Tag: 2020

Cerebral Blood Flow Is Reduced in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients During Mild Orthostatic Stress Testing: An Exploratory Study at 20 Degrees of Head-Up Tilt Testing

Abstract:

Introduction: In a study of 429 adults with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), we demonstrated that 86% had symptoms of orthostatic intolerance in daily life. Using extracranial Doppler measurements of the internal carotid and vertebral arteries during a 30-min head-up tilt to 70 degrees, 90% had an abnormal reduction in cerebral blood flow (CBF). A standard head-up tilt test of this duration might not be tolerated by the most severely affected bed-ridden ME/CFS patients. This study examined whether a shorter 15-min test at a lower 20 degree tilt angle would be sufficient to provoke reductions in cerebral blood flow in severe ME/CFS patients.

Methods and results: Nineteen severe ME/CFS patients with orthostatic intolerance complaints in daily life were studied: 18 females. The mean (SD) age was 35(14) years, body surface area (BSA) was 1.8(0.2) m2 and BMI was 24.0(5.4) kg/m2. The median disease duration was 14 (IQR 5-18) years. Heart rate increased, and stroke volume index and end-tidal CO2 decreased significantly during the test (p ranging from <0.001 to <0.0001). The cardiac index decreased by 26(7)%: p < 0.0001. CBF decreased from 617(72) to 452(63) mL/min, a 27(5)% decline. All 19 severely affected ME/CFS patients met the criteria for an abnormal CBF reduction.

Conclusions: Using a less demanding 20 degree tilt test for 15 min in severe ME/CFS patients resulted in a mean CBF decline of 27%. This is comparable to the mean 26% decline previously noted in less severely affected patients studied during a 30-min 70 degree head-up tilt. These observations have implications for the evaluation and treatment of severely affected individuals with ME/CFS.

Source: van Campen CLMC, Rowe PC, Visser FC. Cerebral Blood Flow Is Reduced in Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients During Mild Orthostatic Stress Testing: An Exploratory Study at 20 Degrees of Head-Up Tilt Testing. Healthcare (Basel). 2020;8(2):E169. Published 2020 Jun 13. doi:10.3390/healthcare8020169 https://www.mdpi.com/2227-9032/8/2/169 (Full text)

Predictors of New Onsets of Irritable Bowel Syndrome, Chronic Fatigue Syndrome and Fibromyalgia: The Lifelines Study

Abstract:

Background: It has been claimed that functional somatic syndromes share a common etiology. This prospective population-based study assessed whether the same variables predict new onsets of irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS) and fibromyalgia (FM).

Methods: The study included 152 180 adults in the Dutch Lifelines study who reported the presence/absence of relevant syndromes at baseline and follow-up. They were screened at baseline for physical and psychological disorders, socio-demographic, psycho-social and behavioral variables. At follow-up (mean 2.4 years) new onsets of each syndrome were identified by self-report. We performed separate analyses for the three syndromes including participants free of the relevant syndrome or its key symptom at baseline. LASSO logistic regressions were applied to identify which of the 102 baseline variables predicted new onsets of each syndrome.

Results: There were 1595 (1.2%), 296 (0.2%) and 692 (0.5%) new onsets of IBS, CFS, and FM, respectively. LASSO logistic regression selected 26, 7 and 19 predictors for IBS, CFS and FM, respectively. Four predictors were shared by all three syndromes, four predicted IBS and FM and two predicted IBS and CFS but 28 predictors were specific to a single syndrome. CFS was more distinct from IBS and FM, which predicted each other.

Conclusions: Syndrome-specific predictors were more common than shared ones and these predictors might form a better starting point to unravel the heterogeneous etiologies of these syndromes than the current approach based on symptom patterns. The close relationship between IBS and FM is striking and requires further research.

Source: Monden R, Rosmalen JGM, Wardenaar KJ, Creed F. Predictors of new onsets of irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia: the lifelines study [published online ahead of print, 2020 Jun 17]. Psychol Med. 2020;1-9. doi:10.1017/S0033291720001774 https://pubmed.ncbi.nlm.nih.gov/32546287/

Elevated Perceived Exertion in People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Meta-analysis

Abstract:

Purpose: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia (FM) are two debilitating illnesses primarily characterized by chronic symptoms of fatigue and musculoskeletal pain, respectively. Some investigators have observed an elevated sense of effort in these patient groups, however, this effect has not been substantiated via quantitative review. As such, we conducted a meta-analysis of perceived exertion (RPE) responses to aerobic exercise in ME/CFS and FM compared to healthy adults.

