Newton – Page 5 – American ME and CFS Society

Case definitions integrating empiric and consensus perspectives

Abstract:

BACKGROUND: There has been considerable controversy regarding how to name and define the illnesses known as myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). The IOM report has proposed a new clinical criteria and name for this illness, but aspects of these recommendations have been scrutinized by patients and scientists.

PURPOSE: It is possible that both empiric and consensus approaches could be used to help settle some of these diagnostic challenges. Using patient samples collected in the United States, Great Britain, and Norway (N=556), the current study attempted to categorize patients using more general as well as more restricted case definitions.

RESULTS: Overall, the outcomes suggest that there might be four groupings of patients, with the broadest category involving those with chronic fatigue (N=62), defined by 6 or more months of fatigue which can be cannot be explained by medical or psychiatric conditions. A second category involves those patients that have chronic fatigue that can be explained by a medical or psychiatric condition (N=47). A third category involves more specific criteria that have been posited both by the IOM report, a Canadian Clinical Case criteria, a ME-ICC criteria and a more empiric approach. These efforts have specified domains of substantial reductions of activity, post-exertional malaise, neurocognitive impairment, and sleep dysfunction (N=346). Patients with these characteristics were more functionally impaired than those meeting just chronic fatigue criteria, p < .05. Finally, those meeting even more restrictive ME criteria proposed by Ramsay, identified a smaller and even more impaired group, p < .05.

DISCUSSION: The advantages of using such empirical and consensus approaches to develop reliable classification and diagnostic efforts are discussed.

Source: Jason LA, McManimen S, Sunnquist M, Brown A, Furst J, Newton JL, Strand EB. Case definitions integrating empiric and consensus perspectives. Fatigue. 2016;4(1):1-23. Epub 2016 Jan 19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831204/ (Full article)

Understanding Muscle Dysfunction in Chronic Fatigue Syndrome

Abstract:

Introduction. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown aetiology, characterised by severe disabling fatigue in the absence of alternative diagnosis. Historically, there has been a tendency to draw psychological explanations for the origin of fatigue; however, this model is at odds with findings that fatigue and accompanying symptoms may be explained by central and peripheral pathophysiological mechanisms, including effects of the immune, oxidative, mitochondrial, and neuronal pathways. For example, patient descriptions of their fatigue regularly cite difficulty in maintaining muscle activity due to perceived lack of energy. This narrative review examined the literature for evidence of biochemical dysfunction in CFS/ME at the skeletal muscle level.

Methods. Literature was examined following searches of PUB MED, MEDLINE, and Google Scholar, using key words such as CFS/ME, immune, autoimmune, mitochondria, muscle, and acidosis.

Results. Studies show evidence for skeletal muscle biochemical abnormality in CFS/ME patients, particularly in relation to bioenergetic dysfunction.

Discussion. Bioenergetic muscle dysfunction is evident in CFS/ME, with a tendency towards an overutilisation of the lactate dehydrogenase pathway following low-level exercise, in addition to slowed acid clearance after exercise. Potentially, these abnormalities may lead to the perception of severe fatigue in CFS/ME.

Source: Rutherford G, Manning P, Newton JL. Understanding Muscle Dysfunction in Chronic Fatigue Syndrome. J Aging Res. 2016;2016:2497348. doi: 10.1155/2016/2497348. Epub 2016 Feb 22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779819/ (Full article)

The aetiopathogenesis of fatigue: unpredictable, complex and persistent

Abstract:

BACKGROUND: Chronic fatigue syndrome is a common condition characterized by severe fatigue with post-exertional malaise, impaired cognitive ability, poor sleep quality, muscle pain, multi-joint pain, tender lymph nodes, sore throat or headache. Its defining symptom, fatigue is common to several diseases.

AREAS OF AGREEMENT: Research has established a broad picture of impairment across autonomic, endocrine and inflammatory systems though progress seems to have reached an impasse.

AREAS OF CONTROVERSY: The absence of a clear consensus view of the pathophysiology of fatigue suggests the need to switch from a focus on abnormalities in one system to an experimental and clinical approach which integrates findings across multiple systems and their constituent parts and to consider multiple environmental factors.

GROWING POINTS: We discuss this with reference to three key factors, non-determinism, non-reductionism and self-organization and suggest that an approach based on these principles may afford a coherent explanatory framework for much of the observed phenomena in fatigue and offers promising avenues for future research.

AREAS TIMELY FOR DEVELOPING RESEARCH: By adopting this approach, the field can examine issues regarding aetiopathogenesis and treatment, with relevance for future research and clinical practice.

