Tag: biomarker

The role of clinical neurophysiology in the definition and assessment of fatigue and fatigability

Highlights:

  • Though a common symptom, fatigue is difficult to define and investigate, and occurs in a wide variety of disorders, with differing pathological causes.
  • This review aims to guide clinicians in how to approach fatigue and to suggest that neurophysiological tests may allow an understanding of its origin and severity.
  • The effectiveness of neurophysiological tests as cost-effective objective biomarkers for the assessment of fatigue has been summarised.

Abstract

Though a common symptom, fatigue is difficult to define and investigate, occurs in a wide variety of neurological and systemic disorders, with differing pathological causes. It is also often accompanied by a psychological component. As a symptom of long-term COVID-19 it has gained more attention.

In this review, we begin by differentiating fatigue, a perception, from fatigability, quantifiable through biomarkers. Central and peripheral nervous system and muscle disorders associated with these are summarised. We provide a comprehensive and objective framework to help identify potential causes of fatigue and fatigability in a given disease condition. It also considers the effectiveness of neurophysiological tests as objective biomarkers for its assessment. Among these, twitch interpolation, motor cortex stimulation, electroencephalography and magnetencephalography, and readiness potentials will be described for the assessment of central fatigability, and surface and needle electromyography (EMG), single fibre EMG and nerve conduction studies for the assessment of peripheral fatigability.

The purpose of this review is to guide clinicians in how to approach fatigue, and fatigability, and to suggest that neurophysiological tests may allow an understanding of their origin and interactions. In this way, their differing types and origins, and hence their possible differing treatments, may also be defined more clearly.

Source: Tankisi H, Versace V, Kuppuswamy A, Cole J. The role of clinical neurophysiology in the definition and assessment of fatigue and fatigability. Clin Neurophysiol Pract. 2023 Dec 18;9:39-50. doi: 10.1016/j.cnp.2023.12.004. PMID: 38274859; PMCID: PMC10808861. https://www.sciencedirect.com/science/article/pii/S2467981X23000367 (Full text)

Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/anti-pathogen agent in a retrospective case series

Highlights:

• Both Long COVID and ME/CFS are characterized by dysfunctional CD8 T-cells with severe deficiencies in their abilities to produce IFNγ and TNFα.

• In a small Long COVID and ME/CFS case series, patients’ immune deficiency and health improve during treatment period with a nebulized antioxidant, anti-pathogen and immune-modulatory pharmacological agent.

• This work provides evidence of a useful biomarker, CD8 T-cell dysfunction reminiscent of T cell exhaustion, that may assist diagnosis and have utility for tracking disease outcome during therapy, including response to a potential new treatment.

Abstract:

Background: Patients with post-acute sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (PASC, i.e., Long COVID) have a symptom complex highly analogous to many features of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggesting they may share some aspects of pathogenesis in these similar disorders. ME/CFS is a complex disease affecting numerous organ systems and biological processes and is often preceded by an infection-like episode. It is postulated that the chronic manifestations of illness may result from an altered host response to infection or inability to resolve inflammation, as is being reported in Long COVID. The immunopathogenesis of both disorders is still poorly understood. Here, we show data that suggest Long COVID and ME/CFS may be due to an aberrant response to an immunological trigger-like infection, resulting in a dysregulated immune system with CD8 T-cell dysfunction reminiscent of some aspects of T-cell clonal exhaustion, a phenomenon associated with oxidative stress. As there is an urgent need for diagnostic tools and treatment strategies for these two related disabling disorders, here, in a retrospective case series, we have also identified a potential nebulized antioxidant/anti-pathogen treatment that has evidence of a good safety profile. This nebulized agent is comprised of five ingredients previously reported individually to relieve oxidative stress, attenuate NF-κB signaling, and/or to act directly to inhibit pathogens, including viruses. Administration of this treatment by nebulizer results in rapid access of small doses of well-studied antioxidants and agents with anti-pathogen potential to the lungs; components of this nebulized agent are also likely to be distributed systemically, with potential to enter the central nervous system.