Methods: Case-control studies involving adults with ME/CFS or FM that measured RPE and heart rate responses to acute aerobic exercise were included. Data sources included: PubMed, Scopus/Embase, CINAHL, CENTRAL, and Google Scholar. Risk of bias was assessed by evaluating each study’s description of participant characteristics, matching procedures, and administration of RPE scales. Hedges’ d effect sizes for RPE were calculated and aggregated using random effects models and potential moderators were explored with meta-regression analysis.

Results: Forty-one effects were extracted from 37 studies involving 1016 patients and 686 healthy controls. We observed a large (Hedges’ d=0.85; 95% CI: 0.62, 1.08) effect indicating higher RPE in patients than controls. The mean effect size was significantly moderated (p<0.001; R=0.38) by whether RPE data were analyzed at a peak or submaximal intensity (b=0.60, z=4.6, p<0.001) and the type of patient group that was studied (b = 0.25, z = 2.08, p=0.04).

Conclusions: People with ME/CFS and FM perceive aerobic exercise as more effortful than healthy adults, but the exact causes are unclear. The large magnitude of this effect merits further exploration of underlying mechanisms which could provide insight into the pathophysiology of ME/CFS and FM or the broader debate about the nature of central and/or peripheral signals that influence RPE.

Source: Barhorst EE, Andrae WE, Rayne TJ, Falvo MJ, Cook DB, Lindheimer JB. Elevated Perceived Exertion in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia: A Meta-analysis [published online ahead of print, 2020 Jun 15]. Med Sci Sports Exerc. 2020;10.1249/MSS.0000000000002421. doi:10.1249/MSS.0000000000002421 https://pubmed.ncbi.nlm.nih.gov/32555018/

DNA Methylation and BDNF Expression Account for Symptoms and Widespread Hyperalgesia in Patients With Chronic Fatigue Syndrome and Fibromyalgia

Abstract:

Background: Epigenetics of neurotrophic factors holds the potential to unravel the mechanisms underlying the pathophysiology of complex conditions such as chronic fatigue syndrome (CFS). This study explored the role of brain-derived neurotrophic factor (BDNF) genetics, epigenetics, and protein expression in patients with both CFS and comorbid fibromyalgia (CFS/FM).

Methods: A repeated-measures study in 54 participants (28 patients with CFS/FM and 26 matched healthy controls) was conducted. Participants underwent a comprehensive assessment, including questionnaires, sensory testing, and blood withdrawal. BDNF protein level was measured in serum (sBDNF) using ELISA, while polymorphism and DNA methylation were measured in blood, using pyrosequencing technology. To assess temporal stability of the measures, participants underwent the same assessment twice within four days.

Results: Repeated-measures mixed linear models were performed for between-group analysis. sBNDF was higher in patients with CFS/FM (F=15.703; mean difference: 3.31 ng/ml, 95% C.I. 1.65 to 4.96; p=.001), whereas BDNF DNA methylation was lower in Exon IX (F=9.312; mean difference -2.38%, C.I. -3.93 to -0.83; p=.003). BDNF DNA methylation was mediated by the Val66Met (rs6265) polymorphism. Lower methylation in the same region predicted higher sBDNF (F=4.910, t= -2.216, p=.029, 95% C.I. = -.712 to -.039) which in turn predicted participants’ symptoms (F=14.410, t= 3.796, 95% C.I.= 1.79 to 5.71, p=.001) and widespread hyperalgesia (F=4.147, t= 2.036, 95% C.I.= .01 to .08, p=.044).

Discussion: sBDNF is higher in patients with CFS/FM and BDNF methylation in exon IX accounts for regulating protein expression. Altered BDNF might represent a key mechanism explaining CFS/FM pathophysiology.

Source: Polli A, Ghosh M, Bakusic J, et al. DNA methylation and BDNF expression account for symptoms and widespread hyperalgesia in patients with Chronic Fatigue Syndrome and Fibromyalgia [published online ahead of print, 2020 Jun 20]. Arthritis Rheumatol. 2020;10.1002/art.41405. doi:10.1002/art.41405 https://pubmed.ncbi.nlm.nih.gov/32562379/

Post-exertional Symptoms Distinguish Myalgic encephalomyelitis/chronic Fatigue Syndrome Subjects From Healthy Controls

Abstract:

Background: Post-exertional malaise (PEM) is an exacerbation of symptoms that leads to a reduction in functionality. Recognition of PEM is important for the diagnosis and treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Objective: Symptoms following cardiopulmonary exercise testing were compared between ME/CFS patients and healthy controls.

Methods: Open-ended questionnaires were provided to subjects following two maximal exercise tests, 24 hours apart. Subjects evaluated how they felt at five time points. Responses were classified into 19 symptom categories.

