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Brain Sciences Jan 2022Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS and Gulf War Illness (GWI) share features of post-exertional malaise (PEM), exertional exhaustion, or... (Review)
Review
Review of the Midbrain Ascending Arousal Network Nuclei and Implications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Illness (GWI) and Postexertional Malaise (PEM).
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS and Gulf War Illness (GWI) share features of post-exertional malaise (PEM), exertional exhaustion, or postexertional symptom exacerbation. In a two-day model of PEM, submaximal exercise induced significant changes in activation of the dorsal midbrain during a high cognitive load working memory task (Washington 2020) (Baraniuk this issue). Controls had no net change. However, ME/CFS had increased activity after exercise, while GWI had significantly reduced activity indicating differential responses to exercise and pathological mechanisms. These data plus findings of the midbrain and brainstem atrophy in GWI inspired a review of the anatomy and physiology of the dorsal midbrain and isthmus nuclei in order to infer dysfunctional mechanisms that may contribute to disease pathogenesis and postexertional malaise. The nuclei of the ascending arousal network were addressed. Midbrain and isthmus nuclei participate in threat assessment, awareness, attention, mood, cognition, pain, tenderness, sleep, thermoregulation, light and sound sensitivity, orthostatic symptoms, and autonomic dysfunction and are likely to contribute to the symptoms of postexertional malaise in ME/CFS and GWI.
PubMed: 35203896
DOI: 10.3390/brainsci12020132 -
Journal of Translational Medicine Jul 2020Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with unknown causes. From the perspectives on the etiology and pathophysiology,... (Review)
Review
BACKGROUND
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with unknown causes. From the perspectives on the etiology and pathophysiology, ME/CFS has been labeled differently, which influenced changes in case definitions and terminologies. This review sought to feature aspects of the history, developments, and differential symptoms in the case definitions.
METHODS
A search was conducted through PubMed published to February 2020 using the following search keywords: case definition AND chronic fatigue syndrome [MeSH Terms]. All reference lists of the included studies were checked. Of the included studies, the number of citations and the visibility in the literatures of the definitions were considered for comparisons of the criteria.
RESULTS
Since the first 'ME' case definition was developed in 1986, 25 case definitions/diagnostic criteria were created based on three conceptual factors (etiology, pathophysiology, and exclusionary disorders). These factors can be categorized into four categories (ME, ME/CFS, CFS, and SEID) and broadly characterized according to primary disorder (ME-viral, CFS-unknown, ME/CFS-inflammatory, SEID-multisystemic), compulsory symptoms (ME and ME/CFS-neuroinflammatory, CFS and SEID-fatigue and/or malaise), and required conditions (ME-infective agent, ME/CFS, CFS, SEID-symptoms associated with fatigue, e.g., duration of illness). ME and ME/CFS widely cover all symptom categories, while CFS mainly covers neurologic and neurocognitive symptoms. Fatigue, cognitive impairment, PEM, sleep disorder, and orthostatic intolerance were the overlapping symptoms of the 4 categories, which were included as SEID criteria.
CONCLUSIONS
This study comprehensively described the journey of the development of case definitions and compared the symptom criteria. This review provides broader insights and explanations to understand the complexity of ME/CFS for clinicians and researchers.