Methods and Findings: We conducted an analysis of CD8 T-cell function and severity of symptoms by self-report questionnaires in ME/CFS, Long COVID and healthy controls. We developed a CD8 T-cell functional assay, assessing CD8 T-cell dysfunction by intracellular cytokine staining (ICS) in a group of ME/CFS (n = 12) and Long COVID patients (n = 8), comparing to healthy controls (HC) with similar age and sex (n = 10). Magnet-enriched fresh CD8 T-cells in both patient groups had a significantly diminished capacity to produce both cytokines, IFNγ or TNFα, after PMA stimulation when compared to HC. The symptom severity questionnaire showed similar symptom profiles for the two disorders. Fortuitously, through a retrospective case series, we were able to examine the ICS and questionnaire data of 4 ME/CFS and 4 Long COVID patients in conjunction with their treatment (3–15 months). In parallel with the treatment pursued electively by participants in this retrospective case series, there was an increase in CD8 T-cell IFNγ and TNFα production and a decrease in overall self-reported symptom severity score by 54%. No serious treatment-associated side effects or laboratory anomalies were noted in these patients.

Conclusions: Here, in this small study, we present two observations that appear potentially fundamental to the pathogenesis and treatment of Long COVID and ME/CFS. The first is that both disorders appear to be characterized by dysfunctional CD8 T-cells with severe deficiencies in their abilities to produce IFNγ and TNFα. The second is that in a small retrospective Long COVID and ME/CFS case series, this immune dysfunction and patient health improved in parallel with treatment with an immunomodulatory, antioxidant pharmacological treatment with anticipated anti-pathogen activity. This work provides evidence of the potential utility of a biomarker, CD8 T-cell dysfunction, and suggests the potential for benefit from a new nebulized antioxidant/anti-pathogen treatment. These immune biomarker data may help build capacity for improved diagnosis and tracking of treatment outcomes during clinical trials for both Long COVID and ME/CFS while providing clues to new treatment avenues that suggest potential efficacy for both conditions.

Source: Gil, A., Hoag, G.E., Salerno, J.P., Hornig, M., Klimas, N., Selin, L.K. Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/antipathogen agent in a retrospective case series. Brain, Behavior, & Immunity – Health (2024), doi: https://doi.org/10.1016/j.bbih.2023.100720 https://www.sciencedirect.com/science/article/pii/S2666354623001345 (Full text)

Role of pharmacological activity of autoantibodies in ME/CFS

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a condition characterised by extreme fatigue, memory impairment, pain and other symptoms that vary from patient to patient. It affects about 0.9% of the population and is often triggered by an acute viral or bacterial infection, such as Epstein-Barr virus. The underlying physiological and molecular basis of ME/CFS is unknown, and no effective treatments exist.

One proposed mechanism is that the blood flow is altered by autoantibodies against receptors involved in blood flow regulation. Antibodies are generated by the immune system to recognise intruders and under normal conditions, our immune system is trained not to attack our own tissues. However, during a severe infection, the immune system adopts an “all hands on deck” approach, which results in some of the newly-produced antibodies escaping quality control and targeting our own tissues, autoantibodies. Receptors regulation blood flow are located in walls of blood vessels and cause a blood vessel to dilate or contract as the demand for oxygen and nutrients to tissues such as the brain or muscles changes. Research has found increased levels of these autoantibodies in ME/CFS patients and initial trials removing these autoantibodies from the blood using a technique called immunoadsorption have shown improvement in symptoms.

In this project, we will test the hypothesis that autoantibodies can activate or inhibit the receptors responsible for the blood flow regulation, in a similar way medical drugs are used to regulate blood pressure.
We aim to profile serum samples from 325 ME/CFS patients and 130 healthy individuals to determine the presence of autoantibodies against all thirty receptors involved in blood pressure regulation. Importantly, we will study the ability of autoantibodies detected in each sample to activate or inhibit these receptors in order to test the hypothesis that the activity of these autoantibodies is a decisive factor in the disease.
If our hypothesis is correct, we will be able to develop an accurate blood test that may be able to detect ME/CFS earlier or to independently confirm the diagnosis. Ultimately, we hope that these results may also indicate a possible route for therapeutic intervention to counteract the effects of autoantibodies and alleviate the ME/CFS symptoms using a combination of already existing drugs, specific for each individual case.

