TGI Friday! Our weekly round-up of research abstracts, 16 December 2011

December 16, 2011

Our weekly summary of research paper abstracts that have not already appeared on the MEA website.


From Arch Phys Med Rehabil. 2011 Nov;92(11):1820-6.

Symptom fluctuations and daily physical activity in patients with chronic fatigue syndrome: a case-control study.

Meeus M, van Eupen I, van Baarle E, De Boeck V, Luyckx A, Kos D, Nijs J.
Division of Musculoskeletal Physiotherapy, Department of Health Sciences, Artesis University College Antwerp, Belgium.



To compare the activity pattern of patients with chronic fatigue syndrome (CFS) with healthy sedentary subjects and examine the relationship between the different parameters of performed activity (registered by an accelerometer device) and symptom severity and fluctuation (registered by questionnaires) in patients with CFS.


Case-control study. Participants were asked to wear an accelerometer device on the nondominant hand for 6 consecutive days. Every morning, afternoon, and evening patients scored the intensity of their pain, fatigue, and concentration difficulties on a visual analog scale.


Patients were recruited from a specialized chronic fatigue clinic in the university hospital, where all subjects were invited for 2 appointments (for questionnaire and accelerometer adjustments). In between, activity data were collected in the subject's normal home environment.


Female patients (n=67) with CFS and female age-matched healthy sedentary controls.


Not applicable.


Accelerometry (average activity counts, peak activity counts, ratio peak/average, minutes spent per activity category) and symptom severity (intensity of pain, fatigue, and concentration difficulties).


Patients with CFS were less active, spent more time sedentary, and less time lightly active (P.05), peak activity, and the staggering of activities (ratio peak/average) on 1 day were not different between groups (P>.05). Negative correlations (-.242 varying to -.307) were observed for sedentary activity and the ratio with symptom severity and variation on the same and the next day. Light, moderate, and vigorous, as well as the average activity and the peak activity, were positively correlated (.242 varying to .421) with symptom severity and variation.


The more patients with CFS are sedentary and the better activity is dispersed, the fewer symptoms and variations they experience on the same and next day. Inversely, more symptoms and variability is experienced when patients were more active that day or the previous day. The direction of these relations cannot be determined in a cross-sectional study and requires further study.


From Int J Immunopathol Pharmacol. 2011 Jul-Sep;24(3):673-81.

An Italian study on health-related quality of life and fatigue in patients wit h chronic fatigue syndrome and patients with chronic HCV virus infection: similarities and differences.

Racciatti D, Gorgoretti V, Sepede G, Gambi F, Pizzigallo E.
Clinic of Infectious Diseases, Department of Medicine and Aging, G. d'Annunzio University, Chieti, Italy.


Severe fatigue and a significantly reduced health-related quality of life (HRQoL) have been described in patients with chronic fatigue syndrome (CFS) in comparison with patients affected by chronic hepatitis C (CHC) and other chronic medical conditions. We examined 39 CFS and 49 CHC patients to explore whether fatigue and a poor HRQoL represent a greater medical and social problem in CFS than in CHC. The severity of fatigue and the HRQoL were assessed using the Fatigue Impact Scale (FIS) and the Health Status Questionnaire Short Form-36 (SF-36), respectively. The statistical analysis showed both a higher score of fatigue and a lower HRQoL in CFS than in CHC patients. Furthermore, in CHC patients the FIS evaluation showed a significantly reduced score of the psychosocial domain in comparison with the other domains. Multivariate linear regression analysis revealed female gender as the most important positive variable in chronic hepatitis C patients for total score of FIS. In conclusion, CFS was associated with a severe and disabling fatigue and an impaired HRQOL. In particular, both fatigue and all aspects of HRQOL perceived by CFS patients were significantly impaired compared to CHC patients. Consequently, management of fatigue should be considered a priority in order to improve HRQOL in CFS patients. In CHC patients the impact of fatigue on HRQoL was less significant than in CFS patients, even though the FIS evaluation showed a significant impairment of the psychosocial domain.