Topics: Fatigue Syndrome, Chronic; Humans; Orthostatic Intolerance; Sleep Wake Disorders
PubMed: 32727489
DOI: 10.1186/s12967-020-02455-0 -
COVID-19 and post-infectious myalgic encephalomyelitis/chronic fatigue syndrome: a narrative review.Therapeutic Advances in Infectious... 2021Coronavirus disease 2019 (COVID-19) is a viral infection which can cause a variety of respiratory, gastrointestinal, and vascular symptoms. The acute illness phase... (Review)
Review
Coronavirus disease 2019 (COVID-19) is a viral infection which can cause a variety of respiratory, gastrointestinal, and vascular symptoms. The acute illness phase generally lasts no more than 2-3 weeks. However, there is increasing evidence that a proportion of COVID-19 patients experience a prolonged convalescence and continue to have symptoms lasting several months after the initial infection. A variety of chronic symptoms have been reported including fatigue, dyspnea, myalgia, exercise intolerance, sleep disturbances, difficulty concentrating, anxiety, fever, headache, malaise, and vertigo. These symptoms are similar to those seen in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a chronic multi-system illness characterized by profound fatigue, sleep disturbances, neurocognitive changes, orthostatic intolerance, and post-exertional malaise. ME/CFS symptoms are exacerbated by exercise or stress and occur in the absence of any significant clinical or laboratory findings. The pathology of ME/CFS is not known: it is thought to be multifactorial, resulting from the dysregulation of multiple systems in response to a particular trigger. Although not exclusively considered a post-infectious entity, ME/CFS has been associated with several infectious agents including Epstein-Barr Virus, Q fever, influenza, and other coronaviruses. There are important similarities between post-acute COVID-19 symptoms and ME/CFS. However, there is currently insufficient evidence to establish COVID-19 as an infectious trigger for ME/CFS. Further research is required to determine the natural history of this condition, as well as to define risk factors, prevalence, and possible interventional strategies.
PubMed: 33959278
DOI: 10.1177/20499361211009385 -
European Journal of Physical and... Dec 2022Rehabilitation focuses on impairments, activity limitations and participation restrictions being informed by the underlying health condition. In the current absence of... (Review)
Review
INTRODUCTION
Rehabilitation focuses on impairments, activity limitations and participation restrictions being informed by the underlying health condition. In the current absence of direct "evidence on" rehabilitation interventions for people with post-COVID-19 condition (PCC), we can search and synthesize the indirect "evidence relevant to" coming from interventions effective for the symptoms of PCC in other health conditions. The World Health Organization (WHO) required this information to inform expert teams and provide specific recommendations in their Guidelines. With this overview of reviews with mapping, we aimed to synthesize in a map the Cochrane evidence relevant to rehabilitation for fatigue, post-exertional malaise and orthostatic intolerance due to PCC.
EVIDENCE ACQUISITION
We searched the last five years' Cochrane Systematic Review (CSRs) using the terms "fatigue," "orthostatic intolerance," "rehabilitation" and their synonyms in the Cochrane Library. We extracted and summarized the available evidence using a map. We grouped the included CSRs for health conditions and interventions, indicating the effect and the quality of evidence.
EVIDENCE SYNTHESIS
Out of 1397 CSRs published between 2016 and 2021, we included 32 for fatigue and 4 for exercise intolerance. They provided data from 13 health conditions, with cancer (11 studies), chronic obstructive pulmonary disease (7 studies), fibromyalgia (4 studies), and cystic fibrosis (3 studies) being the most studied. Effective interventions for fatigue included exercise training and physical activities, telerehabilitation and multicomponent and educational interventions. Effective interventions for exercise intolerance included combined aerobic/anaerobic training and integrated disease rehabilitation management. The overall quality of evidence was low to very low and moderate in very few cases. We did not identify CSRs that specifically addressed post-exertional malaise or orthostatic intolerance.
CONCLUSIONS
These results are the first step of indirect evidence able to generate helpful hypotheses for clinical practice and future research. They served as the basis for the three recommendations on treatments for these PCC symptoms published in the current WHO Guidelines for clinical practice.