 

Technical Summary:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a condition of extreme tiredness and brain fog, often triggered by an acute infection. Its prevalence is ca 0.9% and here is no effective treatment. Competing theories for the root cause of ME/CFS include metabolic or redox homeostasis disruption, and presence of autoantibodies (AABs) against G protein coupled receptors (GPCRs) involved in regulation of blood flow.
Triggered by acute infection, autoimmunity is a result of reduced immuno-vigilance during severe infections, when an “all hands on deck” approach confers survival advantage. About 30% of ME/CFS patients show increased titre of autoantibodies against beta2-adrenoceptor and M3/4 muscarinic receptors controlling vasodilation/vasoconstriction, but this could become higher if all 30 receptors controlling blood flow would be taken into account.
In this project, we will test a hypothesis that the pharmacological activity of AABs against GPCRs is the key to their involvement in ME/CFS. Similar to medical drugs, AABs can be stimulatory (agonistic) or inhibitory (antagonistic) and induce a therapeutic or an undesired side effect.
We will profile 325 patient samples and 130 control plasma samples for AABs and their pharmacological activity using a state-of-the art GPCR drug screening pipeline we have established, against all 30 GPCRs involved in blood pressure regulation. We also have machine learning expertise that would allow us to interpret this extensive dataset, extract the most salient features. This will advance the understanding of the molecular basis of ME/CFS and could form the basis of a robust diagnostic blood test for ME/CFS. Ultimately, our findings may point in the direction of developing combination therapy using repurposed drugs to counteract the effects of autoantibodies and mitigate ME/CFS symptoms and stimulate the development of specific B-cell elimination strategy to cure ME/CFS.
Source: Lead Research Organisation: University of Nottingham, Department Name: School of Life Sciences. https://gtr.ukri.org/projects?ref=MR%2FY003667%2F1&pn=0&fetchSize=25&selectedSortableField=date&selectedSortOrder=ASC

Characterization of subgroups of myalgic encephalomyelitis/chronic fatigue syndrome based on disease onset, symptoms and biomarkers

Abstract:

Myalgic encephalomyelitis, also called chronic fatigue syndrome (ME/CFS), is an acquired multisystem disease. The core symptoms include fatigue, exercise intolerance and pain as well as cognitive, autonomic and immunological manifestations. The diagnosis of ME/CFS is based on clinical criteria. Specific biomarkers do not currently exist, but studies suggest a role for soluble cluster of differentiation 26 (sCD26) and autoantibodies (AAK) against G protein-coupled receptors (GPCR). In many cases, the disease begins as a result of infections. 

The aim of this work was to determine the pathophysiological significance of potential biomarkers, assuming different development mechanisms in patients with infection-associated disease onset compared to those with other triggers. In a first study, sCD26, also called dipeptidyl peptidase-4 (DPP-4) due to its enzymatic activity, was analyzed and compared in the serum of 205 ME/CFS patients and 98 controls. This was followed by a comprehensive correlation analysis between sCD26 and clinical and laboratory parameters for ME/CFS patients, separated by type of disease onset. In addition, CD26 expression on lymphocyte subpopulations was determined for 12 patients and 12 controls. 

In another study, a correlation analysis was carried out between AAK against vasoregulatory GPCR and symptoms in 116 ME/CFS patients, separated by type of disease onset. It was shown that in ME/CFS patients with infection-associated disease onset, sCD26 correlated with numerous immunological and metabolic parameters, the changes of which have also been described in connection with DPP-4 inhibitors. In addition, there were inverse correlations with AAK against alpha1-adrenergic and M3-acetylcholine receptors. 

In this subgroup, the second study found correlations between numerous GPCR-AAK and the severity of fatigue, muscle pain and cognitive symptoms as well as greater functional impairment relevant to everyday life. None of these correlations were found in patients without infection-associated disease onset. 

