Classification Accuracy and Description of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in an Integrated Health Care System, 2006-2017

Abstract:

Introduction: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic illness characterized by marked functional limitations and fatigue. Electronic health records can be used to estimate incidence of ME/CFS but may have limitations.

Methods: The authors used International Classification of Diseases (ICD) diagnosis codes to identify all presumptive cases of ME/CFS among 9- to 39-year-olds from 2006 to 2017. The authors randomly selected 200 cases for medical record review to classify cases as confirmed, probable, or possible, based on which and how many current clinical criteria they met, and to further characterize their illness. The authors calculated crude annual rates of ME/CFS coding stratified by age and sex using only those ICD codes that had identified confirmed, probable, or possible ME/CFS cases in the medical record review.

Results: The authors identified 522 individuals with presumptive ME/CFS based on having ≥ 1 ICD codes for ME/CFS in their electronic medical record. Of the 200 cases selected, records were available and reviewed for 188. Thirty (15%) were confirmed or probable ME/CFS cases, 39 (19%) were possible cases, 119 (60%) were not cases, and 12 (6%) had no medical record available. Confirmed/probable cases commonly had chronic pain (80%) or anxiety/depression (70%), and only 13 (43%) had completed a sleep study. Overall, 37 per 100,000 had ICD codes that identified confirmed, probable, or possible ME/CFS. Rates increased between 2006 and 2017, with the largest absolute increase among those 30-39 years old.

Conclusions: Using ICD diagnosis codes alone inaccurately estimates ME/CFS incidence.

Source: Liles EG, Irving SA, Koppolu P, Crane B, Naleway AL, Brooks NB, Gee J, Unger ER, Henninger ML. Classification Accuracy and Description of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in an Integrated Health Care System, 2006-2017. Perm J. 2024 Jun 19:1-12. doi: 10.7812/TPP/23.170. Epub ahead of print. PMID: 38980763. https://www.thepermanentejournal.org/doi/10.7812/TPP/23.170 (Full text)

Illness presentation and quality of life in myalgic encephalomyelitis/chronic fatigue syndrome and post COVID-19 condition: a pilot Australian cross-sectional study

Abstract:

Purpose: Post COVID-19 Condition (PCC), being persistent COVID-19 symptoms, is reminiscent of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-a chronic multi-systemic illness characterised by neurocognitive, autonomic, endocrinological and immunological disturbances. This novel cross-sectional investigation aims to: (1) compare symptoms among people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) to inform developing PCC diagnostic criteria; and (2) compare health outcomes between patients and people without acute or chronic illness (controls) to highlight the illness burdens of ME/CFS and PCC.

Methods: Sociodemographic and health outcome data were collected from n = 61 pwME/CFS, n = 31 pwPCC and n = 54 controls via validated, self-administered questionnaires, including the 36-Item Short-Form Health Survey version 2 (SF-36v2) and World Health Organization Disability Assessment Schedule version 2.0 (WHODAS 2.0). PwME/CFS and pwPCC also provided self-reported severity and frequency of symptoms derived from the Canadian and International Consensus Criteria for ME/CFS and the World Health Organization case definition for PCC.

Results: Both illness cohorts similarly experienced key ME/CFS symptoms. Few differences in symptoms were observed, with memory disturbances, muscle weakness, lymphadenopathy and nausea more prevalent, light-headedness more severe, unrefreshed sleep more frequent, and heart palpitations less frequent among pwME/CFS (all p < 0.05). The ME/CFS and PCC participants’ SF-36v2 or WHODAS 2.0 scores were comparable (all p > 0.05); however, both cohorts returned significantly lower scores in all SF-36v2 and WHODAS 2.0 domains when compared with controls (all p < 0.001).

Conclusion: This Australian-first investigation demonstrates the congruent and debilitating nature of ME/CFS and PCC, thereby emphasising the need for multidisciplinary care to maximise patient health outcomes.

