Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is associated with various symptoms, such as depression, pain, and fatigue. To date, the pathological mechanisms and therapeutics remain uncertain. The purpose of this study was to investigate the effect of myelophil (MYP), composed of Astragali Radix and Salviaemiltiorrhizae Radix, on depression, pain, and fatigue behaviors and its underlying mechanisms.

Reserpine (2 mg/kg for 10 days, intraperitoneally) induced depression, pain, and fatigue behaviors in mice. MYP treatment (100 mg/kg for 10 days, intragastrically) significantly improved depression behaviors, mechanical and thermal hypersensitivity, and fatigue behavior. MYP treatment regulated the expression of c-Fos, 5-HT1A/B receptors, and transforming growth factor β (TGF-β) in the brain, especially in the motor cortex, hippocampus, and nucleus of the solitary tract. MYP treatment decreased ionized calcium binding adapter molecule 1 (Iba1) expression in the hippocampus and increased tyrosine hydroxylase (TH) expression and the levels of dopamine and serotonin in the striatum. MYP treatment altered inflammatory and anti-oxidative-related mRNA expression in the spleen and liver.

In conclusion, MYP was effective in recovering major symptoms of ME/CFS and was associated with the regulation of dopaminergic and serotonergic pathways and TGF-β expression in the brain, as well as anti-inflammatory and anti-oxidant mechanisms in internal organs.

Source: Song JH, Won SK, Eom GH, Lee DS, Park BJ, Lee JS, Son CG, Park JY. Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model. Int J Mol Sci. 2021 Sep 22;22(19):10199. doi: 10.3390/ijms221910199. PMID: 34638540. https://pubmed.ncbi.nlm.nih.gov/34638540/

Caring for the patient with severe or very severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can cause a wide range of severity and functional impairment, leaving some patients able to work while others are homebound or bedbound. The most severely ill patients may need total care. Yet, patients with severe or very severe ME/CFS struggle to receive appropriate medical care because they cannot travel to doctors’ offices and their doctors lack accurate information about the nature of this disease and how to diagnose and manage it. Recently published clinical guidance provides updated information about ME/CFS but advice on caring for the severely ill is limited. This article is intended to fill that gap.
Based on published clinical guidance and clinical experience, we describe the clinical presentation of severe ME/CFS and provide patient-centered recommendations on diagnosis, assessment and approaches to treatment and management. We also provide suggestions to support the busy provider in caring for these patients by leveraging partnerships with the patient, their caregivers, and other providers and by using technology such as telemedicine. Combined with compassion, humility, and respect for the patient’s experience, such approaches can enable the primary care provider and other healthcare professionals to provide the care these patients require and deserve.
Source: Montoya JG, Dowell TG, Mooney AE, Dimmock ME, Chu L. Caring for the Patient with Severe or Very Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Healthcare. 2021; 9(10):1331. https://doi.org/10.3390/healthcare9101331 https://www.mdpi.com/2227-9032/9/10/1331/htm (Full text)

Neurochemical abnormalities in chronic fatigue syndrome: a pilot magnetic resonance spectroscopy study at 7 Tesla

Abstract:

Rationale: Chronic fatigue syndrome (CFS) is a common and burdensome illness with a poorly understood pathophysiology, though many of the characteristic symptoms are likely to be of brain origin. The use of high-field proton magnetic resonance spectroscopy (MRS) enables the detection of a range of brain neurochemicals relevant to aetiological processes that have been linked to CFS, for example, oxidative stress and mitochondrial dysfunction.

Methods: We studied 22 CFS patients and 13 healthy controls who underwent MRS scanning at 7 T with a voxel placed in the anterior cingulate cortex. Neurometabolite concentrations were calculated using the unsuppressed water signal as a reference.

Results: Compared to controls, CFS patients had lowered levels of glutathione, total creatine and myo-inositol in anterior cingulate cortex. However, when using N-acetylaspartate as a reference metabolite, only myo-inositol levels continued to be significantly lower in CFS participants.

Conclusions: The changes in glutathione and creatine are consistent with the presence of oxidative and energetic stress in CFS patients and are potentially remediable by nutritional intervention. A reduction in myo-inositol would be consistent with glial dysfunction. However, the relationship of the neurochemical abnormalities to the causation of CFS remains to be established, and the current findings require prospective replication in a larger sample.