Source: Clark JE, Fai Ng W, Watson S, Newton JL. The aetiopathogenesis of fatigue: unpredictable, complex and persistent. Br Med Bull. 2016 Mar;117(1):139-48. doi: 10.1093/bmb/ldv057. Epub 2016 Feb 12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782751/ (Full article)

A systematic review of the comorbidity between Temporomandibular Disorders and Chronic Fatigue Syndrome

Abstract:

The most common cause of chronic oro-facial pain is a group of disorders collectively termed temporomandibular disorders (TMDs). Chronic painful TMD is thought to be a ‘central sensitivity syndrome’ related to hypersensitivity of the nervous system, but the cause is unknown. A similar understanding is proposed for other unexplained conditions, including chronic fatigue syndrome (CFS). Exploring the comorbidity of the two conditions is a valuable first step in identifying potential common aetiological mechanisms or treatment targets.

METHOD: Systematic literature review. Studies were included if they recruited community or control samples and identified how many reported having both TMD and CFS, or if they recruited a sample of patients with either TMD or CFS and measured the presence of the other condition.

RESULTS: Six papers met inclusion criteria. In studies of patients with CFS (n = 3), 21-32% reported having TMD. In a sample of people with CFS and fibromyalgia, 50% reported having TMD. Studies in people with TMD (n = 3) reported 0-43% having CFS. Studies in samples recruited from oro-facial pain clinics (n = 2) reported a lower comorbidity with CFS (0-10%) than a study that recruited individuals from a TMD self-help organisation (43%).

CONCLUSION: The review highlights the limited standard of evidence addressing the comorbidity between oro-facial pain and CFS. There is a valuable signal that the potential overlap in these two conditions could be high; however, studies employing more rigorous methodology including standardised clinical assessments rather than self-report of prior diagnosis are needed.

Source: Robinson LJ, Durham J, Newton JL. A systematic review of the comorbidity between Temporomandibular Disorders and Chronic Fatigue Syndrome. J Oral Rehabil. 2016 Apr;43(4):306-16. doi: 10.1111/joor.12367. Epub 2015 Nov 9. https://www.ncbi.nlm.nih.gov/pubmed/26549386

A Cross Cultural Comparison of Disability and Symptomatology Associated with CFS

Abstract:

Few studies have compared symptomatology and functional differences experienced by patients with chronic fatigue syndrome (CFS) across cultures. The current study compared patients with CFS from the United States (US) to those from the United Kingdom (UK) across areas of functioning, symptomatology, and illness onset characteristics.

Individuals in each sample met criteria for CFS as defined by Fukuda et al. (1994). These samples were compared on two measures of disability and impairment, the DePaul Symptom Questionnarie (DSQ) and the Medical outcomes study 36-item short-form health survey (SF-36).

Results revealed that the UK sample was significantly more impaired in terms of mental health and role emotional functioning, as well as specific symptoms of pain, neurocognitive difficulties, and immune manifestations. In addition, the UK sample was more likely to be working rather than on disability.

Individuals in the US sample reported more difficulties falling asleep, more frequently reported experiencing a sudden illness onset (within 24 hours), and more often reported that the cause of illness was primarily due to physical causes. These findings suggest that there may be important differences in illness characteristics across individuals with CFS in the US and the UK, and this has implications for the comparability of research findings across these two countries.

Source: Zdunek M, Jason LA, Evans M, Jantke R, Newton JL. A Cross Cultural Comparison of Disability and Symptomatology Associated with CFS. Int J Psychol Behav Sci. 2015;5(2):98-107. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4605442/ (Full article)

Chronic Fatigue Syndrome versus Systemic Exertion Intolerance Disease

Abstract:

BACKGROUND: The Institute of Medicine has recommended a change in the name and criteria for Chronic Fatigue Syndrome (CFS), renaming the illness Systemic Exertion Intolerance Disease (SEID). The new SEID case definition requires substantial reductions or impairments in the ability to engage in pre-illness activities, unrefreshing sleep, post-exertional malaise, and either cognitive impairment or orthostatic intolerance.

PURPOSE: In the current study, samples were generated through several different methods and were used to compare this new case definition to previous case definitions for CFS, Myalgic Encephalomyelitis (ME-ICC), Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), as well as a case definition developed through empirical methods.

METHODS: We used a cross-sectional design with samples from tertiary care settings, a biobank sample, and other forums. 796 patients from the US, Great Britain, and Norway completed the DePaul Symptom Questionnaire.