Source: Weigel B, Eaton-Fitch N, Thapaliya K, Marshall-Gradisnik S. Illness presentation and quality of life in myalgic encephalomyelitis/chronic fatigue syndrome and post COVID-19 condition: a pilot Australian cross-sectional study. Qual Life Res. 2024 Jul 3. doi: 10.1007/s11136-024-03710-3. Epub ahead of print. PMID: 38961009. https://link.springer.com/article/10.1007/s11136-024-03710-3 (Full text)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating disease characterised by a wide range of symptoms that severely impact all aspects of life. Despite its significant prevalence, ME/CFS remains one of the most understudied and misunderstood conditions in modern medicine. ME/CFS lacks standardised diagnostic criteria owing to variations in both inclusion and exclusion criteria across different diagnostic guidelines, and furthermore, there are currently no effective treatments available.

Moving beyond the traditional fragmented perspectives that have limited our understanding and management of the disease, our analysis of current information on ME/CFS represents a significant paradigm shift by synthesising the disease’s multifactorial origins into a cohesive model. We discuss how ME/CFS emerges from an intricate web of genetic vulnerabilities and environmental triggers, notably viral infections, leading to a complex series of pathological responses including immune dysregulation, chronic inflammation, gut dysbiosis, and metabolic disturbances.

This comprehensive model not only advances our understanding of ME/CFS’s pathophysiology but also opens new avenues for research and potential therapeutic strategies. By integrating these disparate elements, our work emphasises the necessity of a holistic approach to diagnosing, researching, and treating ME/CFS, urging the scientific community to reconsider the disease’s complexity and the multifaceted approach required for its study and management.

Source: Arron HE, Marsh BD, Kell DB, Khan MA, Jaeger BR, Pretorius E. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease. Front Immunol. 2024 Jun 3;15:1386607. doi: 10.3389/fimmu.2024.1386607. PMID: 38887284; PMCID: PMC11180809. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11180809/ (Full text)

Examining well-being and cognitive function in people with long Covid and ME/CFS, and age-matched healthy controls: A Case-Case-Control Study

Abstract:

Purpose: Well-being and cognitive function had not previously been compared between people with long COVID and people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Therefore, this study examined well-being and cognitive function in people with long COVID (∼16 months illness duration; n= 17) and ME/CFS (∼16 years illness duration; n=24), versus age-matched healthy controls (n=16).

Methods: Well-being was examined using several questionnaires, namely the Health Visual Analogue Scale (VAS), Fatigue Severity Scale (FSS), Post-exertional malaise (PEM), Pittsburgh Sleep Quality Index (PSQI), European Quality of Life-5 Domains (EQ-5D), MRC Dyspnoea, Self-Efficacy (SELTC), The Edinburgh Neurosymptoms Questionnaire (ENS), General Anxiety Disorder 7 (GAD-7), and Patient Health Questionnaire 9 (PHQ-9). Cognitive function was examined using Single Digit Modalities Test (SDMT), Stroop test, and Trails A and B. These were delivered via a mobile application (app) built specifically for this remote data collection.

Results: The main findings of the present investigation were that people with ME/CFS and people with long COVID were generally comparable on all well-being and cognitive function measures, but self-reported worse values for pain, fatigue, Post-exertional malaise, sleep quality, general well-being in relation to mobility, usual activities, self-care, breathlessness, neurological symptoms, self-efficacy, and other well-being such as anxiety and depression, compared to controls. There was no effect of group for cognitive function measures.

Conclusions: These data suggest that both people with long COVID and people with ME/CFS have similar impairment on well-being measures examined herein. Therefore, interventions that target well-being of people with ME/CFS and long COVID are required.

Source: Sanal-Hayes NEM, Mclaughlin M, Hayes LD, Berry ECJ, Sculthorpe NF. Examining well-being and cognitive function in people with long Covid and ME/CFS, and age-matched healthy controls: A Case-Case-Control Study. Am J Med. 2024 May 13:S0002-9343(24)00273-0. doi: 10.1016/j.amjmed.2024.04.041. Epub ahead of print. PMID: 38750713. https://www.amjmed.com/article/S0002-9343(24)00273-0/fulltext (Full text)

Patients with Fibromyalgia Scored Worse in Memory, Attention, Cognitive Function

Press release:

A cross-sectional study demonstrated significant impairments in attention, memory, and higher cognitive functions among a cohort of patients with fibromyalgia and rheumatoid arthritis (RA), according to a study published in Psychology Research and Behavior Management.1

Investigators believe deficits in the fibromyalgia cohort could be explained by secondary symptoms coupled with more severe pain. A cognitive screening could help curate personalized treatment plans to improve the quality of life among patients with RA and fibromyalgia.

