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Bansal AS, Seton KA, Brooks JCW, Carding SR. Cognitive Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Aetiology and Potential Treatments. Int J Mol Sci 2025; 26:1896. [PMID: 40076522 PMCID: PMC11899462 DOI: 10.3390/ijms26051896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 02/07/2025] [Accepted: 02/20/2025] [Indexed: 03/14/2025] Open
Abstract
Systemic infection and inflammation impair mental function through a combination of altered attention and cognition. Here, we comprehensively review the relevant literature and report personal clinical observations to discuss the relationship between infection, peripheral inflammation, and cerebral and cognitive dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Cognitive dysfunction in ME/CFS could result from low-grade persistent inflammation associated with raised pro-inflammatory cytokines. This may be caused by both infectious and non-infectious stimuli and lead to altered regional cerebral blood flow accompanied by disturbed neuronal function. Immune dysregulation that manifests as a subtle immunodeficiency or the autoimmunity targeting of one or more neuronal receptors may also be a contributing factor. Efforts to reduce low-grade systemic inflammation and viral reactivation and to improve mitochondrial energy generation in ME/CFS have the potential to improve cognitive dysfunction in this highly disabling condition.
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Affiliation(s)
| | - Katharine A. Seton
- Food, Microbiome and Health Research Programme, Quadram Institute Bioscience, Norwich NR4 7UQ, UK;
| | | | - Simon R. Carding
- Food, Microbiome and Health Research Programme, Quadram Institute Bioscience, Norwich NR4 7UQ, UK;
- Norwich Medical School, University East Anglia, Norwich NR4 7TJ, UK
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2
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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; 28:3052-3063. [PMID: 36977713 PMCID: PMC10533743 DOI: 10.1080/13548506.2023.2195670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 03/20/2023] [Indexed: 03/30/2023]
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.
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Affiliation(s)
- Kensei I. Maeda
- Center for Community Research, DePaul University, Chicago, IL, USA
| | - Mohammed F. Islam
- Department of Psychology, Chicago State University, Chicago, IL, USA
| | - Karl E. Conroy
- Center for Community Research, DePaul University, Chicago, IL, USA
| | - Leonard Jason
- Center for Community Research, DePaul University, Chicago, IL, USA
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3
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Maciuch J, Jason LA. Alcohol intolerance and myalgic encephalomyelitis/chronic fatigue syndrome. World J Neurol 2023; 9:17-27. [DOI: 10.5316/wjn.v9.i3.17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 04/13/2023] [Accepted: 05/06/2023] [Indexed: 05/30/2023] Open
Abstract
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.
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Affiliation(s)
- Jessica Maciuch
- Center for Community Research, DePaul University, Chicago, IL 60614, United States
| | - Leonard A Jason
- Center for Community Research, DePaul University, Chicago, IL 60614, United States
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4
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Xiong R, Gunter C, Fleming E, Vernon SD, Bateman L, Unutmaz D, Oh J. Multi-'omics of gut microbiome-host interactions in short- and long-term myalgic encephalomyelitis/chronic fatigue syndrome patients. Cell Host Microbe 2023; 31:273-287.e5. [PMID: 36758521 PMCID: PMC10353054 DOI: 10.1016/j.chom.2023.01.001] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 09/14/2022] [Accepted: 12/30/2022] [Indexed: 02/11/2023]
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, debilitating disorder manifesting as severe fatigue and post-exertional malaise. The etiology of ME/CFS remains elusive. Here, we present a deep metagenomic analysis of stool combined with plasma metabolomics and clinical phenotyping of two ME/CFS cohorts with short-term (<4 years, n = 75) or long-term disease (>10 years, n = 79) compared with healthy controls (n = 79). First, we describe microbial and metabolomic dysbiosis in ME/CFS patients. Short-term patients showed significant microbial dysbiosis, while long-term patients had largely resolved microbial dysbiosis but had metabolic and clinical aberrations. Second, we identified phenotypic, microbial, and metabolic biomarkers specific to patient cohorts. These revealed potential functional mechanisms underlying disease onset and duration, including reduced microbial butyrate biosynthesis and a reduction in plasma butyrate, bile acids, and benzoate. In addition to the insights derived, our data represent an important resource to facilitate mechanistic hypotheses of host-microbiome interactions in ME/CFS.
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Affiliation(s)
- Ruoyun Xiong
- The Jackson Laboratory, Farmington, CT 06032, USA; The University of Connecticut Health Center, Farmington, CT 06030, USA
| | | | | | | | | | | | - Julia Oh
- The Jackson Laboratory, Farmington, CT 06032, USA.
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5
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Campagne J, Fornasieri I, Andreani B, Eginard M, de Korwin JD. Separating Patients with SEID from Those with CFS in the French ME/CFS Association, with Some Thoughts on Nomenclature. Diagnostics (Basel) 2022; 12:1095. [PMID: 35626248 PMCID: PMC9139646 DOI: 10.3390/diagnostics12051095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Revised: 04/17/2022] [Accepted: 04/22/2022] [Indexed: 12/04/2022] Open
Abstract
In 2015, the American Institute of Medicine, now called the National Academy of Medicine, (IOM/NAM) proposed new diagnostic criteria for both Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and a new label: Systemic Exertion Intolerance Disease (SEID). This study aimed to evaluate the SEID criteria among members of the French Association of ME/CFS (ASFC) and their opinion about this new name. We sent an anonymous questionnaire to 494 ASFC members, using French-translated questions derived from the IOM/NAM tool kit. Among the 178/231 responding subjects who reported ME/CFS diagnosis, 150 (84%) met the criteria of SEID. For each set of questions, we identified some of them that significantly distinguished SEID from non-SEID patients concerning unrefreshing sleep, cognitive disorders, and orthostatic intolerance items. Forty-six percent of the respondents considered the "SEID" terminology as more appropriate than "CFS", 39% considered it inappropriate, and 15% had no opinion. Some questions better identified the SEID criteria. The IOM/NAM SEID criteria captured a large part of ASFC members suffering from ME/CFS. However, this new SEID label was not well accepted by the subjects, nor were the other denominations, suggesting that a better term should be found. Pending development of specific markers, further work with patient communities is needed to find a more suitable label.