Results: ME/CFS subjects (n = 49) reported an average of 14±7 symptoms compared to 4±3 by controls (n = 10). During the seven days afterwards, ME/CFS subjects reported 4±3 symptoms. None were reported by controls. Fatigue, cognitive dysfunction, and sleep problems were reported with the greatest frequency. ME/CFS patients reported more symptom categories at higher frequencies than controls. The largest differences were observed in cognitive dysfunction, decrease in function, and positive feelings.

Conclusions: A standardized exertional stimulus produced prolonged, diverse symptoms in ME/CFS subjects. This provides clues to the underlying pathophysiology of ME/CFS, leading to improved diagnosis and treatment.

Source: Mateo LJ, Chu L, Stevens S, et al. Post-exertional symptoms distinguish myalgic encephalomyelitis/chronic fatigue syndrome subjects from healthy controls [published online ahead of print, 2020 Jun 16]. Work. 2020;10.3233/WOR-203168. doi:10.3233/WOR-203168 https://pubmed.ncbi.nlm.nih.gov/32568143/

Graded Exercise Therapy Doesn’t Restore the Ability to Work in ME/CFS. Rethinking of a Cochrane Review

Abstract:

Background: Cochrane recently amended its exercise review for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in response to an official complaint.

Objective: To determine if the amended review has addressed the concerns raised about the previous review and if exercise is an effective treatment that restores the ability to work in ME/CFS.

Method: The authors reviewed the amended Cochrane exercise review and the eight trials in it by paying particular interest to the objective outcomes. We also summarised the recently published review of work rehabilitation and medical retirement for ME/CFS.

Results: The Cochrane review concluded that graded exercise therapy (GET) improves fatigue at the end of treatment compared to no-treatment. However, the review did not consider the unreliability of subjective outcomes in non-blinded trials, the objective outcomes which showed that GET is not effective, or the serious flaws of the studies included in the review. These flaws included badly matched control groups, relying on an unreliable fatigue instrument as primary outcome, outcome switching, p-hacking, ignoring evidence of harms, etc. The review did also not take into account that GET does not restore the ability to work.

Conclusion: GET not only fails to objectively improve function significantly or to restore the ability to work, but it’s also detrimental to the health of≥50% of patients, according to a multitude of patient surveys. Consequently, it should not be recommended.

Source: Vink M, Vink-Niese F. Graded exercise therapy doesn’t restore the ability to work in ME/CFS. Rethinking of a Cochrane review [published online ahead of print, 2020 Jun 14]. Work. 2020;10.3233/WOR-203174. doi:10.3233/WOR-203174 https://pubmed.ncbi.nlm.nih.gov/32568149/

Documenting Disability in Myalgic encephalomyelitis/chronic Fatigue Syndrome (ME/CFS)

Abstract:

Background: According to the 2015 National Academy of Medicine report, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) “is a serious, chronic, complex, and systemic disease that frequently and dramatically limits the activities of affected patients.” ME/CFS affects between 1 and 2.5 million Americans, leaving as many as 75% unable to work due to physical, cognitive and functional impairment. Unfortunately, many doctors and lawyers lack the knowledge of how to properly document an ME/CFS disability claim, leaving patients unable to access disability benefits.

Objective: The goal of this article is to summarize the approaches used by experienced clinicians and lawyers in successful ME/CFS disability claims.

Methods: The authors reviewed the types of US disability insurance programs and the evidence commonly required by these programs to demonstrate ME/CFS disability.

Results: This article summarizes the range of methods used in successful US disability claims, which include documentation of the functional impact of post-exertional malaise and the use of methods that provide objective evidence of impairment.

Conclusions: Medical providers and lawyers can use these tested methods to obtaining disability benefits for people with ME/CFS. Physical therapists, occupational therapists, and other specialists play an important role in providing objective evidence for ME/CFS disability claims.

Source: Podell R, Dimmock ME, Comerford BB. Documenting disability in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [published online ahead of print, 2020 Jun 16]. Work. 2020;10.3233/WOR-203178. doi:10.3233/WOR-203178 https://pubmed.ncbi.nlm.nih.gov/32568153/

Research Update: The Relation Between ME/CFS Disease Burden and Research Funding in the USA

Abstract:

Background: Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is a debilitating, chronic, multisystem disease that affects an estimated 1 to 2.5 million Americans. It has no widely accepted biomarkers and no FDA-approved treatment. ME/CFS has traditionally been one of the lowest funded diseases by the United States National Institutes of Health (NIH).

