Hypothalamic-Pituitary-Adrenal (HPA) Axis and Chronic Fatigue Syndrome in Older Adults: The Rehabilitation Perspectives

Chronic fatigue syndrome (CFS) is a long-term and debilitating condition that regards as a neurological disease. Its symptoms include profound physical and mental fatigue (characteristically made worse by exertion), muscle and joint pain, disturbed sleep, and both concentration and memory problems. CFS is a kind of human stress-related disorders that are characterized by alterations in hypothalamic-pituitary-adrenal (HPA) axis activity. Investigation of abnormal activity of the HPA axis in various neurological and neuropsychiatric disorders can date back at least 60 years, and its relation to CFS had been reported in the early 1990s. This chapter further disseminated updated evidence for disruption of HPA function in CFS, with the explanation on the relationship between cytokines and HPA activities. Moreover, very limited literature had addressed the importance of rehabilitation to them . This chapter addresses this gap by sharing a pilot rehabilitation outcome on a single-blinded randomized control trial with a parallel group experimental design in the application of activity scheduling (AS) program of occupational therapy for a group of community-dwelling older adults with CFS. The primary objective is to study the outcome of physical functioning of individual participants. The second objective is to study the outcome of AS on impact of caring role through assessing individual caregivers’ perceived burden in care. The third objective is to study the time that needed in taking care; individuals’ perception of enjoyment and achievement in their participated activities will be evaluated. There was a significant effect of AS on the physical functioning of participants as measured by Functional Independence Measure (FIM), as the primary outcome measure, in experimental group, with Wilk’s λ = 0.72, F (2,57) = 18.75, p < 0.001. Moreover, in secondary outcome measures, there is a significant decrease in the impact of caring role as reflected by their perceived burden as measured by the Chinese Zarit Burden Interview (CZBI) in caring for experimental group, with Wilk’s λ = 0.72, F (2,97) = 18.75, p < 0.001. Another study set out to examine the effect of time on caring activities for those recruited couples in AS group. There was significant effect of AS on caring activities with Wilk’s λ = 0.71, F (2,97) = 12.47, p < 0.001. With proper coaching and regular facilitation regarding AS, activity participation in older adults with CFS can be greatly enhanced. Behavioral intervention, such as AS, can supplement therapeutic treatment or may lead to decline in CFS symptoms

Causes and consequences of autonomic dysfunction in Chronic Fatigue Syndrome

PhD ThesisChronic Fatigue Syndrome (CFS) is an incapacitating condition characterised by extreme fatigue. In the absence of an objective diagnostic test CFS remains a clinical diagnosis based on a broad spectrum of symptoms, including autonomic dysfunction and cognitive impairment. This has given rise to significant challenges, not least the development of multiple sets of diagnostic criteria that may represent different disease phenotypes. This thesis examines autonomic and cognitive features between subgroups that meet different diagnostic criteria to better understand this possibility. It also examines the overlap between symptoms of CFS and depression, a potential confounder. Methods A subset of data from a larger Medical Research Council funded observational study Understanding the pathogenesis of autonomic dysfunction in CFS and its relationship with cognitive impairment was examined. Patients were screened using the SCID-I assessment tool to exclude major depression prior to the main study. Depressive symptoms were compared to CFS Fukuda criteria. The DePaul Symptom Questionnaire (DSQ) was used to differentiate between diagnostic criteria. COMPASS and COGFAIL questionnaires were administered for self-reported autonomic and cognitive features respectively. The Task Force® Monitor was used for autonomic assessment and a battery of neuropsychological tests administered for objective cognitive assessment. Results Subjective autonomic and cognitive symptoms were significantly greater in CFS subjects compared to controls. There were no statistically significant differences in objective autonomic measures between CFS and controls. There were clinically significant differences between DSQ subgroups on objective autonomic testing. Psychomotor speed was significantly slower in CFS compared to controls. Visuospatial memory, verbal memory and psychomotor speed were significantly different between DSQ subgroups. Conclusion The findings indicate phenotypic differences between DSQ subsets and suggest that elucidating the symptoms seen in CFS, or its disease spectrum, will support research into its underlying pathophysiology and enable more tailored treatment. The absence of significant differences in objective autonomic function between CFS and controls in this cohort contrasts to findings of some other studies and may reflect study exclusion for depression. Together with the overlap between CFS and depressive symptoms, this reinforces the need to better understand the underpinning causality to allow appropriate identification and management.Medical Research Counci

The involvement of cerebrospinal fluid and lymphatic drainage in chronic fatigue syndrome (CFS/ME)

