Tag: severely ill patients

The potential causes of myasthenia and fasciculations in severely ill ME/CFS patients: the role of disturbed electrophysiology

Abstract:

Patients with severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are bedridden and suffer from hypersensitivities to light and noise, severe orthostatic intolerance reducing cerebral blood flow, and skeletal muscle symptoms, including loss of force, fatigue, pain, fasciculations, and cramps. Because neurological investigations exclude neuronal causes of myasthenia, we hypothesize a muscular pathomechanism.

In previous articles, we considered insufficient activity of the Na+/K+-ATPase to be the main cause of mitochondrial damage via high intracellular sodium that reverses the transport mode of the sodium-calcium-exchanger to import calcium, causing calcium overload. Low Na+/K+-ATPase activity also causes sarcolemmal depolarization, leading to less effective action potential propagation and loss of force. Depolarization brings the membrane potential closer to the threshold potential, causing hyperexcitability that explains fasciculations and cramps. These increase sodium influx during excitation to further increase the workload of Na+/K+-ATPase. Thereby, depolarization causes further depolarization.

Higher intracellular sodium favors calcium overload and mitochondrial damage, which lowers the energy supply of Na+/K+-ATPase and increases the reactive oxygen species, further inhibiting Na+/K+-ATPase. The muscle is in a state of depolarization even at rest. Depolarization and mitochondrial damage reinforce each other. Thus, dysfunction of Na+/K+-ATPase as a single mechanism can explain the different skeletal muscle symptoms of severely ill ME/CFS patients, comprising loss of force, fatigue, and fasciculations.

Source: Wirth KJ, Steinacker JM. The potential causes of myasthenia and fasciculations in severely ill ME/CFS patients: the role of disturbed electrophysiology. Front Physiol. 2026 Feb 2;16:1693589. doi: 10.3389/fphys.2025.1693589. PMID: 41705124; PMCID: PMC12907180. https://pmc.ncbi.nlm.nih.gov/articles/PMC12907180/ (Full text)

An Overview of Severe Myalgic Encephalomyelitis

Abstract:

In this article, we have reviewed the literature on severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a clinical diagnosis in the absence of a diagnostic test. However, in research settings and disability disputes, 2-day cardiopulmonary exercise testing can be used to diagnose and document the abnormal response to exercise. Biomedical research into this disease has been scarce and underfunded for decades. Consequently, there are no effective treatments.

In its most severe form, it is more disabling than many other diseases, and patients are bedbound 24/7, dependent on carers, and spend their days in dark and quiet rooms. Even the soft sound of a human voice can lead to further deterioration. Some of the very severely ill suffer from life-threatening malnutrition and need to be tube-fed. The COVID-19 pandemic has led to a sharp increase in the number of patients with post-infectious diseases, and many of them fulfill ME/CFS criteria.

Dedicated, focused research using advanced medical technologies is needed to gain further understanding of the underlying disease mechanism. This will enable us to find effective pharmacological treatments and address the unmet medical needs of these very ill people.

Source: Vink M, Vink-Niese A. An Overview of Severe Myalgic Encephalomyelitis. J Clin Med. 2026 Jan 19;15(2):805. doi: 10.3390/jcm15020805. PMID: 41598742. https://www.mdpi.com/2077-0383/15/2/805 (Full text)

A patient perspective on enduring symptoms – the unmet need

Abstract:

This short paper illustrates the lived experience of individuals with severe enduring symptoms: chronic, often debilitating conditions for which no clear medical explanation currently exists. Drawing on qualitative interviews, the paper highlights the profound suffering, isolation, and lack of medical support experienced by this underserved population. It examines the systemic barriers to care, including stigma, the absence of follow-up services, and the traumatising nature of some healthcare encounters, which can lead to healthcare avoidance even in the face of potentially life-threatening symptoms. It concludes with a call for improved training for clinicians, increased capacity within NHS services, and ring-fenced funding for biomedical research.
Source: Katharine Cheston. A patient perspective on enduring symptoms – the unmet need. Future Healthcare Journal: Volume 12, Issue 4, 2025, 100465. ISSN 2514-6645. https://doi.org/10.1016/j.fhj.2025.100465. https://www.sciencedirect.com/science/article/pii/S2514664525002462 (Full text)

