Category: Treatment

Pyridostigmine improves hand grip strength in patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic disease characterized by exertional intolerance and fatigue which is often accompanied by muscle weakness and fatiguability. A study showed efficacy of the acetylcholinesterase inhibitor pyridostigmine on cardiac output in ME/CFS patients. Pyridostigmine is currently used off-label in ME/CFS and postural orthostatic tachycardia syndrome.

Methods: We evaluated the effect of pyridostigmine on hand grip strength in 20 patients with post-infectious ME/CFS. Hand grip strength testing was performed ten times using an electric dynamometer and was repeated after 1 h. In a second test, 30 mg of pyridostigmine was given immediately after the first measurement. Orthostatic function was assessed using a passive standing test. Neurological examination and autoantibody testing were performed to rule out a diagnosis of myasthenia gravis.

Results: All patients had reduced maximum hand grip strength with a median of 16.45 kg (IQR: 11.45 kg–22.8 kg). Hand grip strength was diminished by a median of 4.65 kg after 1 h. In contrast, 1 h after pyridostigmine administration, patients showed an improvement in maximum hand grip strength with a median increase of 2.6 kg. The maximum hand grip strength after exertion was about 1.5-fold higher with then without pyridostigmine (p = 0.01). The increase in heart rate from lying to standing was median 17 beats per minute without pyridostigmine (IQR: 13 beats per minute – 23 beats per minute) and 13 beats per minute (IQR: 9 beats per minute – 20 beats per minute) (p = 0.017) with pyridostigmine. None of the patients tested positive for myasthenia gravis specific autoantibodies.

Conclusion: Pyridostigmine exerts an immediate effect on muscle strength and orthostatic function. This may be attributed to increased acetylcholine availability at neuromuscular junctions, and its augmentation of parasympathetic tone.

Source: Schlömer Ella , Stein Elisa , Kedor Claudia , Rust Rebekka , Brock Anna , Wittke Kirsten , Scheibenbogen Carmen , Kim Laura. Pyridostigmine improves hand grip strength in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Frontiers in Neuroscience, Volume 19 – 2025. DOI: 10.3389/fnins.2025.1637838 ISSN: 1662-453X https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1637838/full (Full text)

Effects of recumbent isometric yoga on the orthostatic cardiovascular response of patients with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Our previous studies demonstrated that the regular practice of recumbent isometric yoga reduced the fatigue of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Some patients with ME/CFS have postural orthostatic tachycardia syndrome (POTS); however, the effects of recumbent isometric yoga on orthostatic cardiovascular responses and whether recumbent isometric yoga improves POTS remain unknown. This pilot study was done to investigate the effect of recumbent isometric yoga on the orthostatic cardiovascular response of patients with ME/CFS.

Main body: Ten adult female patients with ME/CFS performed recumbent isometric yoga for 12 weeks. Changes in their systolic blood pressure (SBP), diastolic blood pressure (DBP), and the pulse rate (PR) during an active standing test were compared before and after the 12-week regimen. Among the 10 patients, 8 manifested a normal orthostatic response and 2 manifested POTS before the yoga intervention. Patients who manifested a normal orthostatic response before yoga also manifested the normal orthostatic pattern after the yoga intervention. In contrast, the two patients who manifested POTS before the regimen showed a normal orthostatic response after completing the yoga intervention.

Conclusions: This study found that the patients who manifested POTS and performed recumbent isometric yoga for 12 weeks had a reduced increase in PR after standing up. This pilot study suggests that recumbent isometric yoga would be useful as an adjunctive nonpharmacological intervention for improving POTS in patients with ME/CFS. This finding should be confirmed in a larger number of cases.

Source: Oka T, Lkhagvasuren B. Effects of recumbent isometric yoga on the orthostatic cardiovascular response of patients with myalgic encephalomyelitis/chronic fatigue syndrome. Biopsychosoc Med. 2025 Sep 1;19(1):16. doi: 10.1186/s13030-025-00336-w. PMID: 40890788. https://bpsmedicine.biomedcentral.com/articles/10.1186/s13030-025-00336-w (Full text)

Nutraceutical Supplementation Effects on Subjective Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating condition marked by severe, long-lasting fatigue and exhaustion that does not improve with rest. ME/CFS is reported in individuals of all ages and various racial, socioeconomic, and ethnic groups. This condition lacks standard treatment. Nutritional supplements and dietary interventions are often used to manage symptoms, but the efficacy of these interventions remains scarce in the current literature. This systematic review aims to evaluate and summarize recent evidence on nutrient supplementation and diet-based interventions in patients with ME/CFS sourced from clinical trial registries and article databases.

