In this video, Dr. Montoya discusses clinical implications of recent scientific reports that are pinning down the development of this disease. Treatment implications and future avenues for research are also discussed.
https://www.youtube.com/watch?time_continue=3532&v=ADVQvzXwDUg
Abstract:
BACKGROUND: Paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a relatively common and disabling condition. The National Institute for Health and Clinical Excellence (NICE) recommends Cognitive Behavioural Therapy (CBT) as a treatment option for paediatric CFS/ME because there is good evidence that it is effective. Despite this, most young people in the UK are unable to access local specialist CBT for CFS/ME. A randomised controlled trial (RCT) showed FITNET was effective in the Netherlands but we do not know if it is effective in the National Health Service (NHS) or if it is cost-effective. This trial will investigate whether FITNET-NHS is clinically effective and cost-effective in the NHS.
METHODS: Seven hundred and thirty-four paediatric patients (aged 11-17 years) with CFS/ ME will be randomised (1:1) to receive either FITNET-NHS (online CBT) or Activity Management (delivered via video call). The internal pilot study will use integrated qualitative methods to examine the feasibility of recruitment and the acceptability of treatment. The full trial will assess whether FITNET-NHS is clinically effective and cost-effective. The primary outcome is disability at 6 months, measured using the SF-36-PFS (Physical Function Scale) questionnaire. Cost-effectiveness is measured via cost-utility analysis from an NHS perspective. Secondary subgroup analysis will investigate the effectiveness of FITNET-NHS in those with co-morbid mood disorders.
DISCUSSION: If FITNET-NHS is found to be feasible and acceptable (internal pilot) and effective and cost-effective (full trial), its provision by the NHS has the potential to deliver substantial health gains for the large number of young people suffering from CFS/ME but unable to access treatment because there is no local specialist service. This trial will provide further evidence evaluating the delivery of online CBT to young people with chronic conditions.
TRIAL REGISTRATION: ISRCTN registry, registration number: ISRCTN18020851 . Registered on 4 August 2016.
Source: Baos S, Brigden A, Anderson E, Hollingworth W, Price S, Mills N, Beasant L, Gaunt D, Garfield K, Metcalfe C, Parslow R, Downing H, Kessler D, Macleod J, Stallard P, Knoop H, Van de Putte E, Nijhof S, Bleijenberg G, Crawley E. Investigating the effectiveness and cost-effectiveness of FITNET-NHS (Fatigue In Teenagers on the interNET in the NHS) compared to Activity Management to treat paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME): protocol for a randomised controlled trial. Trials. 2018 Feb 22;19(1):136. doi: 10.1186/s13063-018-2500-3. https://www.ncbi.nlm.nih.gov/pubmed/29471861
Note: Update published December 19, 2019. https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-019-3895-1
Abstract:
Gastrointestinal (GI) symptoms and irritable bowel (IB) symptoms have been associated with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). The aim of this study was to conduct a systematic review of these symptoms in CFS/ME, along with any evidence for probiotics as treatment. Pubmed, Scopus, Medline (EBSCOHost) and EMBASE databases were searched to source relevant studies for CFS/ME. The review included any studies examining GI symptoms, irritable bowel syndrome (IBS) and/or probiotic use.
Studies were required to report criteria for CFS/ME and study design, intervention and outcome measures. Quality assessment was also completed to summarise the level of evidence available. A total of 3381 publications were returned using our search terms. Twenty-five studies were included in the review. Randomised control trials were the predominant study type (n = 24). Most of the studies identified examined the effect of probiotic supplementation on the improvement of IB symptoms in IBS patients, or IB symptoms in CFS/ME patients, as well as some other significant secondary outcomes (e.g. quality of life, other gastrointestinal symptoms, psychological symptoms).
The level of evidence identified for the use of probiotics in IBS was excellent in quality; however, the evidence available for the use of probiotic interventions in CFS/ME was poor and limited. There is currently insufficient evidence for the use of probiotics in CFS/ME patients, despite probiotic interventions being useful in IBS. The studies pertaining to probiotic interventions in CFS/ME patients were limited and of poor quality overall. Standardisation of protocols and methodology in these studies is required.
