Tag: 2023

Serum GDF-15 Levels Accurately Differentiate Patients with Primary Mitochondrial Myopathy, Manifesting with Exercise Intolerance and Fatigue, from Patients with Chronic Fatigue Syndrome

Abstract:

Primary mitochondrial myopathies (PMM) are a clinically and genetically highly heterogeneous group that, in some cases, may manifest exclusively as fatigue and exercise intolerance, with minimal or no signs on examination. On these occasions, the symptoms can be confused with the much more common chronic fatigue syndrome (CFS).
Nonetheless, other possibilities must be excluded for the final diagnosis of CFS, with PMM being one of the primary differential diagnoses. For this reason, many patients with CFS undergo extensive studies, including extensive genetic testing and muscle biopsies, to rule out this possibility.
This study evaluated the diagnostic performance of growth differentiation factor-15 (GDF-15) as a potential biomarker to distinguish which patient with chronic fatigue has a mitochondrial disorder. We studied 34 adult patients with symptoms of fatigue and exercise intolerance with a definitive diagnosis of PMM (7), CFS (22), or other non-mitochondrial disorders (5).
The results indicate that GDF-15 can accurately discriminate between patients with PMM and CFS (AUC = 0.95) and between PMM and patients with fatigue due to other non-mitochondrial disorders (AUC = 0.94). Therefore, GDF-15 emerges as a promising biomarker to select which patients with fatigue should undergo further studies to exclude mitochondrial disease.
Source: Bermejo-Guerrero L, de Fuenmayor-Fernández de la Hoz CP, Guerrero-Molina MP, Martín-Jiménez P, Blázquez A, Serrano-Lorenzo P, Lora D, Morales-Conejo M, González-Martínez I, López-Jiménez EA, Martín MA, Domínguez-González C. Serum GDF-15 Levels Accurately Differentiate Patients with Primary Mitochondrial Myopathy, Manifesting with Exercise Intolerance and Fatigue, from Patients with Chronic Fatigue Syndrome. Journal of Clinical Medicine. 2023; 12(6):2435. https://doi.org/10.3390/jcm12062435 (Full text)

Health outcomes of sensory hypersensitivities in myalgic encephalomyelitis/chronic fatigue syndrome and multiple sclerosis

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood chronic illness with many case definitions that disagree on key symptoms, including hypersensitivities to noise and lights. The aim of the current study was to understand the prevalence rates and characteristics of these symptoms amongst people with ME/CFS and to compare them to people with another chronic illness, multiple sclerosis (MS).

International datasets consisting of 2,240 people with either ME/CFS or MS have completed the DePaul Symptom Questionnaire (DSQ) and the Short Form Health Survey Questionnaire (SF-36). Hypersensitivities to noise and lights were indicated from items on the DSQ, and participants were analyzed against DSQ and SF-36 subscales through a multivariate analysis of covariance.

There were significantly higher percentages of people with hypersensitivities in the ME/CFS sample compared to the MS sample. Regardless of illness, participants that exhibited both hypersensitivities reported greater symptomology than those without hypersensitivities. Healthcare providers and researchers should consider these symptoms when developing treatment plans and evaluating ME/CFS case diagnostic criteria.

Source: Maeda KI, Islam MF, Conroy KE, Jason L. Health outcomes of sensory hypersensitivities in myalgic encephalomyelitis/chronic fatigue syndrome and multiple sclerosis. Psychol Health Med. 2023 Mar 28:1-12. doi: 10.1080/13548506.2023.2195670. Epub ahead of print. PMID: 36977713. https://pubmed.ncbi.nlm.nih.gov/36977713/

Synbiotic Supplementation Improves Quality of Life and Inmunoneuroendocrine Response in Patients with Fibromyalgia: Influence of Codiagnosis with Chronic Fatigue Syndrome

Abstract:

Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are two medical conditions in which pain, fatigue, immune/inflammatory dysregulation, as well as various mental health disorders predominate in the diagnosis, without evidence of a clear consensus on the treatment of FM and CFS.
The main aim of this research was to analyse the possible effects of a synbiotic (Synbiotic, Gasteel Plus® (Heel España S.A.U.), through the study of pro-inflammatory/anti-inflammatory cytokines (IL-8/IL-10) and neuroendocrine biomarkers (cortisol and DHEA), in order to evaluate the interaction between inflammatory and stress responses mediated by the cytokine-HPA (hypothalamic-pituitary-adrenal) axis, as well as mental and physical health using body composition analysis, accelerometry and previously validated questionnaires.
The participants were women diagnosed with FM with or without a diagnostic of CFS. Each participant was evaluated at baseline and after the intervention, which lasted one month. Synbiotic intervention decreased levels of perceived stress, anxiety and depression, as well as improved quality of life during daily activities. In addition, the synbiotic generated an activation of HPA axis (physiological cortisol release) that can compensate the increased inflammatory status (elevated IL-8) observed at baseline in FM patients. There were no detrimental changes in body composition or sleep parameters, as well as in the most of the activity/sedentarism-related parameters studied by accelerometry.
It is concluded that synbiotic nutritional supplements can improve the dysregulated immunoneuroendocrine interaction involving inflammatory and stress responses in women diagnosed with FM, particularly in those without a previous CFS diagnostic; as well as their perceived of levels stress, anxiety, depression and quality of life.
Source: Hinchado MD, Quero-Calero CD, Otero E, Gálvez I, Ortega E. Synbiotic Supplementation Improves Quality of Life and Inmunoneuroendocrine Response in Patients with Fibromyalgia: Influence of Codiagnosis with Chronic Fatigue Syndrome. Nutrients. 2023; 15(7):1591. https://doi.org/10.3390/nu15071591 https://www.mdpi.com/2072-6643/15/7/1591 (Full text)

LC, POTS, and ME/CFS: Lifting the Fog

Abstract:

These three syndromes – long covid (LC), postural orthostatic tachycardia syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) – have many symptoms in common. The common denominator remains elusive.
The blood brain barrier (BBB) has been a barrier not only to microbes and toxins but also to understanding pathogenetic links. There are several areas within the brain that have no BBB. These are known as circumventricular organs (CVOs) and their location relative to CNS nuclei that direct autonomic and neuroendocrine functions is provocative in the quest for pathogenesis.
In addition the majority afflicted with LC and ME/CFS appear to be those with two MTHFR polymorphisms, present in over 50% of Americans. These polymorphisms elevate homocysteine. When homocysteine is combined with CVOs, the fog of POTS and its paradox are lifted. POTS may represent the intersection of LC and ME/CFS in those with the MTHFR gene (hypermethylation or 677TT).
The gut microbiomes of LC and ME/CFS, deficient in butyrates, GABA, and diversity, are then linked with MTHFR genotype 677TT. Reactivation of neurotropic EBV and VZV, due to loss of surveillance by CD4+/CD8+ T cells, is seen as secondary. The oxidative stress generated by homocysteine, loss of glutathione, low fiber diet, and persistent chronic inflammation exhaust available mitochondria and, assisted by BKN and estrogen, exacerbate all the elements of these post viral fatigue syndromes.
Source: Chambers, P. LC, POTS, and ME/CFS: Lifting the Fog. Preprints.org 2023, 2023030418. https://doi.org/10.20944/preprints202303.0418.v1 (Full text available as PDF file)

Online Health Communities in Controversy over ME/CFS and Long Covid

Abstract:

The condition known variously as myalgic encephalomyelitis, chronic fatigue syndrome, or ME/CFS has been steeped in controversy for 40 years or more. Long Covid, first noticed and named in 2020, has become entangled with the ME/CFS controversy because of striking similarities in the experiences of patients suffering from the two illnesses. Online health communities (OHCs) have played central roles in both controversies, but these are not the kinds of roles that have been so well-documented in prior literature.

While prior research has established many ways in which participation in an OHC may benefit or otherwise affect community members themselves, this essay focuses on how OHCs contribute to positional shifts in health controversies that involve other communities as well. Using a framework for understanding health controversies as argumentative polylogues, I show that OHCs arguing with other players have made contributions that are both effective in gaining ground for the OHCs’ own goals and in elevating the overall quality of the debate. Further, in some cases these contributions have been so innovative as to suggest surprising future trajectories for OHCs.

Source: Jackson, S. (2023). Online Health Communities in Controversy over ME/CFS and Long Covid. European Journal of Health Communication, 4(2), 49–72. https://doi.org/10.47368/ejhc.2023.203 https://ejhc.org/article/view/3559/2989 (Full text)

Multiomic characterisation of the long-term sequelae of SARS survivors: a clinical observational study

Abstract:

Background: We aimed to characterise the long-term health outcomes of survivors of severe acute respiratory syndrome (SARS) and determine their recovery status and possible immunological basis.

Methods: We performed a clinical observational study on 14 health workers who survived SARS coronavirus infection between Apr 20, 2003 and Jun 6, 2003 in Haihe Hospital (Tianjin, China). Eighteen years after discharge, SARS survivors were interviewed using questionnaires on symptoms and quality of life, and received physical examination, laboratory tests, pulmonary function tests, arterial blood gas analysis, and chest imaging. Plasma samples were collected for metabolomic, proteomic, and single-cell transcriptomic analyses. The health outcomes were compared 18 and 12 years after discharge. Control individuals were also health workers from the same hospital but did not infect with SARS coronavirus.

