2010 – Page 14 – American ME and CFS Society

Functional impairment in chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivity

Abstract:

OBJECTIVE: To characterize patients diagnosed with multiple chemical sensitivity (MCS), chronic fatigue syndrome (CFS), or fibromyalgia (FM), to compare their level of function with Canadian population average values, and to assess factors associated with function.

DESIGN: Chart review and abstraction of clinical information.

SETTING: The Environmental Health Clinic (EHC) at Women’s College Hospital in Toronto, Ont, which is a provincial referral centre for patients with illnesses with suspected environmental links, especially MCS, CFS, and FM.

PARTICIPANTS: A total of 128 consecutive patients diagnosed with 1 or more of MCS, CFS, or FM, seen between January 2005 and March 2006 at the EHC.

MAIN OUTCOME MEASURES: Demographic and socioeconomic characteristics, comorbid diagnoses, duration of illness, health services usage, life stresses, helpful therapeutic strategies, and functional impairment measured by the Short Form-36, compared with Canadian population average values. Factors significantly associated with function in bivariate analyses were included in multiple linear and logistic regression models.

RESULTS: The patient population was predominantly female (86.7%), with a mean age of 44.6 years. Seventy-eight patients had discrete diagnoses of 1 of MCS, CFS, or FM, while the remainder had 2 or 3 overlapping diagnoses. Most (68.8%) had stopped work, and on average this had occurred 3 years after symptom onset. On every Short Form-36 subscale, patients had markedly lower functional scores than population average values, more so when they had 2 or 3 of these diagnoses. Having FM, younger age at onset, and lower socioeconomic status were most consistently associated with poor function.

CONCLUSION: Patients seen at the EHC demonstrated marked functional impairment, consistent with their reported difficulties working and caring for their homes and families during what should be their peak productive years. Early comprehensive assessment, medical management, and social and financial support might avoid the deterioration of function associated with prolonged illness. Education and information resources are required for health care professionals and the public, along with further etiologic and prognostic research.

Source: Lavergne MR, Cole DC, Kerr K, Marshall LM. Functional impairment in chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivity. Can Fam Physician. 2010 Feb;56(2):e57-65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821254/ (Full article)

Activity in the hypothalamo-hypophyseal-adrenocortical system on experimental induction of chronic fatigue syndrome

Abstract:

Changes in the activity of the hypothalamo-hypophyseal-adrenocortical system (HHACS) were studied in an experimental model of chronic fatigue syndrome induced by i.p. administration of synthetic doublestranded RNA (polyriboinosinic:polyribocytidylic acid, Poly I:C) at a dose of 3 mg/kg.

Functional changes in the different components of the HHACS were detected using standard tests with i.p. ACTH or hydrocortisone on the background of cold stress and injections of Poly I:C. Single doses of Poly I:C were followed by the development of impairments to HHACS function, with decreases in the ACTH sensitivity of adrenal cells and suppression of the negative feedback mechanism, resulting in significant decreases in corticosterone concentrations in standard tests with administration of ACTH and hydrocortisone.

Source: Fomicheva EE, Filatenkova TA, Rybakina EG. Activity in the hypothalamo-hypophyseal-adrenocortical system on experimental induction of chronic fatigue syndrome. Neurosci Behav Physiol. 2010 Mar;40(3):245-50. doi: 10.1007/s11055-010-9250-3. Epub 2010 Feb 10. https://www.ncbi.nlm.nih.gov/pubmed/20146018

Graded exercise for chronic fatigue syndrome: too soon to dismiss reports of adverse reactions

Sir,

Given there is no formal system to report adverse reactions to non-pharmacological interventions such as graded exercise therapy (GET) for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), other sources of data need to be considered when evaluating safety. As noted by Clark & White, a large survey conducted in 2001 by the charity Action for ME found that 50% of patients who received graded exercise felt worse (1, 2). They also referred to a subsequent study by the same group suggesting that many patients might not have been treated by experienced therapists (3). However, the sample was small and, as in all surveys, therapist competence was not assessed.

A review of all the surveys conducted to date not only supports the view that a significant proportion of patients experience adverse reactions following GET, but also that it is premature to attribute those reactions to practitioner inexperience or inadequate training (1, 4). For example, the results of a recent survey conducted by the ME Association showed that of the 906 individuals who had received GET, 33.1% felt “much worse” and 23.4% judged themselves to be “slightly worse” (4). Similarly, a survey of patients who had been treated in the previous 3 years, i.e. following the refinement of the protocol as discussed by Clark & White, revealed that 34% of the 722 who had tried GET perceived themselves to be worse (5).

