Broadband electrical impedance as a novel characterization of oxidative stress in single L6 skeletal muscle cells

Abstract:

Oxidative stress (OS) is one of the leading causes of cytotoxicity and is linked to many human physio-pathological conditions. In particular, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) induced by OS is debilitating to quality of life, while no clear biological markers have been identified for diagnostic measures. Recently, impedance measurements of peripheral blood cells of ME/CFS patients have been shown as a promising approach to diagnose the disease. Inspired by this study and aiming to interrogate muscle cells directly, we investigated if broadband measurements of single muscle cells could differentiate normal and oxidatively stressed cell populations.

We first optimized a protocol through H2O2 treatment to introduce oxidative stress to cultured rat L6 skeletal muscle cells. The treated cells were further characterized through broadband impedance spectroscopy of single cells using a microfluidic lab-on-a-chip system. The resulting dielectric properties of cytoplasm permittivity and conductivity are electrically distinct from normally cultured cells. The reflection and transmission coefficients, ΔS11 and ΔS21, of the normal cells are tightly clustered and closely resemble those of the cell-free solution across the frequency range of 9 kHz to 9 GHz. On the other hand, dielectric properties of the oxidized cells have a wide distribution in the GHz range, deviating both in the positive and negative directions from the normally cultured cells.

Simulation results guide our hypothesis that the dielectric differences could be linked to ion alterations, while calcium imaging directly supports the contribution of calcium flux to the observed deviation of S parameters. The unique electrical profile associated with oxidized cells in the GHz frequencies provide a framework for future development of technologies to diagnose oxidative-stress related diseases such as ME/CFS.

Source: Ferguson C, Pini N, Du X, Farina M, Hwang JMC, Pietrangelo T, Cheng X. Broadband electrical impedance as a novel characterization of oxidative stress in single L6 skeletal muscle cells. Anal Chim Acta. 2021 Aug 15;1173:338678. doi: 10.1016/j.aca.2021.338678. Epub 2021 May 25. PMID: 34172152. https://pubmed.ncbi.nlm.nih.gov/34172152/

Documenting disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

BACKGROUND: According to the 2015 National Academy of Medicine report, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) “is a serious, chronic, complex, and systemic disease that frequently and dramatically limits the activities of affected patients.” ME/CFS affects between 1 and 2.5 million Americans, leaving as many as 75% unable to work due to physical, cognitive and functional impairment. Unfortunately, many doctors and lawyers lack the knowledge of how to properly document an ME/CFS disability claim, leaving patients unable to access disability benefits.

OBJECTIVE: The goal of this article is to summarize the approaches used by experienced clinicians and lawyers in successful ME/CFS disability claims.

METHODS: The authors reviewed the types of US disability insurance programs and the evidence commonly required by these programs to demonstrate ME/CFS disability.

RESULTS: This article summarizes the range of methods used in successful US disability claims, which include documentation of the functional impact of post-exertional malaise and the use of methods that provide objective evidence of impairment.

CONCLUSIONS: Medical providers and lawyers can use these tested methods to obtain disability benefits for people with ME/CFS. Physical therapists, occupational therapists, and other specialists play an important role in providing objective evidence for ME/CFS disability claims.

Source: Podell, Richard, Dimmock, Mary E., and Comerford, Barbara B. ‘Documenting Disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)’. 1 Jan. 2020 : 339 – 352. https://content.iospress.com/articles/work/wor203178 (Full text)

Physical and Mental Fatigue in Subjects Recovered from COVID-19 Infection: A Case–Control Study

Abstract:

Purpose: Much effort has been directed toward studying COVID-19 symptoms; however, the post–COVID-19 phase remains mysterious. The aim of this work was to conduct a clinical and neurophysiological evaluation of physical and mental fatigue in COVID-19 long-haulers and to study whether markers of COVID-19 severity are able to predict the likelihood of developing postinfectious fatigue syndrome (PIFS) in such patients.

Patients and Methods: This case–control study was conducted on 46 COVID-19 long-haulers who met the criteria for PIFS and 46 recovered COVID-19 subjects without any residuals. Clinical assessment of fatigue was done using a fatigue questionnaire. Repetitive nerve stimulation and single-fiber electromyography were done after excluding neuropathy and myopathy.

Results: The median value for physical fatigue was 4 (IQR 2– 7), while that for mental fatigue was 2 (IQR 0– 3). Each day’s increase in the period of COVID-19 illness increased the odds of PIFS in COVID-19 long-haulers 1.104-fold, and each unit increase in ferritin increased the odds of PIFS 1.006-fold. A significant decrement in at least one muscle was observed in 50% of patients. Patients with PIFS had significantly higher mean consecutive difference (MCD) in the extensor digitorum communis than the control group. There were statistically significant positive correlations between MCD values and physical, mental, and total fatigue scores.