Here, sCD26 correlated inversely with orthostatically induced heart rate increases and AAK against alpha- and beta-adrenergic receptors with the severity of orthostatic symptoms. Different correlation patterns between AAK against GPCR and symptoms allow us to assume that in patients with ME/CFS, an altered function of the AAK or its receptors or signaling pathways has occurred as a result of an infection. The association of sCD26 and GPCR-AAK also indicates the dysregulation of other parts of the immune system with potentially pathological consequences. The differences presented compared to patients with non-infectious genesis suggest two definable subgroups.

Source: Szklarski, Marvin. Characterization of subgroups of myalgic encephalomyelitis/chronic fatigue syndrome based on disease onset, symptoms and biomarkers. Charité – University Medicine Berlin, dissertation. https://refubium.fu-berlin.de/handle/fub188/40276

Dysregulation of the Kynurenine Pathway, Cytokine Expression Pattern, and Proteomics Profile Link to Symptomology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Dysregulation of the kynurenine pathway (KP) is believed to play a significant role in neurodegenerative and cognitive disorders. While some evidence links the KP to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), further studies are needed to clarify the overall picture of how inflammation-driven KP disturbances may contribute to symptomology in ME/CFS.

Here, we report that plasma levels of most bioactive KP metabolites differed significantly between ME/CFS patients and healthy controls in a manner consistent with their known contribution to symptomology in other neurological disorders. Importantly, we found that enhanced production of the first KP metabolite, kynurenine (KYN), correlated with symptom severity, highlighting the relationship between inflammation, KP dysregulation, and ME/CFS symptomology.

Other significant changes in the KP included lower levels of the downstream KP metabolites 3-HK, 3-HAA, QUIN, and PIC that could negatively impact cellular energetics. We also rationalized KP dysregulation to changes in the expression of inflammatory cytokines and, for the first time, assessed levels of the iron (Fe)-regulating hormone hepcidin that is also inflammation-responsive. Levels of hepcidin in ME/CFS decreased nearly by half, which might reflect systemic low Fe levels or possibly ongoing hypoxia.

We next performed a proteomics screen to survey for other significant differences in protein expression in ME/CFS. Interestingly, out of the seven most significantly modulated proteins in ME/CFS patient plasma, 5 proteins have roles in maintaining gut health, which considering the new appreciation of how gut microbiome and health modulates systemic KP could highlight a new explanation of symptomology in ME/CFS patients and potential new prognostic biomarker/s and/or treatment avenues.

Source: Kavyani B, Ahn SB, Missailidis D, Annesley SJ, Fisher PR, Schloeffel R, Guillemin GJ, Lovejoy DB, Heng B. Dysregulation of the Kynurenine Pathway, Cytokine Expression Pattern, and Proteomics Profile Link to Symptomology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Mol Neurobiol. 2023 Nov 28. doi: 10.1007/s12035-023-03784-z. Epub ahead of print. PMID: 38015302. https://pubmed.ncbi.nlm.nih.gov/38015302/

Investigation into the Plasma Proteome Signature in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Background: ME/CFS is a complex disease with unclear etiology. Current diagnostic criteria lack objective laboratory measures.

Aims: This study aimed to investigate the plasma proteomic profile of ME/CFS patients and determine any differentially expressed proteins compared to controls.

Methods: Plasma samples obtained from 19 ME/CFS patients and 9 controls underwent analysis (Somalogic, Inc, CO). The ME/CFS patients met the National Academy of Medicine criteria for the disease. Samples were collected from a mixed venous compartment. Statistical analysis and a Mixed Graphical Model were used to identify candidate biomarker.

Results: Among ~7000 proteins detected, ~400 were differentially expressed between patients and controls (False Discovery Rate<0.05 and Absolute Fold Change ≥1.5). Selectin E (SELE), ATP Synthase Subunit F6 (ATP5PF), and Transcobalamin 2 (TCN2) were identified as top candidates. A classifier of these proteins in pulmonary artery blood of patients were distinguishable from controls (AUC =0.99).

