Page 395 – American ME and CFS Society

The biological challenge of myalgic encephalomyelitis/chronic fatigue syndrome: a solvable problem

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is comparable to multiple sclerosis, diabetes or rheumatoid arthritis in prevalence (∼0.2% to 1%), long-term disability, and quality of life,[1–5] yet the scale of biomedical research and funding has been pitifully limited, as the recent National Institutes of Health (NIH) and Institute of Medicine reports highlight.[6,7] Recently in the USA, NIH Director Francis Collins has stated that the NIH will be ramping up its efforts and levels of funding for ME/CFS,[8] which we hope will greatly increase the interest in, and resources for researching this illness. Despite scant funding to date, researchers in the field have generated promising leads that throw light on this previously baffling illness. We suggest the key elements of a concerted research programme and call on the wider biomedical research community to actively target this condition.

You can read the rest of this article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867862/

Source: Edwards JC, McGrath S, Baldwin A, Livingstone M, Kewley A. The biological challenge of myalgic encephalomyelitis/chronic fatigue syndrome: a solvable problem. Fatigue. 2016 Apr 2;4(2):63-69. Epub 2016 Apr 28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867862/

Simon McGrath 2016 May 30 4:05 p.m.

Authors’ abstract

(An abstract wasn’t required for this editorial, but the authors felt it would be helpful to add this one for PubMed. I am one of the authors.)

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is as prevalent and disabling as multiple sclerosis, diabetes and rheumatoid arthritis but biomedical research into the condition has been grossly underfunded. However, the NIH is committed to ramping up funding for this illness and there are now promising research leads. We indicate clues to the biological mechanisms that may perpetuate the condition and suggest the key elements of a concerted research programme. In the absence of effective treatments, study of mechanism remains a key priority including the possible role of stochastic factors.

We identify the three most interesting major categories of causal model: (1) the brain is responding normally and symptoms are due to persistent signal input from peripheral tissues, such as cytokines or metabolites; (2) there is a persistent abnormality of ‘housekeeping’ processes in the brain, such as an increase in activation of microglia; and (3) there is a persistent abnormality in neural signalling in sensory pathways.

We recommend seven important, practical steps to make progress towards effective treatments: (1) build research infrastructure, including population-based cohorts with close attention to diagnostic criteria; (2) use new, developing techniques for brain imaging; (3) pursue promising immunological leads, such as natural killer cell abnormalities, cytokine shifts, auto-antibodies, and immune responses to viruses such as Epstein-Barr virus; (4) further explore autonomic/endocrine regulation; (5) extend the research on post-exertional changes in physiology; (6) attempt to replicate key findings to determine which are robust; and (7) present data in a way that allows subgroup analysis, and always provide raw data.

We conclude that the problem of ME/CFS now looks solvable and we call on the wider biomedical research community to target the condition.

A potential biomarker for fatigue: Oxidative stress and anti-oxidative activity

Abstract:

We sought to determine whether oxidative stress and anti-oxidative activity could act as biomarkers that discriminate patients with chronic fatigue syndrome (CFS) from healthy volunteers at acute and sub-acute fatigue and resting conditions.

We calculated the oxidative stress index (OSI) from reactive oxygen metabolites-derived compounds (d-ROMs) and the biological antioxidant potential (BAP). We determined changes in d-ROMs, BAP, and OSI in acute and sub-acute fatigue in two healthy groups, and compared their values at rest between patients with CFS (diagnosed by Fukuda 1994 criteria) and another group of healthy controls.

Following acute fatigue in healthy controls, d-ROMs and OSI increased, and BAP decreased. Although d-ROMs and OSI were significantly higher after sub-acute fatigue, BAP did not decrease. Resting condition yielded higher d-ROMs, higher OSI, and lower BAP in patients with CFS than in healthy volunteers, but lower d-ROMs and OSI when compared with sub-acute controls. BAP values did not significantly differ between patients with CFS and controls in the sub-acute condition. However, values were significantly higher than in the resting condition for controls.

Thus, measured of oxidative stress (d-ROMS) and anti-oxidative activity (BAP) might be useful for discriminating acute, sub-acute, and resting fatigue in healthy people from patients with CFS, or for evaluating fatigue levels in healthy people.