Source: Godlewska BR, Williams S, Emir UE, Chen C, Sharpley AL, Goncalves AJ, Andersson MI, Clarke W, Angus B, Cowen PJ. Neurochemical abnormalities in chronic fatigue syndrome: a pilot magnetic resonance spectroscopy study at 7 Tesla. Psychopharmacology (Berl). 2021 Oct 5. doi: 10.1007/s00213-021-05986-6. Epub ahead of print. PMID: 34609538. https://pubmed.ncbi.nlm.nih.gov/34609538/

A retrospective cross-sectional study on tinnitus prevalence and disease associations in the Dutch population-based cohort Lifelines

Abstract:

Tinnitus is a highly prevalent disorder with heterogenous presentation and limited treatment options. Better understanding of its prevalence and disease and lifestyle risk factor associations in the general population is necessary to identify the underlying mechanisms. To this end, we quantified the prevalence of tinnitus and identified disease and lifestyle risk factors associated with tinnitus within a general population cohort. For this study, we used the Lifelines population-based cohort study to perform a retrospective cross-sectional study.

Lifelines is a large, multi-generational, prospective cohort study that includes over 167,000 participants (or 10% of the population) from the northern Netherlands. For this study, conducted between 2018 and 2021, data from the Lifelines population-based cohort study was used to perform a cross-sectional study. Adult participants (age ≥ 18 years) with data on tinnitus perception (collected once between 2011 and 2015) were included in this study. An elastic-net regression analysis was performed with tinnitus as the dependent variable and parameters of diseases and lifestyle risk factors (collected once between 2006 and 2014)-including hearing problems, cardiovascular disease, metabolic disorders, psychiatric disorders, thyroid disease, inflammatory disease, and functional somatic syndromes-as the independent variables.

Among 124,609 participants, N = 8,011 (6.4%) reported perceiving tinnitus constantly (CT: constant tinnitus) and N = 39,625 (31.8%) reported perceiving tinnitus constantly or occasionally (AT: any tinnitus). Our analysis identified 38 parameters that were associated with AT and 48 parameters that were associated with CT. Our study identified established disease associates with tinnitus, including problems with hearing (OR 8.570 with CT), arrythmia (OR 1.742 with CT), transient ischemic attack (OR 1.284 with AT), diabetes mellitus (OR 1.014 with AT) and psychiatric disorders, including major depressive disorder (OR 1.506 with CT). Factors related to lifestyle associated with tinnitus included waist-hip ratio (OR 1.061 with CT) and smoking (OR 1.028 with AT).

Novel disease associates with CT were identified for inflammatory diseases, including rheumatoid arthritis (OR 1.297) and ulcerative colitis (OR 1.588), thyroid disease (as evidenced by the use of thyroid medication) (OR 1.298), and functional somatic syndromes, including chronic fatigue syndrome (OR 1.568). In addition to validating established disease associates in a general population cohort, this study identified novel associations with tinnitus and several disease categories, including functional somatic syndromes, inflammatory diseases, and thyroid disease. Future work will be necessary to identify whether (common) mechanisms underly tinnitus and these associated disorders. Lifelines is an important new resource available for future studies investigating tinnitus in the general population.

Source: Schubert NMA, Rosmalen JGM, van Dijk P, Pyott SJ. A retrospective cross-sectional study on tinnitus prevalence and disease associations in the Dutch population-based cohort Lifelines. Hear Res. 2021 Sep 23;411:108355. doi: 10.1016/j.heares.2021.108355. Epub ahead of print. PMID: 34607212. https://pubmed.ncbi.nlm.nih.gov/34607212/

Fatigue in post-acute sequelae of SARS-CoV2 (PASC) treated with oxygen-ozone autohemotherapy – preliminary results on 100 patients

Abstract:

Objective: Post-acute sequelae of SARS-CoV2 infection (PASC) are a novel terminology used to describe post-COVID persistent symptoms, mimicking somehow the previously described chronic fatigue syndrome (CFS). In this manuscript, we evaluated a therapeutical approach to address PASC-derived fatigue in a cohort of past-COVID-19 positive patients.

Patients and methods: A number of 100 patients, previously diagnosed as COVID-19 positive subjects and meeting our eligibility criteria, was diagnosed having PASC-related fatigue. They were recruited in the study and treated with oxygen-ozone autohemotherapy (O2-O3-AHT), according to the SIOOT protocol. Patients’ response to O2-O3-AHT and changes in fatigue were measured with the 7-scoring Fatigue Severity Scale (FSS), according to previously published protocols.

Results: Statistics assessed that the effects of O2-O3-AHT on fatigue reduced PASC symptoms by 67%, as a mean, in all the investigated cohort of patients (H = 148.4786 p < 0.0001) (Figure 1). Patients following O2-O3-AHT therapy, quite completely recovered for PASC-associated fatigue, a quote amounting to about two fifths (around 40%) of the whole cohort undergoing ozone treatment and despite most of patients were female subjects, the effect was not influenced by sex distribution (H = 0.7353, p = 0.39117).

