Clinical Profile and Aspects of Differential Diagnosis in Patients with ME/CFS from Latvia

Abstract:

Background and objectives: There is still an uncertainty regarding the clinical symptomatology and the diagnostic criteria in terms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), as different diagnostic criteria exist. Our aim is to identify the core symptoms of ME/CFS in the outpatient setting in Riga; to distinguish symptoms in patients with ME/CFS and those with symptoms of fatigue; and to investigate patient thoughts on the onset, symptoms, treatment and effect of ME/CFS.

Materials and methods: Total of 65 Caucasian patients from an ambulatory care setting were included in the study. Questionnaires, specialist evaluation of the patients and visual analogue scale (VAS) measurements were used to objectify the findings.

Results: The study showed that ME/CFS with comorbidities is associated with a more severe disease. A negative correlation was found regarding an increase in age and number of current symptoms, as well as an increase in VAS score and the duration of fatigue and age in the ME/CFS without comorbidities group.

Conclusions: Comorbidities tend to present with a more severe course of ME/CFS. Fatigue, myalgia, arthralgia and sleep disturbances tend to be more prevalent in the ME/CFS patients compared to the non-ME/CFS patients. VAS score has a tendency to decrease with age and duration of fatigue. Nonsteroidal anti-inflammatory drugs are the most commonly used pharmacological drug class that reduces ME/CFS symptoms.

Source: Krumina A, Vecvagare K, Svirskis S, Gravelsina S, Nora-Krukle Z, Gintere S, Murovska M. Clinical Profile and Aspects of Differential Diagnosis in Patients with ME/CFS from Latvia. Medicina (Kaunas). 2021 Sep 11;57(9):958. doi: 10.3390/medicina57090958. PMID: 34577881. https://pubmed.ncbi.nlm.nih.gov/34577881/

An Audit of UK Hospital Doctors’ Knowledge and Experience of Myalgic Encephalomyelitis

Abstract:

Background and Objectives: There is some evidence that knowledge and understanding of ME among doctors is limited. Consequently, an audit study was carried out on a group of hospital doctors attending a training event to establish how much they knew about ME and their attitudes towards it.

Materials and Methods: Participants at the training event were asked to complete a questionnaire, enquiring about prior knowledge and experience of ME and their approaches to diagnosis and treatment. A total of 44 completed questionnaires were returned. Responses were tabulated, proportions selecting available options determined, 95% confidence limits calculated, and the significance of associations determined by Fisher’s exact test.

Results: Few respondents had any formal teaching on ME, though most had some experience of it. Few knew how to diagnose it and most lacked confidence in managing it. None of the respondents who had had teaching or prior experience of ME considered it a purely physical illness. Overall, 91% of participants believed ME was at least in part psychological. Most participants responded correctly to a series of propositions about the general epidemiology and chronicity of ME. There was little knowledge of definitions of ME, diagnosis, or of clinical manifestations. Understanding about appropriate management was very deficient. Similarly, there was little appreciation of the impact of the disease on daily living or quality of life. Where some doctors expressed confidence diagnosing or managing ME, this was misplaced as they were incorrect on the nature of ME, its diagnostic criteria and its treatment.

Conclusion: This audit demonstrates that most doctors lack training and clinical expertise in ME. Nevertheless, participants recognised a need for further training and indicated a wish to participate in this. It is strongly recommended that factually correct and up-to-date medical education on ME be made a priority at undergraduate and postgraduate levels. It is also recommended that this audit be repeated following a period of medical education.

Source: Hng KN, Geraghty K, Pheby DFH. An Audit of UK Hospital Doctors’ Knowledge and Experience of Myalgic Encephalomyelitis. Medicina (Kaunas). 2021 Aug 27;57(9):885. doi: 10.3390/medicina57090885. PMID: 34577808. https://pubmed.ncbi.nlm.nih.gov/34577808/

Complement Component C1q as a Potential Diagnostic Tool for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subtyping

Abstract:

Background: Routine blood analytics are systematically used in the clinic to diagnose disease or confirm individuals’ healthy status. For myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disease relying exclusively on clinical symptoms for its diagnosis, blood analytics only serve to rule out underlying conditions leading to exerting fatigue. However, studies evaluating complete and large blood datasets by combinatorial approaches to evidence ME/CFS condition or detect/identify case subgroups are still scarce.

Methods: This study used unbiased hierarchical cluster analysis of a large cohort of 250 carefully phenotyped female ME/CFS cases toward exploring this possibility.

Results: The results show three symptom-based clusters, classified as severe, moderate, and mild, presenting significant differences (p < 0.05) in five blood parameters. Unexpectedly the study also revealed high levels of circulating complement factor C1q in 107/250 (43%) of the participants, placing C1q as a key molecule to identify an ME/CFS subtype/subgroup with more apparent pain symptoms.

