2019 – Page 12 – American ME and CFS Society

Orthostatic intolerance in chronic fatigue syndrome

Abstract:

BACKGROUND: Orthostatic intolerance (OI) is a significant problem for those with chronic fatigue syndrome (CFS). We aimed to characterize orthostatic intolerance in CFS and to study the effects of exercise on OI.

METHODS: CFS (n = 39) and control (n = 25) subjects had recumbent and standing symptoms assessed using the 20-point, anchored, ordinal Gracely Box Scale before and after submaximal exercise. The change in heart rate (ΔHR ≥ 30 bpm) identified Postural Orthostatic Tachycardia Syndrome (POTS) before and after exercise, and the transient, exercise-induced postural tachycardia Stress Test Activated Reversible Tachycardia (START) phenotype only after exercise.

RESULTS: Dizziness and lightheadedness were found in 41% of recumbent CFS subjects and in 72% of standing CFS subjects. Orthostatic tachycardia did not account for OI symptoms in CFS. ROC analysis with a threshold ≥ 2/20 on the Gracely Box Scale stratified CFS subjects into three groups: No OI (symptoms < 2), Postural OI (only standing symptoms ≥ 2), and Persistent OI (recumbent and standing symptoms ≥ 2).

CONCLUSIONS: Dizziness and Lightheadedness symptoms while recumbent are an underreported finding in CFS and should be measured when doing a clinical evaluation to diagnose orthostatic intolerance. POTS was found in 6 and START was found in 10 CFS subjects. Persistent OI had symptoms while recumbent and standing, highest symptom severity, and lability in symptoms after exercise.

Trial registration: The trial was registered at the following: https://clinicaltrials.gov/ct2/show/NCT03567811.

Source: Garner R, Baraniuk JN. Orthostatic intolerance in chronic fatigue syndrome. J Transl Med. 2019 Jun 3;17(1):185. doi: 10.1186/s12967-019-1935-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547462/ (Full article)

Genetic Predisposition for Immune System, Hormone, and Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study

Abstract:

Introduction: Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a multifactorial illness of unknown etiology with considerable social and economic impact. To investigate a putative genetic predisposition to ME/CFS we conducted genome-wide single-nucleotide polymorphism (SNP) analysis to identify possible variants.

Methods: 383 ME/CFS participants underwent DNA testing using the commercial company 23andMe. The deidentified genetic data was then filtered to include only non-synonymous and nonsense SNPs from exons and microRNAs, and SNPs close to splice sites. The frequencies of each SNP were calculated within our cohort and compared to frequencies from the Kaviar reference database. Functional annotation of pathway sets containing SNP genes with high frequency in ME/CFS was performed using over-representation analysis via ConsensusPathDB. Furthermore, these SNPs were also scored using the Combined Annotation Dependent Depletion (CADD) algorithm to gauge their deleteriousness.

Results: 5693 SNPs were found to have at least 10% frequency in at least one cohort (ME/CFS or reference) and at least two-fold absolute difference for ME/CFS. Functional analysis identified the majority of SNPs as related to immune system, hormone, metabolic, and extracellular matrix organization. CADD scoring identified 517 SNPs in these pathways that are among the 10% most deleteriousness substitutions to the human genome.

Source: Melanie Perez, Rajeev Jaundoo, Kelly Hilton, Ana Del Alamo, Kristina Gemayel, Nancy G. Klimas, Travis J. A. Craddock and Lubov Nathanson. Genetic Predisposition for Immune System, Hormone, and Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study. Front. Pediatr., 24 May 2019 | https://doi.org/10.3389/fped.2019.00206 (Full article)

Healthcare Utilization in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Analysis of US Ambulatory Healthcare Data, 2000-2009

Abstract:

Background: ME/CFS is a complex and disabling illness with substantial economic burden and functional impairment comparable to heart disease and multiple sclerosis. Many patients with ME/CFS do not receive appropriate healthcare, partially due to lack of diagnostic tests, and knowledge/attitudes/beliefs about ME/CFS. This study was to assess the utility of US ambulatory healthcare data in profiling demographics, co-morbidities, and healthcare in ME/CFS.

Methods: Data came from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS) in the U.S. Weighted analysis was performed. We examined 9.06 billion adult visits from 2000 to 2009 NAMCS/NHAMCS data. ME/CFS-related visits were identified by ICD-9-CM code, 780.71, up to tertiary diagnosis.