“Research directly comparing cognitive performance between patients with fibromyalgia and RA is still scarce. Some studies suggested deficits of similar magnitude in both patient groups,” wrote a group of investigators led by Carmen María Galvez Sánchez, PhD, associated with the Department of Personality, Evaluation and Psychological Treatment at the University of Murcia, Spain. “In response to this exigency, there is a requisite for the evaluation of cognitive impairments in individuals with chronic pain, aiming to formulate and implement interventions rooted in neuropsychological training. This approach is intended to ameliorate cognitive performance and mitigate its consequential impact on health-related quality of life.”

In certain patients with fibromyalgia, cognitive impairment was linked to clinical pain severity, depression, fatigue, insomnia, and anxiety. Similarly, these were also reported in patients with RA, although pain and emotional symptoms within the fibromyalgia cohort.2 Symptoms of fibromyalgia and RA often include depression, fatigue, insomnia, and cognitive issues.

Investigators analyzed the performance in cognitive domains between patients with RA and fibromyalgia using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Questionnaire scores were combined to determine the symptom severity factor, which was used as a control variable within the group comparisons.

A total of 64 patients with fibromyalgia, 34 patients with RA, and 32 healthy controls were included in the study. All patients were female.

Without controlling for the severity of symptoms, patients with either fibromyalgia or RA performed worse when compared with controls in terms of cognitive domains including verbal memory, visual memory, and strategic planning.

Additionally, over deficits were observed in the fibromyalgia cohort compared with RA. Patients with fibromyalgia reported more severe symptoms, such as pain intensity, total pain, anxiety, depression, insomnia, and fatigue, compared with patients with RA. After controlling for symptom severity a significant proportion of cognitive test, a large proportion of cognitive test parameters were not different between rheumatologic cohorts.

Limitations included the lack of information regarding the influence of psychotropic and pain medication on cognitive performance among rheumatic patients. Although the limitation could have been determined using subgroup analysis, the current sample size was too small to form these subgroups.

Further, no data on treatment and disease activity were collected in the RA subgroup and the analysis of the effects of clinical symptoms on cognitive performance was limited. Additionally, not all psychological factors that may impact cognition were assessed in the analysis. The generalizability of findings may be hindered as only women were included in the analysis and the recruitment of subjects was not randomly performed. Lastly, the RA and fibromyalgia diagnoses were performed by different rheumatologists, which may have introduced selection bias.

“Based on the present results, it is recommended that screening for cognitive deficits be part of routine diagnostics for fibromyalgia and RA, which may help to guide the design of personalized interventions to optimize cognitive performance of patients with fibromyalgia and RA,” investigators concluded.

Source: Lana Pine. HCP Live.

Research progress in the treatment of chronic fatigue syndrome through interventions targeting the hypothalamus-pituitary-adrenal axis

Abstract:

Chronic fatigue syndrome (CFS) causes great harm to individuals and society. Elucidating the pathogenesis of CFS and developing safe and effective treatments are urgently needed. This paper reviews the functional changes in the hypothalamus-pituitary-adrenal (HPA) axis in patients with CFS and the associated neuroendocrine mechanisms. Despite some controversy, the current mainstream research evidence indicates that CFS patients have mild hypocortisolism, weakened daily variation in cortisol, a weakened response to the HPA axis, and an increase in negative feedback of the HPA axis. The relationship between dysfunction of the HPA axis and the typical symptoms of CFS are discussed, and the current treatment methods are reviewed.