Contested and neglected: Social and medical marginalization in severe Chronic Fatigue Syndrome

Highlights:

  • Severe ME/CFS patients face deep social, medical, and structural exclusion.
  • Delegitimation of illness leads to isolation, distress, and denied support.
  • Gendered stigma shapes how women’s pain is dismissed in health care.
  • Twitter (now X) offers access to the voices of an otherwise unreachable patient group.
  • This study urges reforms in care, disability access, and illness recognition.

Abstract:

This study addresses the persistent invisibility of people with severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in research by centering their voices and examining how social and institutional forces shape their lives. As a medically contested illness, ME/CFS—especially in its severe form—renders patients both physically incapacitated and socially invisible.
Drawing on qualitative content analysis of 342 tweets under the hashtag #severeME, we identify how contested legitimacy, gendered stigma, and systemic marginalization structure the daily realities of 161 individuals with severe ME/CFS or their caregivers. Our findings highlight profound functional debilitation, emotional isolation, and exclusion from care and disability systems. We argue for the urgent need to legitimize contested illnesses, reform models of care, and extend disability protections to restore dignity and support to this neglected population.
Source: Bita Nezamdoust, Erin Ruel. Contested and neglected: Social and medical marginalization in severe Chronic Fatigue Syndrome. Social Science & Medicine, Volume 388, 2026, 118766. ISSN 0277-9536. https://www.sciencedirect.com/science/article/pii/S0277953625010974 (Full text)

Severe COVID-19 induces prolonged elevation of the acute-phase protein pentraxin 3

Abstract:

Introduction: During the acute-phase of COVID-19, elevated levels of several acute-phase proteins, such as C-reactive protein (CRP), mannose-binding lectin (MBL), pentraxin 3 (PTX-3), serum amyloid A (SAA) and surfactant protein D (SP-D), are associated with severe to fatal clinical outcomes. Typically, these markers return to baseline within days after resolution of the acute infection.

Methods: In this study, we assessed the plasma levels of these proteins in a well-defined cohort of 141 COVID-19 convalescent patients 10 weeks after infection and compared them to 98 non-infected controls. In addition, we performed genetic analyses in a subgroup of patients and related the findings with structural equation modelling to disease severity.

Results: In contrast to other acute-phase proteins, PTX-3 levels were significantly higher in severe COVID-19 convalescent patients than in the control group. Furthermore, a higher proportion of patients with severe COVID-19 exhibited PTX-3 levels above 5000 pg/ml even 10 months post-infection, compared to those with mild disease. To explore potential genetic influences, a genetic analysis was performed on all severely affected patients (n=36) and on an age- and sex-matched subset of mild COVID-19 patients (n=38). Results revealed a significantly higher frequency (p<0.0001) of the homozygous wildtype genotype of the PTX-3 SNP rs971145291 in severe (15 out of 36) versus mild (1 out of 38) COVID-19 patients. Using structural equation modelling, the association of this PTX-3 genotype and disease severity was shown to be mediated by elevated PTX-3 levels, with no contribution from other analyzed (clinical) confounders.

Discussion: In summary, severe COVID-19 patients show high PTX-3 serum levels which may be influenced by genetic predisposition, specifically the absence of the rs971145291 SNP variant. PTX-3 may thus serve both as a biomarker for tissue damage and/or long-term immune activation and eventually post-COVID-19 complications.