Registries improve the quality, integrity, and transparency of clinical trials by providing a standardized platform for reporting study design and results and, thus, reducing the biases related to selective reporting practices. Systematic reviews using these registries, therefore, are an efficient pathway to acquire current medical evidence for use in clinical decision-making and the development of practice guidance in various fields. ClinicalTrials.gov, Medline, PubMed, Cochrane, and Web of Science were systematically searched for interventional studies in which patients suffering from ME/CFS supplemented or altered their diet.

The results of this review showed several supplements that suggest improvement in patients’ symptomatology, including nicotinamide adenine dinucleotide (NADH), coenzyme Q10 (CoQ10), wasabi, and probiotics. However, many of these registered clinical trials did not employ the U.S. National Institutes of Health (NIH)’s National Institute of Neurological Disorders and Stroke (NINDS) suggested common data elements (CDEs). These standardized outcome-measuring tools allow the generalization and true comparison of the patient-reported outcomes.

Source: Brito EM, Bonifanti L, Patel R, Jimenez J, Junco J, Rozenfeld IR, Renesca V, Cheema AK. Nutraceutical Supplementation Effects on Subjective Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review. Cureus. 2025 Jul 2;17(7):e87178. doi: 10.7759/cureus.87178. PMID: 40755709; PMCID: PMC12315604. https://pmc.ncbi.nlm.nih.gov/articles/PMC12315604/ (Full text)

Beneficial effects of intermittent intravenous saline infusion in dysautonomic patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a caseseries

Abstract:

Purpose. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition with no single, uniformly effective pharmacologic therapy. Dysautonomic features like orthostatic intolerance and postural tachycardia syndrome are common features in ME/CFS, severely affecting the patient´s quality-of-life. Intermittent saline infusion may reduce symptoms associated with dysautonomia, but this has not been tested scientifically in patients with ME/CFS.

In this case-series, 22 patients with ME/CFS and signs of dysautonomia and/or hypovolemia were treated every third week over 9 weeks with intravenous saline (9 mg/mL NaCl), using standard aseptic technique. Symptoms were monitored throughout the treatment regime, and a follow-up evaluation was conducted.

Results. At treatment start, patients were predominantly female (95%), at mean age 46 ± 10 years, and with a mean body hydration percentage of 48 ± 6. Self-reported health status revealed an overall symptom score of 47 ± 13 on a 0-96 scale, a median POTS score of 64 (IQR 16) on a 0-120 scale, and poor measures of quality-of-life (median 25 IQR 25, on a 0-100 scale) and abilityto-work (median 0, IQR 26, on a 0-100 scale). Following 9 weeks of intermittent saline infusion (mean volume 1600 ± 360 mL), self-reported composite symptom score, quality-of-life and POTS-related symptoms improved significantly (all p<0.001), as did ability-to-work (p<0.05).

Our data derived from a non-controlled case-series indicate health benefits from volume loading with intermittent infusion of saline among patients with ME/CFS, which may stimulate further studies on various forms of intravenous volume loading to patients with ME/CFS and dysautonomia.

Source: Per Sjogren, Helena Huhmar, Bo Christer Bertilson, Björn A Bragée, Olli Polo. Beneficial effects of intermittent intravenous saline infusion in dysautonomic patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: a caseseries. Front. Neurol., Sec. Autonomic Disorders, Volume 16 – 2025 | doi: 10.3389/fneur.2025.1601599 https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1601599/abstract

Plasma cell targeting with the anti-CD38 antibody daratumumab in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) -a clinical pilot study

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) entails low quality of life for patients and massive societal costs. There is an urgent need for elucidation of disease mechanisms and for rational treatment. Our working hypothesis is that ME/CFS in a subgroup of patients is associated with functional autoantibodies emerging after an infection, and that plasma-cell depletion with transient reductions in serum immunoglobulins will have a beneficial effect on symptoms.