From J Infect Dis. 2011 Nov 15;204(10):1632-40. Epub 2011 Sep 29.

Peripheral blood gene expression in postinfective fatigue syndrome following from three different triggering infections.

Galbraith S, Cameron B, Li H, Lau D, Vollmer-Conna U, Lloyd AR.
School of Mathematics and Statistics, Faculty of Science, University of New South Wales, Sydney, Australia.



Several infections trigger postinfective fatigue syndromes, which share key illness characteristics with each other and with chronic fatigue syndrome (CFS). Previous cross-sectional case-control studies of CFS have suggested that unique gene expression signatures are evident in peripheral blood samples.


Peripheral blood transcriptomes in samples collected longitudinally, in 18 subjects with a fatigue syndrome lasting ≥ 6 months after acute infection due to Epstein-Barr virus, Ross River virus, or Coxiella burnetii (Q fever), and 18 matched control subjects who had recovered promptly, were studied by microarray (n = 127) and confirmatory quantitative polymerase chain reaction (PCR). Gene expression patterns associated with CFS were sought by univariate statistics and regression modeling.


There were 23 genes with modest differential expression (0.6-2.3-fold change) in within-subject comparisons of early, symptomatic time points with late, recovered time points. There were modest differences found in 63 genes, either in cross-sectional comparison of cases and controls at 6 months after infection onset or in the regression model. There were 223 genes significantly correlated with individual symptom domains. Quantitative PCR confirmed 33 (73%) of 45 genes-none were consistent across cohorts.


Although the illness characteristics of patients with postinfective fatigue syndromes have more similarities than differences, no reliable peripheral blood gene expression correlate is evident.


From Br J Psychiatry. 2011 Oct;199:323-9. doi: 10.1192/bjp.bp.110.083956. Epub 2011 Aug 18.

Premorbid risk markers for chronic fatigue syndrome in the 1958 British birth cohort.

Clark C, Goodwin L, Stansfeld SA, Hotopf M, White PD.
Centre for Psychiatry, Barts & the London School of Medicine & Dentistry, Queen Mary University of London, Charterhouse Square, UK.



Little is known about the aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME); prospective studies suggest a role for premorbid mood disorder.


To examine childhood and early adult adversity, ill health and physical activity as premorbid risk markers for CFS/ME by 42 years, taking psychopathology into account.


Data were from the 1958 British birth cohort, a prospective study from birth to 42 years (n = 11 419). The outcomes were self-reported CFS/ME (n = 127) and operationally defined CFS-like illness (n = 241) at 42 years.


Adjusting for psychopathology, parental physical abuse (odds ratio (OR) = 2.10, 95% CI 1.16-3.81), childhood gastrointestinal symptoms (OR = 1.58, 95% CI 1.00-2.50) and parental reports of many colds (OR = 1.65, 95% CI 1.09-2.50) were independently associated with self-reported CFS/ME. Female gender and premorbid psychopathology were the only risk markers for CFS-like illness, independent of comorbid psychopathology.


This confirms the importance of premorbid psychopathology in the aetiological pathways of CFS/ME, and replicates retrospective findings that childhood adversity may play a role in a minority.


From Br J Clin Psychol. 2011 Sep;50(3):310-25. doi: 10.1348/014466510X519215. Epub 2011 Mar 8.

Emotional expression, self-silencing, and distress tolerance in anorexia nervosa and chronic fatigue syndrome.

Hambrook D, Oldershaw A, Rimes K, Schmidt U, Tchanturia K, Treasure J, Richards S, Chalder T.
Division of Psychological Medicine and Psychiatry, Section of Eating Disorders, King's College London, Institute of Psychiatry, UK.