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Affiliation(s)
- Julien Campagne
- Internal Medicine Department, University of Lorraine, 34, Cours Leopold, CS 25233, CEDEX, 54052 Nancy, France;
- Internal Medicine Department, University Hospital of Nancy, Rue du Morvan, CEDEX, 54511 Vandœuvre-Lès-Nancy, France
| | - Isabelle Fornasieri
- Faculty of Psychology, University of Strasbourg, 12, Rue Goethe, 67000 Strasbourg, France;
- French Association for Chronic Fatigue Syndrome (ASFC), Maison des Associations Nice Centre, 3 bis, rue Guigonis, 06300 Nice, France
| | - Barbara Andreani
- Regional Center for Scientific Documentation and Clinical Research, Legouest Army Instruction Hospital, 27, Avenue de Plantières, 57077 Metz, France;
| | - Monique Eginard
- French Association for Chronic Fatigue Syndrome (ASFC), 25, Impasse des Lavandes, 13710 Fuveau, France;
| | - Jean-Dominique de Korwin
- Internal Medicine Department, University of Lorraine, 34, Cours Leopold, CS 25233, CEDEX, 54052 Nancy, France;
- Internal Medicine Department, University Hospital of Nancy, Rue du Morvan, CEDEX, 54511 Vandœuvre-Lès-Nancy, France
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Kujawski S, Słomko J, Newton JL, Eaton-Fitch N, Staines DR, Marshall-Gradisnik S, Zalewski P. Network Analysis of Symptoms Co-Occurrence in Chronic Fatigue Syndrome. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph182010736. [PMID: 34682478 PMCID: PMC8535251 DOI: 10.3390/ijerph182010736] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 10/08/2021] [Accepted: 10/10/2021] [Indexed: 11/16/2022]
Abstract
Chronic fatigue syndrome (CFS) is a heterogenous disorder of multiple disabling symptoms with complex manifestations. Network analysis is a statistical and interrogative methodology to investigate the prevalence of symptoms (nodes) and their inter-dependent (inter-nodal) relationships. In the present study, we explored the co-occurrence of symptoms in a cohort of Polish CFS patients using network analysis. A total of 110 patients with CFS were examined (75 females). The mean age of the total sample was 37.93 (8.5) years old while the mean duration of symptoms in years was 4.4 (4). Post-exertional malaise (PEM) was present in 75.45% of patients, unrefreshing sleep was noted in 89.09% and impaired memory or concentration was observed in 87.27% of patients. The least prevalent symptom was tender cervical or axillary lymph nodes, noted in 34.55% of the total sample. Three of the most densely connected nodes were the total number of symptoms, sore throat and PEM. PEM was positively related with impairment in memory or concentration. Both PEM and impairment in memory or concentration presence are related to more severe fatigue measured by CFQ and FIS. PEM presence was positively related with the presence of multi-joint pain and negatively with tender lymph nodes and muscle pain. Sore throat was related with objective and subjective autonomic nervous system impairment. This study helps define symptom presentation of CFS with the pathophysiology of specific systems and links with multidisciplinary contemporary molecular pathology, including comparative MRI.
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Affiliation(s)
- Sławomir Kujawski
- Department of Exercise Physiology and Functional Anatomy, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-094 Bydgoszcz, Poland; (J.S.); (P.Z.)
- Correspondence:
| | - Joanna Słomko
- Department of Exercise Physiology and Functional Anatomy, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-094 Bydgoszcz, Poland; (J.S.); (P.Z.)
| | - Julia L. Newton
- Population Health Sciences Institute, The Medical School, Newcastle University, Newcastle-upon-Tyne NE2 4HH, UK;
| | - Natalie Eaton-Fitch
- National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute of Queensland, Griffith University, Gold Coast, Brisbane, QLD 4222, Australia; (N.E.-F.); (D.R.S.); (S.M.-G.)
- Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Brisbane, QLD 4222, Australia
| | - Donald R. Staines
- National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute of Queensland, Griffith University, Gold Coast, Brisbane, QLD 4222, Australia; (N.E.-F.); (D.R.S.); (S.M.-G.)
- Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Brisbane, QLD 4222, Australia
| | - Sonya Marshall-Gradisnik
- National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute of Queensland, Griffith University, Gold Coast, Brisbane, QLD 4222, Australia; (N.E.-F.); (D.R.S.); (S.M.-G.)
- Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Brisbane, QLD 4222, Australia
| | - Paweł Zalewski
- Department of Exercise Physiology and Functional Anatomy, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-094 Bydgoszcz, Poland; (J.S.); (P.Z.)
- National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute of Queensland, Griffith University, Gold Coast, Brisbane, QLD 4222, Australia; (N.E.-F.); (D.R.S.); (S.M.-G.)
- Consortium Health International for Myalgic Encephalomyelitis, Menzies Health Institute Queensland, Griffith University, Gold Coast, Brisbane, QLD 4222, Australia
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7
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McDonald S, Tan SX, Banu S, van Driel M, McGree JM, Mitchell G, Nikles J. Exploring Symptom Fluctuations and Triggers in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Novel Patient-Centred N-of-1 Observational Designs: A Protocol for a Feasibility and Acceptability Study. PATIENT-PATIENT CENTERED OUTCOMES RESEARCH 2021; 15:197-206. [PMID: 34368926 DOI: 10.1007/s40271-021-00540-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/15/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic condition of unknown aetiology associated with a range of disabling symptoms, including post-exertional malaise, chronic fatigue, musculoskeletal pain, orthostatic intolerance, unrefreshing sleep, and cognitive dysfunction. ME/CFS is a heterogeneous disorder, with significant variation in symptom type and severity between individuals, as well as within individuals over time. The diversity of ME/CFS symptom presentation makes management challenging; treatments supported by data from randomised controlled trials may not work for all individuals due to the variability in experienced symptoms. Studies using quantitative N-of-1 observational designs involve repeated outcome measurements in an individual over time and can generate rigorous individual-specific conclusions about symptom patterns and triggers in individuals with ME/CFS. This study aims to explore the feasibility and acceptability of using novel patient-centred N-of-1 observational designs to explore symptom fluctuations and triggers in ME/CFS at the individual level. METHODS AND ANALYSIS Individuals with a medical diagnosis of ME/CFS will be recruited through ME/CFS patient organisations to participate in a series of patient-centred N-of-1 observational studies. Using a wrist-worn electronic diary, participants will complete ecological momentary assessments of fatigue, stress, mood, and cognitive demand, three times per day for a period of 6-12 weeks. Personally relevant symptoms and triggers will also be incorporated into the questionnaire design. Physical activity will be objectively measured via an integrated accelerometer. Feasibility and acceptability outcomes will be assessed including the percentage of diary entries completed, as well as recruitment and retention rate, feasibility of analysing and interpreting the data collected, and participant views about participation elicited via a post-study semi-structured interview. DISCUSSION This study will assess the feasibility and acceptability of patient-centred N-of-1 observational studies to assess diseases with complex presentations such as ME/CFS, as well as provide individual-level evidence about fluctuations and triggers of ME/CFS symptoms that may aid self-management. TRIAL REGISTRATION Australian and New Zealand Clinical Trials Registry: ACTRN12618001898246. Registered on 22 November 2018.
