Tag: symptoms

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 (p < 0.001), more severe fatigue (p < 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

The Head-Up Tilt Table Test as a Measure of Autonomic Functioning among Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) often experience autonomic symptoms. In the present study, we evaluated 193 adults seeking treatment for ME/CFS, who were recruited from an outpatient clinic. The participants completed a head-up tilt table test to assess two common types of orthostatic intolerance, namely, postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH).
During the tilt test, 32.5% of the participants demonstrated POTS or OH. The participants with either of these two common types of orthostatic intolerance were found to have more problems with sleep and post-exertional malaise as assessed by the DePaul Symptom Questionnaire; these patients also reported more physical and health function limitations. The implications of the findings are discussed.
Source: Jason LA, McGarrigle WJ, Vermeulen RCW. The Head-Up Tilt Table Test as a Measure of Autonomic Functioning among Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Journal of Personalized Medicine. 2024; 14(3):238. https://doi.org/10.3390/jpm14030238 https://www.mdpi.com/2075-4426/14/3/238 (Full text)

Post Viral Pain, Fatigue, and Sleep Disturbance Syndromes: Current knowledge and Future Directions

Abstract:

Post-viral pain syndrome, also known as post-viral syndrome (PVS), is a complex condition characterized by persistent pain, fatigue, musculoskeletal pain, neuropathic pain, neurocognitive difficulties, and sleep disturbances1,2 that can occur after an individual has recovered from a viral infection. Much remains unknown regarding the pathophysiology of post-viral syndromes and few studies have provided a comprehensive summary of the condition, agents that cause it, and successful treatment modalities.

With the COVID-19 pandemic continuing to affect millions of people worldwide, the need for understanding the etiology of post-viral illness and how to help individuals cope with the sequalae is paramount.2 This narrative review provides a summary of the sequelae of post-viral syndromes, viral agents that cause it, the pathophysiology, treatment, and future considerations for research and targeted therapies.

Source: Caleb Tackey, P. Maxwell Slepian, Hance Clarke & Nimish Mittal (2023) Post Viral Pain, Fatigue, and Sleep Disturbance Syndromes: Current knowledge and Future Directions, Canadian Journal of Pain, DOI: 10.1080/24740527.2023.2272999 https://www.tandfonline.com/doi/full/10.1080/24740527.2023.2272999 (Full text)

Dry eye symptoms and signs in United States Gulf War era veterans with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: To examine ocular symptoms and signs of veterans with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) diagnosis, ME/CFS symptoms, and controls.

Methods: This was a prospective, cross-sectional study of 124 South Florida veterans in active duty during the Gulf War era. Participants were recruited at an ophthalmology clinic at the Miami Veterans Affairs Hospital and evaluated for a diagnosis of ME/CFS, or symptoms of ME/CFS (intermediate fatigue, IF) using the Canadian Consensus criteria. Ocular symptoms were assessed via standardised questionnaires and signs via comprehensive slit lamp examination. Inflammatory blood markers were analysed and compared across groups.

Results: Mean age was 55.1 ± 4.7 years, 88.7% identified as male, 58.1% as White, and 39.5% as Hispanic. Ocular symptoms were more severe in the ME/CFS (n = 32) and IF (n = 48) groups compared to controls (n = 44) across dry eye (DE; Ocular Surface Disease Index [OSDI]: 48.9 ± 22.3 vs. 38.8 ± 23.3 vs. 19.1 ± 17.8, p < 0.001; 5 item Dry Eye Questionnaire [DEQ-5]: 10.8 ± 3.9 vs. 10.0 ± 4.6 vs. 6.6 ± 4.2, p < 0.001) and pain-specific questionnaires (Numerical Rating Scale 1-10 [NRS] right now: 2.4 ± 2.8 vs. 2.4 ± 2.9 vs 0.9 ± 1.5; p = 0.007; Neuropathic Pain Symptom Inventory modified for the Eye [NPSI-E]: 23.0 ± 18.6 vs. 19.8 ± 19.1 vs. 6.5 ± 9.0, p < 0.001). Ocular surface parameters and blood markers of inflammation were generally similar across groups.

Conclusion: Individuals with ME/CFS report increased ocular pain but similar DE signs, suggesting that mechanisms beyond the ocular surface contribute to symptoms.