Results: We estimated 2.9 million (95% CI: 1.8-3.9 million) ME/CFS-related visits during 2000-2009, with no statistical evidence (p-trend = 0.31) for a decline or increase in ME/CFS-related visits. Internists, general and family practitioners combined provided 52.12% of these visits. Patients with ME/CFS-related visits were mostly in their 40 and 50 s (47.76%), female (66.07%), white (86.95%), metropolitan/urban residents (92.05%), and insured (87.26%). About 71% of ME/CFS patients had co-morbidities, including depression (35.79%), hypertension (31.14%), diabetes (20.30%), and arthritis (14.11%). As one quality indicator, physicians spent more time on ME/CFS-related visits than non-ME/CFS visits (23.62 vs. 19.38 min, p = 0.065). As additional quality indicators, the top three preventive counseling services provided to patients with ME/CFS-related visits were diet/nutrition (8.33%), exercise (8.21%), and smoking cessation (7.24%). Compared to non-ME/CFS visits, fewer ME/CFS-related visits included counseling for stress management (0.75 vs. 3.14%, p = 0.010), weight reduction (0.88 vs. 4.02%, p = 0.002), injury prevention (0.04 vs. 1.64%, p < 0.001), and family planning/contraception (0.17 vs. 1.45%, p = 0.037).

Conclusions: Visits coded with ME/CFS did not increase from 2000 to 2009. Almost three quarters of ME/CFS-related visits were made by ME/CFS patients with other co-morbid conditions, further adding to complexity in ME/CFS healthcare. While physicians spent more time with ME/CFS patients, a lower proportion of ME/CFS patients received preventive counseling for weight reduction, stress management, and injury prevention than other patients despite the complexity of ME/CFS. NAMCS/NHAMCS data are useful in evaluating co-morbidities, healthcare utilization, and quality indicators for healthcare in ME/CFS.

Source: Bae J, Lin JS. Healthcare Utilization in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Analysis of US Ambulatory Healthcare Data, 2000-2009. Front Pediatr. 2019 May 14;7:185. doi: 10.3389/fped.2019.00185. eCollection 2019. https://www.frontiersin.org/articles/10.3389/fped.2019.00185/full (Full article)

Shared microglial mechanisms underpinning depression and chronic fatigue syndrome and their comorbidities

Abstract:

In 2011, it was reviewed that a) there is a strong co-occurrence between major depression and chronic fatigue syndrome (CFS), with fatigue and physio-somatic symptoms being key symptoms of depression, and depressive symptoms appearing during the course of CFS; and b) the comorbidity between both disorders may in part be explained by activated immune-inflammatory pathways, including increased translocation of Gram-negative bacteria and increased levels of pro-inflammatory cytokines, such as interleukin (IL)-1. Nevertheless, the possible involvement of activated microglia in this comorbidity has remained unclear.

This paper aims to review microglial disturbances in major depression, CFS and their comorbidity. A comprehensive literature search was conducted using the PubMed / MEDLINE database to identify studies, which are relevant to this current review. Depressed patients present neuroinflammatory alterations, probably related to microglial activation, while animal models show that a microglial response to immune challenges including lipopolysaccharides is accompanied by depressive-like behaviors. Recent evidence from preclinical studies indicates that activated microglia have a key role in the onset of fatigue. In chronic inflammatory conditions, such as infections and senescence, microglia orchestrate an inflammatory microenvironment thereby causing fatigue.

In conclusion, based on our review we may posit that shared immune-inflammatory pathways and especially activated microglia underpin comorbid depression and CFS. As such, microglial activation and neuro-inflammation may be promising targets to treat the overlapping manifestations of both depression and CFS.

Source: Filho AJMC, Macedo DS, de Lucena DF, Maes M. Shared microglial mechanisms underpinning depression and chronic fatigue syndrome and their comorbidities. Behav Brain Res. 2019 May 25:111975. doi: 10.1016/j.bbr.2019.111975. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31136774

Autonomic dysfunction in myalgic encephalomyelitis and chronic fatigue syndrome: comparing self-report and objective measures

Myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) have debilitating impacts on affected individuals. Core symptoms include post-exertional malaise, neurocognitive challenges, and sleep dysfunction [1]. Additionally, a significant minority of patients experience autonomic symptoms, including orthostatic intolerance, gastrointestinal disturbances, and circulation issues [2].