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Affiliation(s)
- Suzanne McDonald
- Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia.
| | - Samuel X Tan
- Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia
| | - Shamima Banu
- Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Mieke van Driel
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - James M McGree
- Science Faculty, Queensland University of Technology, Brisbane, QLD, Australia
| | - Geoffrey Mitchell
- Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia.,Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Jane Nikles
- Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia
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8
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Sepúlveda N. Impact of genetic variation on the molecular mimicry between Anoctamin-2 and Epstein-Barr virus nuclear antigen 1 in Multiple Sclerosis. Immunol Lett 2021; 238:29-31. [PMID: 34310987 DOI: 10.1016/j.imlet.2021.07.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 07/19/2021] [Indexed: 12/12/2022]
Affiliation(s)
- Nuno Sepúlveda
- CEAUL - Centro de Estatística e Aplicações da Universidade de Lisboa, Portugal.
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9
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Brown A, Jason LA. Meta-analysis investigating post-exertional malaise between patients and controls. J Health Psychol 2020; 25:2053-2071. [PMID: 29974812 PMCID: PMC7440642 DOI: 10.1177/1359105318784161] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Post-exertional malaise is either required or included in many previously proposed case definitions of myalgic encephalomyelitis/chronic fatigue syndrome. A meta-analysis of odds ratios (ORs; association between patient status and post-exertional malaise status) and a number of potential moderators (i.e. study-level characteristics) of effect size were conducted. Post-exertional malaise was found to be 10.4 times more likely to be associated with a myalgic encephalomyelitis/chronic fatigue syndrome diagnosis than with control status. Significant moderators of effect size included patient recruitment strategy and control selection. These findings suggest that post-exertional malaise should be considered a cardinal symptom of myalgic encephalomyelitis/chronic fatigue syndrome.
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10
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Chu L, Valencia IJ, Garvert DW, Montoya JG. Onset Patterns and Course of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Pediatr 2019; 7:12. [PMID: 30805319 PMCID: PMC6370741 DOI: 10.3389/fped.2019.00012] [Citation(s) in RCA: 116] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 01/14/2019] [Indexed: 12/19/2022] Open
Abstract
Background: Epidemiologic studies of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) have examined different aspects of this disease separately but few have explored them together. Objective: Describe ME/CFS onset and course in one United States-based cohort. Methods: One hundred and fifty subjects fitting Fukuda 1994 CFS criteria completed a detailed survey concerning the initial and subsequent stages of their illness. Descriptive statistics, graphs, and tables were used to illustrate prevalence and patterns of characteristics. Results: The most common peri-onset events reported by subjects were infection-related episodes (64%), stressful incidents (39%), and exposure to environmental toxins (20%). For 38% of subjects, more than 6 months elapsed from experiencing any initial symptom to developing the set of symptoms comprising their ME/CFS. Over time, the 12 most common symptoms persisted but declined in prevalence, with fatigue, unrefreshing sleep, exertion-related sickness, and flu-like symptoms declining the most (by 20-25%). Conversely, cognitive symptoms changed the least in prevalence, rising in symptom ranking. Pregnancy, menopause, and menstrual cycles exacerbated many women's symptoms. Fatigue-related function was not associated with duration of illness or age; during the worst periods of their illness, 48% of subjects could not engage in any productive activity. At the time of survey, 47% were unable to work and only 4% felt their condition was improving steadily with the majority (59%) describing a fluctuating course. Ninety-seven percent suffered from at least one other illness: anxiety (48%), depression (43%), fibromyalgia (39%), irritable bowel syndrome (38%), and migraine headaches (37%) were the most diagnosed conditions. Thirteen percent came from families where at least one other first-degree relative was also afflicted, rising to 27% when chronic fatigue of unclear etiology was included. Conclusions: This paper offers a broad epidemiologic overview of one ME/CFS cohort in the United States. While most of our findings are consistent with prior studies, we highlight underexamined aspects of this condition (e.g., the evolution of symptoms) and propose new interpretations of findings. Studying these aspects can offer insight and solutions to the diagnosis, etiology, pathophysiology, and treatment of this condition.