Difficulties in processing emotional states are implicated in the aetiology and maintenance of diverse health conditions, including anorexia nervosa (AN) and chronic fatigue syndrome (CFS). This study sought to explore distress tolerance, self-silencing, and beliefs regarding the experience and expression of emotions in individuals diagnosed with AN and CFS. These conditions were chosen for this study because their clinical presentation is characterized by physical symptoms, yet cognitive behavioural models suggest that emotional processing difficulties contribute to the aetiology and maintenance of both.


A between-subjects cross-sectional design was employed.


Forty people with AN, 45 with CFS, and 48 healthy controls (HCs) completed the Distress Tolerance Scale (DTS), Silencing the Self Scale (STSS), Beliefs about Emotions Scale (BES), and measures of clinical symptomatology.


Initial group comparisons found that both AN and CFS participants scored higher than HCs on a subscale measuring difficulties in distress tolerance. AN and CFS participants were also more likely to judge themselves by external standards, endorse statements reflecting a tendency to put the needs of others before themselves, and present an outwardly socially compliant image of themselves whilst feeling hostile within. Relative to HCs, AN participants reported more maladaptive beliefs regarding the experience of having negative thoughts and feelings and revealing these emotions to others, with CFS participants showing a non-significant trend in the same direction. After controlling for differences in age, anxiety, and depression the only significant difference to remain was that observed for the STSS care as self-sacrifice subscale. More maladaptive beliefs about the experience and expression of emotions were associated with greater degree of eating disorder symptomatology in the AN group.


Differences in emotional processing are present in AN and CFS compared to HCs, with some disorder-specific variation, and may be associated with greater clinical symptomatology. These findings support current explanatory models of both AN and CFS, and suggest that emotional processing should be addressed in the assessment and treatment of individuals with these illnesses.


From Diagn Microbiol Infect Dis. 2011 Sep;71(1):66-71. Epub 2011 Jul 26.

Xenotropic murine leukemia virus-related virus in monozygotic twins discordant for chronic fatigue syndrome.

Jerome KR, Diem K, Huang ML, Selke S, Corey L, Buchwald D.
Department of Laboratory Medicine, University of Washington, Seattle, WA 98105, USA.


A recent report suggested an association between xenotropic murine leukemia virus-related virus (XMRV) and chronic fatigue syndrome (CFS). If confirmed, this would suggest that antiretroviral therapy might benefit patients suffering from CFS. We validated a set of assays for XMRV and evaluated the prevalence of XMRV in a cohort of monozygotic twins discordant for CFS. Stored peripheral blood mononuclear cell (PBMC) samples were tested with 3 separate polymerase chain reaction (PCR) assays (one of which was nested) for XMRV DNA, and serum/plasma was tested for XMRV RNA by reverse transcription (RT)-PCR. None of the PBMC samples from the twins with CFS or their unaffected co-twins was positive for XMRV, by any of the assays. One plasma sample, from an unaffected co-twin, was reproducibly positive by RT-PCR. However, serum from the same day was negative, as was a follow-up plasma sample obtained 2 days after the positive specimen. These data do not support an association of XMRV with CFS.


From J Clin Gastroenterol. 2011 Aug;45 Suppl:S86-8.

Irritable bowel syndrome and other functional gastrointestinal disorders.

ÅžimÅŸek I.
Medicine Faculty, Department of Gastroenterology, Dokuz Eylul University, Izmir, Turkey.

Irritable bowel syndrome is one of several highly prevalent functional gastrointestinal disorders (FGID) displaying symptoms of gastrointestinal dysmotility and visceral hypersensitivity. Substantial overlap of symptoms and comorbidities occur not only between irritable bowel syndrome and other FGID but also with gastrointestinal disorders that are not related to motility (eg, celiac disease and lactose intolerance) and to somatic conditions (eg, fibromyalgia and chronic fatigue syndrome). Pathogenic mechanisms common among FGIDs may include alternations in intestinal and colonic microflora. Evidence is also emerging of an interplay between gut immune cells/activity and alternations in motility, secretion, and sensation. The role of cytokine activity and inflammation is important in this regard. As recommended by Rome III, diagnostic testing should be guided by the patient's age, primary symptom characteristics, and other clinical and laboratory features. The high prevalence of coexisting conditions suggests the need to routinely assess patients for related disorders. Treatment should be based on an individualized evaluation, explanation, and reassurance.