RESULTS: Findings indicated that the SEID criteria identified 88% of participants in the samples analyzed, which is comparable to the 92% that met the Fukuda criteria. The SEID case definition was compared to a four item empiric criteria, and findings indicated that the four item empiric criteria identified a smaller, more functionally limited and symptomatic group of patients.

CONCLUSION: The recently developed SEID criteria appears to identify a group comparable in size to the Fukuda et al. criteria, but a larger group of patients than the Canadian ME/CFS and ME criteria, and selects more patients who have less impairment and fewer symptoms than a four item empiric criteria.

Source: Jason LA, Sunnquist M, Brown A, Newton JL, Strand EB, Vernon SD. Chronic Fatigue Syndrome versus Systemic Exertion Intolerance Disease. Fatigue. 2015 Jul;3(3):127-141. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556426/ (Full article)

Abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells from individuals with chronic fatigue syndrome

Abstract:

BACKGROUND: Post exertional muscle fatigue is a key feature in Chronic Fatigue Syndrome (CFS). Abnormalities of skeletal muscle function have been identified in some but not all patients with CFS. To try to limit potential confounders that might contribute to this clinical heterogeneity, we developed a novel in vitro system that allows comparison of AMP kinase (AMPK) activation and metabolic responses to exercise in cultured skeletal muscle cells from CFS patients and control subjects.

METHODS: Skeletal muscle cell cultures were established from 10 subjects with CFS and 7 age-matched controls, subjected to electrical pulse stimulation (EPS) for up to 24h and examined for changes associated with exercise.

RESULTS: In the basal state, CFS cultures showed increased myogenin expression but decreased IL6 secretion during differentiation compared with control cultures. Control cultures subjected to 16 h EPS showed a significant increase in both AMPK phosphorylation and glucose uptake compared with unstimulated cells. In contrast, CFS cultures showed no increase in AMPK phosphorylation or glucose uptake after 16 h EPS. However, glucose uptake remained responsive to insulin in the CFS cells pointing to an exercise-related defect. IL6 secretion in response to EPS was significantly reduced in CFS compared with control cultures at all time points measured.

CONCLUSION: EPS is an effective model for eliciting muscle contraction and the metabolic changes associated with exercise in cultured skeletal muscle cells. We found four main differences in cultured skeletal muscle cells from subjects with CFS; increased myogenin expression in the basal state, impaired activation of AMPK, impaired stimulation of glucose uptake and diminished release of IL6. The retention of these differences in cultured muscle cells from CFS subjects points to a genetic/epigenetic mechanism, and provides a system to identify novel therapeutic targets.

Source: Brown AE, Jones DE, Walker M, Newton JL. Abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells from individuals with chronic fatigue syndrome. PLoS One. 2015 Apr 2;10(4):e0122982. doi: 10.1371/journal.pone.0122982. ECollection 2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383615/ (Full article)

The experience of sleep in chronic fatigue syndrome: A qualitative interview study with patients

Abstract:

OBJECTIVES: Sleep disturbances are common in chronic fatigue syndrome (CFS), and one of the key symptom complaints, yet it has been neglected by previous qualitative research. The aim was to explore the specific role of sleep in patients’ experience of their illness.

DESIGN: A qualitative semi-structured interview format facilitated a detailed and open exploration of sleep, and the extent to which its management and problems were linked to the lived experience of CFS.

METHODS: Eleven semi-structured interviews were conducted with individuals with CFS. Data were transcribed verbatim and analysed thematically, to explore and describe patients’ experience of their sleep, and its impact on their condition.

RESULTS: Sleep emerged as a key aspect of the illness experience, and its management and effect on daytime functioning was a central pre-occupation for all 11 participants; all of them saw sleep as playing a critical role in their illness through either maintaining or exacerbating existing symptoms. Exploration of individual experiences presented three overarching themes: (1) sleep pattern variability over illness course and from day to day; (2) effect of sleep on daytime functioning; and (3) attempts at coping and sleep management.

CONCLUSIONS: Each patient with CFS has a unique experience of sleep. Despite the differing narratives regarding the role of sleep in CFS, all participants held the belief that sleep is a vital process for health and well-being which has had a direct bearing on the course and progression of their CFS. Also, every participant regarded their sleep as in some way ‘broken’ and in need of management/repair. Patients’ insights demonstrate sleep-specific influences on their CFS, and the impact of disturbed sleep should be a consideration for clinical and research work.