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Affiliation(s)
- Lily Chu
- Stanford ME/CFS Initiative, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA, United States
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11
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Hulens M, Rasschaert R, Vansant G, Stalmans I, Bruyninckx F, Dankaerts W. The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology. J Pain Res 2018; 11:3129-3140. [PMID: 30573989 PMCID: PMC6292399 DOI: 10.2147/jpr.s186878] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
PURPOSE Idiopathic intracranial hypertension (IICH) is a condition characterized by raised intracranial pressure (ICP), and its diagnosis is established when the opening pressure measured during a lumbar puncture is elevated >20 cm H2O in nonobese patients or >25 cm H2O in obese patients. Papilledema is caused by forced filling of the optic nerve sheath with cerebrospinal fluid (CSF). Other common but underappreciated symptoms of IICH are neck pain, back pain, and radicular pain in the arms and legs resulting from associated increased spinal pressure and forced filling of the spinal nerves with CSF. Widespread pain and also several other characteristics of IICH share notable similarities with characteristics of fibromyalgia (FM) and chronic fatigue syndrome (CFS), two overlapping chronic pain conditions. The aim of this review was to compare literature data regarding the characteristics of IICH, FM, and CFS and to link the shared data to an apparent underlying physiopathology, that is, increased ICP. METHODS Data in the literature regarding these three conditions were compared and linked to the hypothesis of the shared underlying physiopathology of increased cerebrospinal pressure. RESULTS The shared characteristics of IICH, FM, and CFS that can be caused by increased ICP include headaches, fatigue, cognitive impairment, loss of gray matter, involvement of cranial nerves, and overload of the lymphatic olfactory pathway. Increased pressure in the spinal canal and in peripheral nerve root sheaths causes widespread pain, weakness in the arms and legs, walking difficulties (ataxia), and bladder, bowel, and sphincter symptoms. Additionally, IICH, FM, and CFS are frequently associated with sympathetic overactivity symptoms and obesity. These conditions share a strong female predominance and are frequently associated with Ehlers-Danlos syndrome. CONCLUSION IICH, FM, and CFS share a large variety of symptoms that might all be explained by the same pathophysiology of increased cerebrospinal pressure.
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Affiliation(s)
- Mieke Hulens
- Department of Rehabilitation Sciences, Faculty of Kinesiology and Rehabilitation Sciences, Musculoskeletal Rehabilitation Research Unit, University of Leuven, Leuven, Belgium,
| | - Ricky Rasschaert
- Department of Neurosurgery, Sint-Jozefziekenhuis, Bornem, Belgium
| | - Greet Vansant
- Department of Social and Primary Health Care, Public Health Nutrition, University of Leuven, Leuven, Belgium
| | - Ingeborg Stalmans
- Department of Neurosciences, Ophthalmology Research Group, University of Leuven KU Leuven, Leuven, Belgium
- Department of Ophthalmology, University Hospitals UZ Leuven, Leuven, Belgium
| | - Frans Bruyninckx
- Clinical Electromyography Laboratory, Department of Academic Consultants, Faculty of Medicine, University Hospitals UZ Leuven, Leuven, Belgium
| | - Wim Dankaerts
- Department of Rehabilitation Sciences, Faculty of Kinesiology and Rehabilitation Sciences, Musculoskeletal Rehabilitation Research Unit, University of Leuven, Leuven, Belgium,
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12
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Murdock KW, Wang XS, Shi Q, Cleeland CS, Fagundes CP, Vernon SD. The utility of patient-reported outcome measures among patients with myalgic encephalomyelitis/chronic fatigue syndrome. Qual Life Res 2016; 26:913-921. [PMID: 27600520 DOI: 10.1007/s11136-016-1406-3] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/31/2016] [Indexed: 02/01/2023]
Abstract
PURPOSE Debilitating fatigue is a core symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, the utility of patient-reported symptom outcome measures of fatigue for ME/CFS patients is problematic due to ceiling effects and issues with reliability and validity. We sought to evaluate the performance of three patient-reported symptom measures in a sample of ME/CFS patients and matched controls. METHODS Two hundred and forty ME/CFS patients and 88 age, sex, race, and zip code matched controls participated in the study. Participants completed the Multidimensional Fatigue Inventory-20, DePaul Symptom Questionnaire, and RAND SF-36. RESULTS The general and physical fatigue subscales on Multidimensional Fatigue Inventory-20, as well as the role of physical health on the RAND SF-36, demonstrated questionable or unacceptable internal consistency and problematic ceiling effects. The DePaul Symptom Questionnaire demonstrated excellent internal reliability, and less than 5 % of participants were at the ceiling on each subscale. The post-exertional malaise subscale on the DePaul Symptom Questionnaire demonstrated excellent clinical utility as it was able to differentiate between ME/CFS patients and controls (OR 1.23, p < .001) and predicted ceiling effects on other patient-reported outcome subscales. A score of 20 on the post-exertional malaise subscale of the DePaul Symptom Questionnaire optimally differentiated between patients and controls. CONCLUSIONS Significant ceiling effects and concerns with reliability and validity were observed among Multidimensional Fatigue Inventory-20 and RAND SF-36 subscales for ME/CFS patients. The DePaul Symptom Questionnaire addresses a number of concerns typically identified when using patient-reported outcome measures with ME/CFS patients; however, an improved multidimensional patient-reported outcome tool for measuring ME/CFS-related symptoms is warranted.
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Affiliation(s)
- Kyle W Murdock
- Department of Psychology, Rice University, Houston, TX, USA
| | - Xin Shelley Wang
- Department of Symptom Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1450, Houston, TX, 77030, USA.
| | - Qiuling Shi
- Department of Symptom Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1450, Houston, TX, 77030, USA
| | - Charles S Cleeland
- Department of Symptom Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1450, Houston, TX, 77030, USA
| | - Christopher P Fagundes
- Department of Psychology, Rice University, Houston, TX, USA.,Department of Symptom Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1450, Houston, TX, 77030, USA
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Jason LA, Sunnquist M, Brown A, Furst J, Cid M, Farietta J, Kot B, Bloomer C, Nicholson L, Williams Y, Jantke R, Newton JL, Strand EB. Factor Analysis of the DePaul Symptom Questionnaire: Identifying Core Domains. JOURNAL OF NEUROLOGY AND NEUROBIOLOGY 2015; 1:10.16966/2379-7150.114. [PMID: 27088131 PMCID: PMC4830389 DOI: 10.16966/2379-7150.114] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
The present study attempted to identify critical symptom domains of individuals with Myalgic Encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Using patient and control samples collected in the United States, Great Britain, and Norway, exploratory factor analysis (EFA) was used to establish the underlying factor structure of ME and CFS symptoms. The EFA suggested a four-factor solution: post-exertional malaise, cognitive dysfunction, sleep difficulties, and a combined factor consisting of neuroendocrine, autonomic, and immune dysfunction symptoms. The use of empirical methods could help better understand the fundamental symptom domains of this illness.