From BMC Neurol. 2011 Jul 1;11:82.

EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients–a case control study.

Duffy FH, McAnulty GB, McCreary MC, Cuchural GJ, Komaroff AL.
Department of Neurology, Children's Hospital Boston and Harvard Medical School, 300 Longwood Ave, Boston, Massachusetts 02115, USA.



Previous studies suggest central nervous system involvement in chronic fatigue syndrome (CFS), yet there are no established diagnostic criteria. CFS may be difficult to differentiate from clinical depression. The study's objective was to determine if spectral coherence, a computational derivative of spectral analysis of the electroencephalogram (EEG), could distinguish patients with CFS from healthy control subjects and not erroneously classify depressed patients as having CFS.


This is a study, conducted in an academic medical center electroencephalography laboratory, of 632 subjects: 390 healthy normal controls, 70 patients with carefully defined CFS, 24 with major depression, and 148 with general fatigue. Aside from fatigue, all patients were medically healthy by history and examination. EEGs were obtained and spectral coherences calculated after extensive artifact removal. Principal Components Analysis identified coherence factors and corresponding factor loading patterns. Discriminant analysis determined whether spectral coherence factors could reliably discriminate CFS patients from healthy control subjects without misclassifying depression as CFS.


Analysis of EEG coherence data from a large sample (n = 632) of patients and healthy controls identified 40 factors explaining 55.6% total variance. Factors showed highly significant group differentiation (p < .0004) identifying 89.5% of unmedicated female CFS patients and 92.4% of healthy female controls. Recursive jackknifing showed predictions were stable. A conservative 10-factor discriminant function model was subsequently applied, and also showed highly significant group discrimination (p < .001), accurately classifying 88.9% unmedicated males with CFS, and 82.4% unmedicated male healthy controls. No patient with depression was classified as having CFS. The model was less accurate (73.9%) in identifying CFS patients taking psychoactive medications. Factors involving the temporal lobes were of primary importance.


EEG spectral coherence analysis identified unmedicated patients with CFS and healthy control subjects without misclassifying depressed patients as CFS, providing evidence that CFS patients demonstrate brain physiology that is not observed in healthy normals or patients with major depression. Studies of new CFS patients and comparison groups are required to determine the possible clinical utility of this test. The results concur with other studies finding neurological abnormalities in CFS, and implicate temporal lobe involvement in CFS pathophysiology.


From Mitochondrion. 2011 Sep;11(5):735-8. Epub 2011 Jun 2.

Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome.

Smits B, van den Heuvel L, Knoop H, Küsters B, Janssen A, Borm G, Bleijenberg G, Rodenburg R, van Engelen B.
Neuromuscular Center Nijmegen, Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.


We studied the extent of mitochondrial involvement in chronic fatigue syndrome (CFS) and investigated whether measurement of mitochondrial respiratory chain complex (RCC) activities discriminates between CFS and mitochondrial disorders. Mitochondrial content was decreased in CFS compared to healthy controls, whereas RCC activities corrected for mitochondrial content were not. Conversely, mitochondrial content did not discriminate between CFS and two groups of mitochondrial disorders, whereas ATP production rate and complex I, III and IV activity did, all with higher activities in CFS. We conclude that the ATP production rate and RCC activities can reliably discriminate between mitochondrial disorders and CFS.


From Brain Behav Immun. 2011 Aug;25(6):1249-55. Epub 2011 Apr 28.

Fatigue, depressive symptoms, and anxiety from adolescence up to young adulthood: a longitudinal study.

ter Wolbeek M, van Doornen LJ, Kavelaars A, Tersteeg-Kamperman MD, Heijnen CJ.
Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Office KC 03.068.0, P.O. Box 85090, 3508 AB Utrecht, The Netherlands.


