and people with mild to moderate ME/CFS (n=12; 10 women) to complete 8 weeks of IMT. This project was registered as a clinical trial (NCT05196529) with clinicaltrials.gov.

After completion of IMT, all groups experienced improvements in inspiratory muscle pressure (p<0.001), 6-minute walk distance (p=0.002), resting heart rate (p=0.037), heart rate variability (p<0.05), and symptoms related to sleep (p=0.009). In the ME/CFS group only, after completion of IMT, there were additional improvements with regard to vascular function (p=0.001), secretomotor function (p=0.023), the total weighted score (p=0.005) of the COMPASS 31 autonomic questionnaire, and symptoms related to pain (p=0.016).

We found that after 8 weeks of IMT, people with PASC and/or ME/CFS could see some overall improvements in their autonomic function and symptomology.

Source: Edgell H, Pereira TJ, Kerr K, Bray R, Tabassum F, Sergio L, Badhwar S. Inspiratory muscle training improves autonomic function in myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of SARS-CoV-2: a pilot study. Respir Physiol Neurobiol. 2024 Oct 5:104360. doi: 10.1016/j.resp.2024.104360. Epub ahead of print. PMID: 39374820. https://www.sciencedirect.com/science/article/pii/S1569904824001538 (Full text)

A multimodal approach for treating post-acute infectious syndrome

Abstract:

Long-term complications, such as extensive fatigue and cognitive issues, are known from various infections, including SARS-CoV-2, influenza
virus, or Borrelia burgdorferi. The pathology is mostly unknown and differs between patients. Unfortunately, there is currently no common and
effective treatment. In this perspective, we imply that post-acute infectious syndromes are due to a variety of factors, including among others
diminished tissue perfusion, tissue infiltration by viruses, inflammation, and oxidative stress, and that not one specific biomarker can be used
to measure these syndromes. Thus, we suggest that a score based on a number of criteria/factors should be used to assess post-acute infectious
syndromes.

Consequently, probably not one single treatment can be used to treat this group of patients, and we suggest a multimodal
treatment regimen comprising a combination of pharmacotherapy, such as metformin and naltrexone with anti-inflammatory effects,
alongside physical therapies such as extracorporeal apheresis and transcutaneous neurotherapy. This combined approach aims to reduce
biomarker levels and enhance cognitive functions. This implies that a reset of the systems can be achieved by a multimodal approach based on a
score for post-acute infectious syndromes.

Source:  Charlotte Steenblock, Nicole Toepfner, Yannick P. Kok, Philip Mavberg, Horst Bruckmoser, Alfons Breu, Johannes Korth, Harald Heidecke, Milo A. Puhan, and Stefan R. Bornstein. A multimodal approach for treating post-acute infectious syndrome. Brain Medicine (2024) 1, 1–7; doi: https://doi.org/10.61373/bm024p.0064; Published online: 30 August 2024. https://bm.genomicpress.com/wp-content/uploads/2024/08/BM0064-Steenblock-2024.pdf (Full text)

Six-year follow-up of participants in two clinical trials of rituximab or cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Objectives: In this six-year follow-up study, we used patient-reported outcome measures (PROMs) to compare values at baseline, at 18 months, and at six-year follow up from the CycloME and the RituxME trials.

Methods: Based on the hypothesis that ME/CFS in a subgroup of patients is a variant of an autoimmune disease, we performed two clinical trials between 2014 and 2017. The RituxME trial was a randomized, double-blind and placebo-controlled phase III trial of 151 patients, assessing the B-cell depleting antibody rituximab. The CycloME trial was an open-label phase II trial of 40 patients using intravenous cyclophosphamide. Here we report six-year follow-up from both trials, using the Short Form 36 Physical Function (SF-36 PF) and DePaul short form (DSQ-SF) questionnaires.

Result: Of the patients available after six years, 75.7% of RituxME and 94.4% of CycloME patients participated. In the RituxME rituximab group, the mean SF-36 PF scores were 32.9 at baseline, 42.4 at 18 months and 45.5 at six years. In the placebo group, the mean SF-36 PF scores were 32.3 at baseline, 45.5 at 18 months and 43.1 at six years. In the CycloME trial, mean SF-36 PF increased from 35.4 at baseline to 54.4 at 18 months, and 56.7 at six years. At six-year follow-up, 44.1% of cyclophosphamide-, 27.6% of rituximab- and 20.4% of placebo-treated patients had an SF-36 PF ≥ 70, and further, 17.6%, 8.6% and 7.4% of the corresponding patient groups had an SF-36 PF ≥ 90, which is within normal range. In terms of worsening at six years, 5.9% of cyclophosphamide-treated, 10.3% of rituximab-, and 14.8% of placebo-treated patients had a drop in SF-36 PF of 20 points or more from baseline. There were no serious unexpected adverse reactions.

Conclusions: After six years, 44.1% of the cyclophosphamide group scored an SF-36 PF of at least 70, and 17.6% of at least 90, suggesting that cyclophosphamide in a subgroup may modulate the disease course in a beneficial way. However, cyclophosphamide carries toxicity concerns and should not be used for ME/CFS patients outside clinical trials. Rather, these data should encourage efforts to better understand the disease mechanisms and to search for targeted and less toxic immune modulatory treatment for this patient group.

Source: Rekeland IG, Sørland K, Neteland LL, Fosså A, Alme K, Risa K, Dahl O, Tronstad KJ, Mella O, Fluge Ø. Six-year follow-up of participants in two clinical trials of rituximab or cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. PLoS One. 2024 Jul 23;19(7):e0307484. doi: 10.1371/journal.pone.0307484. PMID: 39042627; PMCID: PMC11265720. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265720/ (Full text)