Conclusion: Higher ferritin levels and prolonged COVID-19 infection were independent predictors of PIFS in COVID-19 long-haulers. There was electrophysiological evidence of abnormalities in the peripheral portion of the motor unit in COVID-19 long-haulers with PIFS.

Source: Elanwar R, Hussein M, Magdy R, Eid RA, Yassien A, Abdelsattar AS, Alsharaway LA, Fathy W, Hassan A, Kamal YS. Physical and Mental Fatigue in Subjects Recovered from COVID-19 Infection: A Case–Control Study. Neuropsychiatr Dis Treat. 2021;17:2063-2071 https://doi.org/10.2147/NDT.S317027 https://www.dovepress.com/physical-and-mental-fatigue-in-subjects-recovered-from-covid-19-infect-peer-reviewed-fulltext-article-NDT (Full text)

Migraine Is More Than Just Headache: Is the Link to Chronic Fatigue and Mood Disorders Simply Due to Shared Biological Systems?

Abstract:

Migraine is a symptomatically heterogeneous condition, of which headache is just one manifestation. Migraine is a disorder of altered sensory thresholding, with hypersensitivity among sufferers to sensory input. Advances in functional neuroimaging have highlighted that several brain areas are involved even prior to pain onset. Clinically, patients can experience symptoms hours to days prior to migraine pain, which can warn of impending headache. These symptoms can include mood and cognitive change, fatigue, and neck discomfort. Some epidemiological studies have suggested that migraine is associated in a bidirectional fashion with other disorders, such as mood disorders and chronic fatigue, as well as with other pain conditions such as fibromyalgia. This review will focus on the literature surrounding alterations in fatigue, mood, and cognition in particular, in association with migraine, and the suggested links to disorders such as chronic fatigue syndrome and depression.

We hypothesize that migraine should be considered a neural disorder of brain function, in which alterations in aminergic networks integrating the limbic system with the sensory and homeostatic systems occur early and persist after headache resolution and perhaps interictally. The associations with some of these other disorders may allude to the inherent sensory sensitivity of the migraine brain and shared neurobiology and neurotransmitter systems rather than true co-morbidity.

Source: Karsan N, Goadsby PJ. Migraine Is More Than Just Headache: Is the Link to Chronic Fatigue and Mood Disorders Simply Due to Shared Biological Systems? Front Hum Neurosci. 2021 Jun 3;15:646692. doi: 10.3389/fnhum.2021.646692. PMID: 34149377; PMCID: PMC8209296. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209296/ (Full text)

Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis?

Abstract:

As millions of patients have been infected by SARS-CoV-2 virus a vast number of individuals complain about continuing breathlessness and fatigue even months after the onset of the disease. This overwhelming phenomenon has not been well defined and has been called “post-COVID syndrome” or “long-COVID” [1]. There are striking similarities to myalgic encephalomyelitis also called chronic fatigue syndrome linked to a viral and autoimmune pathogenesis. In both disorders neurotransmitter receptor antibodies against ß-adrenergic and muscarinic receptors may play a key role. We found similar elevation of these autoantibodies in both patient groups.

Extracorporeal apheresis using a special filter seems to be effective in reducing these antibodies in a significant way clearly improving the debilitating symptoms of patients with chronic fatigue syndrome. Therefore, such a form of neuropheresis may provide a promising therapeutic option for patients with post-COVID-19 syndrome. This method will also be effective when other hitherto unknown antibodies and inflammatory mediators are involved.

Source: Bornstein SR, Voit-Bak K, Donate T, Rodionov RN, Gainetdinov RR, Tselmin S, Kanczkowski W, Müller GM, Achleitner M, Wang J, Licinio J, Bauer M, Young AH, Thuret S, Bechmann N, Straube R. Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis? Mol Psychiatry. 2021 Jun 17. doi: 10.1038/s41380-021-01148-4. Epub ahead of print. PMID: 34140635. https://pubmed.ncbi.nlm.nih.gov/34140635/

Central Sensitivity and Fibromyalgia

Abstract:

Fibromyalgia presents with symptoms of widespread pain, fatigue, sleeping and cognitive disturbances as well as other somatic symptoms. It often overlaps with other conditions termed ‘central sensitivity syndromes’ such as irritable bowel syndrome, chronic fatigue syndrome and temporomandibular disorder. Central sensitisation, mediated by amplified processing in the central nervous system, has been identified as the key pathogenic mechanism in these disorders. The term ‘central sensitivity’ can be used to collectively describe the clinical presentation of these disorders.