Source: Yi-Dan Zhang, Li-Na Wang. Research progress in the treatment of chronic fatigue syndrome through interventions targeting the hypothalamus-pituitary-adrenal axis. Front. Endocrinol., 09 April 2024, Sec. Neuroendocrine Science, Volume 15 – 2024 | https://doi.org/10.3389/fendo.2024.1373748 https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1373748/full

Imbalanced Brain Neurochemicals in long COVID and ME/CFS: A Preliminary Study using MRI

Abstract:

Purpose: Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients experience multiple complex symptoms, potentially linked to imbalances in brain neurochemicals. This study aims to measure brain neurochemical levels in long COVID and ME/CFS patients as well as healthy controls to investigate associations with severity measures.

Methods: Magnetic resonance spectroscopy (MRS) data was acquired with a 3T Prisma MRI scanner. We measured absolute levels of brain neurochemicals in the posterior cingulate cortex in long COVID (n=17), ME/CFS (n=17), and healthy controls (n=10) using Osprey software. The statistical analyses were performed using SPSS version 29. Age and sex were included as nuisance covariates.

Results: Glutamate levels were significantly higher in long COVID (p=0.02) and ME/CFS (p=0.017) than in healthy controls. No significant difference was found between the two patient cohorts. Additionally, N-acetyl-aspartate levels were significantly higher in long COVID patients (p=0.012). Importantly, brain neurochemical levels were associated with self-reported severity measures in long COVID and ME/CFS.

Conclusion: Our study identified significantly elevated Glutamate and N-acetyl-aspartate levels in long COVID and ME/CFS patients compared with healthy controls. No significant differences in brain neurochemicals were observed between the two patient cohorts, suggesting a potential overlap in their underlying pathology. These findings suggest that imbalanced neurochemicals contribute to the complex symptoms experienced by long COVID and ME/CFS patients.

Source: Thapaliya K, Marshall-Gradisnik S, Eaton-Fitch N, Eftekhari Z, Inderyas M, Barnden L. Imbalanced Brain Neurochemicals in long COVID and ME/CFS: A Preliminary Study using MRI. Am J Med. 2024 Apr 6:S0002-9343(24)00216-X. doi: 10.1016/j.amjmed.2024.04.007. Epub ahead of print. PMID: 38588934. https://www.sciencedirect.com/science/article/pii/S000293432400216X (Full text)

Impaired Hand Grip Strength Correlates with Greater Disability and Symptom Severity in Post-COVID Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Post-COVID syndrome (PCS) encompasses a diverse array of symptoms persisting beyond 3 months after acute SARS-CoV-2 infection, with mental as well as physical fatigue being the most frequent manifestations.
Methods: In 144 female patients with PCS, hand grip strength (HGS) parameters were assessed as an objective measure of muscle fatigue, with 78 meeting the Canadian Consensus Criteria for postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The severity of disability and key symptoms was evaluated using self-reported questionnaires.
Results: Patients with ME/CFS exhibited heightened overall symptom severity, including lower physical function (p < 0.001), a greater degree of disability (< 0.001), more severe fatigue (< 0.001), postexertional malaise (p < 0.001), and autonomic dysfunction (p = 0.004) compared to other patients with PCS. While HGS was impaired similarly in all patients with PCS and exhibited a significant correlation with physical function across the entire patient group, HGS of patients with ME/CFS uniquely demonstrated associations with key symptoms.
Conclusions: Thus, impaired HGS serves as an objective marker of physical function in patients with PCS. Only in patients meeting ME/CFS criteria is impaired HGS also associated with the severity of hallmark symptoms. This suggests a common mechanism for muscle fatigue and other symptoms in the ME/CFS subtype, distinct from that in other types of PCS.
Source: Paffrath A, Kim L, Kedor C, Stein E, Rust R, Freitag H, Hoppmann U, Hanitsch LG, Bellmann-Strobl J, Wittke K, et al. Impaired Hand Grip Strength Correlates with Greater Disability and Symptom Severity in Post-COVID Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Journal of Clinical Medicine. 2024; 13(7):2153. https://doi.org/10.3390/jcm13072153 https://www.mdpi.com/2077-0383/13/7/2153

Do people with ME/CFS and joint hypermobility represent a disease subgroup? An analysis using registry data

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, multifaceted disease that affects millions globally. Despite its significant impact, the disease’s etiology remains poorly understood, and symptom heterogeneity poses challenges for diagnosis and treatment. Joint hypermobility, commonly seen in hypermobile Ehlers-Danlos Syndrome (hEDS), has been observed in ME/CFS patients but its prevalence and clinical significance within this population are not well-characterized.