STATEMENT OF CONTRIBUTION: What is already known on this subject? Sleep disturbances are common in CFS, and one of the key symptom complaints, yet it has been neglected by previous qualitative research. Ontology of CFS is a matter of dispute, with models ranging from the biological to the psychological competing to explain symptomatology in this illness. A qualitative study has the potential to add some clarity to the debate by making the patients’ lived experience of the condition, and their own understanding of it, the focus of research. What this study adds? Coping and attempts at managing sleep problems in CFS adds to the ‘illness burden’ experienced by patients. Disturbed sleep is universally seen by patients with CFS as impacting on other daytime symptoms. Broken sleep may contribute to a biopsychosocial cycle that serves to maintain this illness.

Source: Gotts ZM, Newton JL, Ellis JG, Deary V. The experience of sleep in chronic fatigue syndrome: A qualitative interview study with patients. Br J Health Psychol. 2016 Feb;21(1):71-92. doi: 10.1111/bjhp.12136. Epub 2015 Feb 26. https://www.ncbi.nlm.nih.gov/pubmed/25728396

The association between daytime napping and cognitive functioning in chronic fatigue syndrome

Abstract:

OBJECTIVES: The precise relationship between sleep and physical and mental functioning in chronic fatigue syndrome (CFS) has not been examined directly, nor has the impact of daytime napping. This study aimed to examine self-reported sleep in patients with CFS and explore whether sleep quality and daytime napping, specific patient characteristics (gender, illness length) and levels of anxiety and depression, predicted daytime fatigue severity, levels of daytime sleepiness and cognitive functioning, all key dimensions of the illness experience.

METHODS: 118 adults meeting the 1994 CDC case criteria for CFS completed a standardised sleep diary over 14 days. Momentary functional assessments of fatigue, sleepiness, cognition and mood were completed by patients as part of usual care. Levels of daytime functioning and disability were quantified using symptom assessment tools, measuring fatigue (Chalder Fatigue Scale), sleepiness (Epworth Sleepiness Scale), cognitive functioning (Trail Making Test, Cognitive Failures Questionnaire), and mood (Hospital Anxiety and Depression Scale).

RESULTS: Hierarchical Regressions demonstrated that a shorter time since diagnosis, higher depression and longer wake time after sleep onset predicted 23.4% of the variance in fatigue severity (p <.001). Being male, higher depression and more afternoon naps predicted 25.6% of the variance in objective cognitive dysfunction (p <.001). Higher anxiety and depression and morning napping predicted 32.2% of the variance in subjective cognitive dysfunction (p <.001). When patients were classified into groups of mild and moderate sleepiness, those with longer daytime naps, those who mainly napped in the afternoon, and those with higher levels of anxiety, were more likely to be in the moderately sleepy group.

CONCLUSIONS: Napping, particularly in the afternoon is associated with poorer cognitive functioning and more daytime sleepiness in CFS. These findings have clinical implications for symptom management strategies.

Source: Gotts ZM, Ellis JG, Deary V, Barclay N, Newton JL. The association between daytime napping and cognitive functioning in chronic fatigue syndrome. PLoS One. 2015 Jan 9;10(1):e0117136. doi: 10.1371/journal.pone.0117136. ECollection 2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289075/ (Full article)

Examining the Institute of Medicine’s Recommendations Regarding Chronic Fatigue Syndrome: Clinical Versus Research Criteria

Abstract:

The Institute of Medicine (2015) has proposed a new clinical case definition for what had been known as chronic fatigue syndrome (CFS). This new criteria involved the following domains: substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities; post-exertional malaise; unrefreshing sleep; and at least one of the two following symptoms: cognitive impairment or orthostatic intolerance.

In addition, in August of 2015, the CFS Advisory Committee, which makes recommendations to the Secretary of US Department of Health and Human Services, proposed that the Canadian 2003 criteria should serve as the research case for CFS. Up to now, there have not been any published investigations comparing these clinical and research criteria.

Using patient samples collected in the United States, Great Britain, and Norway, the current study compared and contrasted patients who met the clinical and research criteria. Overall findings indicated that those meeting the research criteria in comparison to those meeting the clinical criteria were significantly more impaired on a wide variety of symptoms and functional areas. The implications of these findings are discussed.

Source: Jason LA, McManimen S, Sunnquist M, Brown A, Newton JL, Strand EB. Examining the Institute of Medicine’s Recommendations Regarding Chronic Fatigue Syndrome: Clinical Versus Research Criteria. J Neurol Psychol. 2015;2015(Suppl 2). pii: http://www.avensonline.org/wp-content/uploads/JNP-2332-3469-S2-0002.pdf. Epub 2015 Nov 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008852/ (Full article)