Objective: To evaluate feasibility and toxicity of plasma-cell targeting treatment using subcutaneous anti-CD38 antibody daratumumab (Darzalex) in moderate to severe ME/CFS, and to assess the clinical course through 12-24 months follow-up. Methods: We performed an open-label pilot trial (EudraCT 2022-000281-18). Ten female patients were enrolled. Following 12 weeks run-in, six patients received four daratumumab injections. The next four patients received four, followed by three additional injections from week 20.

Results: All planned treatments were administered, and there were no serious adverse events. Four patients had no significant clinical changes. Six patients experienced marked improvement. For all ten patients, mean SF-36 Physical Function (SF-36 PF) increased from 25.9 to 55.0 at eight to nine months (p=0.002). In six responders, mean SF-36 PF increased from 32.2 to 78.3. Five of these had major and sustained improvement with a mean SF-36 PF of 88 (range 80 to 95) toward end of follow-up. Mean steps per 24 hours was 3359 (range 1493 to 6277) at baseline. At eight to nine months, the mean number of steps was 5862, and 7392 in the six responders. All five patients with sustained improvement reached a mean step count above 10000/24h for some weeks, and above 15000 on individual days. Relative reduction of serum IgG levels was 54% in patients with clinical improvement, and 40% in those with no benefit. Low baseline NK-cell count in blood was associated with lack of clinical response.

Conclusion: Subcutaneous daratumumab was well tolerated. In six ME/CFS patients, treatment was associated with clinical improvement and concurrent transient reduction of serum IgG levels, indicating pathomechanistic roles for long-lived plasma cells and functional autoantibodies. No definite conclusions should be drawn before a randomized study has been performed.

See: Correction

Source: Øystein Fluge, Ingrid Gurvin Rekeland, Kari Sørland, Kine Alme. Kristin Risa, Ove Bruland, Karl Johan Tronstad, Olav Mella. Plasma cell targeting with the anti-CD38 antibody daratumumab in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) -a clinical pilot study.
Front. Med., Sec. Infectious Diseases: Pathogenesis and Therapy, Volume 12 – 2025 | doi: 10.3389/fmed.2025.1607353  https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1607353/abstract

Medication use and symptomology in North American women with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: There are no known curative treatments for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and current therapeutic regimens often yield inconsistent results. Despite the profound physical and mental burden experienced by those living with ME/CFS, patients often face a trial-and-error process in finding medications that offer some relief.

Method: The current study surveyed 135 North American women diagnosed with ME/CFS to characterize medication use in relation to disease features, symptomology, and function. Medications were classified into 9 categories according to their primary mechanism of action and therapeutic use.

Results: Participants were primarily middle-aged (47.1 ± 15.3 years) and were diagnosed for a mean duration of 8.4 ± 9.5 years (mean ± SD). Responses showed 68.6% of participants reported taking medications specifically for ME/CFS. Of those taking ME/CFS-related symptom medications, the average use was 3.0 medications per patient, with higher use in US compared to Canadian participants. Analgesic medications (31.7%) were the most frequently used, followed by psychotropic (26.4%), and immune-related medications (10.6%). These trends persisted across different symptom profiles, apart from gastrointestinal associated medication use replacing immune-related medications in those with gastrointestinal, neurological, and psychiatric symptoms. There was no significant correlation found between the number of medications used with disease duration, age, or age at diagnosis. However, a U-shaped relationship between ME/CFS-related symptom medication use and functional capacity as assessed by self-reported physical movement (hours/week) was evident.

Conclusion: Our study highlights the diverse and complex patterns in pharmacological treatment regimens for ME/CFS in women, while also underscoring the need for more tailored and evidence-based therapeutic strategies to address the varied symptom profiles.

