An Etiological Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Kindling might represent a heuristic model for understanding the etiology of Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS). Kindling occurs when an organism is exposed repeatedly to an initially sub-threshold stimulus re-sulting in hypersensitivity and spontaneous seizure-like activity. Among patients with ME/CFS, chronically repeated low-intensity stimulation due to an infectious illness might cause kindling of the limbic-hypothalamic-pituitary axis. Kindling might also occur by high-intensity stimulation (e.g., brain trauma) of the limbic-hypothalamic-pituitary axis. Once this system is charged or kindled, it can sustain a high level of arousal with little or no external stimulus and eventually this could lead to hypocortisolism. Seizure activity may spread to adjacent structures of the limbic-hypothalamic-pituitary axis in the brain, which might be responsible for the varied symptoms that occur among patients with ME/CFS. In addition, kindling may also be responsible for high levels of oxidative stress, which has been found in patients with ME/CFS.

Accurate diagnosis of myalgic encephalomyelitis and chronic fatigue syndrome based upon objective test methods for characteristic symptoms

Although myalgic encephalomyelitis(ME) and chronic fatigue syndrome(CFS) are considered to be synonymous,the definitional criteria for ME and CFS define two distinct,partially overlapping,clinical entities.ME,whether defined by the original criteria or by the recently proposed criteria,is not equivalent to CFS,let alone a severe variant of incapacitating chronic fatigue.Distinctive features of ME are:muscle weaknessand easy muscle fatigability,cognitive impairment,circulatory deficits,a marked variability of the symptoms in presence and severity,but above all,post-exertional "malaise":a(delayed) prolonged aggravation of symptoms after a minor exertion.In contrast,CFS is primarily defined by(unexplained) chronic fatigue,which should be accompanied by four out of a list of 8 symptoms,e.g.,headaches.Due to the subjective nature of several symptoms of ME and CFS,researchers and clinicians have questioned the physiological origin of these symptoms and qualified ME and CFS as functional somatic syndromes.However,various characteristic symptoms,e.g.,post-exertional "malaise" and muscle weakness,can be assessed objectively using wellaccepted methods,e.g.,cardiopulmonary exercise tests and cognitive tests.The objective measures acquired by these methods should be used to accurately diagnose patients,to evaluate the severity and impact of the illness objectively and to assess the positive and negative effects of proposed therapies impartially.

The Effect of Curcumin on Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An Open Label Study

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), recently renamed as systemic exertion intolerance disease (SEID), is a chronic and often disabling disease. Although the exact pathophysiological mechanism of ME/CFS is unknown, immunological abnormalities may play an important role. Curcumin is a herb with powerful anti-oxidative, and anti-inflammatory properties. Therefore, we hypothesized that curcumin has favorable effects on symptomatology in ME/CFS patients. In total 52 patients participated, nine stopped the use of curcumin because of side effects. All remaining patients (n = 43) met the criteria for CFS;72% met the criteria for ME. Before and 8 weeks after the use of curcumin complexed with phosphatidyl choline, 500 mg bid, the CDC inventory for assessment of Chronic Fatigue Syndrome was filled in. The CDC questions (n = 19) were scored and divided into 2 parts: the first being specific for CFS complaints (n = 9), the second being scores of less specific symptoms (n = 10);denoted as CDC rest score. Results showed that 8 weeks curcumin use significantly decreased the CFS related symptom scores, but not the CDC rest scores. Analyzing the data separately for ME and CFS patients, the same significance for the CFS symptom scores was present. Conclusion: in this open-labeled study, 8 weeks curcumin use in a phosphatidyl choline complex reduced ME/CFS symptomatology. Therefore, a randomized placebo controlled study is warranted to assess its efficacy in ME/CFS patients.

Quantification of the Beneficial Effects of Compression Stockings on Symptoms of Exercise and Orthostatic Intolerance in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients

Chronic fatigue syndrome and myalgic encephalomyelitis (CFS/ME) are, amongst others, characterized by exercise intolerance, pain, post exertional malaise and orthostatic intolerance. It has been shown in venous disease and sport participation that compression stockings may improve exercise performance and reduce post exercise muscle soreness. Moreover, its use is advocated in orthostatic hypotension. Therefore, it was hypothesized that compression stockings may reduce symptomatology in CFS/ME patients. Methods: 100 patients used compression stockings class II for minimally 3 weeks and thereafter filled in a questionnaire, based on the Rand 36 physical activity questions (n = 9), whether compression stockings changed perceived symptoms or not. Moreover, 7 questions referring to prolonged standing and sitting, to recovery post exercise, muscle pain during or immediately post exercise, and to dizziness/light-headedness during or immediately post exercise, while standing and during prolonged sitting were added. Questions were scored as 1: able to perform activity much less while wearing the stockings, 2: perform activity somewhat less, 3: no perceived change in activity, 4: perform activity slightly better, 5: able to perform activity much better while wearing the stockings. Results: In patients able to answer the question, all mean scores per activity were significantly higher than 3, being no perceived change in activity while wearing the stockings. Subgroup analysis showed that patients with orthostatic intolerance reported higher effects than patients without orthostatic intolerance. Conclusion: This pilot study suggests that compression stockings may be useful to reduce symptomatology of physical activities in CFS/ME patients, especially in patients with orthostatic intolerance. Larger prospective studies with hard endpoints are warranted.