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Meeus M, Ickmans K, Struyf F, Kos D, Lambrecht L, Willekens B, Cras P, Nijs J. What is in a name? Comparing diagnostic criteria for chronic fatigue syndrome with or without fibromyalgia. Clin Rheumatol 2014; 35:191-203. [PMID: 25308475 DOI: 10.1007/s10067-014-2793-x] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2014] [Revised: 09/11/2014] [Accepted: 09/29/2014] [Indexed: 02/06/2023]
Abstract
The current study had two objectives. (1) to compare objective and self-report measures in patients with chronic fatigue syndrome (CFS) according to the 1994 Center for Disease Control (CDC) criteria, patients with multiple sclerosis (MS), and healthy controls, and (2) to contrast CFS patients who only fulfill CDC criteria to those who also fulfill the criteria for myalgic encephalomyelitis (ME), the 2003 Canadian criteria for ME/CFS, or the comorbid diagnosis of fibromyalgia (FM). One hundred six participants (48 CFS patients diagnosed following the 1994 CDC criteria, 19 MS patients, and 39 healthy controls) completed questionnaires assessing symptom severity, quality of life, daily functioning, and psychological factors. Objective measures consisted of activity monitoring, evaluation of maximal voluntary contraction and muscle recovery, and cognitive performance. CFS patients were screened whether they also fulfilled ME criteria, the Canadian criteria, and the diagnosis of FM. CFS patients scored higher on symptom severity, lower on quality of life, and higher on depression and kinesiophobia and worse on MVC, muscle recovery, and cognitive performance compared to the MS patients and the healthy subjects. Daily activity levels were also lower compared to healthy subjects. Only one difference was found between those fulfilling the ME criteria and those who did not regarding the degree of kinesiophobia (lower in ME), while comorbidity for FM significantly increased the symptom burden. CFS patients report more severe symptoms and are more disabled compared to MS patients and healthy controls. Based on the present study, fulfillment of the ME or Canadian criteria did not seem to give a clinically different picture, whereas a diagnosis of comorbid FM selected symptomatically worse and more disabled patients.
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Affiliation(s)
- Mira Meeus
- Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
- Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
- Pain in Motion International Research Group, .
- Rehabilitation Sciences and Physiotherapy, Ghent University, Campus Heymans (UZ) 3 B3, De Pintelaan 185, Ghent, Belgium.
| | - Kelly Ickmans
- Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Pain in Motion International Research Group
- Departments of Human Physiology and & Rehabilitation Sciences, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Brussel, Belgium
- Department of Physiotherapy and Rehabilitation, University Hospital Brussels, Brussel, Belgium
| | - Filip Struyf
- Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Pain in Motion International Research Group
| | - Daphne Kos
- Pain in Motion International Research Group
- Division of Occupational Therapy, Artesis Plantijn University College Antwerp, Antwerp, Belgium
- Rehabilitation Sciences, KU Leuven, Leuven, Belgium
| | - Luc Lambrecht
- Private practice for internal medicine, Ghent, Belgium
| | - Barbara Willekens
- Department of Neurology, Faculty of Medicine, University and University Hospital Antwerp, Antwerp, Belgium
| | - Patrick Cras
- Department of Neurology, Faculty of Medicine, University and University Hospital Antwerp, Antwerp, Belgium
| | - Jo Nijs
- Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- Pain in Motion International Research Group
- Departments of Human Physiology and & Rehabilitation Sciences, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Brussel, Belgium
- Department of Physiotherapy and Rehabilitation, University Hospital Brussels, Brussel, Belgium
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Brown AA, Jason LA. Validating a measure of myalgic encephalomyelitis/chronic fatigue syndrome symptomatology. FATIGUE-BIOMEDICINE HEALTH AND BEHAVIOR 2014; 2:132-152. [PMID: 27213118 DOI: 10.1080/21641846.2014.928014] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
OBJECTIVES The present study sought to validate a comprehensive self-report measure of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptomatology to aid in clinical and research assessment. METHOD Exploratory factor analysis (EFA) was used to establish the underlying factor structure of the DePaul Symptom Questionnaire (DSQ) (Jason, Evans, et al., 2010) using a well-characterized sample of individuals (92.6% met the Fukuda et al. criteria (1994) and/or the Clinical Canadian Criteria (Carruthers et al., 2003)), and this structure was then tested on a less stringently recruited sample of individuals utilizing a confirmatory factor analysis (CFA). Convergent and discriminant validity of the DSQ were also examined utilizing alternative measures of symptomatology and functioning. RESULTS A 3-factor solution was found using EFA (Neuroendocrine, Autonomic & Immune Dysfunction; Neurological/Cognitive Dysfunction; Post-Exertional Malaise) and the fit of this factor structure was adequate for the second sample. DISCUSSION The DSQ is a valid measure of ME/CFS symptomatology. The emergent factors were consistent with previous literature on symptom clusters, and convergent and discriminant validity were established.