Source: Kratzer B, Stieger RB, Durmus S, Trapin D, Gattinger P, Ettel P, Sehgal ANA, Borochova K, Dorofeeva Y, Tulaeva I, Grabmeier-Pfistershammer K, Tauber PA, Gerdov M, Perkmann T, Fae I, Wenda S, Kundi M, Wrighton S, Fischer GF, Valenta R, Pickl WF. Severe COVID-19 induces prolonged elevation of the acute-phase protein pentraxin 3. Front Immunol. 2025 Oct 1;16:1672485. doi: 10.3389/fimmu.2025.1672485. PMID: 41103408; PMCID: PMC12520919. https://pmc.ncbi.nlm.nih.gov/articles/PMC12520919/ (Full text)

Specialised care for severely affected ME/CFS patients

Abstract:

Introduction: A specialised care unit for severely and very severely ill ME/CFS patients opened in 2021. The results from the first 3 years are reported.

Methods: People with ME/CFS who were diagnosed according to the Canadian Consensus Criteria, who are aged 18 or above with severe or very severe ME/CFS according to the UK NICE guidelines, are eligible to stay at Røysumtunet. The study design is a retrospective review of medical records.

Results: Between June 2021 and June 2024, 24 ME/CFS patients, 20 women and 4 men with a confirmed diagnosis of ME, were admitted to the unit for stays of at least 3 months. Seventeen were very severely affected and 7 were severely affected. Ages ranged from 18 to 68 years, with mean (SD) 37.5 (12.8) years. Seven patients showed significant improvement (p < 0.01), and five others showed some improvement. In total 50% improved (p < 0.01). Patients who improved were borderline significantly younger than those who did not, with a mean age of 30.3 (SD 12.6) years compared to 39.8 (SD 11.8) years (p = 0.06). The mean duration of disease was 2.3 (1.3) years for those who improved versus 6.7 (3.9) years for those who did not improve (p < 0.05).

Conclusion: This is the first report of a specialised care unit for the most severely ill ME/CFS patients. Fifty per cent of patients showed significant or partial improvement. The mechanisms behind these improvements are discussed but require further exploration in future studies.

Source: Saugstad, O. D., Sollie, M. G., Torp, H. A., & Storla, D. G. (2025). Specialised care for severely affected ME/CFS patients. Fatigue: Biomedicine, Health &amp; Behavior, 1–13. https://doi.org/10.1080/21641846.2025.2565101 https://www.tandfonline.com/doi/full/10.1080/21641846.2025.2565101 (Full text)

Patients with severe ME/CFS deserve better than unproven theories

Rapid Response:

Patients with severe ME/CFS deserve better than unproven theories

Dear Editor

Miller et al argue that chronic fatigue conditions are “a dysfunctional biological response orchestrated in the brain, influenced by expectations and conditioned responses,” and as a result, even people with severe ME/CFS can recover by “reframing beliefs about illness, along with specialist rehabilitation.”

Interventions based on this model have been tested in randomised trials in people since the 1990s in people with mild to moderate symptoms. Many of the participants would not have had ME/CFS as currently diagnosed, which carries a higher risk of harm from exertion. [1-3] Even in that easier context, short-term effects have been negligible or modest, without longterm benefits. Harms were not thoroughly studied. [1-3] This does not amount to strong evidence of substantial symptomatic improvement, let alone disease modification or full recovery.

Miller et al offer no direct strong evidence to support their claim that with their approach, “even those with severe ME/CFS can recover.” They cite the experience of a unit in Leeds, based on charts of discharged patients from a quality assurance report, where no patients were rated as “not at all ill” on discharge. [4] This kind of data is not defined as research, intended to be generalisable to other patients. [5] It was a very small group, too: Only six of the patients in that report had the diagnosis ME/CFS.

The weight of the authors’ argument, then, relies on their pathophysiologic rationale, which does not account for the full range of physical impacts of the illness. They point to other literature positing similar hypotheses, but these theories remain unproven. The pathophysiology of ME/CFS remains uncertain, [1-3] and it is not even clear that there is just one type of ME/CFS with the same underlying mechanisms. [6] Heterogeneous results in studies that have attempted to establish a core part of the model – that activity level and biological impairment are related – may be related to varying diagnostic criteria. [7]

Medicine has a long history of ascribing beliefs and/or responses to stress as the cause of diseases that were not yet fully understood. It wasn’t all that long ago that asthma, rheumatoid arthritis, and peptic ulcers fell into this category. [8] It’s been proven wrong so often now, we should be highly skeptical of these theories.