Source: Fukuda S, Nojima J, Motoki Y, Yamaguti K, Nakatomi Y, Okawa N, Fujiwara K, Watanabe Y, Kuratsune H. A potential biomarker for fatigue: Oxidative stress and anti-oxidative activity. Biol Psychol. 2016 Jul;118:88-93. doi: 10.1016/j.biopsycho.2016.05.005. Epub 2016 May 17. https://www.ncbi.nlm.nih.gov/pubmed/27224647

Chronic fatigue syndrome in adolescents

Dear Editor:

Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is a rare disease in adolescents, in whom the incidence is 0.5%. In adults, it has a multifactorial aetiology with no determining factor, primarily affects women (ratio, 2–3:1) aged 20–40 years, and in some cases its onset is associated with an infectious cause (usually viral). In adulthood, CFS is diagnosed based on clinical manifestations and is a diagnosis of exclusion (Table 1),1 and while the literature includes descriptions of differences in the paediatric population, few series present data on its particular features in this age group. The management is symptomatic with the goal of improving quality of life. Treatment with selective serotonin reuptake inhibitors (SSRIs), melatonin, methylphenidate, cognitive-behavioural therapy (CBT) and graded exercise has been proven to be effective in these patients.

You can read the full letter here: http://www.analesdepediatria.org/en/chronic-fatigue-syndrome-in-adolescents/articulo/S2341287916301168/

Source: Calle Gómez Á, Delgado Díez B, Campillo I López F, Salmerón Ruiz MA, Casas Rivero J. Chronic fatigue syndrome in adolescents. An Pediatr (Barc). 2016 Dec;85(6):318-320. doi: 10.1016/j.anpedi.2016.03.010. Epub 2016 May 20. [Article in Spanish] http://www.analesdepediatria.org/en/chronic-fatigue-syndrome-in-adolescents/articulo/S2341287916301168/ (Full article)

A qualitative investigation of eating difficulties in adolescents with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

BACKGROUND: An estimated 10% of children and adolescents with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) experience eating difficulties; however, little is known about why these difficulties develop, what the impact is or how to manage them.

METHODS: Semi-structured interviews were conducted with adolescents (aged 12-17 years) attending a specialist service who have a primary diagnosis of CFS/ME and experience nausea, abdominal pain and/or eating difficulties. A total of 11 adolescents were interviewed (eight female, mean age: 15 years). Transcripts were analysed thematically using techniques of constant comparison which commenced soon after data collection and informed further interview protocols.

RESULTS: Adolescents perceived their eating difficulties were caused by abdominal symptoms, being too fatigued to eat and changes to their senses of taste and smell. Some of the adolescents recognised how their eating difficulties were exacerbated and maintained by psychological factors of low mood and anxiety. The adolescents eating difficulties had a negative impact on their weight, fatigue, socialising and family life. They perceived helpful interventions to include modifying their diets, families adjusting and also medical interventions (e.g. medication). Adolescents identified that early education and support about diet and eating habits would have been helpful.

CONCLUSIONS: If adolescents diagnosed with CFS/ME develop eating difficulties, this has a significant impact on their quality of life, illness and on their families. Not eating increases fatigue, low mood and anxiety which further exacerbates the eating difficulties. Clinicians should screen for eating difficulties in those with symptoms of nausea and abdominal pain, warn adolescents and their families of the risk of developing eating difficulties and provide interventions and support as early as possible.

Source: Harris S, Gilbert M, Beasant L, Linney C, Broughton J, Crawley E. A qualitative investigation of eating difficulties in adolescents with chronic fatigue syndrome/myalgic encephalomyelitis. Clin Child Psychol Psychiatry. 2017 Jan;22(1):128-139. doi: 10.1177/1359104516646813. Epub 2016 Jul 26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5207298/ (Full article)

Effect of Acute Exercise on Fatigue in People with ME/CFS/SEID: A Meta-analysis

Abstract:

PURPOSE: A prominent symptom of myalgic encephalomyelitis, chronic fatigue syndrome, or systemic exertion intolerance disease (ME/CFS/SEID) is persistent fatigue that is worsened by physical exertion. Here the population effect of a single bout of exercise on fatigue symptoms in people with ME/CFS/SEID was estimated and effect moderators were identified.

METHODS: Google Scholar was systematically searched for peer-reviewed articles published between February 1991 and May 2015. Studies were included where people diagnosed with ME/CFS/SEID and matched control participants completed a single bout of exercise and fatigue self-reports were obtained before and after exercise. Fatigue means, standard deviations, and sample sizes were extracted to calculate effect sizes and the 95% confidence interval. Effects were pooled using a random-effects model and corrected for small sample bias to generate mean Δ. Multilevel regression modeling adjusted for nesting of effects within studies. Moderators identified a priori were diagnostic criteria, fibromyalgia comorbidity, exercise factors (intensity, duration, and type), and measurement factors.

RESULTS: Seven studies examining 159 people with ME/CFS/SEID met inclusion criteria, and 47 fatigue effects were derived. The mean fatigue effect was Δ = 0.73 (95% confidence interval = 0.24-1.23). Fatigue increases were larger for people with ME/CFS/SEID when fatigue was measured 4 h or more after exercise ended rather than during or immediately after exercise ceased.