Topics: Humans; COVID-19; Exercise; Fatigue; Fibromyalgia; Orthostatic Intolerance; Quality of Life; Systematic Reviews as Topic
PubMed: 36472558
DOI: 10.23736/S1973-9087.22.07802-9 -
Reumatologia 2016Erythema nodosum is the most common form of panniculitis. It may have many aetiological factors. Erythema nodosum occurs three to five times more often in female... (Review)
Review
Erythema nodosum is the most common form of panniculitis. It may have many aetiological factors. Erythema nodosum occurs three to five times more often in female patients. It appears as erythematous painful rounded nodules, located most often on the anterior surface of the lower extremities, and may be accompanied by systemic symptoms such as fever, malaise and arthralgia. During diagnosis, oncological vigilance should be maintained, because erythema nodosum may be a paraneoplastic symptom. It requires an interdisciplinary approach and exclusion of many underlying causes.
PubMed: 27407284
DOI: 10.5114/reum.2016.60217 -
Diabetes, Obesity & Metabolism Jun 2022To evaluate whether the potent hypophagic and weight-suppressive effects of growth differentiation factor-15 (GDF15) and semaglutide combined would be a more efficacious...
AIMS
To evaluate whether the potent hypophagic and weight-suppressive effects of growth differentiation factor-15 (GDF15) and semaglutide combined would be a more efficacious antiobesity treatment than either treatment alone by examining whether the neural and behavioural mechanisms contributing to their anorectic effects were common or disparate.
MATERIALS/METHODS
Three mechanisms were investigated to determine how GDF15 and semaglutide induce anorexia: the potentiation of the intake suppression by gastrointestinal satiation signals; the reduction in motivation to feed; and the induction of visceral malaise. We then compared the effects of short-term, combined GDF15 and semaglutide treatment on weight loss to the individual treatments. Rat pharmaco-behavioural experiments assessed whether GDF15 or semaglutide added to the satiating effects of orally gavaged food and exogenous cholecystokinin (CCK). A progressive ratio operant paradigm was used to examine whether GDF15 or semaglutide reduced feeding motivation. Pica behaviour (ie, kaolin intake) and conditioned affective food aversion testing were used to evaluate visceral malaise. Additionally, fibre photometry studies were conducted in agouti-related protein (AgRP)-Cre mice to examine whether GDF15 or semaglutide, alone or in combination with CCK, modulate calcium signalling in hypothalamic AgRP neurons.
RESULTS
Semaglutide reduced food intake by amplifying the feeding-inhibitory effect of CCK or ingested food, inhibited the activity of AgRP neurons when combined with CCK, reduced feeding motivation and induced malaise. GDF15 induced visceral malaise but, strikingly, did not affect feeding motivation, the satiating effect of ingested food or CCK signal processing. Combined GDF15 and semaglutide treatment produced greater food intake and body weight suppression than did either treatment alone, without enhancing malaise.
CONCLUSIONS
GDF15 and semaglutide reduce food intake and body weight through largely distinct processes that produce greater weight loss and feeding suppression when combined.
Topics: Agouti-Related Protein; Animals; Anorexia; Body Weight; Cholecystokinin; Eating; Glucagon-Like Peptides; Growth Differentiation Factor 15; Mice; Rats; Weight Loss
PubMed: 35129264
DOI: 10.1111/dom.14663 -
Neurology International Dec 2022This study sought to ascertain the prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) among a sample of 465 patients with Long COVID. The...
This study sought to ascertain the prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) among a sample of 465 patients with Long COVID. The participants completed three questionnaires: (1) a new questionnaire measuring both the frequency and severity of 38 common symptoms of COVID and Long COVID, (2) a validated short form questionnaire assessing ME/CFS, and (3) a validated questionnaire measuring post-exertional malaise. The population was predominantly white, female, and living in North America. The mean duration since the onset of COVID-19 symptoms was 70.5 weeks. Among the 465 participants, 58% met a ME/CFS case definition. Of respondents who reported that they had ME/CFS only 71% met criteria for ME/CFS and of those who did not report they had ME/CFS, 40% nevertheless did meet criteria for the disease: both over-diagnosis and under-diagnosis were evident on self-report. This study supports prior findings that ME/CFS occurs with high prevalence among those who have persistent COVID-19 symptoms.