Perhaps part of why psychologically-based rationales for disease can be widely accepted is because the harm this can do is underappreciated. Miller et al argued that their narrative inspires hope, and people with severe ME/CFS deserve that. But when the unproven theory can’t deliver on the claims, what then? In a study Miller et al cited, researchers found that being told the disease was psychosomatic was the most common reason for suicidal thoughts for people with ME/CFS. [9] It’s not the first study to suggest that being told they are effectively to blame for not recovering is a contributing factor to the increased risk of suicidality in people with ME/CFS. [10]

A critical part of hope for people suffering illness is being able to trust that the medical community will work objectively to find better treatments and ways to support them, rather than promote unproven theories. People with ME/CFS deserve better than being told that their minds can overcome what’s the matter with their bodies – if only they try hard enough, for long enough.

References

1. National Institute for Health and Care Excellence. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. 29 Oct 2021. https://www.nice.org.uk/guidance/ng206

2. Chou R, McDonagh M, Griffin JC, Grusing S. Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): An Updated Systematic Evidence Review prepared for Centers for Disease Control and Prevention. 2022. https://stacks.cdc.gov/view/cdc/156092

3. Institute for Quality and Efficiency in Health Care (IQWiG). Current scientific knowledge on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). 2023. https://www.iqwig.de/en/projects/n21-01.html

4. Leeds and York Partnership NHS Foundation Trust. National Inpatient Centre for Psychological Medicine: annual review 2020-21. May 2021. https://www.leedsandyorkpft.nhs.uk/our-services/wp-content/uploads/sites…

5. Health Research Authority. Defining research. October 2022. https://www.hra-decisiontools.org.uk/research/docs/DefiningResearchTable…

6. Bastos VC, Greene KA, Tabachnikova A, et al. Cerebrospinal fluid immune phenotyping reveals distinct immunotypes of myalgic encephalomyelitis/chronic fatigue syndrome. J Immunol 2025;vkaf087. doi:10.1093/jimmun/vkaf087 pmid:40373264

7. Sunnquist M, Jason LA. A reexamination of the cognitive behavioral model of chronic fatigue syndrome. J Clin Psychol 2018;74:7. doi:10.1002/jclp.22593 pmid:29457646

8. Hange D, Bengtsson C, Sundh V, Bjorkelund. The natural history of psychosomatic symptoms and their association with psychological symptoms: Observations from the Population Study of Women in Gothenburg. Eur J Gen Pract 2007;13:2. doi:10.1080/13814780701377497 pmid:17534741

9. König RS, Paris DH, Sollberger M, Tschopp R. Identifying the mental health burden in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients in Switzerland: A pilot study. Heliyon 2024;10:e27031. doi:10.1016/j.heliyon.2024.e27031 pmid:3843435

10. Chu L, Elliott M, Stein E, Jason LA. Identifying and managing suicidality in Myalgic Encephalitis/Chronic Fatigue Syndrome. Healthcare (Basel) 2021;9:6. doi:10.3390/healthcare9060629 pmid:34070367

Source: Hilda Bastian. BMJ 2025;389:r977 https://www.bmj.com/content/389/bmj.r977/rr-30

Reframing beliefs about their illness does not lead to recovery of tube-fed patients with very severe ME/CFS. Analysis of the BMJ article by Miller et al

Abstract:

The narrative which is presented by Miller et al. as new, has dominated the field of ME/CFS for the last 35 years. It has been tested by numerous studies and has been found to be ineffective and harmful, as concluded by for example NICE in 2021. Additionally, it does not lead to objective improvement and it has a negative instead of a positive effect on work and disability status.

What has happened over the last 35 years is that severely ill patients have been ridiculed, gaslit and ignored by the medical profession. These patients have lost hope in the part of the medical profession which has been instrumental in doing and promoting that. They have not lost hope to recover and they are all hoping to get effective pharmacological treatments sooner rather than later as changing their mindset does not lead to recovery. And if it does, then the diagnosis of ME/CFS was simply wrong.