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Affiliation(s)
- Abigail A Brown
- Center for Community Research/DePaul University/990 W. Fullerton Ave. Suite 3100/Chicago, Illinois 60614/USA
| | - Leonard A Jason
- Center for Community Research/DePaul University/990 W. Fullerton Ave. Suite 3100/Chicago, Illinois 60614/USA
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Morris G, Maes M. Mitochondrial dysfunctions in myalgic encephalomyelitis/chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways. Metab Brain Dis 2014; 29:19-36. [PMID: 24557875 DOI: 10.1007/s11011-013-9435-x] [Citation(s) in RCA: 105] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2013] [Accepted: 08/22/2013] [Indexed: 02/07/2023]
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/cfs) is classified by the World Health Organization as a disorder of the central nervous system. ME/cfs is an neuro-immune disorder accompanied by chronic low-grade inflammation, increased levels of oxidative and nitrosative stress (O&NS), O&NS-mediated damage to fatty acids, DNA and proteins, autoimmune reactions directed against neoantigens and brain disorders. Mitochondrial dysfunctions have been found in ME/cfs, e.g. lowered ATP production, impaired oxidative phosphorylation and mitochondrial damage. This paper reviews the pathways that may explain mitochondrial dysfunctions in ME/cfs. Increased levels of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-α, and elastase, and increased O&NS may inhibit mitochondrial respiration, decrease the activities of the electron transport chain and mitochondrial membrane potential, increase mitochondrial membrane permeability, interfere with ATP production and cause mitochondrial shutdown. The activated O&NS pathways may additionally lead to damage of mitochondrial DNA and membranes thus decreasing membrane fluidity. Lowered levels of antioxidants, zinc and coenzyme Q10, and ω3 polyunsaturated fatty acids in ME/cfs may further aggravate the activated immuno-inflammatory and O&NS pathways. Therefore, it may be concluded that immuno-inflammatory and O&NS pathways may play a role in the mitochondrial dysfunctions and consequently the bioenergetic abnormalities seen in patients with ME/cfs. Defects in ATP production and the electron transport complex, in turn, are associated with an elevated production of superoxide and hydrogen peroxide in mitochondria creating adaptive and synergistic damage. It is argued that mitochondrial dysfunctions, e.g. lowered ATP production, may play a role in the onset of ME/cfs symptoms, e.g. fatigue and post exertional malaise, and may explain in part the central metabolic abnormalities observed in ME/cfs, e.g. glucose hypometabolism and cerebral hypoperfusion.
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Meyer JD, Light AR, Shukla SK, Clevidence D, Yale S, Stegner AJ, Cook DB. Post-exertion malaise in chronic fatigue syndrome: symptoms and gene expression. FATIGUE-BIOMEDICINE HEALTH AND BEHAVIOR 2013. [DOI: 10.1080/21641846.2013.838444] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Van Oosterwijck J, Nijs J, Meeus M, Van Loo M, Paul L. Lack of Endogenous Pain Inhibition During Exercise in People With Chronic Whiplash Associated Disorders: An Experimental Study. THE JOURNAL OF PAIN 2012; 13:242-54. [DOI: 10.1016/j.jpain.2011.11.006] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/28/2011] [Revised: 11/09/2011] [Accepted: 11/20/2011] [Indexed: 10/14/2022]
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Role of psychological aspects in both chronic pain and in daily functioning in chronic fatigue syndrome: a prospective longitudinal study. Clin Rheumatol 2012; 31:921-9. [DOI: 10.1007/s10067-012-1946-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2011] [Revised: 11/16/2011] [Accepted: 01/23/2012] [Indexed: 10/28/2022]
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20
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Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powles ACP, Speight N, Vallings R, Bateman L, Baumgarten-Austrheim B, Bell DS, Carlo-Stella N, Chia J, Darragh A, Jo D, Lewis D, Light AR, Marshall-Gradisnik S, Mena I, Mikovits JA, Miwa K, Murovska M, Pall ML, Stevens S. Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med 2011; 270:327-38. [PMID: 21777306 PMCID: PMC3427890 DOI: 10.1111/j.1365-2796.2011.02428.x] [Citation(s) in RCA: 763] [Impact Index Per Article: 54.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The label 'chronic fatigue syndrome' (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term 'myalgic encephalomyelitis' (ME) because it indicates an underlying pathophysiology. It is also consistent with the neurological classification of ME in the World Health Organization's International Classification of Diseases (ICD G93.3). Consequently, an International Consensus Panel consisting of clinicians, researchers, teaching faculty and an independent patient advocate was formed with the purpose of developing criteria based on current knowledge. Thirteen countries and a wide range of specialties were represented. Collectively, members have approximately 400 years of both clinical and teaching experience, authored hundreds of peer-reviewed publications, diagnosed or treated approximately 50 000 patients with ME, and several members coauthored previous criteria. The expertise and experience of the panel members as well as PubMed and other medical sources were utilized in a progression of suggestions/drafts/reviews/revisions. The authors, free of any sponsoring organization, achieved 100% consensus through a Delphi-type process. The scope of this paper is limited to criteria of ME and their application. Accordingly, the criteria reflect the complex symptomatology. Operational notes enhance clarity and specificity by providing guidance in the expression and interpretation of symptoms. Clinical and research application guidelines promote optimal recognition of ME by primary physicians and other healthcare providers, improve the consistency of diagnoses in adult and paediatric patients internationally and facilitate clearer identification of patients for research studies.
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Affiliation(s)
- B M Carruthers
- Department of Physiology and Medicine, Vrije University of Brussels, Himmunitas Foundation, Brussels, Belgium.
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Haywood KL, Staniszewska S, Chapman S. Quality and acceptability of patient-reported outcome measures used in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review. Qual Life Res 2011; 21:35-52. [DOI: 10.1007/s11136-011-9921-8] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/21/2011] [Indexed: 12/26/2022]
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Van Oosterwijck J, Nijs J, Meeus M, Lefever I, Huybrechts L, Lambrecht L, Paul L. Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an experimental study. J Intern Med 2010; 268:265-78. [PMID: 20412374 DOI: 10.1111/j.1365-2796.2010.02228.x] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVES To examine the efficacy of the pain inhibitory systems in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) during two different types of exercise and to examine whether the (mal)functioning of pain inhibitory systems is associated with symptom increases following exercise. DESIGN A controlled experimental study. SETTING AND SUBJECTS Twenty-two women with ME/CFS and 22 healthy sedentary controls were studied at the Department of Human Physiology, Vrije Universiteit Brussel. INTERVENTIONS All subjects performed a submaximal exercise test and a self-paced, physiologically limited exercise test on a cycle ergometer. The exercise tests were undertaken with continuous cardiorespiratory monitoring. Before and after the exercise bouts, subjects filled out questionnaires to assess health status, and underwent pressure pain threshold measurements. Throughout the study, subjects' activity levels were assessed using accelerometry. RESULTS In patients with ME/CFS, pain thresholds decreased following both types of exercise, whereas they increased in healthy subjects. This was accompanied by a worsening of the ME/CFS symptom complex post-exercise. Decreased pressure thresholds during submaximal exercise were associated with postexertional fatigue in the ME/CFS group (r = 0.454; P = 0.034). CONCLUSIONS These observations indicate the presence of abnormal central pain processing during exercise in patients with ME/CFS and demonstrate that both submaximal exercise and self-paced, physiologically limited exercise trigger postexertional malaise in these patients. Further study is required to identify specific modes and intensity of exercise that can be performed in people with ME/CFS without exacerbating symptoms.