Fibromyalgia is highly prevalent in most rheumatic diseases as well as non-rheumatic chronic diseases and if unrecognised results in high morbidity. It is diagnosed clinically after excluding important differential diagnoses. Diagnostic criteria have been developed as tools to help identify and diagnose fibromyalgia. Such tools can fulfill an important need when managing patients with rheumatic disease and other chronic diseases as a way to identify fibromyalgia and improve patient outcomes. Treatment involves an integrated approach including education, exercise, stress reduction and pharmacological therapies targeting the central nervous system. This approach is suitable for all presentations of central sensitivity and some central sensitivity syndromes have additional treatment options specific to the clinical presentation.

Source: Mezhov V, Guymer E, Littlejohn G. Central Sensitivity and Fibromyalgia. Intern Med J. 2021 Jun 17. doi: 10.1111/imj.15430. Epub ahead of print. PMID: 34139045. https://pubmed.ncbi.nlm.nih.gov/34139045/

Chronic fatigue and post-exertional malaise in people living with long COVID

Abstract:

Purpose People living with long COVID describe a high symptom burden, and a more detailed assessment of chronic fatigue and post-exertional malaise (PEM) may inform the development of rehabilitation recommendations. The aims of this study were to use validated questionnaires to measure the severity of fatigue and compare this with normative data and thresholds for clinical relevance in other diseases; measure and describe the impact of PEM; and describe symptoms of dysfunctional breathing, self-reported physical activity/sitting time, and health-related quality of life.

Methods This was an observational study involving an online survey for adults living with long COVID (data collection from February-April, 2021) following a confirmed or suspected SARS-CoV-2 infection. Questionnaires included the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) and DePaul Symptom Questionnaire-Post-Exertional Malaise.

Results After data cleaning, n=213 participants were included in the analysis. Participants primarily identified as women (85.5%), aged 40-59 (78.4%), who had been experiencing long COVID symptoms for ≥6 months (72.3%). The total FACIT-F score was 18±10 (where the score can range from 0-52, and a lower score indicates more severe fatigue), and 71.4% were experiencing chronic fatigue. Post-exertional symptom exacerbation affected most participants, and 58.7% met the scoring thresholds used in people living with myalgic encephalomyelitis/chronic fatigue syndrome. PEM occurred alongside a reduced capacity to work, be physically active, and function both physically and socially.

Conclusion Long COVID is characterized by chronic fatigue that is clinically relevant and is at least as severe as fatigue in several other clinical conditions, including cancer. PEM appears to be a common and significant challenge for the majority of this patient group. Patients, researchers, and allied health professionals are seeking information on safe rehabilitation for people living with long COVID, particularly regarding exercise. Fatigue and post-exertional symptom exacerbation must be monitored and reported in studies involving interventions for people with long COVID.

Source: Rosie Twomey, Jessica DeMars, Kelli Franklin, S. Nicole Culos-Reed, Jason Weatherald, James G. Wrightson. Chronic fatigue and post-exertional malaise in people living with long COVID. medRxiv 2021.06.11.21258564; doi: https://doi.org/10.1101/2021.06.11.21258564 https://www.medrxiv.org/content/10.1101/2021.06.11.21258564v1

Epistemic in/justice in patient participation. A discourse analysis of the Dutch ME/CFS Health Council advisory process

Abstract:

In healthcare settings, patient participation is increasingly adopted as a possible remedy to ill people suffering from ‘epistemic injustices’ – that is to their unfair harming as knowers. In exploring and interpreting patient participation discourses within the 2013-2018 Dutch Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) Health Council advisory process, this paper assesses the epistemological emancipatory value of this participatory practice. It reveals that in the analysed case, patient representatives predominantly offer biomedical knowledge about ME/CFS. They frame this condition as primarily somatic, and accordingly, perceive appropriate diagnostic criteria, research avenues and treatment options as quantifiable, objectifiable and explicitly non-psychogenic.

This paper argues that such a dominant biomedical patient participatory practice is ambiguous in terms of its ability to correct epistemic injustices towards ill people. Biomedicalized patient participation may enhance people’s credibility and their ability to make sense of their illness, but it may also undermine their valid position within participatory practices as well as lead to (sustaining) biased and reductive ideas about who ill people are and what kind of knowledge they hold. The final section of this paper offers a brief reflection on how to navigate such biomedicalized participatory practices in order to attain more emancipatory ones.