Source: Corbitt M, Campagnolo N, Staines D, Marshall-Gradisnik S. A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and Irritable Bowel Syndrome in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Probiotics Antimicrob Proteins. 2018 Feb 20. doi: 10.1007/s12602-018-9397-8. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29464501
Abstract:
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating disorder. With the exception of disabling fatigue, there are few definitive clinical features of the condition. As a consequence, patients often have difficulty gaining an appropriate diagnosis. As such, identifying distinct clinical feature of ME/CFS is an important issue. One under researched area of ME/CFS associated symptoms concerns problems related to vision.
People with ME/CFS consistently report a range of symptoms related to the quality of their vision including pain in the eyes, hypersensitivity to light, difficulty focusing on images, slow eye movements, and difficulty tracking object movement. However, there has been little attempt to verify patients’ self-reports using objective methods. The purpose of the experiments presented in this thesis was to determine the effects of ME/CFS on: (i) performance on a range of tests of visual sensitivity and (ii) the morphology of the retina.
Compared to controls, the ME/CFS group exhibited reduced accommodation, larger pupil diameters, reduced colour discrimination and poorer contrast sensitivity towards lower spatial frequencies. Thinning in the photoreceptor layers of the retina (the Outer Segment & the Outer Nuclear layer) was also apparent. These findings support the claims of people with ME/CFS that they experience problems related to their vision and its function. They also represent a potential marker of ME/CFS that may aid in its diagnosis.
Abstract:
OBJECTIVE: The cognitive behavioral model of chronic fatigue syndrome (CFS) suggests that cognitions and reduced activity level perpetuate the fatigue and impairment that individuals with CFS experience. The two empirical evaluations of this model resulted in conflicting findings. The current study examines the influence of case definition fulfillment on the applicability of this model to CFS.
METHOD: A moderated mediation analysis was conducted on 990 individuals with CFS to reexamine the behavioral pathway of this model. Case definition fulfillment was entered as a moderator.
RESULTS: Findings were generally inconsistent with the cognitive behavioral model of CFS. Case definition fulfillment significantly moderated the relation between activity level and physical impairment (β = -0.08, p = 0.03); individuals who met more stringent case definitions demonstrated a weaker relation between activity level and impairment.
CONCLUSIONS: This model may not accurately represent the experience of individuals with CFS, particularly those who fulfill more stringent case definitions.
© 2018 Wiley Periodicals, Inc.
Source: Sunnquist M, Jason LA. A reexamination of the cognitive behavioral model of chronic fatigue syndrome. J Clin Psychol. 2018 Feb 19. doi: 10.1002/jclp.22593. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29457646
Abstract:
OBJECTIVE: Dyspnea perception is distorted in patients with medically unexplained dyspnea. The goals of this study were 1) to replicate these results in patients with fibromyalgia and/or chronic fatigue syndrome (CFS), and 2) to investigate predictors of distorted symptom perception within the patient group, with a focus on negative affectivity (NA), psychiatric comorbidity and somatic symptom severity.
METHODS: Seventy-three patients diagnosed with fibromyalgia and/or CFS and 38 healthy controls (HC) completed a rebreathing paradigm, consisting of a baseline (60s of room air), a rebreathing phase (150s, gradually increasing ventilation, partial pressure of CO2 in the blood, and self-reported dyspnea), and a recovery phase (150s of room air). Dyspnea, respiratory flow and FetCO2 levels were measured continuously.
RESULTS: Patients reported more dyspnea than HC in the recovery phase (p=0.039), but no differences between patients and HC were found in the baseline (p=0.07) or rebreathing phase (p=0.17). No significant differences between patients and HC were found in physiological reactivity. Within the patient group, the effect in the recovery phase was predicted by somatic symptom severity (p=0.046), but not by negative affectivity or by the number of psychiatric comorbidities.
CONCLUSION: This study extended earlier findings in patients with medically unexplained dyspnea to patients with fibromyalgia and CFS. This suggests that altered symptom perception is a non-symptom-specific mechanism underlying functional somatic syndromes in general, particularly in patients with high levels of somatic symptom severity. The results are discussed in a predictive coding framework of symptom perception.
