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

 

Demographic and clinical aspects of an Italian patient population with chronic fatigue syndrome

Abstract:

OBJECTIVE: The purpose of this study was to investigate demographic and clinical aspects of a group of Italian patients with Chronic Fatigue Syndrome (CFS) which have not yet been described, in order to compare them with International literature, and to better define certain clinical aspects of the syndrome with respect to the Fukuda et al. case definition.

METHODS: A detailed questionnaire was sent to patients with certified CFS diagnosed in a referral center and the data were collected two weeks later.

RESULTS AND CONCLUSIONS: Besides persistent fatigue, a clinical syndrome with infectious, neurological and rheumatological characteristics is outlined from the data. Demographic characteristics of Italian patients are very similar to those described in international literature. Therapy has yet to be validated with evidence-based studies in Italy. Studies on the prevalence of CFS in Italy are lacking and would be useful to better define the syndrome in this Mediterranean population.

 

Source: Carlo-Stella N, Cuccia M. Demographic and clinical aspects of an Italian patient population with chronic fatigue syndrome. Reumatismo. 2009 Oct-Dec;61(4):285-9. http://www.reumatismo.org/index.php/reuma/article/view/reumatismo.2009.285/440 (Full article)

 

Cellular and molecular mechanisms of interaction between the neuroendocrine and immune systems under chronic fatigue syndrome in experiment

Abstract:

One of the main mechanisms of chronic fatigue syndrome development involves disturbances of interaction between the immune and neuroendocrine systems. The adequate experimental model for the search of these mechanisms is induction of fatigue in animals via the single intraperitoneal administration of synthetic double-stranded RNA – Poly I : C.

Investigation of alterations in cytotoxic and proliferation activities of splenocytcs, the intensity of immunomodulatory cytokines signaling via the sphingomyelin pathways in membrane P2 fraction of the brain cortex, as well as the activity of hypothalamic-pituitary adrenal (HP A) axis in the dynamics of chronic fatigue syndrome in rats has performed. Inhibition of both cytotoxic and proliferative activities of splenocytes during the period of fatigue development has been shown. Priority data concerning the suppression of the activity of neutral sphingomyelinase (nSMase) – the key enzyme of the sphingomyelin cascade – in membranes ofthe cells from the brain cortex on the 3d day after Poly I : C administration to rats have been obtained.

It was found that Poly I : C injection to rats led to disturbed HPA axis functions which was manifested by decreased corticosterone concentration in standard functional assays with ACTH and hydrocortisone administration.

It is suggested that disturbances in interaction between the immune and neuroendocrine systems during development of chronic fatigue syndrome, including alterations in HPA axis activity, are realized both on the level of changes in the activity of immune-competent cells and immediately on membranes of the brain cells.

 

Source: Rybakina EG, Shanin SN, Fomicheva EE, Korneva EA. Cellular and molecular mechanisms of interaction between the neuroendocrine and immune systems under chronic fatigue syndrome in experiment. Ross Fiziol Zh Im I M Sechenova. 2009 Dec;95(12):1324-35. [Article in Russian] https://www.ncbi.nlm.nih.gov/pubmed/20141043

 

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.

©Copyright 2010 Physicians Postgraduate Press, Inc.

 

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

 

Can pacing self-management alter physical behavior and symptom severity in chronic fatigue syndrome? A case series

Abstract:

Given the lack of evidence in support of pacing self-management for patients with chronic fatigue syndrome (CFS), we examined whether physical behavior and health status of patients with CFS would improve in response to a pacing self-management program.

We performed an observational study of pacing self-management in seven CFS patients using a single-case study design. Stages A1 and A2 (7-day assessment periods) of the A1-B-A2 design corresponded to the baseline and posttreatment measurements of physical behavior (real-time activity monitoring) and health status (self-reported measures), respectively. Stage B (3 weeks of treatment) consisted of three individual treatment sessions of pacing self-management.

When comparing pre- versus posttreatment data, we found that the patients’ ability to perform daily activities and the severity of their symptom complexes were improved (p = 0.043). Concentration difficulties, mood swings, muscle weakness, and intolerance to bright light improved as well. A statistically significant decrease in the mean time spent doing light activity (<3 metabolic equivalents) was observed, but a change in the way physical activity was spread throughout the day was not.

We found that 3 weeks of pacing self-management was accompanied by a modest improvement in symptom severity and daily functioning. The outcome of the present study calls for a randomized controlled clinical trial to examine the effectiveness of pacing self-management for people with CFS.

 

Source: Nijs J, van Eupen I, Vandecauter J, Augustinus E, Bleyen G, Moorkens G, Meeus M. Can pacing self-management alter physical behavior and symptom severity in chronic fatigue syndrome? A case series. J Rehabil Res Dev. 2009;46(7):985-96. http://www.rehab.research.va.gov/jour/09/46/7/Nijs.html (Full article)

 

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

 

Postexertional malaise in women with chronic fatigue syndrome

Abstract:

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.

Source: VanNess JM, Stevens SR, Bateman L, Stiles TL, Snell CR. Postexertional malaise in women with chronic fatigue syndrome. J Womens Health (Larchmt). 2010 Feb;19(2):239-44. doi: 10.1089/jwh.2009.1507. https://www.ncbi.nlm.nih.gov/pubmed/20095909

 

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)