Decreased Expression of TRPM3 and mAChRM3 in the Small Intestine in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Introduction: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is often associated with gastrointestinal disturbance and inflammatory markers;however, there have been no histological studies performed in the small intestine from CFS/ME patients. The aim of this investigation was to assess the expression of certain inflammatory markers and inflammatory receptors, namely transient receptor potential melastin 3 (TRPM3) ion channels and muscarinic acetylcholine M3 (mAChRM3) receptors, in small intestinal tissues in a case controlled study comprising a CFS/ME patient and a healthy non-fatigued control. Method: Immunohistochemistry was performed on a small intestinal biopsy from a CFS/ME patient (age = 50;female) with self-reported symptoms of gastrointestinal disturbance and a non-fatigued control (NFC), (age = 28;female). Semi-quantitative analysis of expression was undertaken for interferon-gamma (IFNy), interleukin-1 alpha (IL-1α), tumour necrosis factor-alpha (TNFα), TRPM3 ion channels and mAChRM3 acetylcholine receptors. Results: There was significantly decreased expression of TRPM3 in the CFS/ME patient (35% ±9%) and a significant decrease in mAChRM3 in the CFS/ME patient (54% ±9%). There was no difference in IL-1α between CFS/ME patient and NFC, however;there was an increase in IFNy (13% ±6%) in the CFS/ME patient compared to NFC. There was a difference observed in TNFα in CFS/ME compared to NFC. Conclusion: Differences were noted in the expression of specific TRP ion channels and cholinergic receptors in CFS/ME compared with NFC, with CFS/ME demonstrating decreased TRPM3 and mAChRM3. Further, IFNy was increased, and TNFα decreased, in the small intestine of the CFS/ME patient with reported gastrointestinal disturbance.

Induced pluripotent stem cells as suitable sensors for fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome

BACKGROUND Fibromyalgia(FM)and myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS)are devastating metabolic neuroimmune diseases that are difficult to diagnose because of the presence of numerous symptoms and a lack of specific biomarkers.Despite patient heterogeneity linked to patient subgroups and variation in disease severity,anomalies are found in the blood and plasma of these patients when compared with healthy control groups.The seeming specificity of these“plasma factors”,as recently reported by Ron Davis and his group at Stanford University,CA,United States,and observations by our group,have led to the proposal that induced pluripotent stem cells(iPSCs)may be used as metabolic sensors for FM and ME/CFS,a hypothesis that is the basis for this indepth review.AIM To identify metabolic signatures in FM and/or ME/CFS supporting the existence of disease-associated plasma factors to be sensed by iPSCs.METHODS A PRISMA(Preferred Reported Items for Systematic Reviews and Meta-analysis)-based systematic review of the literature was used to select original studies evaluating the metabolite profiles of FM and ME/CFS body fluids.The MeSH terms“metabolomic”or“metabolites”in combination with FM and ME/CFS disease terms were screened against the PubMed database.Only original studies applying omics technologies,published in English,were included.The data obtained were tabulated according to the disease and type of body fluid analyzed.Coincidences across studies were searched and P-values reported by the original studies were gathered to document significant differences found in the disease groups.RESULTS Eighteen previous studies show that some metabolites are commonly altered in ME/CFS and FM body fluids.In vitro cell-based assays have the potential to be developed as screening platforms,providing evidence for the existence of factors in patient body fluids capable of altering morphology,differentiation state and/or growth patterns.Moreover,they can be further developed using approaches aimed at blocking or reversing the effects of specific plasma/serum factors seen in patients.The documented high sensitivity and effective responses of iPSCs to environmental cues suggests that these pluripotent cells could form robust,reproducible reporter systems of metabolic diseases,including ME/CFS and FM.Furthermore,culturing iPSCs,or their mesenchymal stem cell counterparts,in patient-conditioned medium may provide valuable information to predict individual outcomes to stem-cell therapy in the context of precision medicine studies.CONCLUSION This opinion review explains our hypothesis that iPSCs could be developed as a screening platform to provide evidence of a metabolic imbalance in FM and ME/CFS.