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Affiliation(s)
- J Van Oosterwijck
- Department of Human Physiology, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium
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Nijs J, Van Oosterwijck J, Meeus M, Lambrecht L, Metzger K, Frémont M, Paul L. Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta. J Intern Med 2010; 267:418-35. [PMID: 20433584 DOI: 10.1111/j.1365-2796.2009.02178.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
OBJECTIVES Too vigorous exercise or activity increase frequently triggers postexertional malaise in people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a primary characteristic evident in up to 95% of people with ME/CFS. The present study aimed at examining whether two different types of exercise results in changes in health status, circulating elastase activity, interleukin (IL)-1beta and complement C4a levels. DESIGN Comparative experimental design. SETTING University. SUBJECTS Twenty-two women with ME/CFS and 22 healthy sedentary controls INTERVENTIONS participants were subjected to a submaximal exercise (day 8) and a self-paced, physiologically limited exercise (day 16). Each bout of exercise was preceded and followed by blood sampling, actigraphy and assessment of their health status. RESULTS Both submaximal exercise and self-paced, physiologically limited exercise resulted in postexertional malaise in people with ME/CFS. However, neither exercise bout altered elastase activity, IL-1beta or complement C4a split product levels in people with ME/CFS or healthy sedentary control subjects (P > 0.05). Postexercise complement C4a level was identified as a clinically important biomarker for postexertional malaise in people with ME/CFS. CONCLUSIONS Submaximal exercise as well as self-paced, physiologically limited exercise triggers postexertional malaise in people with ME/CFS, but neither types of exercise alter acute circulating levels of IL-1beta, complement C4a split product or elastase activity. Further studying of immune alterations in relation to postexertional malaise in people with ME/CFS using multiple measurement points postexercise is required.
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Affiliation(s)
- J Nijs
- Department of Human Physiology, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.
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Nijs J, Almond F, De Becker P, Truijen S, Paul L. Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial. Clin Rehabil 2008; 22:426-35. [PMID: 18441039 DOI: 10.1177/0269215507084410] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE It was hypothesized that the use of exercise limits prevents symptom increases and worsening of their health status following a walking exercise in people with chronic fatigue syndrome. DESIGN An uncontrolled clinical trial (semi-experimental design). SETTING Outpatient clinic of a university department. SUBJECTS Twenty-four patients with chronic fatigue syndrome. INTERVENTIONS Subjects undertook a walking test with the two concurrent exercise limits. Each subject walked at an intensity where the maximum heart rate was determined by heart rate corresponding to the respiratory exchange ratio = 1.0 derived from a previous submaximal exercise test and for a duration calculated from how long each patient felt they were able to walk. MAIN OUTCOME MEASURES The Short Form 36 Health Survey or SF-36, the Chronic Fatigue Syndrome Symptom List, and the Chronic Fatigue Syndrome -Activities and Participation Questionnaire were filled in prior to, immediately after and 24 hours after exercise. RESULTS The fatigue increase observed immediately post-exercise (P= 0.006) returned to pre-exercise levels 24 hours post-exercise. The increase in pain observed immediately post-exercise was retained at 24 hours post-exercise (P=0.03). Fourteen of the 24 subjects experienced a clinically meaningful change in bodily pain (change of SF-36 bodily pain score > or =10); 6 indicated that the exercise bout had slightly worsened their health status, and 2 had a clinically meaningful decrease in vitality (change of SF-36 vitality score > or =20). There was no change in activity limitations/participation restrictions. CONCLUSION It was shown that the use of exercise limits (limiting both the intensity and duration of exercise) prevents important health status changes following a walking exercise in people with chronic fatigue syndrome, but was unable to prevent short-term symptom increases.
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Affiliation(s)
- Jo Nijs
- Department of Human Physiology, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Belgium.
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Nijs J, Thielemans A. Kinesiophobia and symptomatology in chronic fatigue syndrome: a psychometric study of two questionnaires. Psychol Psychother 2008; 81:273-83. [PMID: 18644213 DOI: 10.1348/147608308x306888] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
OBJECTIVES The aims of the study were to examine the reliability of the Dutch and French versions of the Tampa scale kinesiophobia (TSK) version chronic fatigue syndrome (CFS), and to examine the reliability and validity of the Dutch and French versions of the CFS symptom list. DESIGN Repeated-measures design. METHODS Native Dutch speakers (N=100) and native French (N=48) speakers fulfilling the diagnostic criteria for CFS were asked to list the five most important symptoms and to complete the TSK-CFS, the CFS symptom list, and the Short Form 36 Health Status Survey or SF-36. A modified version of the TSK-CFS and the CFS symptom list was filled in within 24 hours of the first assessment. RESULTS The French and Dutch version of the TSK-CFS and CFS symptom lists displayed good reliability (ICC>or=.83). The CFS symptom list was internally consistent (Cronbach's alpha>or=.93) and concurrently valid with the SF-36. For the native Dutch and French speakers, respectively, 82 and 78% of the self-reported symptoms matched the content of CFS symptom list. CONCLUSIONS The results are in support of the psychometric properties of the French and Dutch versions of both the TSK-CFS and the CFS symptom list for assessing kinesiophobia and symptom severity, respectively.
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Affiliation(s)
- Jo Nijs
- Department of Human Physiology, Vrije Universiteit Brussel, Brussel, Belgium.
