Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To design and validate an instrument to capture the characteristic post-exertional exacerbation of fatigue in patients with chronic fatigue syndrome (CFS).

METHODS: Firstly, patients with CFS (N=19) participated in five focus group discussions to jointly explore the nature of fatigue and dynamic changes after activity, and inform development of a self-report instrument – the Fatigue and Energy Scale (FES). The psychometric properties of the FES were then examined in two case-control challenge studies: a physically-demanding challenge (moderate-intensity aerobic exercise; N=10 patients), and a cognitively-demanding challenge (simulated driving; N=11 patients). Finally, ecological validity was evaluated by recording in association with tasks of daily living (N=9).

RESULTS: Common descriptors for fatigue included ‘exhaustion’, ‘tiredness’, ‘drained of energy’, ‘heaviness in the limbs’, and ‘foggy in the head’. Based on the qualitative data, fatigue was conceptualised as consisting of ‘physical’ and ‘cognitive’ dimensions. Analysis of the psychometric properties of the FES showed good sensitivity to the changing symptoms during a post-exertional exacerbation of fatigue following both physical exercise and driving simulation challenges, as well as tasks of daily living.

CONCLUSION: The ‘fatigue’ experienced by patients with CFS covers both physical and cognitive components. The FES captured the phenomenon of a post-exertional exacerbation of fatigue commonly reported by patients with CFS. The characteristics of the symptom response to physical and cognitive challenges were similar. Both the FES and the challenge paradigms offer key tools to reliably investigate biological correlates of the dynamic changes in fatigue.

Copyright © 2015 Elsevier Inc. All rights reserved.

 

Source: Keech A, Sandler CX, Vollmer-Conna U, Cvejic E, Lloyd AR, Barry BK. Capturing the post-exertional exacerbation of fatigue following physical and cognitive challenge in patients with chronic fatigue syndrome. J Psychosom Res. 2015 Dec;79(6):537-49. doi: 10.1016/j.jpsychores.2015.08.008. Epub 2015 Sep 2. https://www.ncbi.nlm.nih.gov/pubmed/26359713

 

Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a common and disabling condition in adolescence with few treatment options. A central feature of CFS is orthostatic intolerance and abnormal autonomic cardiovascular control characterized by sympathetic predominance. We hypothesized that symptoms as well as the underlying pathophysiology might improve by treatment with the alpha2A-adrenoceptor agonist clonidine.

METHODS: A total of 176 adolescent CFS patients (12-18 years) were assessed for eligibility at a single referral center recruiting nation-wide. Patients were randomized 1:1 by a computer system and started treatment with clonidine capsules (25 μg or 50 μg twice daily, respectively, for body weight below/above 35 kg) or placebo capsules for 9 weeks. Double-blinding was provided. Data were collected from March 2010 until October 2012 as part of The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL). Effect of clonidine intervention was assessed by general linear models in intention-to-treat analyses, including baseline values as covariates in the model.

RESULTS: A total of 120 patients (clonidine group n = 60, placebo group n = 60) were enrolled and started treatment. There were 14 drop-outs (5 in the clonidine group, 9 in the placebo group) during the intervention period. At 8 weeks, the clonidine group had lower plasma norepinephrine (difference = 205 pmol/L, p = 0.05) and urine norepinephrine/creatinine ratio (difference = 3.9 nmol/mmol, p = 0.002). During supine rest, the clonidine group had higher heart rate variability in the low-frequency range (LF-HRV, absolute units) (ratio = 1.4, p = 0.007) as well as higher standard deviation of all RR-intervals (SDNN) (difference = 12.0 ms, p = 0.05); during 20° head-up tilt there were no statistical differences in any cardiovascular variable. Symptoms of orthostatic intolerance did not change during the intervention period.

CONCLUSIONS: Low-dose clonidine reduces catecholamine levels in adolescent CFS, but the effects on autonomic cardiovascular control are sparse. Clonidine does not improve symptoms of orthostatic intolerance.

TRIAL REGISTRATION: Clinical Trials ID: NCT01040429, date of registration 12/28/2009.

 

Source: Fagermoen E, Sulheim D, Winger A, Andersen AM, Gjerstad J, Godang K, Rowe PC, Saul JP, Skovlund E, Wyller VB. Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial. BMC Pediatr. 2015 Sep 10;15:117. doi: 10.1186/s12887-015-0428-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566847/ (Full article)

 

Activity Pacing Self-Management in Chronic Fatigue Syndrome: A Randomized Controlled Trial

Abstract:

OBJECTIVE: To evaluate the effectiveness of an activity pacing self-management (APSM) intervention in improving performance of daily life activities in women with chronic fatigue syndrome (CFS).

