Attachment to IACFS/ME Newsletter Volume 3, Issue 1 April 2010 s: Recent research findings in CFS/ME Van Ness J et al. Post-exertional Malaise in Women with CFS. J of Women s Health 2010;19:1-6 Objective: Postexertional malaise (PEM) is a defining characteristic of chronic fatigue syndrome (CFS) that remains a source of some controversy. The purpose of this study was to explore the effects of an exercise challenge on CFS symptoms from a patient perspective. Methods: This study included 25 female CFS patients and 23 age-matched sedentary controls. All participants underwent a maximal cardiopulmonary exercise test. Subjects completed a health and well-being survey (SF-36) 7 days postexercise. Subjects also provided, approximately 7 days after testing, written answers to open-ended questions pertaining to physical and cognitive responses to the test and length of recovery. SF-36 data were compared using multivariate analyses. Written questionnaire responses were used to determine recovery time as well as number and type of symptoms experienced. Results: Written questionnaires revealed that within 24 hours of the test, 85% of controls indicated full recovery, in contrast to 0 CFS patients. The remaining 15% of controls recovered within 48 hours of the test. In contrast, only 1 CFS patient recovered within 48 hours. Symptoms reported after the exercise test included fatigue, light-headedness, muscular/joint pain, cognitive dysfunction, headache, nausea, physical weakness, trembling/instability, insomnia, and sore throat/glands. A significant multivariate effect for the SF-36 responses (p < 0.001) indicated lower functioning among the CFS patients, which was most pronounced for items measuring physiological function. Conclusions: The results of this study suggest that PEM is both a real and an incapacitating condition for women with CFS and that their responses to exercise are distinctively different from those of sedentary controls.
Maloney E M et al. CFS is associated with metabolic syndrome: results from a case control study. Metabolism 2010 (ahead of print) We hypothesized that persons with chronic fatigue syndrome (CFS) would have a higher prevalence of metabolic syndrome compared with well controls, and that unwell persons with insufficient symptoms or fatigue for CFS (termed ISF) would have a prevalence of metabolic syndrome intermediate between those with CFS and the controls. We also sought to examine the relationship between metabolic syndrome and measures of functional impairment, fatigue, and other symptoms. Our analysis was based on a populationbased case-control study conducted in metropolitan, urban, and rural areas of Georgia, United States, between September 2004 and July 2005. There were 111 persons with CFS, 259 with ISF, and 123 controls. Metabolic syndrome was determined based on having at least 3 of 5 standard risk components (abdominal obesity, high triglycerides, high blood pressure, elevated fasting glucose, and decreased high-density lipids) according to the National Cholesterol Education Program Adult Treatment Panel III definition. Persons with CFS were 2-fold as likely to have metabolic syndrome (odds ratio = 2.12, confidence interval = 1.06, 4.23) compared with the controls. There was a significant graded relationship between the number of metabolic syndrome factors and CFS; each additional factor was associated with a 37% increase in likelihood of having CFS. The association of ISF with metabolic syndrome was weaker (odds ratio = 1.72, confidence interval = 0.94-3.16). Among persons with CFS, the number of metabolic syndrome factors was significantly correlated with worse fatigue on a standardized summary measure of fatigue (r = 0.20, P =.04). In conclusion, CFS was associated with metabolic syndrome, which further exacerbated fatigue.
Iris Nijrolder et al. Diagnoses during follow-up of patients presenting with fatigue in primary care. CMAJ 2009;181:(10) Background: Little is known about the distribution of diagnoses that account for fatigue in patients in primary care. We evaluated the diagnoses established within 1 year after presentation with fatigue in primary care that were possibly associated with the fatigue. Methods: We conducted a prospective observational cohort study with 1-year follow-up. We included adult patients who presented with a new episode of fatigue between June 2004 and January 2006. We extracted data on diagnoses during the follow-up period from the patients' medical records as well as data on preexisting chronic diseases. Results: Of the 571 patients for whom diagnostic data were available, 268 (46.9%) had received one or more diagnoses that could be associated with fatigue. The diagnoses were diverse and mostly included symptom diagnoses, with main categories being musculoskeletal (19.4%) and psychological problems (16.5%). Clear somatic pathology was diagnosed in 47 (8.2%) of the patients. Most diagnoses were not made during the consultation when fatigue was presented. Interpretation: Only a minority of patients were diagnosed with serious pathology. Half of the patients did not receive any diagnosis that could explain their fatigue. Nevertheless, because of the wide range of conditions and symptoms that may explain or co-occur with the fatigue, fatigue is a complex problem that deserves attention not only as a symptom of underlying specific disease.