Several case definitions for ME and CFS require the presence of autonomic dysfunction for diagnosis [2], while other researchers have proposed an “autonomic dysfunction” subtype of ME and CFS [3]. Identifying the appropriate measures of autonomic symptomatology for individuals with ME and CFS will further contribute to understanding the role of the autonomic system in this illness.

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Source: Kemp J, Sunnquist M, Jason LA, Newton JL. Autonomic dysfunction in myalgic encephalomyelitis and chronic fatigue syndrome: comparing self-report and objective measures. Clin Auton Res. 2019 May 21. doi: 10.1007/s10286-019-00615-x. [Epub ahead of print] https://sci-hub.se/10.1007/s10286-019-00615-x (Full article)

Resting-state functional connectivity, cognition, and fatigue in response to cognitive exertion: a novel study in adolescents with chronic fatigue syndrome

Abstract:

Emerging evidence suggests that central nervous system dysfunction may underlie the core symptoms of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in adults, such as cognitive disturbance, fatigue and post-exertional malaise. Research into brain dysfunction in the pediatric CFS/ME context, however, is severely lacking. It is unclear whether the adolescent CFS/ME brain functions differently compared with healthy peers, particularly in situations where significant mental effort is required. This study used resting-state functional MRI in a novel repeated-measures design to evaluate intrinsic connectivity, cognitive function, and subjective fatigue, before and after a period of cognitive exertion in 48 adolescents (25 CFS/ME, 23 healthy controls).

Results revealed little evidence for a differential effect of cognitive exertion in CFS/ME compared with controls. Both groups demonstrated a similar rate of reduced intrinsic functional connectivity within the default mode network (DMN), reduced sustained attentional performance, slower processing speed, and increased subjective fatigue as a result of cognitive exertion.

However, CFS/ME adolescents consistently displayed higher subjective fatigue, and controls outperformed the CFS/ME group overall on cognitive measures of processing speed, sustained attention and new learning. No brain-behavior relationships were observed between DMN connectivity, cognitive function, and fatigue over time.

These findings suggest that effortful cognitive tasks may elicit similar levels of energy expenditure across all individuals in the form of reduced brain functioning and associated fatigue. However, CFS/ME may confer a lower starting threshold from which to access energy reserves and cognitive resources when cognitive effort is required.

Source: Josev EK, Malpas CB, Seal ML, Scheinberg A6, Lubitz L, Rowe K, Knight SJ. Resting-state functional connectivity, cognition, and fatigue in response to cognitive exertion: a novel study in adolescents with chronic fatigue syndrome. Brain Imaging Behav. 2019 May 17. doi: 10.1007/s11682-019-00119-2. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31102168

Increased risk of chronic fatigue syndrome following psoriasis: a nationwide population-based cohort study

Abstract:

BACKGROUND: The onset of chronic fatigue syndrome (CFS) has been shown to be associated with several immunological conditions such as infections or atopy. The aim of this study was to clarify the risk of chronic fatigue syndrome following the diagnosis of psoriasis, an immune-related dermatological disease, by analyzing the National Health Insurance Research Database of Taiwan.

METHOD: 2616 patients aged 20 years or older with newly diagnosed psoriasis during 2004-2008 and 10,464 participants without psoriasis were identified. Both groups were followed up until the diagnoses of CFS were made at the end of 2011.

RESULTS: The relationship between psoriasis and the subsequent risk of CFS was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 2.27 and 3.58 per 1000 person-years among the non-psoriasis and psoriasis populations, respectively (adjusted hazard ratio [HR] = 1.48, with 95% confidence interval [CI] 1.07-2.06). In the stratified analysis, the psoriasis group were consistently associated with a higher risk of CFS in male sex (HR = 2.05, 95% CI 1.31-3.20) and age group of ≥ 60 years old (HR = 2.32, 95% CI 1.33-4.06). In addition, we discovered that the significantly increased risk of CFS among psoriasis patients is attenuated after they receive phototherapy and/or immunomodulatory drugs.

CONCLUSIONS: The data from this population-based retrospective cohort study revealed that psoriasis is associated with an elevated risk of subsequent CFS, which is differentiated by sex and age.