CONCLUSIONS: This preliminary evidence indicates that acute exercise increases fatigue in people with ME/CFS/SEID more than that in control groups, but effects were heterogeneous between studies. Future studies with no-exercise control groups of people with ME/CFS/SEID are needed to obtain a more precise estimate of the effect of exercise on fatigue in this population.

Source: Loy BD, O’Connor PJ, Dishman RK. Effect of Acute Exercise on Fatigue in People with ME/CFS/SEID: A Meta-analysis. Med Sci Sports Exerc. 2016 Oct;48(10):2003-12. doi: 10.1249/MSS.0000000000000990. https://www.ncbi.nlm.nih.gov/pubmed/27187093

Cow’s milk protein intolerance in adolescents and young adults with chronic fatigue syndrome

Abstract:

AIM: To examine the prevalence, clinical features and influence on illness severity of cow’s milk protein intolerance in young people with chronic fatigue syndrome.

METHODS: In a two-year prospective study of 55 adolescents and young adults with chronic fatigue syndrome, we defined intolerance to milk protein if subjects reported (i) no evidence of immediate or anaphylactic reactions to milk, (ii) at least 2 of the following 3 chronic symptoms: gastroesophageal reflux, early satiety and epigastric/abdominal pain, (iii) improvement in upper gastrointestinal symptoms on a milk protein elimination diet and (iv) at least 2 recurrences of upper gastrointestinal symptoms >two hours following open re-exposure to milk protein. Subjects completed three quality of life surveys at baseline and at six months.

RESULTS: The mean (SD) age of the 55 participants was 16.5 (2.1) years. Seventeen (31%; 95% CI, 19-43%) met study criteria for cow’s milk protein intolerance. Compared to milk-tolerant subjects, milk-sensitive participants had significantly worse health-related quality of life at baseline but not at six months (after institution of the milk-free diet).

CONCLUSION: Cow’s milk protein intolerance is a common problem in young people with chronic fatigue syndrome and is a treatable contributor to their symptoms.

Source: Rowe PC, Marden CL, Jasion SE, Cranston EM, Flaherty MA, Kelly KJ. Cow’s milk protein intolerance in adolescents and young adults with chronic fatigue syndrome. Acta Paediatr. 2016 Sep;105(9):e412-8. doi: 10.1111/apa.13476. Epub 2016 Jun 3. https://www.ncbi.nlm.nih.gov/pubmed/27177188

Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: a cross-sectional study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a common and disabling disorder, and a major threat against adolescent health. The pathophysiology is unknown, but alteration of neuroendocrine control systems might be a central element, resulting in attenuation of the hypothalamus-pituitary-adrenalin (HPA) axis and enhancement of the sympathetic/adrenal medulla (SAM) system. This study explored differences in neuroendocrine control mechanisms between adolescent CFS patients and healthy controls, and whether characteristics of the control mechanisms are associated with important clinical variables within the CFS group.

METHODS: CFS patients 12-18 years of age were recruited nation-wide to a single referral center as part of the NorCAPITAL project. A broad case definition of CFS was applied. A comparable group of healthy controls were recruited from local schools. A total of nine hormones were assayed and subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and daily physical activity was recorded by an accelerometer.

RESULTS: A total of 120 CFS patients and 68 healthy controls were included. CFS patients had significantly higher levels of plasma norepinephrine, plasma epinephrine and plasma FT4, and significantly lower levels of urine cortisol/creatinine ratio. Subgrouping according to other case definitions as well as adjusting for confounding factors did not alter the results. Multivariate linear regression models as well as network analyses revealed different interrelations between hormones of the HPA axis, the SAM system, and the thyroid system in CFS patients and healthy controls. Also, single hormone degree centrality was associated with clinical markers within the CFS group.

CONCLUSION: This study reveals different interrelation between hormones of the HPA axis, the SAM system, and the thyroid system in CFS patients and healthy controls, and an association between hormone control characteristics and important clinical variables in the CFS group. These results add to the growing insight of CFS disease mechanisms.

Trial registration Clinical Trials NCT010404

Source: Wyller VB, Vitelli V, Sulheim D, Fagermoen E, Winger A, Godang K, Bollerslev J. Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: a cross-sectional study. J Transl Med. 2016 May 5;14(1):121. doi: 10.1186/s12967-016-0873-1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858924/ (Full article)

Housebound versus nonhousebound patients with myalgic encephalomyelitis and chronic fatigue syndrome

Abstract:

OBJECTIVES: The objective of this study was to examine individuals with myalgic encephalomyelitis and chronic fatigue syndrome who are confined to their homes due to severe symptomatology. The existing literature fails to address differences between this group, and less severe, nonhousebound patient populations.