METHOD: A total of 33 women with CFS (age 41.1±11.2 yr) were randomly allocated to APSM (experimental group; n=16) or relaxation (control group; n=17). Main outcome measures included the Canadian Occupational Performance Measure (COPM; primary) and Checklist Individual Strength (CIS).

RESULTS: COPM scores changed significantly over time in both groups (p=.03). The change in Satisfaction scores showed a significant difference in favor only of APSM (effect size=0.74 [0.11, 1.4]). CIS scores decreased significantly in the experimental group only (p<.01).

CONCLUSION: APSM was found to be feasible and effective in optimizing participation in desired daily life activities in women with CFS. Replication in a larger sample with long-term follow-up is required.

Copyright © 2015 by the American Occupational Therapy Association, Inc.

 

Source: Kos D, van Eupen I, Meirte J, Van Cauwenbergh D, Moorkens G, Meeus M, Nijs J. Activity Pacing Self-Management in Chronic Fatigue Syndrome: A Randomized Controlled Trial. Am J Occup Ther. 2015 Sep-Oct;69(5):6905290020. doi: 10.5014/ajot.2015.016287. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564796/ (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)

 

Effect of Milnacipran Treatment on Ventricular Lactate in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract:

Milnacipran, a serotonin/norepinephrine reuptake inhibitor, has been approved by the US Food and Drug Administration for the treatment of fibromyalgia (FM). This report presents the results of a randomized, double-blind, placebo-controlled trial of milnacipran conducted to test the hypotheses that a) similar to patients with chronic fatigue syndrome, patients with FM have increased ventricular lactate levels at baseline; b) 8 weeks of treatment with milnacipran will lower ventricular lactate levels compared with baseline levels and with ventricular lactate levels after placebo; and c) treatment with milnacipran will improve attention and executive function in the Attention Network Test compared with placebo. In addition, we examined the results for potential associations between ventricular lactate and pain. Baseline ventricular lactate measured by proton magnetic resonance spectroscopic imaging was found to be higher in patients with FM than in healthy controls (F1,37 = 22.11, P < .0001, partial η(2) = .37). Milnacipran reduced pain in patients with FM relative to placebo but had no effect on cognitive processing.

At the end of the study, ventricular lactate levels in the milnacipran-treated group had decreased significantly compared with baseline and after placebo (F1,18 = 8.18, P = .01, partial η(2) = .31). A significantly larger proportion of patients treated with milnacipran showed decreases in both ventricular lactate and pain than those treated with placebo (P = .03). These results suggest that proton magnetic resonance spectroscopic imaging measurements of lactate may serve as a potential biomarker for a therapeutic response in FM and that milnacipran may act, at least in part, by targeting the brain response to glial activation and neuroinflammation.

PERSPECTIVE: Patients treated with milnacipran showed decreases in both pain and ventricular lactate levels compared with those treated with placebo, but, even after treatment, levels of ventricular lactate remained higher than in controls. The hypothesized mechanism for these decreases is via drug-induced reductions of a central inflammatory state.

TRIAL REGISTRATION: ClinicalTrials.gov NCT01108731.

Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

 

Source: Natelson BH, Vu D, Mao X, Weiduschat N, Togo F, Lange G, Blate M, Kang G, Coplan JD, Shungu DC. Effect of Milnacipran Treatment on Ventricular Lactate in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Trial. J Pain. 2015 Nov;16(11):1211-9. doi: 10.1016/j.jpain.2015.08.004. Epub 2015 Aug 31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630071/ (Full article)

 

The impact of chronic fatigue syndrome on cognitive functioning in adolescents

Abstract:

Chronic fatigue syndrome (CFS) is characterized by persistent fatigue and severe disability. Most adolescent patients report attention and concentration problems, with subsequent poor performance at school. This study investigated the impact of CFS on intellectual capacity by (1) assessing discrepancies between current intelligence quotient (IQ) and school level and (2) exploring differences in current IQ and pre-CFS school performance, compared with healthy individuals. Current data was cross-sectionally gathered and compared with retrospective pre-CFS school performance data. Fifty-nine CFS adolescents and 40 controls were evaluated on performance on age-appropriate intelligence tests and school level. Current IQ scores of CFS adolescents were lower than expected on the basis of their school level. Furthermore, there was a difference in intelligence performance across time when current IQ scores were compared with pre-CFS cognitive achievement. Healthy controls did not show any discrepancies.