Conclusions: The results obtained have important implications for the research of ME/CFS etiology and, most likely, for the implementation of future diagnosis methods and treatments of ME/CFS in the clinic.

Source: Castro-Marrero J, Zacares M, Almenar-Pérez E, Alegre-Martín J, Oltra E. Complement Component C1q as a Potential Diagnostic Tool for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subtyping. J Clin Med. 2021 Sep 15;10(18):4171. doi: 10.3390/jcm10184171. PMID: 34575280. https://pubmed.ncbi.nlm.nih.gov/34575280/

Evaluation of Immune Dysregulation in an Austrian Patient Cohort Suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe multi-systemic disease characterized by debilitating fatigue that is not relieved by rest. The causes of the disease are still largely unexplained, and no causative treatment is currently available. Changes in the immune response are considered as fundamental in the development of ME/CFS. Thus, we aimed to evaluate the immunological profile of ME/CFS patients in a retrospective data analysis.

As part of the routine workup for ME/CFS patients, a differential blood count, leukocyte subtyping, and quantification of immunoglobulins and IgG subclasses, as well as a complement analysis, was performed. Out of 262 ME/CFS patients, 64.9% had a reduction or deficiency in at least one of the listed immune parameters. In contrast, 26.3% showed signs of immune activation or inflammation. A total of 17.6% of the ME/CFS patients had an unclassified antibody deficiency, with IgG3 and IgG4 subclass deficiencies as the most common phenotypes. Reduced MBL (mannose-binding lectin) levels were found in 32% of ME/CFS patients, and MBL deficiency in 7%.

In summary, the present results confirmed the relevance of immune dysfunction in ME/CFS patients underlining the involvement of a dysfunctional immune response in the disease. Thus, immune parameters are relevant disease biomarkers, which might lead to targeted therapeutic approaches in the future.

Source: Lutz L, Rohrhofer J, Zehetmayer S, Stingl M, Untersmayr E. Evaluation of Immune Dysregulation in an Austrian Patient Cohort Suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Biomolecules. 2021 Sep 14;11(9):1359. doi: 10.3390/biom11091359. PMID: 34572574. https://pubmed.ncbi.nlm.nih.gov/34572574/

Turning a Corner in ME/CFS Research

Abstract:

This collection of research papers addresses fundamental questions concerning the nature of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS), the problem of disbelief and lack of knowledge and understanding of the condition among many doctors and the origins of this problem, and its impact on patients and their families. We report briefly the growing knowledge of the underlying pathological processes in ME/CFS, and the development of new organizations, including Doctors with ME, the US ME/CFS Clinical Coalition and EUROMENE, to address aspects of the challenges posed by the illness. We discuss the implications of COVID-19, which has much in common with ME/CFS, with much overlap of symptoms, and propose a new taxonomic category, which we are terming post-active phase of infection syndromes (PAPIS) to include both.
This collection of papers includes a number of papers reporting similar serious impacts on the quality of life of patients and their families in various European countries. The advice of EUROMENE experts on diagnosis and management is included in the collection. We report this in light of guidance from other parts of the world, including the USA and Australia, and in the context of current difficulties in the UK over the promulgation of a revised guideline from the National Institute for Health and Care Excellence (NICE). We also consider evidence on the cost-effectiveness of interventions for ME/CFS, and on the difficulties of determining the costs of care when a high proportion of people with ME/CFS are never diagnosed as such.
The Special Issue includes a paper which is a reminder of the importance of a person-centred approach to care by reviewing mind–body interventions. Finally, another paper reviews the scope for prevention in minimizing the population burden of ME/CFS, and concludes that secondary prevention, through early detection and diagnosis, could be of value.
Source: Pheby DFH, Friedman KJ, Murovska M, Zalewski P. Turning a Corner in ME/CFS Research. Medicina. 2021; 57(10):1012. https://doi.org/10.3390/medicina57101012  https://www.mdpi.com/1648-9144/57/10/1012 (Full article available as PDF file)

Induced pluripotent stem cells as suitable sensors for fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: Fibromyalgia (FM) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are devastating metabolic neuroimmune diseases that are difficult to diagnose because of the presence of numerous symptoms and a lack of specific biomarkers. Despite patient heterogeneity linked to patient subgroups and variation in disease severity, anomalies are found in the blood and plasma of these patients when compared with healthy control groups. The seeming specificity of these “plasma factors”, as recently reported by Ron Davis and his group at Stanford University, CA, United States, and observations by our group, have led to the proposal that induced pluripotent stem cells (iPSCs) may be used as metabolic sensors for FM and ME/CFS, a hypothesis that is the basis for this in-depth review.

Aim: To identify metabolic signatures in FM and/or ME/CFS supporting the existence of disease-associated plasma factors to be sensed by iPSCs.