Findings: Fatigue was the most common symptom in SARS survivors 18 years after discharge, with osteoporosis and necrosis of the femoral head being the main sequelae. The respiratory function and hip function scores of the SARS survivors were significantly lower than those of the controls. Physical and social functioning at 18 years was improved compared to that after 12 years but still worse than the controls. Emotional and mental health were fully recovered. Lung lesions on CT scans remained consistent at 18 years, especially in the right upper lobe and left lower lobe lesions. Plasma multiomics analysis indicated an abnormal metabolism of amino acids and lipids, promoted host defense immune responses to bacteria and external stimuli, B-cell activation, and enhanced cytotoxicity of CD8+ T cells but impaired antigen presentation capacity of CD4+ T cells.

Interpretation: Although health outcomes continued to improve, our study suggested that SARS survivors still suffered from physical fatigue, osteoporosis, and necrosis of the femoral head 18 years after discharge, possibly related to plasma metabolic disorders and immunological alterations.

Funding: This study was funded by the Tianjin Haihe Hospital Science and Technology Fund (HHYY-202012) and Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-063B, TJYXZDXK-067C).

Source: Li K, Wu Q, Li H, Sun H, Xing Z, Li L, Chen H. Multiomic characterisation of the long-term sequelae of SARS survivors: a clinical observational study. EClinicalMedicine. 2023 Apr;58:101884. doi: 10.1016/j.eclinm.2023.101884. Epub 2023 Feb 27. PMID: 36873427; PMCID: PMC9969173.

Neurologic manifestations of long COVID differ based on acute COVID-19 severity

Abstract:

Objective: To characterize neurologic manifestations in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients.

Methods: Prospective study of the first 100 consecutive PNP and 500 NNP patients evaluated at a Neuro-COVID-19 clinic between 5/2020 and 8/2021.

Results: PNP were older than NNP patients (mean 53.9 vs 44.9 y; p < 0.0001) with a higher prevalence of pre-existing comorbidities. An average 6.8 months from onset, the main neurologic symptoms were “brain fog” (81.2%), headache (70.3%), and dizziness (49.5%) with only anosmia, dysgeusia and myalgias being more frequent in the NNP compared to the PNP group (59 vs 39%, 57.6 vs 39% and 50.4 vs 33%, all p < 0.003). Moreover, 85.8% of patients experienced fatigue. PNP more frequently had an abnormal neurologic exam than NNP patients (62.2 vs 37%, p < 0.0001). Both groups had impaired quality of life in cognitive, fatigue, sleep, anxiety, and depression domains. PNP patients performed worse on processing speed, attention, and working memory tasks than NNP patients (T-score 41.5 vs 55, 42.5 vs 47 and 45.5 vs 49, all p < 0.001) and a US normative population. NNP patients had lower results in attention task only. Subjective impression of cognitive ability correlated with cognitive test results in NNP but not in PNP patients.

Interpretation: PNP and NNP patients both experience persistent neurologic symptoms affecting their quality of life. However, they harbor significant differences in demographics, comorbidities, neurologic symptoms and findings, as well as pattern of cognitive dysfunction. Such differences suggest distinct etiologies of Neuro-PASC in these populations warranting targeted interventions.

Source: Perez Giraldo GS, Ali ST, Kang AK, Patel TR, Budhiraja S, Gaelen JI, Lank GK, Clark JR, Mukherjee S, Singer T, Venkatesh A, Orban ZS, Lim PH, Jimenez M, Miller J, Taylor C, Szymanski AL, Scarpelli J, Graham EL, Balabanov RD, Barcelo BE, Cahan JG, Ruckman K, Shepard AG, Slutzky MW, LaFaver K, Kumthekar PU, Shetty NK, Carroll KS, Ho SU, Lukas RV, Batra A, Liotta EM, Koralnik IJ. Neurologic manifestations of long COVID differ based on acute COVID-19 severity. Ann Neurol. 2023 Mar 26. doi: 10.1002/ana.26649. Epub ahead of print. PMID: 36966460. https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.26649 (Full text available as PDF file)

 

Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC)

Abstract:

COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, and cognitive dysfunction that last for months and impact everyday functioning, is referred to as Long COVID under the general category of post-acute sequelae of SARS-CoV-2 infection (PASC). PASC is highly heterogenous and may be associated with multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular syndromes, neuropsychiatric disorders, pulmonary damage, renal failure, stroke, and vascular endothelial dysregulation. A better understanding of the pathophysiologic mechanisms underlying PASC is essential to guide prevention and treatment.

This review addresses potential mechanisms and hypotheses that connect SARS-CoV-2 infection to long-term health consequences. Comparisons between PASC and other virus-initiated chronic syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome will be addressed. Aligning symptoms with other chronic syndromes and identifying potentially regulated common underlining pathways may be necessary for understanding the true nature of PASC.