Source: de Boer ML. Epistemic in/justice in patient participation. A discourse analysis of the Dutch ME/CFS Health Council advisory process. Sociol Health Illn. 2021 Jun 17. doi: 10.1111/1467-9566.13301. Epub ahead of print. PMID: 34137042. https://pubmed.ncbi.nlm.nih.gov/34137042/

Performance Validity and Outcome of Cognitive Behavior Therapy in Patients with Chronic Fatigue Syndrome

Abstract:

Objective: There is limited research examining the impact of the validity of cognitive test performance on treatment outcome. All known studies to date have operationalized performance validity dichotomously, leading to the loss of predictive information. Using the range of scores on a performance validity test (PVT), we hypothesized that lower performance at baseline was related to a worse treatment outcome following cognitive behavioral therapy (CBT) in patients with Chronic Fatigue Syndrome (CFS) and to lower adherence to treatment.

Method: Archival data of 1081 outpatients treated with CBT for CFS were used in this study. At baseline, all patients were assessed with a PVT, the Amsterdam Short-Term Memory test (ASTM). Questionnaires assessing fatigue, physical disabilities, psychological distress, and level of functional impairment were administered before and after CBT.

Results: Our main hypothesis was not confirmed: the total ASTM score was not significantly associated with outcomes at follow-up. However, patients with a missing follow-up assessment had a lower ASTM performance at baseline, reported higher levels of physical limitations, and completed fewer therapy sessions.

Conclusions: CFS patients who scored low on the ASTM during baseline assessment are more likely to complete fewer therapy sessions and not to complete follow-up assessment, indicative of limited adherence to treatment. However, if these patients were retained in the intervention, their response to CBT for CFS was comparable with subjects who score high on the ASTM. This finding calls for more research to better understand the impact of performance validity on engagement with treatment and outcomes.

Source: Roor JJ, Dandachi-FitzGerald B, Peters MJV, Knoop H, Ponds RWHM. Performance Validity and Outcome of Cognitive Behavior Therapy in Patients with Chronic Fatigue Syndrome. J Int Neuropsychol Soc. 2021 Jun 16:1-10. doi: 10.1017/S1355617721000643. Epub ahead of print. PMID: 34130768. https://pubmed.ncbi.nlm.nih.gov/34130768/

IN MEMORIAM: DR. PAUL CHENEY

I was deeply saddened to learn that Dr. Paul Cheney had passed away on June 10th. Along with Dr. Dan Peterson, Dr. Cheney  practiced in Incline Village, Nevada during the outbreak of what appeared to be a new disease. It had the hallmarks of a viral infection, but their patients were not recovering. That disease would later be called “Chronic Fatigue Syndrome.”

Dr. Cheney’s passing has personal significance for me, because he was the doctor who diagnosed me in 1993. I had heard about him through the leader of our support group in Austin, Texas, who generously allowed me to listen to a tape she had made of her consult with him. I was impressed with Dr. Cheney’s wealth of knowledge, which stemmed not just from his clinical practice, but from his research background in immunology. He not only had an MD, but held a PhD in physics and had been a research associate in the Division of Immunology at the CDC. He had also served as Chief of Medicine at the USAF Hospital in Mt. Home, Idaho for three years before going into private practice.

On the wall of Dr. Cheney’s office was a map with pushpins indicating where his patients came from. There were pushpins in every state and all over the world. Over the course of his practice he saw thousands of patients, whom he tested extensively for immune and metabolic dysfunctions, cardiac function, co-infections (including Lyme disease), indicators of viral reactivation, antigen sensitivity, and autoimmune activity, among others. I don’t think anyone understood ME/CFS as well as he did. Dr. Cheney was our “resident genius.”

Dr. Cheney spent four hours with me during our initial consult. He was not just thorough, he was kind. When he pronounced me “severely ill” there was genuine concern in his eyes. He gave me a piece of advice that I never forgot. “You are in a leaky boat,” he said. “How much can you throw overboard?” Throwing things overboard has saved me on many occasions.

The last time I saw Dr. Cheney was at the IACFS/ME Conference in San Francisco in 2014. I gave him a big hug and introduced myself as a former patient. “I remember you,” he said. It had been 21 years.

RIP Dr. Cheney. The world is poorer without you in it.

More information

Dr Cheney on heart function – from Dr. Myhill’s site: “Dr Paul Cheney has been working with the CFS patients clinically and experimentally for decades and this page is based on many of his ideas. This pulls together many clinical issues which hitherto were inexplicable to me and provides the basis for new therapies for CFS.”

Phoenix Rising Dr. Cheney page – Contains many links to protocols, treatment plans, etc. Some links are dead, but most are still active.

The Cheney Chronicles #2: His Protocol For Chronic Fatigue Syndrome – Cort Johnson’s blog, Health Rising, has two articles detailing one patient’s consult with Dr. Cheney.

ProHealth has a number of articles about Dr. Cheney’s treatment approach.

A Colossus in the ME/CFS Field Passes: Remembering Paul Cheney MD, Ph.D. – Cort Johnson talks about the treatments Dr. Cheney used, as well as his theories about the pathophysiology of ME/CFS.