Source: Pochakom A, MacNevin G, Madden RF, Moss AC, Martin JM, Lalonde-Bester S, Parnell JA, Stein E, Shearer J. Medication use and symptomology in North American women with myalgic encephalomyelitis/chronic fatigue syndrome. Front Med (Lausanne). 2025 Jun 6;12:1543158. doi: 10.3389/fmed.2025.1543158. PMID: 40547918; PMCID: PMC12179203. https://pmc.ncbi.nlm.nih.gov/articles/PMC12179203/ (Full text)

Low Dose Rapamycin Alleviates Clinical Symptoms of Fatigue and PEM in ME/CFS Patients via Improvement of Autophagy

Abstract:

Background: mTOR activation is associated with chronic inflammation in ME/CFS. Previous studies have shown that sustained mTOR activation can cause chronic muscle fatigue by inhibiting ATG13-mediated autophagy. This highlights the pivotal role of mTOR in the pathogenesis of ME/CFS.

Methods: We conducted a decentralized, uncontrolled trial of rapamycin in 86 patients with ME/CFS to evaluate its safety and efficacy. Low-dose rapamycin (6 mg/week) was administered, and core ME/CFS symptoms were assessed on days 30 (T1), 60 (T2), and 90 (T3). Plasma levels of autophagy metabolites, such as pSer258-ATG13 and BECLIN-1, were measured and correlated with clinical outcomes, specifically MFI.

Results: Rapamycin (6 mg/week) was tolerated without any SAEs. Of the 40 patients, 29 (72.5%) showed strong recovery in PEM, fatigue, and OI, along with improvements in MFI fatigue domains and SF-36 aspects. High levels of BECLIN-1 were detected in T3. Plasma pSer258-ATG13 levels were strongly downregulated at T1. Spearman’s correlation analysis indicated an association between autophagy impairment and reduced activity.

Conclusions: Low-dose rapamycin effectively reduced PEM and other key symptoms in patients with ME/CFS, as measured by BAS, SSS, MFI, and SF-36.  Future studies should encompass dose optimization and develop a diagnostic tool to identify responders with mTOR-mediated autophagy disruption.

Source: Brian T. Ruan, Sarojini Bulbule, Amy Reyes et al. Low Dose Rapamycin Alleviates Clinical Symptoms of Fatigue and PEM in ME/CFS Patients via Improvement of Autophagy, 03 June 2025, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-6596158/v1] https://www.researchsquare.com/article/rs-6596158/v1 (Full text)

HERV Dysregulation in a Case of Myalgic Encephalomyelitis and Multiple Sclerosis Responsive to Rituximab

Abstract:

This article summarizes the case of 30-year-old male diagnosed with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and its longitudinal follow-up, which provided a secondary diagnosis of Multiple Sclerosis (MS) eight years later. The most impactful result was his response to rituximab treatment after the systematic failure of prior treatments.

Although the expression of endogenous retroviral proteins has been associated with autoimmunity, the patient did not show increased expression of the toxic protein HERV (human endogenous retrovirus)-W ENV, a target of the ongoing clinical trials with temelimab in MS and long COVID-19 cases. However, genome-wide HERV transcriptome analysis by high density microarrays clearly revealed a distinct profile in the patient’s blood supportive of an altered immune system.

Limitations of the study include sub-optimal frequency of magnetic resonance imaging to monitor lesion progression, and similarly for reassessment of HERV profiles after rituximab. Overall, the coincidence of HERV alterations and the impactful response to rituximab presents the possibility of additional, more specific, therapeutic targets encoded by other HERV elements yet to be discovered.

Source: Martín-Martínez E, Gil-Perotin S, Giménez-Orenga K, Barea-Moya L, Oltra E. HERV Dysregulation in a Case of Myalgic Encephalomyelitis and Multiple Sclerosis Responsive to Rituximab. Int J Mol Sci. 2025 May 20;26(10):4885. doi: 10.3390/ijms26104885. PMID: 40430026; PMCID: PMC12111851. https://pmc.ncbi.nlm.nih.gov/articles/PMC12111851/ (Full text)

The potential therapeutic approaches targeting gut health in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a narrative review

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disorder characterized by persistent fatigue and cognitive impairments, with emerging evidence highlighting the role of gut health in its pathophysiology. The main objective of this review was to synthesize qualitative and quantitative data from research examining the gut microbiota composition, inflammatory markers, and therapeutic outcomes of interventions targeting the microbiome in the context of ME/CFS.