Source: Tsai SY, Chen HJ, Chen C, Lio CF, Kuo CF, Leong KH, Wang YT, Yang TY, You CH, Wang WS. Increased risk of chronic fatigue syndrome following psoriasis: a nationwide population-based cohort study. J Transl Med. 2019 May 14;17(1):154. doi: 10.1186/s12967-019-1888-1. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-019-1888-1 (Full article)

Cognitive behavioural therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective. Re-analysis of a Cochrane review

Abstract:

Analysis of the 2008 Cochrane review of cognitive behavioural therapy for chronic fatigue syndrome shows that seven patients with mild chronic fatigue syndrome need to be treated for one to report a small, short-lived subjective improvement of fatigue. This is not matched by an objective improvement of physical fitness or employment and illness benefit status. Most studies in the Cochrane review failed to report on safety or adverse reactions. Patient evidence suggests adverse outcomes in 20 per cent of cases. If a trial of a drug or surgical procedure uncovered a similar high rate, it would be unlikely to be accepted as safe. It is time to downgrade cognitive behavioural therapy to an adjunct support-level therapy, rather than a treatment for chronic fatigue syndrome.

Source: Vink M, Vink-Niese A. Cognitive behavioural therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective. Re-analysis of a Cochrane review. Health Psychol Open. 2019 May 2;6(1):2055102919840614. doi: 10.1177/2055102919840614. eCollection 2019 Jan-Jun. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498783/ (Full article)

Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, and Chronic Fatigue: Three Distinct Entities Requiring Complete Different Approaches

Abstract:

PURPOSE OF REVIEW: A recent review implicates that myalgic encephalomyelitis (ME), chronic fatigue syndrome (CFS), and chronic fatigue are part of the “fatigue spectrum” and recommends “longitudinal studies integrating biopsychosocial approaches to inform early management and targeted rehabilitation strategies.”

RECENT FINDINGS: ME is a neuromuscular disease distinguished by muscle fatigability (prolonged muscle weakness after minor exertion) and specific signs of neurological dysfunction. ME is not equivalent to CFS, as proposed by the authors. CFS is defined as unexplained chronic fatigue accompanied by at least four out of a list of eight specific symptoms. CFS is a distinct clinical entity and not merely a severe variant of CF, as suggested. Proof that CF, CFS, and ME are part of a “fatigue continuum” and that CF can convert to CFS at a later stage is lacking. Biopsychosocial approaches for early management and rehabilitation of CF, as promoted by the authors, are at odds with the current understandings of ME, CFS, and CF. The (bio)psychosocial explanatory models for ME and CFS have proven to be invalid, and the associated interventions, cognitive behavioral therapy and graded exercise therapy, have shown to be ineffective and even potentially harmful. ME, CFS, and CF are three very distinct clinical entities. Interventions justified by (bio)psychosocial models appear to be unsuccessful and potentially noxious. To develop effective treatments, it is crucial to make a clear distinction between ME, CFS, and CF and to leave the (bio)psychosocial explanations and therapies behind us.

Source: Twisk FNM. Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, and Chronic Fatigue: Three Distinct Entities Requiring Complete Different Approaches. Curr Rheumatol Rep. 2019 May 9;21(6):27. doi: 10.1007/s11926-019-0823-z. https://www.ncbi.nlm.nih.gov/pubmed/31073713

Assessment of the scientific rigour of randomized controlled trials on the effectiveness of cognitive behavioural therapy and graded exercise therapy for patients with myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review

Abstract:

Cognitive behavioural therapy and graded exercise therapy have been promoted as effective treatments for patients with myalgic encephalomyelitis/chronic fatigue syndrome. However, criticism on the scientific rigour of these studies has been raised. This review assessed the methodological quality of studies on the effectiveness of cognitive behavioural therapy and graded exercise therapy. The methodological quality of the 18 included studies was found to be relatively low, as bias was prominently found, affecting the main outcome measures of the studies (fatigue, physical functioning and functional impairment/status). Future research should focus on including more objective outcome measures in a well-defined patient population.

Source: Ahmed SA, Mewes JC, Vrijhoef H. Assessment of the scientific rigour of randomized controlled trials on the effectiveness of cognitive behavioural therapy and graded exercise therapy for patients with myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review. J Health Psychol. 2019 May 10:1359105319847261. doi: 10.1177/1359105319847261. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31072121