Alcohol intolerance and myalgic encephalomyelitis/chronic fatigue

BACKGROUND The literature is mixed about the occurrence of alcohol intolerance among patients with myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS).Surveys that asked respondents with ME/CFS whether they experienced alcohol intolerance within a recent time frame might produce inaccurate results because respondents may indicate that the symptom was not present if they avoid alcohol due to alcohol intolerance.AIM To overcome this methodologic problem,participants in the current study were asked whether they have avoided alcohol in the past 6 mo,and if they had,how severe their alcohol intolerance would be if they were to drink alcohol.METHODS The instrument used was a validated scale called the DePaul symptom questionnaire.Independent t-tests were performed among the alcohol intolerant or not alcohol intolerant group.The alcohol intolerant group had 208 participants,and the not alcohol intolerant group had 96 participants.RESULTS Using specially designed questions to properly identify those with alcohol intolerance,those who experienced alcohol intolerance vs those who did not experience alcohol intolerance experienced more frequent/severe symptoms and domains.In addition,using a multiple regression analysis,the orthostatic intolerance symptom domain was related to alcohol intolerance.CONCLUSION The findings from the current study indicated that those with ME/CFS are more likely to experience alcohol intolerance.In addition,those with this symptom have more overall symptoms than those without alcohol intolerance.

When a 17-Year-Old Girl Is Diagnosed with Myalgic Encephalomyelitis: A Case Study from the Swedish Health Care System—A Parent Perspective

This case study presents different strategies that were explored by the patient’s mother (who is a researcher in music and medicine) when her 17-year-old daughter was diagnosed with ME (Myalgic Encephalomyelitis), also known as Chronic Fatigue Syndrome (CFS). ME is not widely recognized in the Global as well as the Swedish population at large, and within healthcare, there are no standardized recommended treatments, partly due to the lack of published evidence-based studies. This case study aims to provide insights into how the Swedish healthcare system works, how different clinics and hospitals within it operate and interconnect;and how these contribute to health outcomes after 15 months of treatment.

Posttreatment Lyme disease syndrome and myalgic encephalomyelitis/chronic fatigue syndrome:A systematic review and comparison of pathogenesis

Lyme disease is the most common vector-borne illness in the United States and has been causing significant morbidity since its discovery in 1977.It is well-documented that about 10%of patients properly treated with antibiotics never fully recover,but instead go on to develop a chronic illness dubbed,posttreatment Lyme disease syndrome(PTLDS)characterized by severe fatigue,cognitive slowing,chronic pain,and sleep difficulties.This review includes 18 studies that detail the symptoms of patients with PTLDS and uses qualitative analysis to compare them to myalgic encephalitis/chronic fatigue syndrome(ME/CFS),a strikingly similar syndrome.In the majority of the PTLDS studies,at least four of the six major symptoms of ME/CFS were also noted,including substantial impairment in activity level and fatigue for more than 6 months,post-exertional malaise,and unrefreshing sleep.In one of the included PTLDS articles,26 of the 29 ME/CFS symptoms were noted.This study adds to the expanding literature on the post-active phase of infection syndromes,which suggests that chronic illnesses such as PTLDS and ME/CFS have similar pathogenesis despite different infectious origins.

慢性疲劳综合征诊断标志物的研究进展

慢性疲劳综合征(CFS)以至少6个月以上致残性疲劳为特征,并伴有其他精神、躯体症状。临床上CFS主要通过疲劳等主观症状进行诊断,而对于其病理机制和治疗效果的评估则需要精确的客观标志物来验证。可靠的诊断标志物可以为CFS临床诊断提供可重复、简便、科学的依据,但由于CFS疾病本身的复杂性,目前尚无明确的诊断标志物可作为诊断的金标准。近年来,随着免疫学和微生物学研究的发展,CFS的诊断逐渐客观化。未来CFS的诊断、治疗将更加快捷、精确。

慢性疲劳综合征/肌痛性脑脊髓炎的治疗药物研究指南简介

美国食品和药品监督管理局(FDA)于2014年3月发布了"慢性疲劳综合症/肌痛性脑脊髓炎(CFS/ME)指南草案"。指南草案介绍CFS/ME的临床症状,严重的CFS/ME影响患者的工作、学习和日常生活。目前CFS/ME的诊断比较困难,也没有任何有效药物获批用于该病的治疗,CFS/ME已成为远未得到满足的公众健康问题。在草案中,FDA从药物的临床试验设计等多方面,如目标人群定位、疗效终点、安全性等来指导相关新药的研发。介绍了指南的主要内容,期望为我国这方面的临床试验及药物的开发提供参考。