Methods: A PRISMA (Preferred Reported Items for Systematic Reviews and Meta-analysis)-based systematic review of the literature was used to select original studies evaluating the metabolite profiles of FM and ME/CFS body fluids. The MeSH terms “metabolomic” or “metabolites” in combination with FM and ME/CFS disease terms were screened against the PubMed database. Only original studies applying omics technologies, published in English, were included. The data obtained were tabulated according to the disease and type of body fluid analyzed. Coincidences across studies were searched and P-values reported by the original studies were gathered to document significant differences found in the disease groups.

Results: Eighteen previous studies show that some metabolites are commonly altered in ME/CFS and FM body fluids. In vitro cell-based assays have the potential to be developed as screening platforms, providing evidence for the existence of factors in patient body fluids capable of altering morphology, differentiation state and/or growth patterns. Moreover, they can be further developed using approaches aimed at blocking or reversing the effects of specific plasma/serum factors seen in patients. The documented high sensitivity and effective responses of iPSCs to environmental cues suggests that these pluripotent cells could form robust, reproducible reporter systems of metabolic diseases, including ME/CFS and FM. Furthermore, culturing iPSCs, or their mesenchymal stem cell counterparts, in patient-conditioned medium may provide valuable information to predict individual outcomes to stem-cell therapy in the context of precision medicine studies.

Conclusion: This opinion review explains our hypothesis that iPSCs could be developed as a screening platform to provide evidence of a metabolic imbalance in FM and ME/CFS.

Source: Monzón-Nomdedeu MB, Morten KJ, Oltra E. Induced pluripotent stem cells as suitable sensors for fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome. World J Stem Cells. 2021 Aug 26;13(8):1134-1150. doi: 10.4252/wjsc.v13.i8.1134. PMID: 34567431; PMCID: PMC8422931. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422931/ (Full article)

Evolving phenotypes of non-hospitalized patients that indicate long COVID

Abstract:

Background: For some SARS-CoV-2 survivors, recovery from the acute phase of the infection has been grueling with lingering effects. Many of the symptoms characterized as the post-acute sequelae of COVID-19 (PASC) could have multiple causes or are similarly seen in non-COVID patients. Accurate identification of PASC phenotypes will be important to guide future research and help the healthcare system focus its efforts and resources on adequately controlled age- and gender-specific sequelae of a COVID-19 infection.

Methods: In this retrospective electronic health record (EHR) cohort study, we applied a computational framework for knowledge discovery from clinical data, MLHO, to identify phenotypes that positively associate with a past positive reverse transcription-polymerase chain reaction (RT-PCR) test for COVID-19. We evaluated the post-test phenotypes in two temporal windows at 3-6 and 6-9 months after the test and by age and gender. Data from longitudinal diagnosis records stored in EHRs from Mass General Brigham in the Boston Metropolitan Area was used for the analyses. Statistical analyses were performed on data from March 2020 to June 2021. Study participants included over 96 thousand patients who had tested positive or negative for COVID-19 and were not hospitalized.

Results: We identified 33 phenotypes among different age/gender cohorts or time windows that were positively associated with past SARS-CoV-2 infection. All identified phenotypes were newly recorded in patients’ medical records 2 months or longer after a COVID-19 RT-PCR test in non-hospitalized patients regardless of the test result. Among these phenotypes, a new diagnosis record for anosmia and dysgeusia (OR 2.60, 95% CI [1.94-3.46]), alopecia (OR 3.09, 95% CI [2.53-3.76]), chest pain (OR 1.27, 95% CI [1.09-1.48]), chronic fatigue syndrome (OR 2.60, 95% CI [1.22-2.10]), shortness of breath (OR 1.41, 95% CI [1.22-1.64]), pneumonia (OR 1.66, 95% CI [1.28-2.16]), and type 2 diabetes mellitus (OR 1.41, 95% CI [1.22-1.64]) is one of the most significant indicators of a past COVID-19 infection. Additionally, more new phenotypes were found with increased confidence among the cohorts who were younger than 65.

Conclusions: The findings of this study confirm many of the post-COVID-19 symptoms and suggest that a variety of new diagnoses, including new diabetes mellitus and neurological disorder diagnoses, are more common among those with a history of COVID-19 than those without the infection. Additionally, more than 63% of PASC phenotypes were observed in patients under 65 years of age, pointing out the importance of vaccination to minimize the risk of debilitating post-acute sequelae of COVID-19 among younger adults.

