2011 – Page 10 – American ME and CFS Society

Evidence for a heritable predisposition to Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS) came to attention in the 1980s, but initial investigations did not find organic causes. Now decades later, the etiology of CFS has yet to be understood, and the role of genetic predisposition in CFS remains controversial. Recent reports of CFS association with the retrovirus xenotropic murine leukemic virus-related virus (XMRV) or other murine leukemia related retroviruses (MLV) might also suggest underlying genetic implications within the host immune system.

METHODS: We present analyses of familial clustering of CFS in a computerized genealogical resource linking multiple generations of genealogy data with medical diagnosis data of a large Utah health care system. We compare pair-wise relatedness among cases to expected relatedness in the Utah population, and we estimate risk for CFS for first, second, and third degree relatives of CFS cases.

RESULTS: We observed significant excess relatedness of CFS cases compared to that expected in this population. Significant excess relatedness was observed for both close (p <0.001) and distant relationships (p = 0.010). We also observed significant excess CFS relative risk among first (2.70, 95% CI: 1.56-4.66), second (2.34, 95% CI: 1.31-4.19), and third degree relatives (1.93, 95% CI: 1.21-3.07).

CONCLUSIONS: These analyses provide strong support for a heritable contribution to predisposition to Chronic Fatigue Syndrome. A population of high-risk CFS pedigrees has been identified, the study of which may provide additional understanding.

Source: Albright F, Light K, Light A, Bateman L, Cannon-Albright LA. Evidence for a heritable predisposition to Chronic Fatigue Syndrome. BMC Neurol. 2011 May 27;11:62. doi: 10.1186/1471-2377-11-62. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128000/ (Full article)

The functional status and well being of people with myalgic encephalomyelitis/chronic fatigue syndrome and their carers

Abstract:

BACKGROUND: Diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome or ME/CFS is largely based on clinical history, and exclusion of identifiable causes of chronic fatigue. Characterization of cases and the impact of interventions have been limited due to clinical heterogeneity and a lack of reliable biomarkers for diagnosis and outcome measures. People with ME/CFS (PWME) often report high levels of disability, which are difficult to measure objectively. The well being of family members and those who care for PWME are also likely to be affected. This study aimed to investigate the functional status and well being of PWME and their lay carers, and to compare them with people with other chronic conditions.

METHODS: We used a cross sectional design to study 170 people aged between 18 and 64 years with well characterized ME/CFS, and 44 carers, using SF-36 v2™. Mean physical and mental domains scores (scales and component summaries) were calculated and compared internally and externally with reference standards for the general population and for population groups with 10 chronic diseases.

: SF-36 scores in PWME were significantly reduced, especially within the physical domain (mean norm-based Physical Component Summary (PCS) score = 26.8), but also within the mental domain (mean norm-based score for Mental Component Summary (MCS) = 34.1). The lowest and highest scale scores were for “Role-Physical” (mean = 25.4) and “Mental Health” (mean = 36.7) respectively. All scores were in general lower than those for the general population and diseased-specific norms for other diseases. Carers of those with ME/CFS tended to have low scores in relation to population norms, particularly within the mental domain (mean = 45.4).

CONCLUSIONS: ME/CFS is disabling and has a greater impact on functional status and well being than other chronic diseases such as cancer. The emotional burden of ME/CFS is felt by lay carers as well as by people with ME/CFS. We suggest the use of generic instruments such as SF-36, in combination of other objective outcome measurements, to describe patients and assess treatments.

Source: Nacul LC, Lacerda EM, Campion P, Pheby D, Drachler Mde L, Leite JC, Poland F, Howe A, Fayyaz S, Molokhia M. The functional status and well being of people with myalgic encephalomyelitis/chronic fatigue syndrome and their carers. BMC Public Health. 2011 May 27;11:402. doi: 10.1186/1471-2458-11-402. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123211/ (Full article)

Chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is defined by a profound, debilitating fatigue, lasting for at least 6 months and resulting in a substantial reduction of occupational, personal, social and educational status. CFS is a relatively poorly recognized clinical entity, although everyday experience shows that there are many patients with CFS symptoms.

The incidence and prevalence of CFS remain unknown in most countries; however, the working population is most affected with predominantly female patients in generative period. Although, CFS was first mentioned four centuries ago, mysterious aethiopathogensis of CFS still intrigues scientists as hundreds of studies are still published every year on the subject. About 80 different aetiological CFS factors are mentioned, which can be classified into five basic groups: genetics, immunology, infectious diseases, endocrinology and neuropsychiatry-psychology.

Even today the condition is passed established based on the diagnosis by exclusion of organic and psychiatric disorders, which demands a multidisciplinary approach. As the syndrome is often misdiagnosed and mistreated, self-medication is not uncommon in CFS patients’. In addition, such patients usually suffer for years tolerating severe fatigue. Thus, at the moment there are three priorities regarding CFS; understanding pathogenesis, development of diagnostic tests and creating efficient treatment program.