The discussed contributors to PASC symptoms include sequelae from acute SARS-CoV-2 injury to one or more organs, persistent reservoirs of the replicating virus or its remnants in several tissues, re-activation of latent pathogens such as Epstein-Barr and herpes viruses in COVID-19 immune-dysregulated tissue environment, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation dysregulation, dysfunctional brainstem/vagus nerve signaling, dysautonomia or autonomic dysfunction, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage specific patients.

Source: Sherif ZA, Gomez CR, Connors TJ, Henrich TJ, Reeves WB; RECOVER Mechanistic Pathway Task Force. Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC). Elife. 2023 Mar 22;12:e86002. doi: 10.7554/eLife.86002. PMID: 36947108; PMCID: PMC10032659. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10032659/ (Full text)

The Behavior of Muscle Oxygen Saturation, Oxy and Deoxy Hemoglobin during a Fatigue Test in Fibromyalgia

Abstract:

Previous studies have reported that people with fibromyalgia (FM) could suffer from mitochondrial dysfunction. However, the consumption of muscle oxygen during physical exercise has been poorly studied. Therefore, this study aimed to explore the response of muscle oxygen during a fatigue protocol in people with FM and healthy controls (HC). In addition, the peak torque and the total work were assessed.

A total of 31 participants (eighteen were people with fibromyalgia and thirteen were healthy controls) were enrolled in this cross-sectional study. All the participants underwent a fatigue protocol consisting of 20 repetitions at 180°·s−1 of quadriceps flexions and extensions using a Biodex System 3. The muscle oxygen saturation (SmO2), total hemoglobin (THb), deoxygenated hemoglobin (HHb) and oxygenated hemoglobin (O2Hb) values were measured using a portable near-infrared spectroscopy (NIRS) device. Significant differences between people with FM and healthy controls were found at baseline: SmO2 (FM: 56.03 ± 21.36; HC: 77.41 ± 10.82; p = 0.036), O2Hb (FM: 6.69 ± 2.59; HC: 9.37 ± 1.31; p = 0.030) and HHb (FM: 5.20 ± 2.51; HC: 2.73 ± 1.32; p = 0.039); during the fatigue protocol: SmO2 (FM: 48.54 ± 19.96; HC: 58.87 ± 19.72; p = 0.038), O2Hb (FM: 5.70 ± 2.34; HC: 7.06 ± 2.09; p = 0.027) and HHb (FM: 5.69 ± 2.65; HC: 4.81 ± 2.39; p = 0.048); and in the recovery at three min and six min for SmO2, O2Hb and HHb (p < 0.005).

Furthermore, healthy control values of SmO2, O2Hb and HHb have been significantly altered by the fatigue protocol (p < 0.005). In contrast, people with FM did not show any significant alteration in these values. Moreover, significant differences were found in the peak torque at extension (FM: 62.48 ± 24.45; HC: 88.31 ± 23.51; p = 0.033) and flexion (FM: 24.16 ± 11.58; HC: 42.05 ± 9.85; p = 0.010), and the total work performed at leg extension (FM: 1039.78 ± 434.51; HC: 1535.61 ± 474.22; p = 0.007) and flexion (FM: 423.79 ± 239.89; HC: 797.16 ± 194.37; p = 0.005).

Source: Villafaina S, Tomas-Carus P, Silva V, Costa AR, Fernandes O, Parraca JA. The Behavior of Muscle Oxygen Saturation, Oxy and Deoxy Hemoglobin during a Fatigue Test in Fibromyalgia. Biomedicines. 2023 Jan 4;11(1):132. doi: 10.3390/biomedicines11010132. PMID: 36672640; PMCID: PMC9856161. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856161/ (Full text)

An Orthomolecular Protocol for Long COVID

Abstract:

A significant number of COVID-19 patients suffer from SARS-CoV-2 post-acute chronic sequelae, also known as post-COVID syndrome or long COVID. These patients report a broad range of persistent and debilitating symptoms such as fatigue, brain fog, pain, breathlessness, and dysrhythmias. These chronic symptoms are believed to be a consequence of excessive production of reactive oxygen species (ROS), inflammation, tissue damage, and mitochondrial dysfunction. Patients at higher risk of long-term sequelae are those who experienced severe COVID-19 infection, are immunocompromised and likely have depleted reserves of biological factors and micronutrients necessary for prompt recovery.

Based on biochemical principles and studies in conditions that share common traits with long COVID patients such as chronic fatigue syndrome and fibromyalgia, symptom relief and sustained recovery can be expected by administering an orthomolecular protocol consisting of a combination of precursors, cofactors, and biological response modifiers.

Source: Gonzalez MJ et al. (2023) An Orthomolecular Protocol for Long-COVID. J Orthomol Med. 38(1) https://www.researchgate.net/publication/369328211_An_Orthomolecular_Protocol_for_Long_COVID (Full text)