Conclusion: The study highlighted potential biomarkers for ME/CFS, the top candidates of which are involved in inflammation, cellular energy metabolism, and Vitamin B12 transport. The plasma proteomic signature identifies ME/CFS from normals and suggests that the disease’s pathophysiology is driven by abnormalities of aerobic metabolism, vascular dysregulation, and Vitamin B12 metabolism.

Source: Johanna Squires, Sarra Al-Zayer, Peng Li, Wenzhong Xiao, David Systrom. Investigation into the Plasma Proteome Signature in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). European Respiratory Journal Sep 2023, 62 (suppl 67) PA2960; DOI: 10.1183/13993003.congress-2023.PA2960 https://erj.ersjournals.com/content/62/suppl_67/PA2960.abstract

Bioimpedance spectroscopy characterization of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) peripheral blood mononuclear cells

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling and chronic disease, importantly related to the current COVID-19 pandemic. Currently, there are no specific laboratory tests to directly diagnose ME/CFS. In this work, the use of impedance spectroscopy is studied as a potential technique for the diagnosis of ME/CFS. A specific device for the electrical characterization of peripheral blood mononuclear cells was designed and implemented.

Impedance spectroscopy measurements in the range from 1 Hz to 500 MHz were carried out after the osmotic stress of the samples with sodium chloride solution at 1M concentration. The evolution in time after the osmotic stress at two specific frequencies (1.36 kHz and 154 kHz) was analyzed.

The device showed its sensitivity to the presence of cells and the evolution of the osmotic processes. Higher values of impedance (around 15% for both the real and imaginary part) were measured at 1.36 kHz in ME/CFS patients compared to control samples. No significant difference was found between patient samples and control samples at 154 kHz. Results help to further understand the diagnosis of ME/CFS patients and the relation of their blood samples with bioimpedance measurements.

Source: Sara Martinez Rodriguez, Alberto Olmo Fernandez, Daniel Martin Fernandez, Isabel Martin-Garrido. Bioimpedance spectroscopy characterization of Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) peripheral blood mononuclear cells. Biomedical Letters, Volume 9, Issue 2: 121-128. http://thesciencepublishers.com/biomed_lett/v9i2abstract6.html (Full text available as PDF file)

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)

THU581 Possible Markers For Myalgic Encephalomyelitis / Chronic Fatigue Syndrome Developed In Long Covid: Utility Of Serum Ferritin And Insulin-like Growth Factor-I

Abstract:

Almost three years have passed since coronavirus disease 2019 (COVID-19) pandemic broke out, and along with the number of acute COVID-19 patients, the number of patients suffering from chronic prolonged symptoms after COVID-19, long COVID, or post COVID-19 condition, has also increased.

We established an outpatient clinic specialized for COVID-19 after care (CAC) in Okayama University Hospital in Japan in February 2021. Our recent study has revealed that the most common symptom is “fatigue”, a part of which potentially may develop into myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, the pathogenesis and specific prognosticator have yet to be elucidated. The aim of this study was to elucidate the clinical characteristics of patients who developed ME/CFS after COVID-19.

This retrospective observational study investigated the patients who visited our CAC outpatient clinic between February 2021 and March 2022. Of the 234 patients, 139 (59.4%) had fatigue symptoms, of whom 50 (21.4%) met the criteria for ME/CFS (ME/CFS group), while other 89 did not (non-ME/CFS group); 95 patients had no fatigue complaints (no-fatigue group). Although the patients’ backgrounds were not significantly different among the three groups, the ME/CFS group presented the highest scores on the self-rating symptom scales, including the Fatigue Assessment Scale (FAS), EuroQol, and Self-Rating Depression Scale (SDS).

Of note, serum ferritin levels, which were correlated to FAS and SDS scores, were significantly higher in the ME/CFS group (193.0 μg/mL; interquartile range (IQR), 58.8-353.8) than those of non-ME/CFS (98.2 μg/mL; 40.4-251.5) and no-fatigue (86.7 μg/mL; 37.5-209.0) groups, and this trend was prominent in the female patients. Endocrine workup further showed that the ME/CFS group had higher thyrotropin levels but lower growth hormone levels in the serum, and that insulin-like growth factor (IGF)-I levels were inversely correlated with ferritin levels (R = -0.328, p < 0.05).