CONCLUSION: According to their pre-CFS intelligence assessments, CFS patients started with appropriate secondary school levels at the age of 12. Our data suggest that CFS may be accompanied by a decline in general cognitive functioning. Given the critical age for intellectual development, we recommend a timely diagnosis followed by appropriate treatment of CFS in adolescents.

WHAT IS KNOWN: Adolescent chronic fatigue syndrome (CFS) is a debilitating condition with major impact on social and intellectual development. Most patients report concentration problems, with subsequent poor performance at school. Little is known about the influence of CFS on intellectual performances.

WHAT IS NEW: IQ scores of CFS adolescents are lower than the IQ scores of healthy peers with an equivalent school level. There is a decrease in intelligence performance across time when current IQ scores are compared with pre-CFS cognitive achievement. Healthy controls do not show any discrepancies between their current IQ, school level and previous cognitive functioning. This suggest that adolescent CFS may be accompanied by a decline in general cognitive functioning.

 

Source: Nijhof LN, Nijhof SL, Bleijenberg G, Stellato RK, Kimpen JL, Hulshoff Pol HE, van de Putte EM. The impact of chronic fatigue syndrome on cognitive functioning in adolescents. Eur J Pediatr. 2016 Feb;175(2):245-52. doi: 10.1007/s00431-015-2626-1. Epub 2015 Sep 3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724362/ (Full article)

 

Mitoprotective dietary approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Caloric restriction, fasting, and ketogenic diets

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is an idiopathic illness characterized by debilitating fatigue and neuro-immune abnormalities. A growing body of evidence proposes mitochondrial dysfunction as a central perpetrator of the illness due to activation of immune-inflammatory pathways that burden the mitochondria.

Under a model of mitochondrial dysfunction, this paper explores dietary strategies that are mitoprotective. Studied for decades, the cellular mechanisms of ketogenic diets, fasting, and caloric restriction now reveal mitochondria-specific mechanisms which could play a role in symptom reduction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Future research should examine the physiological effects of these dietary strategies in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Copyright © 2015 Elsevier Ltd. All rights reserved.

 

Source: Craig C. Mitoprotective dietary approaches for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Caloric restriction, fasting, and ketogenic diets. Med Hypotheses. 2015 Nov;85(5):690-3. doi: 10.1016/j.mehy.2015.08.013. Epub 2015 Aug 21. https://www.ncbi.nlm.nih.gov/pubmed/26315446

 

Multidisciplinary rehabilitation treatment versus cognitive behavioural therapy for patients with chronic fatigue syndrome: a randomized controlled trial

Abstract:

OBJECTIVES: The aim of this trial was to evaluate the difference in treatment effect, at 26 and 52 weeks after the start of treatment, between cognitive behavioural therapy (CBT) and multidisciplinary rehabilitation treatment (MRT) for patients with chronic fatigue syndrome (CFS).

DESIGN: Multicentre, randomized controlled trial of patients with CFS. Participants were randomly assigned to MRT or CBT.

SETTING: Four rehabilitation centres in the Netherlands.

SUBJECTS: A total of 122 patients participated in the trial.

MAIN OUTCOME MEASURES: Primary outcomes were fatigue measured by the fatigue subscale of the Checklist Individual Strength and health-related quality of life measured by the Short-Form 36. Outcomes were assessed prior to treatment and at 26 and 52 weeks after treatment initiation.

RESULTS: A total of 114 participants completed the assessment at 26 weeks, and 112 completed the assessment at 52 weeks. MRT was significantly more effective than CBT in reducing fatigue at 52 weeks. The estimated difference in fatigue between the two treatments was -3.02 [95% confidence interval (CI) -8.07 to 2.03; P = 0.24] at 26 weeks and -5.69 (95% CI -10.62 to -0.76; P = 0.02) at 52 weeks. Patients showed an improvement in quality of life over time, but between-group differences were not significant.

CONCLUSION: This study provides evidence that MRT is more effective in reducing long-term fatigue severity than CBT in patients with CFS. Although implementation in comparable populations can be recommended based on clinical effectiveness, it is advisable to analyse the cost-effectiveness and replicate these findings in another multicentre trial.

© 2015 The Association for the Publication of the Journal of Internal Medicine.