Objective: To compare the characteristics of ME/CFS patients with and without joint hypermobility (JH+ and JH-) as assessed using the Beighton scoring system, and to explore whether JH+ ME/CFS patients exhibit distinct disease characteristics, comorbidities, and health-related quality of life (HRQOL).

Methods: The study used cross-sectional, self-reported data from 815 participants of the You + ME Registry. Participants were categorized as JH+ or JH- based on self–assessed Beighton scores and compared across demographics, comorbidities, family history, and symptoms. HRQOL was assessed using the Short Form-36 RAND survey and Karnofsky Performance Status.

Results: 15.5% (N = 126) of participants were classified as JH+. JH+ participants were more likely to be female, report Ehlers-Danlos Syndrome (EDS), Postural Orthostatic Tachycardia Syndrome (POTS), and a family history of EDS. They experienced worse HRQOL, particularly in physical functioning and pain, and a higher number of autonomic, neurocognitive, headache, gut, and musculoskeletal symptoms. Sensitivity analysis suggested that ME/CFS with concurrent JH+ and EDS was associated with more severe symptoms and greater functional impairment.

Conclusion: ME/CFS patients with joint hypermobility, particularly those with EDS, demonstrate distinct clinical characteristics, including more severe symptomatology and reduced HRQOL. These findings highlight the need for comprehensive clinical assessments of ME/CFS patients with joint hypermobility. Understanding these relationships could aid in subgroup identification, improving diagnosis, and informing targeted therapeutic approaches. Further research is warranted to explore these associations and their implications for clinical practice.

Source: Kathleen Mudie, Allison Ramiller, Sadie Whittaker, Leslie E. Phillips. Do people with ME/CFS and joint hypermobility represent a disease subgroup? An analysis using registry data. Front. Neurol., 12 March 2024, Sec. Autonomic Disorders, Volume 15 – 2024 | https://doi.org/10.3389/fneur.2024.1324879 https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1324879/full (Full text)

Association between fatigue, peripheral serotonin, and L-carnitine in hypothyroidism and in chronic fatigue syndrome

Abstract:

Background: Fatigue of unknown origin is a hallmark symptom in chronic fatigue syndrome (CFS) and is also found in 20% of hypothyroidism patients despite appropriate levothyroxine treatment. Here, we suggest that in these disorders, peripheral serotonin levels are low, and elevating them to normal range with L-carnitine is accompanied with reduced fatigue.

Methods: We conducted a retrospective analysis of follow-up clinical data (CFS N=12; hypothyroidism with fatigue N=40) where serum serotonin and fatigue levels were compared before vs. after 7 weeks of oral L-carnitine supplementation.

Results: After L-carnitine, serotonin increased (8-fold in CFS, Sig. = 0.002, 6-fold in hypothyroidism, Sig. < 0.001) whereas fatigue decreased (2-fold in both CFS and hypothyroidism, Sig. = 0.002 for CFS, Sig. < 0.001 for hypothyroidism). There was a negative correlation between serotonin level and fatigue (for CFS, rho = -0.49 before and -0.67 after L-carnitine; for hypothyroidism, rho = -0.24 before and -0.83 after L-carnitine).

Conclusions: These findings suggest a new link between low peripheral serotonin, L-carnitine, and fatigue.

Source: Tommi Raij, Kari Raij. Association between fatigue, peripheral serotonin, and L-carnitine in hypothyroidism and in chronic fatigue syndrome. Front. Endocrinol. Sec. Neuroendocrine Science, Volume 15 – 2024 | doi: 10.3389/fendo.2024.1358404 https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1358404/abstract