Conclusions: Ozone therapy is able to recover normal functionality and to relief pain and discomfort in the form of PASC-associated fatigue in at least 67% of patients suffering from post-COVID sequelae, aside from sex and age distribution.

Source: Tirelli U, Franzini M, Valdenassi L, Pisconti S, Taibi R, Torrisi C, Pandolfi S, Chirumbolo S. Fatigue in post-acute sequelae of SARS-CoV2 (PASC) treated with oxygen-ozone autohemotherapy – preliminary results on 100 patients. Eur Rev Med Pharmacol Sci. 2021 Sep;25(18):5871-5875. doi: 10.26355/eurrev_202109_26809. PMID: 34604980. https://pubmed.ncbi.nlm.nih.gov/34604980/

Please Help David Tuller, Our Champion!

David Tuller’s fundraiser is now live! Tuller has been tireless in his battle against the GET/CBT ideological onslaught! He has much more work to do and he needs our support.

Tuller has written more than seventy-five  posts on Vincent Racaniello’s Virology Blog, spanning seven years. His articles comprise a full history of how the PACE trial was used to mislead health care providers into thinking ME/CFS could be cured with “a walk and a talk.” Tuller has taken on some of the authors of the PACE study and, despite threats from them, has continued to challenge their findings.

This year, Tuller will be looking at intersections between the pandemic and ME, such as concerns about whether some COVID-19 patients will develop an ME-like disease. He will be keeping an eye out for new bad research (think: CBT and GET) and keeping an eye on goings-on at the CDC, the NIH and elsewhere.

Last year, Tuller successfully raised money through Crowdrise  in order to continue investigating and blogging about the PACE trial. The funds went to the School of Public Health at the University of California, Berkeley, which created a position for Tuller to continue his investigative work. Now, a year later, the funds have run out, and Tuller has to depend on the generosity of our community to continue his work.

PLEASE DONATE HERE!

Central sensitisation in chronic fatigue syndrome and fibromyalgia; a case control study

Abstract:

Introduction: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are both complex conditions that are challenging to treat. This may be related to an incomplete understanding of their pathophysiology, itself obfuscated by their heterogeneity. The symptomatic overlap between them and their common comorbidity suggests a shared vulnerability, which might be explained by central sensitisation.

Methods: 19 CFS cases, 19 FM cases and 20 age and sex matched healthy controls (HC) were recruited primarily from secondary care clinics in London. Those with other pain disorders, psychiatric diagnoses and those taking centrally acting or opiate medications were excluded. Participants were asked to abstain from alcohol and over the counter analgaesia 48 h prior to assessment by static and dynamic quantitative sensory tests, including measures of temporal summation (TS) and conditioned pain modulation (CPM).

Results: CS, as defined by the presence of both enhanced TS and inefficient CPM, was present in 16 (84%) CFS cases, 18 (95%) FM cases, and none of the HC (p < 0.001). Pressure pain thresholds were lower in CFS (Median222kPaIQR 146-311; p = 0.04) and FM cases (Median 189 kPa; IQR 129-272; p = 0.003) compared to HC (Median 311 kPa; IQR 245-377). FM cases differed from HC in cold-induced (FM = 22.6 °C (15.3-27.7) vs HC = 14.2 °C (9.0-20.5); p = 0.01) and heat-induced (FM = 38.0 °C (35.2-44.0) vs HC = 45.3 °C (40.1-46.8); p = 0.03) pain thresholds, where CFS cases did not.

Conclusion: Central sensitisation may be a common endophenotype in chronic fatigue syndrome and fibromyalgia. Further research should address whether central sensitisation is a cause or effect of these disorders.

Source: Bourke JH, Wodehouse T, Clark LV, Constantinou E, Kidd BL, Langford R, Mehta V, White PD. Central sensitisation in chronic fatigue syndrome and fibromyalgia; a case control study. J Psychosom Res. 2021 Sep 21;150:110624. doi: 10.1016/j.jpsychores.2021.110624. Epub ahead of print. PMID: 34600309. https://pubmed.ncbi.nlm.nih.gov/34600309/

A Comprehensive Examination of Severely Ill ME/CFS Patients

Abstract:

One in four myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients are estimated to be severely affected by the disease, and these house-bound or bedbound patients are currently understudied. Here, we report a comprehensive examination of the symptoms and clinical laboratory tests of a cohort of severely ill patients and healthy controls.
The greatly reduced quality of life of the patients was negatively correlated with clinical depression. The most troublesome symptoms included fatigue (85%), pain (65%), cognitive impairment (50%), orthostatic intolerance (45%), sleep disturbance (35%), post-exertional malaise (30%), and neurosensory disturbance (30%). Sleep profiles and cognitive tests revealed distinctive impairments. Lower morning cortisol level and alterations in its diurnal rhythm were observed in the patients, and antibody and antigen measurements showed no evidence for acute infections by common viral or bacterial pathogens.
These results highlight the urgent need of developing molecular diagnostic tests for ME/CFS. In addition, there was a striking similarity in symptoms between long COVID and ME/CFS, suggesting that studies on the mechanism and treatment of ME/CFS may help prevent and treat long COVID and vice versa.
Source: Chang C-J, Hung L-Y, Kogelnik AM, Kaufman D, Aiyar RS, Chu AM, Wilhelmy J, Li P, Tannenbaum L, Xiao W, Davis RW. A Comprehensive Examination of Severely Ill ME/CFS Patients. Healthcare. 2021; 9(10):1290. https://doi.org/10.3390/healthcare9101290 https://www.mdpi.com/2227-9032/9/10/1290/htm  (Full text)

Inflammation plays a causal role in fatigue-like behavior induced by pelvic irradiation in mice

Abstract:

Fatigue is a persistent and debilitating symptom following radiation therapy for prostate cancer. However, it is not well-understood how radiation targeted to a small region of the body can lead to broad changes in behavior. In this study, we used targeted pelvic irradiation of healthy male mice to test whether inflammatory signaling mediates changes in voluntary physical activity levels.

First, we tested the relationship between radiation dose, blood cell counts, and fatigue-like behavior measured as voluntary wheel-running activity. Next, we used oral minocycline treatments to reduce inflammation and found that minocycline reduces, but does not eliminate, the fatigue-like behavioral changes induced by radiation. We also used a strain of mice lacking the MyD88 adaptor protein and found that these mice also showed less fatigue-like behavior than the wild-type controls. Finally, using serum and brain tissue samples, we determined changes in inflammatory signaling induced by irradiation in wild-type, minocycline treated, and MyD88 knockout mice.

We found that irradiation increased serum levels of IL-6, a change that was partially reversed in mice treated with minocycline or lacking MyD88. Overall, our results suggest that inflammation plays a causal role in radiation-induced fatigue and that IL-6 may be an important mediator.

Source: Wolff BS, Alshawi SA, Feng LR, Juneau PL, Saligan LN. Inflammation plays a causal role in fatigue-like behavior induced by pelvic irradiation in mice. Brain Behav Immun Health. 2021 May 19;15:100264. doi: 10.1016/j.bbih.2021.100264. PMID: 34589770; PMCID: PMC8474574. https://pubmed.ncbi.nlm.nih.gov/34589770/

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A neurological entity?

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disorder of unknown physiopathology with multisystemic repercussions, framed in ICD-11 under the heading of neurology (8E49). There is no specific test to support its clinical diagnosis. Our objective is to review the evidence in neuroimaging and dysautonomia evaluation in order to support the neurological involvement and to find biomarkers serving to identify and/or monitor the pathology.
The symptoms typically appear acutely, although they can develop progressively over years; an essential trait for diagnosis is “central” fatigue together with physical and/or mental exhaustion after a small effort. Neuroimaging reveals various morphological, connectivity, metabolic, and functional alterations of low specificity, which can serve to complement the neurological study of the patient. The COMPASS-31 questionnaire is a useful tool to triage patients under suspect of dysautonomia, at which point they may be redirected for deeper evaluation. Recently, alterations in heart rate variability, the Valsalva maneuver, and the tilt table test, together with the presence of serum autoantibodies against adrenergic, cholinergic, and serotonin receptors were shown in a subgroup of patients.
This approach provides a way to identify patient phenotypes. Broader studies are needed to establish the level of sensitivity and specificity necessary for their validation. Neuroimaging contributes scarcely to the diagnosis, and this depends on the identification of specific changes. On the other hand, dysautonomia studies, carried out in specialized units, are highly promising in order to support the diagnosis and to identify potential biomarkers. ME/CFS orients towards a functional pathology that mainly involves the autonomic nervous system, although not exclusively.
Source: Gandasegui IM, Laka LA, Gargiulo P-Á, Gómez-Esteban J-C, Sánchez J-VL. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Neurological Entity? Medicina. 2021; 57(10):1030. https://doi.org/10.3390/medicina57101030 https://www.mdpi.com/1648-9144/57/10/1030 (Full article available as PDF file)