Source: Van Den Houte M, Bogaerts K, Van Diest I, De Bie J, Persoons P, Van Oudenhove L, Van den Bergh O. Perception of induced dyspnea in fibromyalgia and chronic fatigue syndrome. J Psychosom Res. 2018 Mar;106:49-55. doi: 10.1016/j.jpsychores.2018.01.007. Epub 2018 Jan 11. https://www.ncbi.nlm.nih.gov/pubmed/29455899
Reprinted with the kind permission of ME Research UK.
Publication
Tomas et al, Open Heart, 2017 Dec 27; 4(2):e000697
Comment by ME Research UK
An increasing amount of research has revealed heart abnormalities in patients with ME/CFS. For example, people with the illness have been found to have a short QT interval (a measure of the electrical activity of the heart) and a reduced cardiac output (the amount of blood pumped by the heart per minute). These changes may occur before any symptoms are apparent.
Much of the recent work on cardiac dysfunction in ME/CFS has been carried out by Prof. Julia Newton and her team at Newcastle University, including studies funded by ME Research UK.
In 2012, they used magnetic resonance imaging and cardiac tagging technology to asses a group of ME/CFS patients, and found that several measures of the heart were lower in patients than in healthy control subjects:
Then, in 2016, they repeated some of these assessments along with measures of blood volume. The total volume of blood (plasma plus red cells) was slightly less in ME/CFS patients than in controls, but there was a strong association between blood volume and cardiac end-diastolic wall mass.
Continuing their work in this area, the team has recently published a paper in the journal Open Heart looking at levels of brain natriuretic peptide in ME/CFS, and correlating these with measures of cardiac dysfunction.
Despite its name, brain natriuretic peptide (or BNP) is a hormone that is actually secreted by the muscle cells of the heart, and is produced when the ventricles are overstretched to accommodate an increase in blood volume.
Circulating BNP causes a decrease in blood pressure and in cardiac output, and has found use clinically as a diagnostic and prognostic marker of heart failure.
In their current study, the investigators recruited 42 patients with ME/CFS and no other illness, as well as 10 sedentary control subjects matched for age and sex.
The participants’ hearts were examined using magnetic resonance techniques to provide a number of measures of cardiac function, including cardiac volumes at the end of systole (after the ventricles have contracted and pumped out their blood) and at the end of diastole (when the ventricles are relaxed and have refilled with blood).
In addition, blood samples were taken, and plasma BNP levels were measured using an enzyme immunoassay.
The first important finding was that BNP levels were significantly higher in ME/CFS patients than in sedentary control subjects, with mean levels of approximately 500 versus 300 pg/mL, respectively.
Furthermore, both end-systolic and end-diastolic cardiac volumes were significantly lower among patients with high BNP levels (defined as being greater than 400 pg/mL) than in those with low BNP levels.
BNP tends to be a sign of cardiac volume overload, so this association is not what one would normally expect to see. One explanation suggested by the researchers is that the high BNP is causing an excessive production of urine, which reduces the total volume of circulating blood (as seen in their earlier study), leading to a smaller cardiac volume.
It is important to note that none of these measures were related to the patients’ duration of ME/CFS, indicating that the results are unlikely to be due to deconditioning (i.e. they were not the result of the heart adapting to less physical activity).
What might these results mean to patients? One possibility put forward by the investigators is that measurement of BNP levels may be a convenient way by which to identify those ME/CFS patients with cardiac abnormalities who might benefit from specific treatments, although additional studies would be needed to confirm this.
This approach may also be valuable in identifying a specific cardiac subgroup of ME/CFS patients, and better understand the diverse nature of this illness.
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ME Research UK commissions and funds high-quality scientific (biomedical) investigation into ME/CFS.
A pattern emerged, giving rise to an explanatory model. ME/CFS often starts after or during an infection. A logical explanation is that the infection initiates an autoreactive process, which affects several functions, including brain and energy metabolism. According to our model for ME/CFS pathogenesis, patients with a genetic predisposition and dysbiosis experience a gradual development of B cell clones prone to autoreactivity. Under normal circumstances these B cell offsprings would have led to tolerance. Subsequent exogenous microbial exposition (triggering) can lead to comorbidities such as fibromyalgia, thyroid disorder, and orthostatic hypotension.