Source: Estiri H, Strasser ZH, Brat GA, Semenov YR; Consortium for Characterization of COVID-19 by EHR (4CE), Patel CJ, Murphy SN. Evolving phenotypes of non-hospitalized patients that indicate long COVID. BMC Med. 2021 Sep 27;19(1):249. doi: 10.1186/s12916-021-02115-0. PMID: 34565368. https://pubmed.ncbi.nlm.nih.gov/34565368/

Electroacupuncture improves cognitive function by inhibiting NF-κB activity in rats with chronic fatigue syndrome

Abstract:

in English, Chinese

Objective: To observe the effect of electroacupuncture (EA) on the expression of NF-κB p65 in hippocampus and the morphology of hippocampus in rats with chronic fatigue syndrome (CFS), so as to explore its mechanism in improving cognitive dysfunction of CFS.

Methods: Forty-eight SD rats were randomly divided into control, model, EA and inhibitor groups (n=12 in each group). The CFS model was established by multi-factor compound stress stimulation method. Rats of the EA group received EA (50 Hz, 1 mA) at “Baihui” (GV20), Emotional Area I and bilateral Sensory Area for 30 min, once daily for 15 days. For rats in the inhibitor group, pyrrolidine dithiocarbamate (100 mg·kg-1·d-1) was injected intraperitoneally, once a day for 15 days. Learning and memory ability was evaluated by Morris water maze test. HE staining was used to observe the morphology of hippocampus. Western blot was used to determine the expression level of NF-κB p65 in hippocampus.

Results: After mode-ling, the general status score was increased （P<0.01）, the escape latency was prolonged(P<0.01), the times of crossing the platform was decreased(P<0.01), and the expression level of NF-κB p65 in hippocampus tissue was significantly increased (P<0.05) in the model group compared with the control group. Compared with the model group, the general status score was decreased （P<0.01）, the escape latency was shortened(P<0.01), the times of crossing the platform was increased(P<0.01), and the expression level of NF-κB p65 in hippocampus tissue was significantly decreased (P<0.05) in the EA and inhibitor groups. HE staining showed that in the model group, the hippocampal nerve cells were arranged disorderly, the structure was loose, and the number of apoptotic bodies and inflammatory cells was significantly increased. The degree of tissue damage of the EA and inhibitor groups was milder than that of the model group.

Conclusion: EA can improve the cognitive function in CFS rats, which may be associated with its effect in inhibiting the expression of NF-κB and reducing the inflammation response in hippocampus.

Source: Feng CW, Qu YY, Sun ZR, Wang YL, Zhang P, Wang QY, Lin WJ, Zhang L, Yang TS. [Electroacupuncture improves cognitive function by inhibiting NF-κB activity in rats with chronic fatigue syndrome]. Zhen Ci Yan Jiu. 2021 Sep 25;46(9):775-81. Chinese. doi: 10.13702/j.1000-0607.200827. PMID: 34558244. https://pubmed.ncbi.nlm.nih.gov/34558244/ [Article in Chinese]

The ‘medically unexplained symptoms’ syndrome concept and the cognitive-behavioural treatment model

Abstract:

The American Psychiatric Association’s, 2013 DSM-5 abandoned the use of the term ‘medically unexplained symptoms’ for non-neurological disorders. In the UK, treatments for various medical illnesses with unexplained aetiology, such as chronic fatigue syndrome, irritable bowel syndrome and fibromyalgia, continue to fall under an MUS umbrella with cognitive behavioural therapy promoted as a primary therapeutic approach. In this editorial, we comment on whether the MUS concept is a viable diagnostic term, the credibility of the cognitive-behavioural MUS treatment model, the necessity of practitioner training and the validity of evidence of effectiveness in routine practice.

Source: Scott MJ, Crawford JS, Geraghty KJ, Marks DF. The ‘medically unexplained symptoms’ syndrome concept and the cognitive-behavioural treatment model. J Health Psychol. 2021 Sep 23:13591053211038042. doi: 10.1177/13591053211038042. Epub ahead of print. PMID: 34554009. https://journals.sagepub.com/doi/10.1177/13591053211038042 (Full text)

Patient perceptions of infectious illnesses preceding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Objectives: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is often reported to be caused by an infectious agent. However, it is unclear whether one infectious agent might be the cause or whether there might be many different infectious agents. The objective of this study was to identify self-reported infectious illnesses associated with the onset of ME/CFS.

Methods: The present study involved data from multiple sites in several countries. 1773 individuals diagnosed with either ME, CFS or ME/CFS provided qualitative data concerning infectious triggers which were coded and classified for analysis.

Results: 60.3% of patients report a variety of infectious illnesses some time before onset of ME/CFS. The most frequently reported infectious illness was Mononucleosis, which occurred in 30% of infections. However, over 100 other infectious illnesses were mentioned.

Discussion: The findings suggest that many infectious agents might be associated with the onset of ME/CFS.

Source: Jason LA, Yoo S, Bhatia S. Patient perceptions of infectious illnesses preceding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Chronic Illn. 2021 Sep 20:17423953211043106. doi: 10.1177/17423953211043106. Epub ahead of print. PMID: 34541918. https://pubmed.ncbi.nlm.nih.gov/34541918/