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Nijs J, Adriaens J, Schuermans D, Buyl R, Vincken W. Breathing retraining in patients with chronic fatigue syndrome: a pilot study. Physiother Theory Pract 2008; 24:83-94. [PMID: 18432511 DOI: 10.1080/09593980701429406] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
The study aimed to 1) examine the point prevalence of asynchronous breathing in chronic fatigue syndrome (CFS) patients; 2) examine whether CFS patients with an asynchronous breathing pattern present with diminished lung function in comparison with CFS patients with a synchronous breathing pattern; and 3) examine whether one session of breathing retraining in CFS patients with an asynchronous breathing pattern is able to improve lung function. Twenty patients fulfilling the diagnostic criteria for CFS were recruited for participation in a pilot controlled clinical trial with repeated measures. Patients presenting with an asynchronous breathing pattern were given 20-30 minutes of breathing retraining. Patients presenting with a synchronous breathing pattern entered the control group and received no intervention. Of the 20 enrolled patients with CFS, 15 presented with a synchronous breathing pattern and the remaining 5 patients (25%) with an asynchronous breathing pattern. Baseline comparison revealed no group differences in demographic features, symptom severity, respiratory muscle strength, or pulmonary function testing data (spirometry). In comparison to no treatment, the session of breathing retraining resulted in an acute (immediately postintervention) decrease in respiratory rate (p < 0.001) and an increase in tidal volume (p < 0.001). No other respiratory variables responded to the session of breathing retraining. In conclusion, the present study provides preliminary evidence supportive of an asynchronous breathing pattern in a subgroup of CFS patients, and breathing retraining might be useful for improving tidal volume and respiratory rate in CFS patients presenting with an asynchronous breathing motion.
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Affiliation(s)
- Jo Nijs
- Department of Human Physiology, Faculty of Physical Education and Physiotherapy, Vrije Universiteit, Brussel, Belgium.
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Nijs J, De Meirleir K, Meeus M, McGregor NR, Englebienne P. Chronic fatigue syndrome: intracellular immune deregulations as a possible etiology for abnormal exercise response. Med Hypotheses 2004; 62:759-65. [PMID: 15082102 DOI: 10.1016/j.mehy.2003.11.030] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2003] [Accepted: 11/09/2003] [Indexed: 02/06/2023]
Abstract
The exacerbation of symptoms after exercise differentiates Chronic fatigue syndrome (CFS) from several other fatigue-associated disorders. Research data point to an abnormal response to exercise in patients with CFS compared to healthy sedentary controls, and to an increasing amount of evidence pointing to severe intracellular immune deregulations in CFS patients. This manuscript explores the hypothetical interactions between these two separately reported observations. First, it is explained that the deregulation of the 2-5A synthetase/RNase L pathway may be related to a channelopathy, capable of initiating both intracellular hypomagnesaemia in skeletal muscles and transient hypoglycemia. This might explain muscle weakness and the reduction of maximal oxygen uptake, as typically seen in CFS patients. Second, the activation of the protein kinase R enzyme, a characteristic feature in atleast subsets of CFS patients, might account for the observed excessive nitric oxide (NO) production in patients with CFS. Elevated NO is known to induce vasidilation, which may limit CFS patients to increase blood flow during exercise, and may even cause and enhanced postexercise hypotension. Finally, it is explored how several types of infections, frequently identified in CFS patients, fit into these hypothetical pathophysiological interactions.
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Affiliation(s)
- Jo Nijs
- Department of Human Physiology, Faculty of Physical Education and Physical Therapy Science, Vrije Universiteit Brussel, Brussel 1090, Belgium.
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Tritt K, Nickel M, Mitterlehner F, Nickel C, Forthuber P, Leiberich P, Rother W, Loew T. Chronic fatigue and indicators of long-term employment disability in psychosomatic inpatients. Wien Klin Wochenschr 2004; 116:182-9. [PMID: 15088993 DOI: 10.1007/bf03040485] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
The major goal of this study was to determine indictors of long-term disability for psychosomatic inpatients with chronic fatigue syndrome. To this end, a cross-sectional study was performed with a random sample of patients (n=1000, response rate: 83.9%) at a psychosomatic inpatient clinic. 51.1% of the patients (n=429) reported intensely persistent exhaustion that had no logical relation to actual exertion. 159 (37.1%) patients in this group were disabled from working and these comprised the main target group of this study. Significantly more patients in the target group worked part time, were disabled for a disproportionately long period of time (50.9% of all were disabled for more than 6 months in the previous year), and felt stressed because of conflicts with their superiors and/or colleagues (in each case, P<0.01). While more frequent psychological comorbidity was not found, they reported physical complaints more often. It was not the patients fit for work who felt more burdened with chronic fatigue, but rather the employment-disabled, who were actually exposed to fewer demands. These patients had, in comparison with those fit to work, a stronger fixation on somatic complaints, inadequate perception of physical and psychic sensations, difficulties getting along with other people and in coping with a regular job (in each case, P<0.01). Prospective examination of these indicators could help detect predictor variables for long-term disability in chronic fatigue. Such predictors could contribute to timely social-medical assessment and treatment.
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Affiliation(s)
- Karin Tritt
- Section of Psychosomatic Medicine, University Clinic of the University Regensburg, Regensburg, Germany
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Andersen MM, Permin H, Albrecht F. Illness and disability in Danish Chronic Fatigue Syndrome patients at diagnosis and 5-year follow-up. J Psychosom Res 2004; 56:217-29. [PMID: 15016582 DOI: 10.1016/s0022-3999(03)00065-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2001] [Accepted: 03/03/2003] [Indexed: 01/04/2023]
Abstract
OBJECTIVE Evaluation of the life impact of Chronic Fatigue Syndrome (CFS) over 5 years. METHODS Thirty-three adult patients meeting 1988 and 1994 CDC case criteria answered identical questionnaires at diagnosis and 5 years later, when a retrospective questionnaire was also completed. RESULTS Work disability was very high and increased further, social isolation remained high, emotional adjustment improved. There were increased problems with reading and with allergies. Two measures of improvement were used: The relation between these measures was weak. Length of illness, extent of disability and emotional adjustment were poorly related to measures of improvement. Average illness scores were unchanged, but most individuals improved in some ways while worsening or remaining the same in others. Only one participant (3%) neared recovery, one other was substantially better but still severely disabled. CONCLUSION CFS patients exhibit severe, long-term functional impairment. Substantial improvement is uncommon, less than 6%. Allergies and aspects of cognition may worsen, emotional adjustment often improves.
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Affiliation(s)
- M M Andersen
- Department of Infectious Diseases M5132, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
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30
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