Without details of the training of the therapist and their fidelity to the treatment manual, one can only speculate about the factors associated with poor outcome. Nijs et al. (6) discussed some of the possible reasons. However, there are additional factors that deserve consideration when evaluating the efficacy and safety of GET. Firstly, the survey results may reflect, at least in part, the experiences of patients receiving treatment in a clinical setting. As has been shown in studies on other interventions, the outcomes documented in routine practice may be more realistic than those obtained in randomized controlled trials (7). Secondly, many patients may not be able to complete graded activity schedules for various reasons, including ongoing pathology. For instance, Black & McCully (8) used an accelerometer to measure activity levels before, during and after a 4-week “training period” consistent with GET. They documented an increase in activity counts lasting between 4 and 10 days, and this was associated with higher scores for pain and fatigue. The inability to sustain target activity levels was also noted by Friedberg (9), who followed the progress of one patient during 26 sessions of GET. He recorded a 10.6% decrease in mean weekly step counts, leading Friedberg to speculate that the subjective measures of improvement might have been the result of activity substitution and a corresponding reduction in perceived stress.

Finally, we were surprised that neither of the letters cited the research by White et al. (10). This elegant study supports the growing evidence of abnormal metabolic and immunological reactions to exercise in subsets with CFS. Although their sample was small, White et al. found elevated concentrations of the pro-inflammatory cytokine tumour necrosis factor-alpha at time-points of 3 h and 3 days after exercise. In addition, they documented increased levels of the anti-inflammatory cytokine transforming growth factor-beta after normal exertion. We therefore concur with Nijs et al. (6) as well as other researchers, that GET may not be appropriate for all patients with CFS and that pacing may provide a useful, acceptable and safe alternative (6, 11, 12).

You can read the rest of this letter here: https://www.medicaljournals.se/jrm/content/abstract/10.2340/16501977-0493

Comment on: Chronic fatigue syndrome. [J Rehabil Med. 2008]

Source: Kindlon T, Goudsmit EM. Graded exercise for chronic fatigue syndrome: too soon to dismiss reports of adverse reactions. J Rehabil Med. 2010 Feb;42(2):184; author reply 184-6. doi: 10.2340/16501977-0493. https://www.medicaljournals.se/jrm/content/abstract/10.2340/16501977-0493 (Full article)

The effect of ondansetron, a 5-HT3 receptor antagonist, in chronic fatigue syndrome: a randomized controlled trial

Abstract:

BACKGROUND: Accumulating data support the involvement of the serotonin (5-hydroxytryptamine [5-HT]) system in the pathophysiology of chronic fatigue syndrome. Neuropharmacologic studies point to a hyperactive 5-HT system, and open-label treatment studies with 5-HT(3) receptor antagonists have shown promising results. In this randomized controlled clinical trial, the effect of ondansetron, a 5-HT(3) receptor antagonist, was assessed on fatigue severity and functional impairment in adult patients with chronic fatigue syndrome.

METHOD: A randomized, placebo-controlled, double-blind clinical trial was conducted at Radboud University Nijmegen Medical Centre, The Netherlands. Sixty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention (CDC) criteria for chronic fatigue syndrome and who were free from current psychiatric comorbidity participated in the clinical trial. Participants received either ondansetron 16 mg per day or placebo for 10 weeks. The primary outcome variables were fatigue severity (Checklist Individual Strength fatigue severity subscale [CIS-fatigue]) and functional impairment (Sickness Impact Profile-8 [SIP-8]). The effect of ondansetron was assessed by analysis of covariance. Data were analyzed on an intention-to-treat basis. All patients were recruited between June 2003 and March 2006.

RESULTS: Thirty-three patients were allocated to the ondansetron condition, 34 to the placebo condition. The 2 groups were well matched in terms of age, sex, fatigue severity, functional impairment, and CDC symptoms. Analysis of covariance showed no significant differences between the ondansetron- and placebo-treated groups during the 10-week treatment period in fatigue severity and functional impairment.

CONCLUSIONS: This clinical trial demonstrates no benefit of ondansetron compared to placebo in the treatment of chronic fatigue syndrome.

TRIAL REGISTRATION: www.trialregister.nl: ISRCTN02536681.