Fatigue is a common complaint among adolescents. We investigated the course of fatigue in females during the transition from adolescence to young adulthood and examined psychological, immunological, and life style risk factors for development of fatigue and chronic fatigue syndrome (CFS)-related symptoms. Six hundred and thirty-three healthy females (age 14.63±1.37 years) filled out questionnaires measuring fatigue severity, depressive symptoms, anxiety, chronic fatigue syndrome (CFS)-related symptoms, sleep features, and life style characteristics at baseline and 4½ years thereafter. Of 64 participants LPS- and CD2CD28-induced cytokine data at baseline were available. The best predictor of fatigue in young adulthood was previous fatigue severity. In participants who were non-fatigued during adolescence and who experienced a notable increase in fatigue, fatigue development was preceded by emotional problems and CFS-related complaints during adolescence. Increases as well as decreases in fatigue severity were accompanied by respectively increase and decrease in depressive symptoms and anxiety, suggesting that these symptoms cluster and co-vary over time. Higher interferon (IFN)-γ, higher IFN-γ/interleukin (IL)-4 ratio, lower tumor necrosis factor-α and lower IL-10 at baseline were related to fatigue severity at follow up. The rise in total number of CFS-related symptoms at follow up was predicted by anxiety and decreased physical activity during adolescence. Sleep and substance use were associated with fatigue severity and anxiety and depression. In conclusion, vulnerability to develop fatigue and associated symptoms in young adulthood can to a certain extent be identified already years before the manifestation of complaints.


From QJM. 2011 Aug;104(8):681-7. Epub 2011 Mar 7.

Physical activity intensity but not sedentary activity is reduced in chronic fatigue synd rome and is associated with autonomic regulation.

Newton JL, Pairman J, Hallsworth K, Moore S, Plötz T, Trenell MI.
UK National Institute for Health Research Biomedical Research Centre in Ageing & Age-related Disease, Institute for Ageing and Health, Newcastle University, Newcastle, UK.



Chronic fatigue syndrome (CFS) is a common debilitating condition associated with reduced function and impaired quality of life. The cause is unknown and treatments limited. Studies confirm that CFS is associated with impaired autonomic regulation and impaired muscle function.


Define the relationship between sedentary behaviour, physical activity and autonomic regulation in people with CFS.


Cohort study.


Physical activity was assessed objectively in 107 CFS patients (Fukuda) and age, sex and body mass index (BMI)-matched sedentary controls (n= 107). Fatigue severity was determined using the Fatigue Impact Scale in all participants and heart rate variability performed in the CFS group.


The CFS group had levels and patterns of sedentary behaviour similar to non-fatigue controls (P > 0.05). Seventy-nine percent of the CFS group did not achieve the WHO recommended 10,000 steps per day. Active energy expenditure [time >3 METs (metabolic equivalents)] was reduced in CFS when compared with controls (P < 0.0001). Physical activity duration was inversely associated with resting heart rate (P = 0.04; r(2) = 0.03), with reduced activity significantly associating with reduced heart rate variability in CFS. There were no relationships between fatigue severity and any parameter of activity. Thirty-seven percent of the CFS group were overweight (BMI 25-29.9) and 20% obese (BMI ≥ 30).


Low levels of physical activity reported in CFS represent a significant and potentially modifiable perpetuating factor in CFS and are not attributable to high levels of sedentary activity, rather a decrease in physical activity intensity. The reduction in physical activity can in part be explained by autonomic dysfunction but not fatigue severity.


From Acta Paediatr (impaired web link). 2011 Aug;100(8):1069-76. doi: 10.1111/j.1651-2227.2011.02223.x. Epub 2011 Mar 15.

Anxiety in children and adolescents with chronic physical illnesses: a meta-analysis.

Pinquart M, Shen Y.
Philipps University, Department of Psychology, Marburg, Germany.

Comment in

Acta Paediatr. 2011 Aug;100(8):1066-8.