Source: Brkić S, Tomić S, Ruzić M, Marić D. Chronic fatigue syndrome. Srp Arh Celok Lek. 2011 Mar-Apr;139(3-4):256-61. https://www.ncbi.nlm.nih.gov/pubmed/21618868

Factors affecting duration of chronic fatigue syndrome in pediatric patients

Abstract:

OBJECTIVE: To determine factors affecting duration of chronic fatigue syndrome (CFS) in pediatric patients.

METHODS: This Retrospective cohort consisted of patients with CFS at the regional referral infectious disease clinic for evaluation of fatigue in children and adolescents. Demographic, clinical, and laboratory data were analyzed to identify the impact on duration and severity of pediatric CFS.

RESULTS: A total number of 53 predominantly white (98.1%) patients with CFS, aged 9-18 years, were included in the study. Other than fatigue, headaches and sleep disturbance were the most common symptoms of pediatric CFS. Seropositive status for Borrelia burgdorferi (B. burgdorferi) and Epstein-Barr virus (EBV) was identified in 66% of the patients with the diagnosis of CFS by CDC criteria. No association was found between the CFS symptoms, gender, or age at diagnosis and duration of fatigue symptoms. Duration of CFS was associated with high Body-Mass Index (BMI) in a regression model after adjustment for patient’s age, gender, and seropositive status for B. burgdorferi and/or EBV (0.34 ± 0.15, P < 0.04).

CONCLUSIONS: BMI is significantly associated with prolonged duration of CFS.

Source: Petrov D, Marchalik D, Sosin M, Bal A. Factors affecting duration of chronic fatigue syndrome in pediatric patients. Indian J Pediatr. 2012 Jan;79(1):52-5. doi: 10.1007/s12098-011-0463-4. Epub 2011 May 27. https://www.ncbi.nlm.nih.gov/pubmed/21617905

Chronic fatigue syndrome

Abstract:

INTRODUCTION: Chronic fatigue syndrome (CFS) affects between 0.006% and 3% of the population depending on the criteria of definition used, with women being at higher risk than men.

METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for chronic fatigue syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

RESULTS: We found 46 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressants, cognitive behavioural therapy (CBT), corticosteroids, dietary supplements, evening primrose oil, galantamine, graded exercise therapy, homeopathy, immunotherapy, intramuscular magnesium, oral nicotinamide adenine dinucleotide, and prolonged rest.

Source: Reid S, Chalder T, Cleare A, Hotopf M, Wessely S. Chronic fatigue syndrome. BMJ Clin Evid. 2011 May 26;2011. pii: 1101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3275316/ (Full article)

Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome

Abstract:

OBJECTIVES: To determine mRNA expression differences in genes involved in signalling and modulating sensory fatigue, and muscle pain in patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FM) at baseline, and following moderate exercise.

DESIGN: Forty-eight patients with CFS only, or CFS with comorbid FM, 18 patients with FM that did not meet criteria for CFS, and 49 healthy controls underwent moderate exercise (25 min at 70% maximum age-predicted heart rate). Visual-analogue measures of fatigue and pain were taken before, during and after exercise. Blood samples were taken before and 0.5, 8, 24 and 48 h after exercise. Leucocytes were immediately isolated from blood, number coded for blind processing and analyses and flash frozen. Using real-time, quantitative PCR, the amount of mRNA for 13 genes (relative to control genes) involved in sensory, adrenergic and immune functions was compared between groups at baseline and following exercise. Changes in amounts of mRNA were correlated with behavioural measures and functional clinical assessments.

RESULTS: No gene expression changes occurred following exercise in controls. In 71% of patients with CFS, moderate exercise increased most sensory and adrenergic receptor’s and one cytokine gene’s transcription for 48 h. These postexercise increases correlated with behavioural measures of fatigue and pain. In contrast, for the other 29% of patients with CFS, adrenergic α-2A receptor’s transcription was decreased at all time-points after exercise; other genes were not altered. History of orthostatic intolerance was significantly more common in the α-2A decrease subgroup. FM-only patients showed no postexercise alterations in gene expression, but their pre-exercise baseline mRNA for two sensory ion channels and one cytokine were significantly higher than controls.

CONCLUSIONS: At least two subgroups of patients with CFS can be identified by gene expression changes following exercise. The larger subgroup showed increases in mRNA for sensory and adrenergic receptors and a cytokine. The smaller subgroup contained most of the patients with CFS with orthostatic intolerance, showed no postexercise increases in any gene and was defined by decreases in mRNA for α-2A. FM-only patients can be identified by baseline increases in three genes. Postexercise increases for four genes meet published criteria as an objective biomarker for CFS and could be useful in guiding treatment selection for different subgroups.

Source: Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, Light KC. Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome. J Intern Med. 2012 Jan;271(1):64-81. doi: 10.1111/j.1365-2796.2011.02405.x. Epub 2011 Jul 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175315/ (Full article)

The relationship between posttraumatic stress disorder, illness cognitions, defence styles, fatigue severity and psychological well-being in chronic fatigue syndrome

Abstract:

This study investigated, firstly, the rate of posttraumatic stress disorder (PTSD) and the level of psychological well-being amongst people with chronic fatigue syndrome (CFS); and secondly, the extent to which illness cognitions, defence styles and PTSD symptom severity related to fatigue severity and psychological well-being.