METHODS: Participants completed the DePaul Symptom Questionnaire, a measure of myalgic encephalomyelitis and chronic fatigue syndrome symptomology, and the SF-36, a measure of health impact on physical/mental functioning. ANOVAs and, where appropriate, MANCOVAS were used to compare housebound and nonhousebound patients with myalgic encephalomyelitis and chronic fatigue syndrome across areas of functioning, symptomatology, and illness onset characteristics.

RESULTS: Findings indicated that the housebound group represented one quarter of the sample, and were significantly more impaired with regards to physical functioning, bodily pain, vitality, social functioning, fatigue, postexertional malaise, sleep, pain, neurocognitive, autonomic, neuroendocrine, and immune functioning compared to individuals who were not housebound.

DISCUSSION: Findings indicated that housebound patients have more impairment on functional and symptom outcomes compared to those who were not housebound. Understanding the differences between housebound and not housebound groups holds implications for physicians and researchers as they develop interventions intended for patients who are most severely affected by this chronic illness.

Source: Pendergrast T, Brown A, Sunnquist M, Jantke R, Newton JL, Strand EB, Jason LA. Housebound versus nonhousebound patients with myalgic encephalomyelitis and chronic fatigue syndrome. Chronic Illn. 2016 Dec;12(4):292-307. Epub 2016 Apr 28. https://www.ncbi.nlm.nih.gov/pubmed/27127189

Ubiquinol-10 supplementation improves autonomic nervous function and cognitive function in chronic fatigue syndrome

Abstract:

The aim of this study was to evaluate the benefit of oral ubiquinol-10 supplementation in CFS patients using an open-label study and a randomized, double-blinded, placebo-controlled (RCT) study.

Twenty patients with CFS were randomly enrolled in an 8-week open-label oral ubiquinol-10 (150 mg ubiquinol-10/day) study. The patients and the attending physicians were not blinded to the supplementation. Forty-three patients with CFS were randomly assigned to receive either ubiquinol-10 (150 mg/day) or placebo every day for 12 weeks. The patients and the attending physicians were blinded to the supplementation, and a total of 31 patients (N = 17 in the ubiquinol group and 14 in the placebo group) completed the study.

The beneficial effects of ubiquinol-10 were observed in the open-label study we conducted prior to the RCT. The RCT results suggest that supplementation with ubiquinol-10 for 12 weeks is effective for improving several CFS symptoms. © 2016 BioFactors, 42(4):431-440, 2016.

Source: Fukuda S, Nojima J, Kajimoto O, Yamaguti K, Nakatomi Y, Kuratsune H, Watanabe Y. Ubiquinol-10 supplementation improves autonomic nervous function and cognitive function in chronic fatigue syndrome. Biofactors. 2016 Jul 8;42(4):431-40. doi: 10.1002/biof.1293. Epub 2016 Apr 29. https://www.ncbi.nlm.nih.gov/pubmed/27125909

Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study

Abstract:

PURPOSE: To examine progressive brain changes associated with chronic fatigue syndrome (CFS).

MATERIALS AND METHODS: We investigated progressive brain changes with longitudinal MRI in 15 CFS and 10 normal controls (NCs) scanned twice 6 years apart on the same 1.5 Tesla (T) scanner. MR images yielded gray matter (GM) volumes, white matter (WM) volumes, and T1- and T2-weighted signal intensities (T1w and T2w). Each participant was characterized with Bell disability scores, and somatic and neurological symptom scores. We tested for differences in longitudinal changes between CFS and NC groups, inter group differences between pooled CFS and pooled NC populations, and correlations between MRI and symptom scores using voxel based morphometry. The analysis methodologies were first optimized using simulated atrophy.

RESULTS: We found a significant decrease in WM volumes in the left inferior fronto-occipital fasciculus (IFOF) in CFS while in NCs it was unchanged (family wise error adjusted cluster level P value, PFWE < 0.05). This longitudinal finding was consolidated by the group comparisons which detected significantly decreased regional WM volumes in adjacent regions (PFWE< 0.05) and decreased GM and blood volumes in contralateral regions (PFWE < 0.05). Moreover, the regional GM and WM volumes and T2w in those areas showed significant correlations with CFS symptom scores (PFWE < 0.05).

CONCLUSION: The results suggested that CFS is associated with IFOF WM deficits which continue to deteriorate at an abnormal rate. J. Magn. Reson. Imaging 2016;44:1301-1311.

Source: Shan ZY, Kwiatek R, Burnet R, Del Fante P, Staines DR, Marshall-Gradisnik SM, Barnden LR. Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study. J Magn Reson Imaging. 2016 Nov;44(5):1301-1311. doi: 10.1002/jmri.25283. Epub 2016 Apr 28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111735/ (Full article)