To compare levels of anxiety of children with chronic illness with healthy peers and population norms. Meta-analysis integrated results from 332 studies. Children with chronic illness had elevated levels of anxiety (d=0.18 standard deviation units). Strongest elevations were found for chronic fatigue syndrome, migraine/tension headache, sensory impairment and epilepsy. Paediatricians should screen for anxiety symptoms in children at risk and offer interventions, if needed.


From Expert Opin Pharmacother. 2011 May;12(7):1087-98. Epub 2011 Jan 22.

Treatment of central sensitization in patients with ‘unexplained' chronic pain: what options do we have?

Nijs J, Meeus M, Van Oosterwijck J, Roussel N, De Kooning M, Ickmans K, Matic M.
Artesis University College Antwerp, Antwerp, Belgium.



Central sensitization accounts for chronic ‘unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients.


This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed.

EXPERT OPINION: Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that – theoretically – desensitize the CNS in humans. To provide a comprehensive treatment for ‘unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization.


From Disabil Rehabil. 2011;33(17-18):1493-500. Epub 2010 Dec 20

Tired of being inactive: a systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome.

Nijs J, Aelbrecht S, Meeus M, Van Oosterwijck J, Zinzen E, Clarys P.
Department of Human Physiology, Faculty of Physical Education & Physiotherapy, Vrije Universiteit Brussel, Belgium.


A systematic review was undertaken to examine whether patients with chronic fatigue syndrome (CFS) differ from healthy sedentary controls in physiological exercise capacity, physical activity level and muscle strength. From the available literature, it can be concluded that patients with CFS perform less physical activity during daily life, and have less peak isometric muscle strength compared to healthy sedentary control subjects. Conflicting data in relation to physiological exercise capacity of patients with CFS have been reported, but the weighted available evidence points towards a reduced physiological exercise capacity in CFS. Future studies should use a wash-out period for medication use, blinded assessments, a priori power calculation and a sedentary control group comparable for age, gender, body weight, body length and current physical activity level.


From Eur J Public Health. 2010 Jun;20(3):251-7. Epub 2009 Aug 18.

Fatigue and chronic fatigue syndrome-like complaints in the general population.

van't Leven M, Zielhuis GA, van der Meer JW, Verbeek AL, Bleijenberg G.
Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, the Netherlands.



Most knowledge on chronic fatigue (CF) and chronic fatigue syndrome (CFS) is based on clinical studies, not representative of the general population. This study aimed to assess the prevalence of fatigue in an adult general population and to identify associations with lifestyle factors.


Total 22,500 residents of Nijmegen were selected at random and interviewed by questionnaire. Data on 9062 respondents (43% response) were analysed, taken into account age, gender and concomitant disease. Subjects were classified into four groups: not fatigued (NF, reference group), short-term fatigue (SF,or=6 months) and CFS-like fatigue (in accordance with the Center for Disease Control criteria for CFS, without clinical confirmation).


Our study population showed the following breakdown: NF 64.4% (95% CI 63.6-65.6%), SF 4.9% (95% CI 4.5-5.4%), CF 30.5% (95% CI 29.5-31.4%) and CFS-like fatigue 1.0% (95% CI 0.8-1.2%). Compared with the NF group, more of the CFS respondents were female [odds ratio (OR) = 1.9], obese (OR = 4.1), using analgesics (OR = 7.8), had a low alcohol intake (OR = 0.4), were eating less healthy food (OR = 0.5) and were physically less active (OR = 0.1). These associations largely applied to the SF and CF group. The fatigue could have been due to a concomitant disease in 34 and 55.5% of the SF and CF cases, respectively.


The prevalence of CF in the general population appears to be much higher than previously indicated. Even with strict criteria for CFS, it is estimated that approximately 1% of the adult population experiences this condition. Interestingly, a large part of this group remains unrecognized by the general practitioner. A striking similarity in lifestyle pattern between SF, CF and CFS calls for further research.

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