TGI Friday! Our weekly round-up of recently published research abstracts | 1 January 2016

January 1, 2016

From Clinical Rehabilitation, 16 December 2015.

Effectiveness of a group-based self-management program for people with chronic fatigue syndrome: A randomized controlled trial

Irma Pinxsterhuis(1,2,3), Leiv Sandvik(4), Elin Bolle Strand(1), Erik Bautz-Holter(5),
Unni Sveen(5,2,3)
1) Division of Medicine, Oslo University Hospital, Oslo, Norway
2) Department of Occupational Therapy, Prosthetics and Orthotics, Oslo, Norway
3) Akershus University College of Applied Sciences, Oslo, Norway
4) Center for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway
5) Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Oslo, Norway



To evaluate the effectiveness of a group-based self-management program for people with chronic fatigue syndrome.


A randomized controlled trial.


Four mid-sized towns in southern Norway and two suburbs of Oslo.


A total of 137 adults with chronic fatigue syndrome.


A self-management program including eight biweekly meetings of 2.5 hours duration. The control group received usual care.


Primary outcome measure: Medical Outcomes Study-Short Form-36 physical functioning subscale. Secondary outcome measures: Fatigue severity scale, self-efficacy scale, physical and mental component summary of the Short Form-36, and the illness cognition questionnaire (acceptance subscale). Assessments were performed at baseline, and at six-month and one-year follow-ups.


At the six-month follow-up, a significant difference between the two groups was found concerning fatigue severity (p = 0.039) in favor of the control group, and concerning self-efficacy in favor of the intervention group (p = 0.039). These significant differences were not sustained at the one-year follow-up. No significant differences were found between the groups concerning physical functioning, acceptance, and health status at any of the measure points. The drop-out rate was 13.9% and the median number of sessions attended was seven (out of eight).


The evaluated self-management program did not have any sustained effect, as compared with receiving usual care.

From Magnetic Resonance Imaging, 17 December 2015.

Abnormal resting state functional connectivity in patients with chronic fatigue syndrome: An arterial spin-labeling fMRI study

Jeff Boissoneault, Janelle Letzen, Song Lai, Andrew O'Shea, Jason Craggs, Mike Robinson, Roland Staud*
*Corresponding author at: Department of Medicine, College of Medicine, University of Florida, PO Box 100277, Gainesville, FL 32610-0277.



Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by severe fatigue and neurocognitive dysfunction. Recent work from our laboratory and others utilizing arterial spin labeling functional magnetic resonance imaging (ASL) indicated that ME/CFS patients have lower resting state regional cerebral blood flow (rCBF) in several brain areas associated with memory, cognitive, affective, and motor function. This hypoperfusion may underlie ME/CFS pathogenesis and may result in alterations of functional relationships between brain regions. The current report used ASL to compare functional connectivity of regions implicated in ME/CFS between patients and healthy controls (HC).


Participants were 17 ME/CFS patients (Mage = 48.88 years, SD = 12) fulfilling the 1994 CDC criteria and 17 age/sex matched HC (Mage = 49.82 years, SD = 11.32). All participants underwent T1-weighted structural MRI as well as a 6-min pseudo-continuous arterial spin labeling (pCASL) sequence, which quantifies CBF by magnetically labeling blood as it enters the brain. Imaging data were preprocessed using SPM 12 and ASL tbx, and seed-to-voxel functional connectivity analysis was conducted using the CONN toolbox. All effects noted below are significant at p < 0.05 with cluster-wise FDR correction for multiple comparisons.RESULTSME/CFS patients demonstrated greater functional connectivity relative to HC in bilateral superior frontal gyrus, ACC, precuneus, and right angular gyrus to regions including precuneus, right postcentral gyrus, supplementary motor area, posterior cingulate gyrus, and thalamus. In contrast, HC patients had greater functional connectivity than ME/CFS in ACC, left parahippocampal gyrus, and bilateral pallidum to regions including right insula, right precentral gyrus, and hippocampus. Connectivity of the left parahippocampal gyrus correlated strongly with overall clinical fatigue of ME/CFS patients.CONCLUSIONThis is the first ASL based connectivity analysis of patients with ME/CFS. Our results demonstrate altered functional connectivity of several regions associated with cognitive, affective, memory, and higher cognitive function in ME/CFS patients. Connectivity to memory related brain areas (para-hippocampal gyrus) was correlated with clinical fatigue ratings, providing supporting evidence that brain network abnormalities may contribute to ME/CFS pathogenesis.

From PLoS One, 18 December 2015 (open access).

Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Sanjay K. Shukla(1*), Dane Cook(2,3), Jacob Meyer(2), Suzanne D. Vernon(4), Thao Le(1), Derek Clevidence(3), Charles E. Robertson(5), Steven J. Schrodi(1), Steven Yale(6), Daniel N. Frank(5).
1) Marshfield Clinic Research Foundation, Marshfield, WI, United States of America,
2) William S. Middleton Memorial Veterans Hospital, Madison, WI, United States of America,
3) University of Wisconsin, Madison, WI, United States of America,
4) Bateman Horne Center of Excellence, Salt Lake City, UT, United States of America,
5) University of Colorado Denver Anschutz Medical Campus, Aurora, CO, United States of America,
6) Marshfield Clinic, Marshfield, WI, United States of America


Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease characterized by intense and debilitating fatigue not due to physical activity that has persisted for at least 6 months, post-exertional malaise, unrefreshing sleep, and accompanied by a number of secondary symptoms, including sore throat, memory and concentration impairment, headache, and muscle/joint pain.

In patients with post-exertional malaise, significant worsening of symptoms occurs following physical exertion and exercise challenge serves as a useful method for identifying biomarkers for exertion intolerance. Evidence suggests that intestinal dysbiosis and systemic responses to gut microorganisms may play a role in the symptomology of ME/CFS. As such, we hypothesized that post-exertion worsening of ME/CFS symptoms could be due to increased bacterial translocation from the intestine into the systemic circulation.

To test this hypothesis, we collected symptom reports and blood and stool samples from ten clinically characterized ME/CFS patients and ten matched healthy controls before and 15 minutes, 48 hours, and 72 hours after a maximal exercise challenge. Microbiomes of blood and stool samples were examined. Stool sample microbiomes differed between ME/CFS patients and healthy controls in the abundance of several major bacterial phyla.

Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005). There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls.

These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon
exercise challenge, there were significant changes in the abundance of major bacterial phyla in the gut in ME/CFS patients not observed in healthy controls. In addition, compared to controls clearance of bacteria from the blood was delayed in ME/CFS patients following exercise.

These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients.

From the Journal of Psychosomatic Research, 22 December 2015.

Chronic Fatigue Syndrome (CFS) symptom-based phenotypes in two clinical cohorts of adult patients in the UK and The Netherlands

Simon M. Collin(1), Stephanie Nikolaus(2), Jon Heron(1), Hans Knoop(2), Peter D. White(3), Esther Crawley(4)
1) School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 8BN, UK
2) Expert Centre for Chronic Fatigue, Radboud University Medical Centre Nijmegen, The Netherlands
3) Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
4) School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 8BN, UK


•We explore chronic fatigue syndrome (CFS) phenotypes in two large clinical cohorts.
•Adults with CFS may have one of 6 symptom-based phenotypes.
•Phenotypes were associated with sex, duration of illness, and comorbidity.
•Polysymptomatic patients had more severe illness and more comorbidities.
•Phenotypes in UK patients were replicated in Dutch patients.



Studies have provided evidence of heterogeneity within chronic fatigue syndrome (CFS), but few have used data from large cohorts of CFS patients or replication samples.


29 UK secondary-care CFS services recorded the presence/absence of 12 CFS-related symptoms; 8 of these symptoms were recorded by a Dutch tertiary service. Latent Class Analysis (LCA) was used to assign symptom profiles (phenotypes). Regression models were fitted with phenotype as outcome (in relation to age, sex, BMI, duration of illness) and exposure (in relation to comorbidities and patient-reported measures).


Data were available for 7,041 UK and 1,392 Dutch patients. Almost all patients in both cohorts presented with post-exertional malaise, cognitive dysfunction and disturbed/unrefreshing sleep, and these 3 symptoms were excluded from LCA. In UK patients, six phenotypes emerged: ‘full’ polysymptomatic (median 8, IQR 7-9 symptoms) 32.8%; ‘pain-only’ (muscle/joint) 20.3%; ‘sore throat/painful lymph node’ 4.5%; ‘oligosymptomatic’ (median 1, IQR 0-2 symptoms) 4.7%. Two ‘partial’ polysymptomatic phenotypes were similar to the ‘full’ phenotype, bar absence of dizziness/nausea/palpitations (21.4%) or sore throat/painful lymph nodes (16.3%). Women and patients with longer duration of illness were more likely to be polysymptomatic. Polysymptomatic patients had more severe illness and more comorbidities. LCA restricted to 5 symptoms recorded in both cohorts indicated 3 classes (polysymptomatic, oligosymptomatic, pain-only), which were replicated in Dutch data.


Adults with CFS may have one of 6 symptom-based phenotypes associated with sex, duration and severity of illness, and comorbidity. Future research needs to determine whether phenotypes predict treatment outcomes, and require different treatments.

3 thoughts on “TGI Friday! Our weekly round-up of recently published research abstracts | 1 January 2016”

  1. This is the best one I’ve seen in a while. The gut study and MRI sound very positive. I just wish there was more momentum with collaborative research initiatives.

  2. Agree with Pappy1986 above. Very encouraging. Lots of clues for further research in both those studies.

  3. Yes indeed, the fMRI and gut/plasma microbiome studies add to a large cohort of evidence which shows that the widely discredited behavioural approach to ME, and the use of the Oxford Criteria (which should never have been created in the first place), should be firmly dumped once and for all- OK, thirty years or so overdue – but better late than never.
    A good opportunity to sign and share the following Avaaz petition:

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