Source: The GK, Bleijenberg G, Buitelaar JK, van der Meer JW. The effect of ondansetron, a 5-HT3 receptor antagonist, in chronic fatigue syndrome: a randomized controlled trial. J Clin Psychiatry. 2010 May;71(5):528-33. doi: 10.4088/JCP.08m04719whi. Epub 2010 Jan 26. https://www.ncbi.nlm.nih.gov/pubmed/20122367

Chronic fatigue syndrome is associated with metabolic syndrome: results from a case-control study in Georgia

Abstract:

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 population-based 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.

Source: Maloney EM, Boneva RS, Lin JM, Reeves WC. Chronic fatigue syndrome is associated with metabolic syndrome: results from a case-control study in Georgia. Metabolism. 2010 Sep;59(9):1351-7. doi: 10.1016/j.metabol.2009.12.019. Epub 2010 Jan 27. https://www.ncbi.nlm.nih.gov/pubmed/20102774

Mood volatility with rumination but neither attentional nor interpretation biases in chronic fatigue syndrome

Abstract:

OBJECTIVES: This study tested whether (1) chronic fatigue syndrome (CFS) individuals have a bias in the initial orientation of attention to illness-related information, which is enhanced by rumination. (2) CFS individuals have an illness interpretation bias (IB) in their early automatic processing of ambiguous information. (3) CFS individuals experience a greater degree of mood fluctuation following rumination and distraction inductions.

DESIGN: Thirty-three CFS participants who had received a medical practitioner’s diagnosis of CFS were compared to 33 healthy matched controls on an exogenous cueing task and a lexical decision task.

METHOD: All participants underwent either a rumination or distraction induction. They then completed an exogenous cueing task to assess bias to illness and social threat compared with neutral stimuli, as well as a lexical decision task to assess their interpretation of ambiguous words having illness, social threat, or neutral interpretations.

RESULTS: Reaction time data revealed that CFS individuals did not have an attentional bias (AB) in the initial orientation of attention to illness-related material. Nor was there an IB towards illness in CFS individual’s automatic response to ambiguous information. However, as hypothesized, CFS individuals showed a greater degree of mood fluctuation following the rumination/distraction induction.

CONCLUSION: Rumination and distraction lead to greater mood volatility in CFS individuals than in controls, but not to attentional nor interpretation biases in the early automatic stages of information processing in CFS individuals.

Source: Martin M, Alexeeva I. Mood volatility with rumination but neither attentional nor interpretation biases in chronic fatigue syndrome. Br J Health Psychol. 2010 Nov;15(Pt 4):779-96. doi: 10.1348/135910709X480346. Epub 2010 Jan 22. https://www.ncbi.nlm.nih.gov/pubmed/20100398

Protective effect of epigallocatechin gallate in murine water-immersion stress model of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a specific clinical condition that characterizes unexplained disabling fatigue. In the present study, chronic fatigue was produced in mice by subjecting them to forced swim inside a rectangular jar of specific dimensions for 6 min. daily for 15 days.

Epigallocatechin gallate (EGCG; 25, 50 and 100 mg/kg, p.o.) was administered daily 30 min. before forced swim session. Immobility period and post-swim fatigue was assessed on alternate days. On the 16th day, after assessment of various behavioural parameters, mice were killed to harvest the brain, spleen and thymus.

There was significant increase in oxidative-nitrosative stress and tumour necrosis factor-alpha levels in the brain of mice subjected to water-immersion stress as compared with naive group. These behavioural and biochemical alterations were restored after chronic treatment with EGCG. The present study points out that EGCG could be of therapeutic potential in the treatment of chronic fatigue.

Source: Sachdeva AK, Kuhad A, Tiwari V, Arora V, Chopra K. Protective effect of epigallocatechin gallate in murine water-immersion stress model of chronic fatigue syndrome. Basic Clin Pharmacol Toxicol. 2010 Jun;106(6):490-6. doi: 10.1111/j.1742-7843.2009.00525.x. Epub 2010 Jan 18. http://onlinelibrary.wiley.com/doi/10.1111/j.1742-7843.2009.00525.x/full (Full article)

Chronic fatigue syndrome: is there a role for non-antidepressant pharmacotherapy?

Abstract:

IMPORTANCE OF THE FIELD: Chronic fatigue syndrome (CFS) is a prevalent but poorly understood condition mainly characterized by debilitating, persistent or recurrent fatigue; increased physical and mental fatigability; cognitive impairment and widespread musculoskeletal pain. Despite intensive treatment research, the role of pharmacotherapy in the illness remains uncertain.

: An updated review is given of pharmacotherapy in CFS, with a focus on non-antidepressant, controlled drug trials performed between 1988 and August 2009.