Zhang L et al. Microbial infections in 8 genomic subtypes of CFS/ME. J Clin Pathol 2010;63:156-164 Background The authors have previously reported genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) based on expression of 88 human genes. Aim To attempt to reproduce these findings, determine the specificity of this signature to CFS/ME, and test for associations between CFS/ME subtype and infection. Methods Expression levels of 88 human genes were determined in blood of 62 new patients with idiopathic CFS/ME (according to Fukuda criteria), six patients with Q-fever-associated CFS/ME from the Birmingham Q- fever outbreak (according to Fukuda criteria), 14 patients with endogenous depression (according to DSM-IV criteria) and 29 normal blood donors. Results In patients with CFS/ME, differential expression was confirmed for all 88 genes. Q-CFS/ME had similar patterns of gene expression to idiopathic CFS/ME. Gene expression in patients with endogenous depression was similar to that in the normal controls, except for upregulation of five genes (APP, CREBBP, GNAS, PDCD2 and PDCD6). Clustering of combined gene data in CFS/ME patients for this and the authors' previous study (117 CFS/ME patients) revealed genomic subtypes with distinct differences in SF36 scores, clinical phenotypes, severity and geographical distribution. Antibody testing for Epstein Barr virus, enterovirus, Coxiella burnetii and parvovirus B19 revealed evidence of subtype-specific relationships for Epstein Barr virus and enterovirus, the two most common infectious triggers of CFS/ME. Conclusions This study confirms the involvement of these genes in CFS/ME.
Jones DEJ, Gray JC, Newton JL. Perceived fatigue is comparable between different disease groups. Quarterly Journal of Medicine 2009; 102(9): 617 24 Background: Studies have established that levels of fatigue vary between different patient groups. It is less clear whether the nature, as opposed to severity of fatigue differs between groups. Objective: To examine descriptions of fatigue by patients with a range of chronic diseases and determine the relationship between symptom domains. Design: Retrospective review of Fatigue Impact Scale (FIS) data. Setting: Fatigue Research Group. Participants: Six hundred subjects in five chronic disease groups and one (n = 45) normal control group. Main outcome measures: Statistical analysis was performed to assess the effect of increasing fatigue and the overlap of FIS domain scores between disease groups by calculation of geometric means as proportions summed to 1 in each FIS domains, whilst controlling for total score. Results: Those with lower scores exhibit relatively higher physical scores than patients with higher total scores. In contrast, as total score increases, so does the proportion accounted for by the cognitive and psychosocial scores. This was not related to a threshold effect as the maximum total score of 40 in the physical domain was only achieved in three patients (<1%). Average domain proportions between patient groups did not vary to any degree among physical (0.30 0.39), cognitive (0.15 0.23) and psychosocial (0.42 0.47) domain proportions of the patient groups. Conclusion: Perceived fatigue is similar between patient groups. Increasing scores were not related to simply reaching the maximum threshold in the physical domain. Studies have confirmed a positive-structured approach to symptom management in one fatigue-associated chronic disease, primary biliary cirrhosis, leads to significant improvements in quality of life. We suggest that, with a similar approach, the same might be true in other chronic diseases where moderate fatigue is a significant problem.
Newton JL et al.lower ambulatory blood pressure in chronic fatigue syndrome.psychosomatic Medicine 2009; 71(3): 361 5. OBJECTIVE: To examine blood pressure circadian rhythm in subjects with chronic fatigue syndrome (CFS) and appropriate normal and fatigued controls to correlate parameters of blood pressure regulation with perception of fatigue in an observational cohort study. The cause of CFS remains unknown and there are no effective treatments. METHODS: To address whether inactivity was a confounder, we performed a 24-hour ambulatory blood pressure monitoring in the following three subject groups: 1) CFS patients (Fukuda Diagnostic criteria) (n = 38); 2) normal controls (n = 120); and 3) a fatigue comparison group (n = 47) with the autoimmune liver disease primary biliary cirrhosis (PBC). All patients completed a measure of fatigue severity (Fatigue Impact Scale). In view of the different demographics between the patient groups, patients were ageand sex-matched on a case-by-case basis to normal controls and blood pressure parameters were compared. RESULTS: Compared with the control population, the CFS group had significantly lower systolic blood pressure (p <.0001) and mean arterial blood pressure (p =.0002) and exaggerated diurnal variation (p =.009). There was a significant inverse relationship between increasing fatigue and diurnal variation of blood pressure in both the CFS and PBC groups (p <.05). CONCLUSION: Lower blood pressure and abnormal diurnal blood pressure regulation occur in patients with CFS. We would suggest the need for a randomized, placebo-controlled trial of agents to increase blood pressure such as midodrine in CFS patients with an autonomic phenotype.