 

Source: Vos-Vromans DC, Smeets RJ, Huijnen IP, Köke AJ, Hitters WM, Rijnders LJ, Pont M, Winkens B, Knottnerus JA. Multidisciplinary rehabilitation treatment versus cognitive behavioural therapy for patients with chronic fatigue syndrome: a randomized controlled trial. J Intern Med. 2016 Mar;279(3):268-82. doi: 10.1111/joim.12402. Epub 2015 Aug 26. https://www.ncbi.nlm.nih.gov/pubmed/26306716

 

Polymorphism in COMT is associated with IgG3 subclass level and susceptibility to infection in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is considered as a neuroimmunological disease but the etiology and pathophysiology is poorly understood. Patients suffer from sustained exhaustion, cognitive impairment and an increased sensitivity to pain and sensory stimuli. A subset of patients has frequent respiratory tract infections (RRTI). Dysregulation of the sympathetic nervous system and an association with genetic variations in the catechol-O-methyltransferase (COMT) and glucocorticoid receptor genes influencing sympathetic and glucocorticoid metabolism were reported in CFS. Here, we analyzed the prevalence of SNPs of COMT and glucocorticoid receptor-associated genes in CFS patients and correlated them to immunoglobulin levels and susceptibility to RRTI.

METHODS: We analyzed blood cells of 74 CFS patients and 76 healthy controls for polymorphisms in COMT, FKBP5 and CRHR1 by allelic discrimination PCR. Serum immunoglobulins were determined by immunoturbidimetric technique, cortisol levels by ECLIA.

RESULTS: Contrary to previous reports, we found no difference between CFS patients and healthy controls in the prevalence of SNPs for COMT, FKBP5 and CRHR1. In patients with the Met/Met variant of COMT rs4680 we observed enhanced cortisol levels providing evidence for its functional relevance. Both enhanced IgE and diminished IgG3 levels and an increased susceptibility to RRTI were observed in CFS patients with the Met/Met variant. Such an association was not observed in 68 non-CFS patients with RRTI.

CONCLUSION: Our results indicate a relationship of COMT polymorphism rs4680 with immune dysregulation in CFS providing a potential link for the association between stress and infection susceptibility in CFS.

 

Source: Löbel M, Mooslechner AA, Bauer S, Günther S, Letsch A, Hanitsch LG, Grabowski P, Meisel C, Volk HD, Scheibenbogen C. Polymorphism in COMT is associated with IgG3 subclass level and susceptibility to infection in patients with chronic fatigue syndrome. J Transl Med. 2015 Aug 14;13:264. doi: 10.1186/s12967-015-0628-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536662/ (Full article)

 

Timed loaded standing in female chronic fatigue syndrome compared with other populations

Erratum in

  • J Rehabil Res Dev. 2015;52(7):859.

Abstract:

Patients with chronic fatigue syndrome (CFS), like patients with osteoporosis, have similar difficulties in standing and sitting. The aim of the study was to compare combined trunk and arm endurance among women with CFS (n = 72), women with osteoporosis (n = 30), nondisabled women (n = 55), and women from non-industrialized countries (n = 58) using the timed loaded standing (TLS) test. TLS measures how long a person can hold a 1 kg dumbbell in each hand in front of him or her with straight arms. TLS was higher in the industrialized nondisabled population than in the non-industrialized study population (p < 0.001) and in patients with osteoporosis (p = 0.002).

TLS was lower in patients with CFS than in nondisabled controls (p < 0.001). After adjusting for age, body height, and weight, combined trunk and arm endurance was lower in CFS patients than in osteoporotic patients, even though the patients with osteoporosis were more than 25 yr older (p < 0.001) [corrected]. In CFS, TLS was lower than in the non-industrialized group (p = 0.02). Since only women were studied, external validity of the results is limited to adult female patients with CFS. TLS revealed a specific biomechanical weakness in CFS patients that can be taken into account from the onset of a rehabilitation program. We propose that influencing the quality, rather than the quantity, of movement could be used in the rehabilitation.

 

Source: Eyskens JB, Nijs J, D’Août K, Sand A, Wouters K, Moorkens G. Timed loaded standing in female chronic fatigue syndrome compared with other populations. J Rehabil Res Dev. 2015;52(1):21-9. doi: 10.1682/JRRD.2014.03.0086. http://www.rehab.research.va.gov/jour/2015/521/JRRD-2014-03-0086.html (Full article)