WHAT THE READER WILL GAIN: Antiviral, immunological and antibiotic therapies, although sometimes associated with symptom amelioration, can be more harmful than beneficial in CFS. Stimulants seem to benefit some CFS patients but their long-term effects is uncertain. Although antidepressants are not curative for the illness, they might be useful for some symptomatic aspects and co-morbid anxiety and depression. There is little or no evidence that CFS patients benefit from other pharmacological agents (e.g., steroids) or from dietary supplements and complementary medicine products. Future research into treatment should take specific subgroups into account and should target immunological aspects of the illness as well as the complex relationships between CFS, stress and depression.

TAKE HOME MESSAGE: Pharmacotherapy can currently not be considered first-line treatment in CFS and should always be used in a context of self-management and rehabilitation.

Source: Van Houdenhove B, Pae CU, Luyten P. Chronic fatigue syndrome: is there a role for non-antidepressant pharmacotherapy? Expert Opin Pharmacother. 2010 Feb;11(2):215-23. Doi: 10.1517/14656560903487744. https://www.ncbi.nlm.nih.gov/pubmed/20088743

Evidence for generalized hyperalgesia in chronic fatigue syndrome: a case control study

Abstract:

Several studies provided evidence for generalized hyperalgesia in fibromyalgia or whiplash-associated disorders. In chronic fatigue syndrome, however, pain is a frequently reported complaint, but up to now, evidence for generalized hyperalgesia is lacking.

The aim of this study is to examine whether the pressure pain thresholds (PPTs) at both symptomatic and asymptomatic sites differ in chronic fatigue syndrome (CFS) patients with chronic pain, compared to healthy controls.

Therefore, 30 CFS patients with chronic pain and 30 age- and gender-matched healthy controls indicated on a Margolis Pain Diagram where they felt pain lasting longer than 24 h in the past 4 weeks. After completing a test battery of questionnaires evaluating pain cognitions, functional status and symptomatology, a blinded researcher assessed PPTs bilaterally at seven nonspecific sites on both trunk and extremities. PPTs were compared for the two complete groups.

In addition, PPTs of patients and controls who did not report pain in a respective zone were compared. PPTs of the patients were significantly lower (p<0.001) compared to those of the control group, also when pain-free samples per zone were compared (p<0.001). The mean PPT was 3.30 kg/cm2 in all CFS patients and 8.09 kg/cm2 in the controls. No confounding factors responsible for the observed differences, as, e.g., catastrophizing and depression, could be revealed.

These findings provide evidence for the existence of hyperalgesia even in asymptomatic areas (generalized secondary hyperalgesia). The generalized hyperalgesia may represent the involvement of a sensitized central nervous system.

Source: Meeus M, Nijs J, Huybrechts S, Truijen S. Evidence for generalized hyperalgesia in chronic fatigue syndrome: a case control study. Clin Rheumatol. 2010 Apr;29(4):393-8. doi: 10.1007/s10067-009-1339-0. https://www.ncbi.nlm.nih.gov/pubmed/20077123

Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome

Abstract:

BACKGROUND: In October 2009 it was reported that 68 of 101 patients with chronic fatigue syndrome (CFS) in the US were infected with a novel gamma retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), a virus previously linked to prostate cancer. This finding, if confirmed, would have a profound effect on the understanding and treatment of an incapacitating disease affecting millions worldwide. We have investigated CFS sufferers in the UK to determine if they are carriers of XMRV.

METHODOLOGY: Patients in our CFS cohort had undergone medical screening to exclude detectable organic illness and met the CDC criteria for CFS. DNA extracted from blood samples of 186 CFS patients were screened for XMRV provirus and for the closely related murine leukaemia virus by nested PCR using specific oligonucleotide primers. To control for the integrity of the DNA, the cellular beta-globin gene was amplified. Negative controls (water) and a positive control (XMRV infectious molecular clone DNA) were included. While the beta-globin gene was amplified in all 186 samples, neither XMRV nor MLV sequences were detected.

CONCLUSION: XMRV or MLV sequences were not amplified from DNA originating from CFS patients in the UK. Although we found no evidence that XMRV is associated with CFS in the UK, this may be a result of population differences between North America and Europe regarding the general prevalence of XMRV infection, and might also explain the fact that two US groups found XMRV in prostate cancer tissue, while two European studies did not.

Source: Erlwein O, Kaye S, McClure MO, Weber J, Wills G, Collier D, Wessely S, Cleare A. Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome. PLoS One. 2010 Jan 6;5(1):e8519. doi: 10.1371/journal.pone.0008519. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795199/ (Full article)