Collectively, we revealed that serum ferritin levels could be a possible predictor for developing ME/CFS related to long COVID, especially in female patients. Earlier studies have suggested that hyperferritinemia is a clinical feature in the patients of long COVID, in which hepcidin-like effects could also be involved. Our present study also uncovered a relationship between hyperferrinemia and endocrine disorders among patients developing ME/CFS after COVID-19, although further investigations are necessary to understand the characteristics of ferritin metabolism.

Presentation: Thursday, June 15, 2023

Source: Yukichika Yamamoto, Yuki Otsuka, Kazuki Tokumasu, Naruhiko Sunada, Yasuhiro Nakano, Hiroyuki Honda, Yasue Sakurada, Toru Hasegawa, Hideharu Hagiya, Fumio Otsuka, THU581 Possible Markers For Myalgic Encephalomyelitis / Chronic Fatigue Syndrome Developed In Long Covid: Utility Of Serum Ferritin And Insulin-like Growth Factor-I, Journal of the Endocrine Society, Volume 7, Issue Supplement_1, October-November 2023, bvad114.1370, https://doi.org/10.1210/jendso/bvad114.1370 (Full text available as PDF file)

Unsupervised cluster analysis reveals distinct subtypes of ME/CFS patients based on peak oxygen consumption and SF-36 scores

Abstract:

Purpose: Myalgic encephalomyelitis, commonly referred to as chronic fatigue syndrome (ME/CFS), is a severe, disabling chronic disease and an objective assessment of prognosis is crucial to evaluate the efficacy of future drugs. Attempts are ongoing to find a biomarker to objectively assess the health status of (ME/CFS), patients. This study therefore aims to demonstrate that oxygen consumption is a biomarker of ME/CFS provides a method to classify patients diagnosed with ME/CFS based on their responses to the Short Form-36 (SF-36) questionnaire, which can predict oxygen consumption using cardiopulmonary exercise testing (CPET).

Methods: Two datasets were used in the study. The first contained SF-36 responses from 2,347 validated records of ME/CFS diagnosed participants, and an unsupervised machine learning model was developed to cluster the data. The second dataset was used as a validation set and included the cardiopulmonary exercise test (CPET) results of 239 participants diagnosed with ME/CFS. Participants from this dataset were grouped by peak oxygen consumption according to Weber’s classification. The SF-36 questionnaire was correctly completed by only 92 patients, who were clustered using the machine learning model. Two categorical variables were then entered into a contingency table: the cluster with values {0,1} and Weber classification {A, B, C, D} were assigned. Finally, the Chi-square test of independence was used to assess the statistical significance of the relationship between the two parameters.

Findings: The results indicate that the Weber classification is directly linked to the score on the SF-36 questionnaire. Furthermore, the 36-response matrix in the machine learning model was shown to give more reliable results than the subscale matrix (p – value < 0.05) for classifying patients with ME/CFS.

Implications: Low oxygen consumption on CPET can be considered a biomarker in patients with ME/CFS. Our analysis showed a close relationship between the cluster based on their SF-36 questionnaire score and the Weber classification, which was based on peak oxygen consumption during CPET. The dataset for the training model comprised raw responses from the SF-36 questionnaire, which is proven to better preserve the original information, thus improving the quality of the model.

Source: Lacasa M, Launois P, Prados F, Alegre J, Casas-Roma J. Unsupervised cluster analysis reveals distinct subtypes of ME/CFS patients based on peak oxygen consumption and SF-36 scores. Clin Ther. 2023 Oct 4:S0149-2918(23)00352-1. doi: 10.1016/j.clinthera.2023.09.007. Epub ahead of print. PMID: 37802746. https://www.clinicaltherapeutics.com/article/S0149-2918(23)00352-1/fulltext (Full text)