Methods: The data collection involved a detailed search of peer-reviewed English literature from January 1995 to January 2025, focusing on studies related to the microbiome and ME/CFS. This comprehensive search utilized databases such as PubMed, Scopus, and Web of Science, with keywords including “ME/CFS,” “Gut-Brain Axis,” “Gut Health,” “Intestinal Dysbiosis,” “Microbiome Dysbiosis,” “Pathophysiology,” and “Therapeutic Approaches.” Where possible, insights from clinical trials and observational studies were included to enrich the findings. A narrative synthesis method was also employed to effectively organize and present these findings.

Results: The study found notable changes in the gut microbiota diversity and composition in ME/CFS patients, contributing to systemic inflammation and worsening cognitive and physical impairments. As a result, various microbiome interventions like probiotics, prebiotics, specific diets, supplements, fecal microbiota transplantation, pharmacological interventions, improved sleep, and moderate exercise training are potential therapeutic strategies that merit further exploration.

Conclusions: Interventions focusing on the gut-brain axis may help reduce neuropsychiatric symptoms in ME/CFS by utilizing the benefits of the microbiome. Therefore, identifying beneficial microbiome elements and incorporating their assessments into clinical practice can enhance patient care through personalized treatments. Due to the complexity of ME/CFS, which involves genetic, environmental, and microbial factors, a multidisciplinary approach is also necessary. Since current research lacks comprehensive insights into how gut health might aid ME/CFS treatment, standardized diagnostics and longitudinal studies could foster innovative therapies, potentially improving quality of life and symptom management for those affected.

Source: Hsu CY, Ahmad I, Maya RW, Abass MA, Gupta J, Singh A, Joshi KK, Premkumar J, Sahoo S, Khosravi M. The potential therapeutic approaches targeting gut health in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a narrative review. J Transl Med. 2025 May 11;23(1):530. doi: 10.1186/s12967-025-06527-x. PMID: 40350437. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06527-x (Full text)

The PACE Trial’s GET Manual for Therapists Exposes the Fixed Incremental Nature of Graded Exercise Therapy for ME/CFS

Abstract:

The British National Institute for Health and Care Excellence (NICE) published its updated guidelines for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in October 2021. NICE concluded, after an extensive review of the literature, that graded exercise therapy (GET) is harmful and should not be used, and that cognitive behavioural therapy (CBT) is only an adjunctive and not a curative treatment. An article by White et al., which is written by 51 researchers, claims that there are eight anomalies in the review process and the interpretation of the evidence by NICE. In this article, we reviewed the evidence they used to support their claims.

Their three most important claims are that NICE redefined the disease, that CBT and GET are effective, and that fixed incremental increases are not part of GET. However, our analysis shows that the disease was not redefined by NICE. Instead, it was redefined in the 1990s by a group of doctors, including a number of authors of White et al., when they erased the main characteristic of the disease (an abnormally delayed muscle recovery after trivial exertion, which, over the years, has evolved into post-exertional malaise) and replaced it with chronic disabling severe fatigue. Their own studies show that CBT and GET do not lead to a substantial improvement of the quality-of-life scores or a reduction in CFS symptom count, nor do they lead to objective improvement.

Also, both treatments have a negative instead of a positive effect on work and disability status. Moreover, a recent systematic review, which included one of the authors of White et al., showed that ME/CFS patients remain severely disabled after treatment with CBT. Our analysis of, for example, the PACE trial’s GET manual for therapists exposes the fixed incremental nature of GET.

Why the authors are not aware of that is unclear because eight of them were involved in the PACE trial. Three of them were centre leaders and its principal investigators, four others were also centre leaders, and another one was one of the three independent safety assessors of the trial. Moreover, many of these eight authors wrote, or were involved in writing, this manual.

In conclusion, our analysis shows that the arguments that are used to claim that there are eight anomalies in the review process and the interpretation of the evidence by NICE are anomalous and highlight the absence of evidence for the claims that are made. Furthermore, our analysis not only exposes the fixed incremental nature of GET, but also of CBT for ME/CFS.

Source:Vink M, Partyka-Vink K. The PACE Trial’s GET Manual for Therapists Exposes the Fixed Incremental Nature of Graded Exercise Therapy for ME/CFS. Life (Basel). 2025 Apr 2;15(4):584. doi: 10.3390/life15040584. PMID: 40283139. https://www.mdpi.com/2075-1729/15/4/584 (Full text)