Seventy-eight participants with a diagnosis of CFS completed the Chalder Fatigue Scale, the General Health Questionnaire-28, the Posttraumatic Stress Diagnostic Scale, the Illness Cognition Questionnaire and the Defence Style Questionnaire. Fifty-nine participants were recruited from the general public to form the non-fatigued control group.

CFS participants had significantly higher levels of PTSD symptoms, lower levels of psychological well-being and more traumatic life events compared to the non-fatigued controls. Trauma exposure and PTSD severity both predicted CFS status. However, regression analyses demonstrated no significant relationship between PTSD symptoms and fatigue severity or the degree of psychological well-being. ‘Helplessness’ predicted both physical and mental fatigue and psychological well-being, whilst the ‘mature’ defence styles predicted fatigue severity only.

The results offer support to previous research showing that the rate of traumatic life events and PTSD are significantly higher amongst the CFS population. The lack of relationship between PTSD symptoms and fatigue severity or psychological well-being indicates that these processes may operate independently of one another, via different appraisal processes. This study focused on fatigue severity, but it may be that the role of pain in CFS is a key element in the previously reported association between PTSD and CFS.

Source: Eglinton R, Chung MC. The relationship between posttraumatic stress disorder, illness cognitions, defence styles, fatigue severity and psychological well-being in chronic fatigue syndrome. Psychiatry Res. 2011 Jul 30;188(2):245-52. doi: 10.1016/j.psychres.2011.04.012. Epub 2011 May 19. https://www.ncbi.nlm.nih.gov/pubmed/21600664

Quality and acceptability of patient-reported outcome measures used in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review

Abstract:

PURPOSE: To review the quality and acceptability of condition-specific, domain-specific and generic multi-item patient-reported outcome measures (PROMs) used in the assessment of adults with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

METHODS: Systematic literature searches were made to identify PROMs. Quality and acceptability was assessed against an appraisal framework, which captured evidence of both the thoroughness and results of evaluations: evidence of measurement (reliability, validity, responsiveness, interpretability, data quality/precision) and practical properties (feasibility, patient acceptability), and the extent of active patient involvement was sought.

RESULTS: A total of 11 CFS/ME-specific, 55 domain-specific and 11 generic measures were reviewed. With the exception of the generic SF-36, all measures had mostly limited evidence of measurement and/or practical properties. Patient involvement was poorly reported and often cursory.

CONCLUSIONS: The quality and acceptability of reviewed PROMs is limited, and recommendations for patient-reported assessment are difficult. Significant methodological and quality issues in PROM development/evaluation were identified by the appraisal framework, which must be addressed in future research. Clear discrepancies exist between what is measured in research and how patients define their experience of CFS/ME. Future PROM development/evaluation must seek to involve patients more collaboratively to measure outcomes of importance using relevant and credible methods of assessment.

Source: Haywood KL, Staniszewska S, Chapman S. Quality and acceptability of patient-reported outcome measures used in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): a systematic review. Qual Life Res. 2012 Feb;21(1):35-52. doi: 10.1007/s11136-011-9921-8. Epub 2011 May 18. https://www.ncbi.nlm.nih.gov/pubmed/21590511

Immunologic and psychosocial status in chronic fatigue syndrome

Abstract:

OBJECTIVE: The aim of the study was to investigate the immunologic functions and psychosocial status in patients with chronic fatigue syndrome (CFS).

METHODS: Twenty-five patients with CFS diagnosed by the international CFS definition criteria and 20 age- and gender-matched healthy controls were recruited. Depression was assessed by Beck Depression Inventory (BDI) and health status was assessed by Nottingham Health Profile (NHP). Monoclonal antibodies (MAbs) were measured to identify the following NK cell subsets: CD3, CD4, CD8 and CD56 and cytokine measurements were performed for IL2r, IL6 and IL8 in both patients and control subjects.

RESULTS: The BDI and NHP scores of CFS group were found to be significantly higher than in the control group. The absolute numbers of CD56 cell were also significantly decreased in the patients with CFS compared with the healthy controls. There were no other significant differences of NK cell activity (CD3, CD4 and CD8) and there were significant differences in IL6 and IL2r levels between patients and controls. There were significant correlations between serum IL-6 level and sleep, social isolation and physical ability NHP subscores, and between CD56 NK cell activity and emotional reaction NHP sub score in CFS patients.

CONCLUSION: Significantly higher ratios of psychological and physical disturbances were found in patients with CFS. Decreased CD56 NK cell activity and increased IL2r levels seem to be important immunopathologic changes in CFS. IL-6 and CD 56 NK cell activity may play an important role in sleep, physical, social, and physicological manifestations of CFS (Tab. 3, Fig. 1, Ref. 36).

Full Text in free PDF http://bmj.fmed.uniba.sk/2011/11204-12.pdf

Source: Nas K, Cevik R, Batum S, Sarac AJ, Acar S, Kalkanli S. Immunologic and psychosocial status in chronic fatigue syndrome. Bratisl Lek Listy. 2011;112(4):208-12. https://www.ncbi.nlm.nih.gov/pubmed/21585130