Source: Vink, Mark and Vink-Niese, Friso, Reframing beliefs about their illness does not lead to recovery of tube-fed patients with very severe ME/CFS. Analysis of the BMJ article by Miller et al. (June 06, 2025). No., Available at SSRN: https://ssrn.com/abstract=5284667 https://papers.ssrn.com/sol3/papers.cfm?abstract_id=5284667 (Full text available as PDF file)

The Implications and Predictability of Sleep Reversal for People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Machine Learning Approach

Abstract:

Background/objectives: Impaired sleep is one of the core symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), yet the mechanisms and impact of sleep-related issues are poorly understood. Sleep dysfunctions for patients with ME/CFS include frequent napping, difficulties falling asleep, waking up early, and sleep reversal patterns (e.g., sleeping throughout the day and staying awake throughout the night). The current study focuses on sleep reversal for patients with ME/CFS.

Methods: We explored the symptoms and functional impairment of those with and without sleep reversal by analyzing the responses of a large international sample (N = 2313) using the DePaul Symptom Questionnaire (DSQ) and Medical Outcomes Study 36-item Short-Form Health Survey (SF-36).

Results: We found that those in our Sleep Reversal group (N = 327) compared to those without sleep reversal (N = 1986) reported higher symptom burden for 53 out of 54 DSQ symptoms and greater impairments for all six SF-36 subscales. The most accurate predictors of sleep reversal included age (p < 0.05), body mass index (p < 0.05), eleven DSQ symptoms (p < 0.01), and two SF-36 subscales (p < 0.01).

Conclusions: These features provide clues regarding some of the possible pathophysiological underpinnings of sleep reversal among those with ME/CFS.

Source: Dietrich MP, Pravin R, Furst J, Jason LA. The Implications and Predictability of Sleep Reversal for People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Machine Learning Approach. Healthcare (Basel). 2025 May 26;13(11):1255. doi: 10.3390/healthcare13111255. PMID: 40508869. https://www.mdpi.com/2227-9032/13/11/1255 (Full text)

Prevalence of EBV, HHV6, HCMV, HAdV, SARS-CoV-2, and Autoantibodies to Type I Interferon in Sputum from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Abstract:

An exhausted antiviral immune response is observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-SARS-CoV-2 syndrome, also termed long COVID. In this study, potential mechanisms behind this exhaustion were investigated.

First, the viral load of Epstein-Barr virus (EBV), human adenovirus (HAdV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV6), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was determined in sputum samples (n = 29) derived from ME/CFS patients (n = 13), healthy controls (n = 10), elderly healthy controls (n = 4), and immunosuppressed controls (n = 2). Secondly, autoantibodies (autoAbs) to type I interferon (IFN-I) in sputum were analyzed to possibly explain impaired viral immunity.

We found that ME/CFS patients released EBV at a significantly higher level compared to controls (p = 0.0256). HHV6 was present in ~50% of all participants at the same level. HAdV was detected in two cases with immunosuppression and severe ME/CFS, respectively. HCMV and SARS-CoV-2 were found only in immunosuppressed controls. Notably, anti-IFN-I autoAbs in ME/CFS and controls did not differ, except in a severe ME/CFS case showing an increased level.

We conclude that ME/CFS patients, compared to controls, have a significantly higher load of EBV. IFN-I autoAbs cannot explain IFN-I dysfunction, with the possible exception of severe cases, also reported in severe SARS-CoV-2. We forward that additional mechanisms, such as the viral evasion of IFN-I effect via the degradation of IFN-receptors, may be present in ME/CFS, which demands further studies.

Source: Hannestad U, Allard A, Nilsson K, Rosén A. Prevalence of EBV, HHV6, HCMV, HAdV, SARS-CoV-2, and Autoantibodies to Type I Interferon in Sputum from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Viruses. 2025 Mar 14;17(3):422. doi: 10.3390/v17030422. PMID: 40143349; PMCID: PMC11946815. https://pmc.ncbi.nlm.nih.gov/articles/PMC11946815/ (Full text)