PubMed: 36648965
DOI: 10.3390/neurolint15010001 -
Proceedings of the National Academy of... Oct 2023Travel can induce motion sickness (MS) in susceptible individuals. MS is an evolutionary conserved mechanism caused by mismatches between motion-related sensory...
Travel can induce motion sickness (MS) in susceptible individuals. MS is an evolutionary conserved mechanism caused by mismatches between motion-related sensory information and past visual and motion memory, triggering a malaise accompanied by hypolocomotion, hypothermia, hypophagia, and nausea. Vestibular nuclei (VN) are critical for the processing of movement input from the inner ear. Motion-induced activation of VN neurons recapitulates MS-related signs. However, the genetic identity of VN neurons mediating MS-related autonomic and aversive responses remains unknown. Here, we identify a central role of cholecystokinin (CCK)-expressing VN neurons in motion-induced malaise. Moreover, we show that CCK VN inputs onto the parabrachial nucleus activate -expressing neurons and are sufficient to establish avoidance to novel food, which is prevented by CCK-A receptor antagonism. These observations provide greater insight into the neurobiological regulation of MS by identifying the neural substrates of MS and providing potential targets for treatment.
Topics: Animals; Mice; Motion Sickness; Movement; Neurons; Vestibular Nuclei; Vestibule, Labyrinth
PubMed: 37847729
DOI: 10.1073/pnas.2304933120 -
Frontiers in Immunology 2018Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of... (Review)
Review
Myalgic encephalomyelitis (ME) often also called chronic fatigue syndrome (ME/CFS) is a common, debilitating, disease of unknown origin. Although a subject of controversy and a considerable scientific literature, we think that a solid understanding of ME/CFS pathogenesis is emerging. In this study, we compiled recent findings and placed them in the context of the clinical picture and natural history of the disease. A pattern emerged, giving rise to an explanatory model. ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism. According to our model for ME/CFS pathogenesis, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. Under normal circumstances these B cell offsprings would have led to tolerance. Subsequent exogenous microbial exposition (triggering) can lead to comorbidities such as fibromyalgia, thyroid disorder, and orthostatic hypotension. A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing postexertional malaise and ME/CFS, affecting both muscle and brain. In principle, cloning and sequencing of immunoglobulin variable domains could reveal the evolution of pathogenic clones. Although evidence consistent with the model accumulated in recent years, there are several missing links in it. Hopefully, the hypothesis generates testable propositions that can augment the understanding of the pathogenesis of ME/CFS.
Topics: Autoantigens; Autoimmunity; B-Lymphocytes; Dysbiosis; Fatigue Syndrome, Chronic; Genetic Predisposition to Disease; Humans; Immune Tolerance; Immunoglobulin Variable Region; Infections; Models, Biological; Physical Exertion
PubMed: 29497420
DOI: 10.3389/fimmu.2018.00229 -
The Journal of the American Osteopathic... Oct 1999The chronic fatigue syndrome is an illness of unknown etiology characterized by severe fatigue, myalgias, lymphadenopathy, arthralgias, chills, fevers, and...
The chronic fatigue syndrome is an illness of unknown etiology characterized by severe fatigue, myalgias, lymphadenopathy, arthralgias, chills, fevers, and postexertional malaise. Recognizing chronic fatigue syndrome is primarily a method of exclusion with no definitive diagnostic test or physical findings. As research continues to delve into the many possible etiologic agents for chronic fatigue syndrome-infectious, immunologic, neurologic, or psychiatric alone or in combination- the answer remains elusive. What is known is that chronic fatigue syndrome is a heterogeneous disorder very possibly involving an interaction of biological systems. Therefore, chronic fatigue syndrome may describe a large subset of patients, each exhibiting unique symptoms and serologic profiles dependent on the nature of the onset of illness and the genetic profile of individual patients.
PubMed: 26983059
DOI: 10.7556/jaoa.1999.99.10.S1