Objectives: We provide here an update to our 2016 article, which estimated the disease burden of ME/CFS in the United States in 2013 and its relation to NIH’s 2015 analysis of research funding and disease burden. This update incorporates more recent burden data from 2015 and funding data from 2017.

Methods: We perform a regression analysis on funding versus disease burden to determine 2017 funding levels that would be commensurate with burden. Burden figures for 2017 are estimated using population-based extrapolations of earlier data.

Results: We find the disease burden of ME/CFS is double that of HIV/AIDS and over half that of breast cancer. We also find that ME/CFS is more underfunded with respect to burden than any disease in NIH’s analysis of funding and disease burden, with ME/CFS receiving roughly 7% of that commensurate with disease burden.

Conclusions: To be commensurate with disease burden, NIH funding would need to increase roughly 14-fold.

Source: Mirin AA, Dimmock ME, Jason LA. Research update: The relation between ME/CFS disease burden and research funding in the USA [published online ahead of print, 2020 Jun 16]. Work. 2020;10.3233/WOR-203173. doi:10.3233/WOR-203173 https://pubmed.ncbi.nlm.nih.gov/32568148/

Properties of Measurements Obtained During Cardiopulmonary Exercise Testing in Individuals With Myalgic encephalomyelitis/chronic Fatigue Syndrome

Abstract:

Background: Diminished cardiopulmonary exercise test (CPET) performance indicates the physiological basis for reduced capacity for activities of daily living and work. Thus, it may be a biomarker for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Objective: To determine statistical properties of cardiac, pulmonary, and metabolic measurements obtained during CPET in people with ME/CFS.

Methods: Fifty-one females with ME/CFS and 10 sedentary females with similar age and body mass received cardiac, pulmonary, and metabolic measurements during 2 CPETs separated by 24 hours. Two-way analysis of variance and effect size calculations (Cohen’s d) were used to assess the magnitude and statistical significance of differences in measurements between groups. Reliability of CPET measurements was estimated using intraclass correlation coefficients (formula 2,1; ICC2,1). Responsiveness of CPET measurements was assessed using minimum detectable change outside the 95% confidence interval (MDC95) and coefficients of variation (CoV).

Results: CPET measurements demonstrated moderate to high reliability for individuals with ME/CFS. Comparing subjects with ME/CFS and control subjects yielded moderate to large effect sizes on all CPET measurements. MDC95 for all individuals with ME/CFS generally exceeded control subjects and CoVs for CPET measurements were comparable between groups.

Conclusions: CPET measurements demonstrate adequate responsiveness and reproducibility for research and clinical applications.

Source: Davenport TE, Stevens SR, Stevens MAJ, Snell CR, Van Ness JM. Properties of measurements obtained during cardiopulmonary exercise testing in individuals with myalgic encephalomyelitis/chronic fatigue syndrome [published online ahead of print, 2020 Jun 16]. Work. 2020;10.3233/WOR-203170. doi:10.3233/WOR-203170

Clinically Accessible Tools for Documenting the Impact of Orthostatic Intolerance on Symptoms and Function in ME/CFS

Abstract:

Background: Clinical observations have indicated that hours of upright activity (HUA) reported by Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients correlated with orthostatic symptoms and impaired physical function. This study examined the relationship between HUA and orthostatic intolerance (OI).

Methods: Twenty-five female ME/CFS subjects and 25 age and race matched female healthy controls (HCs) were enrolled. Subjects reported HUA (defined as hours per day spent with feet on the floor) and completed questionnaires to assess the impact of OI on daily activities and symptoms. ME/CFS patients were categorized into those with <5 HUA and ≥5 HUA and analyzed by employment status. Data analysis used one-way ANOVA.

Results: ME/CFS patients had fewer HUA, worse symptoms and greater interference with daily activities due to OI than HCs. The <5 HUA ME/CFS subjects had more severe OI related symptoms than ≥5 HUA ME/CFS subjects even though OI interfered with daily activities similarly. Only 33% of ME/CFS subjects were employed and all were ≥5 HUA ME/CFS subjects with an average HUA of 8.

Conclusions: ME/CFS subjects experienced more frequent and severe OI symptoms, higher interference with daily activities, and reduced ability to work than HCs. Reported HUA and assessment of OI using standardized instruments may be useful clinical tools for physicians in the diagnosis, treatment and management of ME/CFS patients.

Source: Lee J, Wall P, Kimler C, Bateman L, Vernon SD. Clinically accessible tools for documenting the impact of orthostatic intolerance on symptoms and function in ME/CFS [published online ahead of print, 2020 Jun 16]. Work. 2020;10.3233/WOR-203169. doi:10.3233/WOR-203169 https://pubmed.ncbi.nlm.nih.gov/32568144/