A novel osteopathic treatment has been discovered during the clinical practice of the author which alleviates many of the symptoms of chronic fatigue syndrome (CFS) known in the UK as CFS/ME. The efficacy of this manual approach was tested using two separate clinical trials. The first examined the change in the symptoms following a year of treatment. The second repeated the first study and examined the possible mechanisms of the improvement. The studies were designed to develop a greater understanding of the disorder, for which there is much scientific uncertainty regarding the cause, diagnosis and treatment. Phase 1 of the research trials included self report questionnaires to examine overall symptom change. With post-exercise fatigue being a major symptom of CFS/ME, the treatment protocol was best evaluated by determining its effects on muscle function which was analysed utilising isometric testing of the knee extensor muscles measuring the impulse torque. The second trial, which included the same self report questionnaires assessing symptom relief as in the initial trial, was divided into two parallel phases. Phase 2 primarily took the form of brain analysis using magnetic resonance imaging (MRI) to confirm if brain abnormalities seen in previous research were found in sufferers of CFS/ME. No cerebral abnormality was detected in the patient group. Central lymph scans were also carried out showing a possible trend of enlargement in CFS/ME sufferers. In the other part, phase 3, isometric tests were repeated with more accurate equipment than in phase 1. Integrated EMG and median frequency of the power spectrum were measured using surface electromyography (sEMG). Overall this study has provided strong evidence that an important component of CFS/ME involves a disturbance of lymphatic drainage of the brain and muscles. The novel osteopathic treatment developed by the author has been statistically validated in both phases of the study, emphasising the need to focus future research on the biomechanical aspectso f this disorder.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Creatine Supplementation for Health and Clinical Diseases

Creatine plays a critical role in cellular metabolism, primarily by binding with phosphate to form phosphocreatine (PCr) as well as shuttling high-energy phosphate compounds in and out of the mitochondria for metabolism. Increasing the dietary availability of creatine increases the tissue and cellular availability of PCr, and thereby enhances the ability to maintain high-energy states during intense exercise. For this reason, creatine monohydrate has been extensively studied as an ergogenic aid for exercise, training, and sport. Limitations in the ability to synthesize creatine and transport and/or store dietary creatine can impair metabolism and is a contributor to several disease states. Additionally, creatine provides an important source of energy during metabolically stressed states, particularly when oxygen availability is limited. Thus, researchers have assessed the role of creatine supplementation on health throughout the lifespan, as well as whether creatine availability may improve disease management and/or therapeutic outcomes. This book provides a comprehensive overview of scientific and medical evidence related to creatine's role in metabolism, health throughout the lifespan, and our current understanding of how creatine can promote brain, heart, vascular and immune health; reduce the severity of musculoskeletal and brain injury; and may provide therapeutic benefits in glucose management and diabetes, cancer therapy, inflammatory bowel disease, and post-viral fatigue

The involvement of cerebrospinal fluid and lymphatic drainage in chronic fatigue syndrome (CFS/ME)

A novel osteopathic treatment has been discovered during the clinical practice of the authorwhich alleviates many of the symptoms of chronic fatigue syndrome (CFS) known in theUK as CFS/ME. The efficacy of this manual approach was tested using two separateclinical trials. The first examined the change in the symptoms following a year of treatment.The second repeated the first study and examined the possible mechanisms of theimprovement. The studies were designed to develop a greater understanding of the disorder,for which there is much scientific uncertainty regarding the cause, diagnosis and treatment.Phase 1 of the research trials included self report questionnaires to examine overallsymptom change. With post-exercise fatigue being a major symptom of CFS/ME, thetreatment protocol was best evaluated by determining its effects on muscle function whichwas analysed utilising isometric testing of the knee extensor muscles measuring the impulsetorque.The second trial, which included the same self report questionnaires assessing symptomrelief as in the initial trial, was divided into two parallel phases. Phase 2 primarily took theform of brain analysis using magnetic resonance imaging (MRI) to confirm if brainabnormalities seen in previous research were found in sufferers of CFS/ME. No cerebralabnormality was detected in the patient group. Central lymph scans were also carried outshowing a possible trend of enlargement in CFS/ME sufferers. In the other part, phase 3,isometric tests were repeated with more accurate equipment than in phase 1. IntegratedEMG and median frequency of the power spectrum were measured using surfaceelectromyography (sEMG).Overall this study has provided strong evidence that an important component of CFS/MEinvolves a disturbance of lymphatic drainage of the brain and muscles. The novelosteopathic treatment developed by the author has been statistically validated in bothphases of the study, emphasising the need to focus future research on the biomechanicalaspectso f this disorder

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

This Special Issue on CFS/ME collects 18 papers with an interdisciplinary view on the current demographic and epidemiological data and immunological characteristics of CFS/ME and examines the different pathogenic hypotheses, as well as giving information about the latest knowledge on diagnostic investigations, pharmacological, integrative, physical, cognitive-behavioral and psychological curative approaches