A decisive infectious trigger may then lead to immunization against autoantigens involved in aerobic energy production and/or hormone receptors and ion channel proteins, producing postexertional malaise and ME/CFS, affecting both muscle and brain. In principle, cloning and sequencing of immunoglobulin variable domains could reveal the evolution of pathogenic clones. Although evidence consistent with the model accumulated in recent years, there are several missing links in it. Hopefully, the hypothesis generates testable propositions that can augment the understanding of the pathogenesis of ME/CFS.
Abstract:
Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) is a heterogeneous syndrome in which patients often experience severe fatigue and malaise following exertion. Immune and cardiovascular dysfunction have been postulated to play a role in the pathophysiology. We therefore, examined whether cytokine profiling or cardiovascular testing following exercise would differentiate patients with ME/CFS.
Twenty-four ME/CFS patients were matched to 24 sedentary controls and underwent cardiovascular and circulating immune profiling. Cardiovascular analysis included echocardiography, cardiopulmonary exercise and endothelial function testing. Cytokine and growth factor profiles were analyzed using a 51-plex Luminex bead kit at baseline and 18 hours following exercise. Cardiac structure and exercise capacity were similar between groups.
Sparse partial least square discriminant analyses of cytokine profiles 18 hours post exercise offered the most reliable discrimination between ME/CFS and controls (κ = 0.62(0.34,0.84)). The most discriminatory cytokines post exercise were CD40L, platelet activator inhibitor, interleukin 1-β, interferon-α and CXCL1. In conclusion, cytokine profiling following exercise may help differentiate patients with ME/CFS from sedentary controls.
Source: Kegan J. Moneghetti, Mehdi Skhiri, Kévin Contrepois, Yukari Kobayashi, Holden Maecker, Mark Davis, Michael Snyder, Francois Haddad & Jose G. Montoya. Value of Circulating Cytokine Profiling During Submaximal Exercise Testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Scientific Reports volume 8, Article number: 2779 (2018). doi:10.1038/s41598-018-20941-w. Received:02 November 2017. Accepted:26 January 2018. Published online:09 February 2018. https://www.nature.com/articles/s41598-018-20941-w (Full article)
Abstract:
Chronic fatigue syndrome (CFS) is a heterogeneous disease which presents with pronounced disabling fatigue, sleep disturbances, and cognitive impairment that negatively affects patients’ functional capability. CFS remains a poorly defined entity and its etiology is still in question. CFS is neither a novel diagnosis nor a new medical condition. From as early as the eighteenth century, a constellation of perplexing symptoms was observed that resembled symptoms of CFS. Commencing with “febricula” and ending with CFS, many names for the disease were proposed including neurocirculatory asthenia, atypical poliomyelitis, Royal Free disease, effort syndrome, Akureyri disease, Tapanui disease, chronic Epstein-Barr virus syndrome, and myalgic encephalitis. To date, it remains unclear whether CFS has an autoimmune component or is a condition that precedes a full-blown autoimmune disease.
Research suggests that CFS may overlap with other diseases including postural orthostatic tachycardia syndrome (POTS), autoimmune syndrome induced by adjuvants (ASIA), and Sjögren’s syndrome. Additionally, it has been postulated that the earliest manifestations of some autoimmune diseases can present with vague non-specific symptoms similar to CFS. Sometimes only when exposed to a secondary stimulus (e.g., antigen) which could accelerate the natural course of the disease would an individual develop the classic autoimmune disease. Due to the similarity of symptoms, it has been postulated that CFS could simply be an early manifestation of an autoimmune disease. This paper will provide a historical background review of this disease and a discussion of CFS as an entity overlapping with multiple other conditions.
Source: Sharif K, Watad A, Bragazzi NL, Lichtbroun M, Martini M, Perricone C, Amital H, Shoenfeld Y. On chronic fatigue syndrome and nosological categories. Clin Rheumatol. 2018 Feb 7. doi: 10.1007/s10067-018-4009-2. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29417255