Robinson M et al. Plasma IL-6, its soluble receptors and F-isoprostanes at rest and during exercise in chronic fatigue syndrome. Scandinavian Journal of Medicine in Science and Sports 2009; epub. The aim of the current study was to investigate the levels of interleukin-6 (IL-6), its soluble receptors (sil-6r and sgp130) and F(2)-isoprostanes, at rest and during exercise, in patients with chronic fatigue syndrome (CFS). Six male CFS patients and six healthy controls performed an incremental exercise test to exhaustion and a submaximal exercise bout to exhaustion. Blood samples taken in the submaximal test at rest, immediately post-exercise and 24 h post-exercise were analyzed for IL-6, sil-6r, sgp130 and F(2)- isoprostanes. A further 33 CFS and 33 healthy control participants gave a resting blood sample for IL-6 and sil-6r measurement. During the incremental exercise test only power output at the lactate threshold was lower (P<0.05) in the CFS group. F(2)-isoprostanes were higher (P<0.05) in CFS patients at rest and this difference persisted immediately and 24 h post-exercise. The exercise study found no differences in IL-6, sil- 6R or sgp130 at any time point between groups. In the larger resting group, there were no differences in IL-6 and sil-6r between CFS and control groups. This investigation has demonstrated that patients with CFS do not have altered plasma levels of IL-6, sil-6r or sgp130 either at rest or following exercise. F(2)-isoprostanes, however, were consistent.
Puri BK et al. An in vivo proton neurospectroscopy study of cerebral oxidative stress in myalgic encephalomyelitis (chronic fatigue syndrome). Prostaglandins, Leukotrienes and Essential Fatty Acids 2009; 81(5 6): 303 5 A particularly important family of antioxidant defence enzymes in the body are the glutathione peroxidases, which remove H 2 O 2 by coupling its reduction to H 2 O with oxidation of reduced glutathione (GSH) to oxidised glutathione (GSSG). There are suggestions that GSH in the peripheral blood may be reduced in myalgic encephalomyelitis, which is a highly disabling neurological disease of unknown aetiology. Since many of the symptoms relate to cerebral functioning, it would seem probable that peripheral blood GSH findings would be reflected in lower cerebral GSH levels. The aim of this study was to carry out the first direct assessment of cerebral GSH levels in myalgic encephalomyelitis; the hypothesis being tested was that cerebral GSH levels would be reduced in myalgic encephalomyelitis. Cerebral proton neurospectroscopy was carried out at a magnetic field strength of 3 T in 26 subjects; spectra were obtained from 20 20 20 mm 3 voxels using a pointresolved spectroscopy pulse sequence. The mean cerebral GSH level in the myalgic encephalomyelitis patients was 2.703 (SD 2.311) which did not differ significantly from that in age- and gender-matched normal controls who did not have any history of neurological or other major medical disorder (5.191, SD 8.984; NS). Therefore our study does not suggest that GSH is reduced in the brain in myalgic encephalomyelitis. At the present time, based on the results of this study, there is no evidence to support the suggestion that, by taking glutathione supplements, an improvement in the brain-related symptomatology of myalgic encephalomyelitis may occur.
Kiyama Hiroshi. Breakthrough made in diagnosing CFS. Reported in the Yomiuri Shimbun in English Jan.2010 Thursday 14 January 2010 The Japanese newspaper Daily Yomiuri Online reports: Researchers have discovered a protein in blood that can be used to diagnose chronic fatigue syndrome, a breakthrough that could help detect the ailment during physical checkups. There are diagnostic criteria for chronic fatigue syndrome--a disorder involving extreme fatigue of unknown cause that continues for at least six months--that rely primarily on subjective symptoms, but there have been no objective markers such as blood tests. The research team led by Hiroshi Kiyama, a professor of anatomy at Osaka City University, examined the intermediate lobes of the pituitary glands of rats in which they induced extreme fatigue by making them exercise for five consecutive days. They found that the lobes excreted extraordinarily high amounts of a protein called alpha-msh and that alpha-msh levels in the animals' blood also increased. The neurotransmitter dopamine inhibits the secretion of alpha-msh, but the rats' ability to produce dopamine declined as their fatigue grew. The group also tested the levels of alpha-msh in the blood of 57 people diagnosed with chronic fatigue syndrome and the blood of 30 healthy people. The average level among the 37 people who had been diagnosed with chronic fatigue syndrome less than five years before was about 50 percent higher than the healthy people. (Jan. 11, 2010)