The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multi-system disease whose etiological basis has not been established. Enteroviruses (EVs) as a cause of ME/CFS have sometimes been proposed, as they are known agents of acute respiratory and gastrointestinal infections that may persist in secondary infection sites, including the central nervous system, muscle, and heart. To date, the body of research that has investigated enterovirus infections in relation to ME/CFS supports an increased prevalence of chronic or persistent enteroviral infections in ME/CFS patient cohorts than in healthy individuals. Nevertheless, inconsistent results have fueled a decline in related studies over the past two decades. This review covers the aspects of ME/CFS pathophysiology that are consistent with a chronic enterovirus infection and critically reviews methodologies and approaches used in past EV-related ME/CFS studies. We describe the prior sample types that were interrogated, the methods used and the limitations to the approaches that were chosen. We conclude that there is considerable evidence that prior outbreaks of ME/CFS were caused by one or more enterovirus groups. Furthermore, we find that the methods used in prior studies were inadequate to rule out the presence of chronic enteroviral infections in individuals with ME/CFS. Given the possibility that such infections could be contributing to morbidity and preventing recovery, further studies of appropriate biological samples with the latest molecular methods are urgently needed

Non-invasive approaches to identify the cause of premature fatigue in Inflammatory Bowel Disease patients

Inflammatory bowel disease (IBD) fatigue is a pervasive secondary disease symptom. The aetiology is poorly understood, meaning that treatment options are sparse. This is of particular concern for the relatively large proportion of patients with quiescent disease, who continue to report an increased perception of fatigue and demonstrate premature exercise fatigue, relative to healthy individuals. Fatigue is multidimensional and can manifest as a disproportionate perception of tiredness, perturbed cognitive functioning and an inability to sustain a required work output during exercise. In contrast to other chronic disease, to date there has been no mechanistic assessment of IBD fatigue reported in the literature. This is congruent with the essential absence of any effective treatment strategies convincingly shown to reduce IBD fatigue burden, independent of targeting known clinical causes. The application of Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) techniques during exercise represents a unique opportunity to non-invasively probe in-vivo metabolism across multiple organs. This thesis seeks to characterise IBD fatigue aetiology by combining laboratory-based assessment of peripheral muscle function and cardiorespiratory fitness, with proton (1H) MRI and phosphorus (31P) MRS during within-bore exercise. This thesis represents the first attempt to comprehensively interrogate IBD physiology with the aim of identifying potential treatment targets for fatigue. Following an introduction to IBD in Chapter one, a detailed review of IBD fatigue aetiology follows in Chapter 2. Chapters 3 and 4 outline the methodology and developmental experiments undertaken to facilitate the MRI and 31P MRS experiments. Chapter 5 details the assessment of peripheral muscle function and body composition in quiescent Crohn’s disease patients relative to a healthy age and BMI matched control group. This is followed by the assessment of cardiovascular, brain and peripheral muscle deconditioning in Chapter 6 and 7. A final discussion chapter is dedicated to a review of the collective findings of this thesis in the context of existing data within the literature base. Suggestions are then made for future research priorities in the field of IBD fatigue

Non-invasive approaches to identify the cause of premature fatigue in Inflammatory Bowel Disease patients

Inflammatory bowel disease (IBD) fatigue is a pervasive secondary disease symptom. The aetiology is poorly understood, meaning that treatment options are sparse. This is of particular concern for the relatively large proportion of patients with quiescent disease, who continue to report an increased perception of fatigue and demonstrate premature exercise fatigue, relative to healthy individuals. Fatigue is multidimensional and can manifest as a disproportionate perception of tiredness, perturbed cognitive functioning and an inability to sustain a required work output during exercise. In contrast to other chronic disease, to date there has been no mechanistic assessment of IBD fatigue reported in the literature. This is congruent with the essential absence of any effective treatment strategies convincingly shown to reduce IBD fatigue burden, independent of targeting known clinical causes. The application of Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) techniques during exercise represents a unique opportunity to non-invasively probe in-vivo metabolism across multiple organs. This thesis seeks to characterise IBD fatigue aetiology by combining laboratory-based assessment of peripheral muscle function and cardiorespiratory fitness, with proton (1H) MRI and phosphorus (31P) MRS during within-bore exercise. This thesis represents the first attempt to comprehensively interrogate IBD physiology with the aim of identifying potential treatment targets for fatigue. Following an introduction to IBD in Chapter one, a detailed review of IBD fatigue aetiology follows in Chapter 2. Chapters 3 and 4 outline the methodology and developmental experiments undertaken to facilitate the MRI and 31P MRS experiments. Chapter 5 details the assessment of peripheral muscle function and body composition in quiescent Crohn’s disease patients relative to a healthy age and BMI matched control group. This is followed by the assessment of cardiovascular, brain and peripheral muscle deconditioning in Chapter 6 and 7. A final discussion chapter is dedicated to a review of the collective findings of this thesis in the context of existing data within the literature base. Suggestions are then made for future research priorities in the field of IBD fatigue