Source: Victor Sanchez BS, Colin K. Kim BS, Elyana V. T. Locatelli BS, Adam K. Cohen, Kimberly Cabrera MS, Kristina Aenlle PhD, Nancy G. Klimas MD, Robert O’Brien PhD, Anat Galor MD, MSPH. Dry eye symptoms and signs in United States Gulf War era veterans with myalgic encephalomyelitis/chronic fatigue syndrome. First published: 12 November 2023 https://doi.org/10.1111/ceo.14313 https://onlinelibrary.wiley.com/doi/10.1111/ceo.14313 (Full text)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Me/Cfs): The Biology of a Neglected Disease

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic disease with debilitating symptoms that impact all aspects of life. The diverse symptom presentation indicates that ME/CFS is likely to have a multifactorial origin. However, it is an extremely understudied disease with no standardised diagnostic criteria or proven treatment avenues. It is hypothesised that environmental insults (such as acute infection, mainly viral) or stress in genetically susceptible individuals may trigger the development of ME/CFS.

These insults result in acute inflammatory responses, along with aberrant immune activation. A spiralling disruption of homeostasis promotes subsequent patho-mechanisms including gut dysbiosis and systemic inflammation, and eventually a pathological clotting system, chronic endothelialitis, vasoconstriction, and hypoxia. Additionally, dysfunctional energy metabolism including oxidative stress is also present in the development of ME/CFS. Since the exact pathophysiology of ME/CFS remains unclear, additional research is required to reveal further insight into this “neglected” disease.

Source: Arron, Hayley and Marsh, Benamin and Khan, M. Asad and Jaeger, Beate and Kell, Douglas and Pretorius, Etheresia, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Me/Cfs): The Biology of a Neglected Disease. Available at SSRN: https://ssrn.com/abstract=4622074 or http://dx.doi.org/10.2139/ssrn.4622074 (Full text available as PDF file)

An experimental study investigating the link between symptom reporting and heart rate variability in chronic fatigue syndrome patients

Abstract:

Our Master’s thesis falls within the research domain of Rehabilitation Sciences and Physiotherapy. In our study we investigated patients with chronic fatigue syndrome (CFS).

CFS is a complicated disorder of which the pathology is still poorly understood. Due to the significant prevalence, the socio-economic impact of the disorder is high. In addition to the physiological dysfunctions that are often reported in CFS literature, patients can also experience altered symptom perception. Patients for example show increased subjective responses to unpleasant somatic stimuli in comparison with healthy persons (Van den Houte et al., 2018). Therefore, this study project fits within the domain of pain, fatigue and somatically unexplained physical symptoms.

Despite a lot of articles reporting the role of altered symptom perception, they mainly focused on symptom perception in the lab. However, these laboratory measurements do not take day-to-day variability in symptoms into account.

We think that the lack of studies investigating the symptomatology in CFS patients via ecological momentary measurements is a gap in the literature. Therefore, in our study, we executed symptom assessments in the lab and in daily life.

In addition, we investigated the interactions between the reported symptoms and heart rate variability (HRV) in order to investigate, on a small scale, if psychological and physiological dysfunctions in patients do not work independently.

Extra information about the pathology of CFS is useful to all professionals in rehabilitation sciences and physical therapy who work with CFS patients. It will help professionals to understand the complex problem of CFS better and to tailor the care for these patients.

Our study is situated in a larger study project with the title “Identifying (psycho)physiology-based subgroups in chronic fatigue syndrome and their relevance for rehabilitation” and with study number S66452. The project is reimbursed by Fonds Wetenschappelijk Onderzoek. The project runs in collaboration with the Multidisciplinary Diagnostic Center of UZ Leuven, the Multidisciplinary Expertise Center Tumi Therapeutics, the Vlaams Instituut voor Biotechnologie KU Leuven Raes Lab and IMEC. All laboratory tasks were conducted in the University Hospital of Leuven.

The study is written in line with the central format. The study topics and research questions were determined in collaboration with Msc. Y. Dooms and Dr. Maaike Van Den Houte. Due to the fact that the study was a component of an ongoing research project, we were not involved in decisions about research design or methodology.

We carried out the academic writing procedure concerning this Master’s thesis. During the writing procedure, we received input from Msc. Y. Dooms. The thesis was written in close cooperation amongst both of us. We both independently contributed to the thesis, reviewed it, and wrote multiple sections together. The data-analysis was done in collaboration with Dr. Maaike Van Den Houte.

Source: Jentro Dest and Daan Grosemans.An experimental study investigating the link between symptom reporting and heart rate variability in chronic fatigue syndrome patients. Master Thesis [University of Hasselt] https://documentserver.uhasselt.be/bitstream/1942/41042/1/1b9fa48e-2513-4665-8ba1-a6b1eb7f2056.pdf (Full text)