TGI Friday! Our weekly round-up of recently published research abstracts | 7 December 2012

December 7, 2012

From Brain Informatics, Lecture Notes in Computer Science, Volume 7670, 2012, pp 107-118.

An Agent Model for Temporal Dynamics Analysis of a Person with Chronic Fatigue Syndrome

Azizi Ab Aziz(1,2), Faudziah Ahmad(2), Houzifa M. Hintaya(2).
(1) ITU-UUM Asia Pacific Centre of Excellence for Rural IT Development, Universiti Utara Malaysia, 06010 UUM, Sintok, Kedak Malaysia
(2) Bio-Inspired Agent Research Group, Artificial Intelligence Laboratory, School of Computing, College of Arts & Sciences, Universiti Utara Malaysia, 06010 UUM, Sintok, Kedak Malaysia


This paper presents a dynamic agent model of chronic fatigue syndrome for an individual. Chronic fatigue syndrome is the most common name to define a group of cognitive and medical disorders caused by persistent fatigue.

Based on several personal characteristics, viral infection, and a representation of events (i.e. psychological and physiological stressors), the agent model can simulate whether a human agent that experience certain scenarios will fall into a chronic fatigue condition.

A number of well-known relations between events and the course of chronic fatigue are summarized from the literature and it is shown that the model exhibits those patterns. In addition, the agent model has been mathematically analyzed to find out which stable situations exist.

Finally, it is pointed out how this model can be used in therapy, supported by a software agent.

From the Journal of Affective Disorders Volume 141, Issue 2, Pages 130-142, 10 December 2012.

Inflammatory fatigue and sickness behaviour — Lessons for the diagnosis and management of chronic fatigue syndrome

S.V. Arnett, I.A. Clark


Persistent and severe fatigue is a common part of the presentation of a diverse range of disease processes. There is a growing body of evidence indicating a common inflammatory pathophysiology underlying many conditions where fatigue is a primary patient concern, including chronic fatigue syndrome.

This review explores current models of how inflammatory mediators act on the central nervous system to produce fatigue and sickness behaviour, and the commonality of these processes in conditions as diverse as surgical trauma, infection, various cancers, inflammatory bowel disease, connective tissue diseases and autoimmune diseases.

We also discuss evidence indicating chronic fatigue syndrome may have important pathophysiological similarities with cytokine mediated sickness behaviour, and what lessons can be applied from sickness behaviour to chronic fatigue syndrome with regards to the diagnosis and management.

From Brain, Behaviour and Immunity, 29 November 2012.

Altered Immune Pathway Activity under Exercise Challenge in Gulf War Illness: An Exploratory Analysis

Broderick G, Hamo RB, Vashishtha S, Efroni S, Nathanson L, Barnes Z, Fletcher MA, Klimas N.
Department of Medicine, University of Alberta, Edmonton, Canada.


Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating illness presenting with a complex constellation of immune, endocrine and neurological symptoms.

Here we compared male GWI(n=20) with healthy veterans (n=22) and subjects with chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME) (n=7).

Blood was drawn during a Graded eXercise Test (GXT) prior to exercise, at peak effort (VO2 max) and 4-hours post exercise. Affymetrix HG U133 plus 2.0 microarray gene expression profiling in peripheral blood mononuclear cells (PBMCs) was used to estimate activation of over 500 documented pathways.

This was cast against ELISA-based measurement of 16 cytokines in plasma and flow cytometric assessment of lymphocyte
populations and cytotoxicity. A 2-way ANOVA corrected for multiple comparisons (q statistic <0.05) indicated significant increases in neuroendocrine-immune signaling and inflammatory activity in GWI, with decreased apoptotic signaling.Conversely, cell cycle progression and immune signaling were broadly subdued in CFS. Partial correlation networks linking pathways with symptom severity via changes in immune cell abundance, function and signaling were constructed.Central to these were changes in IL-10 and CD2+ cell abundance and their link to two pathway clusters. The first consisted of pathways supporting neuronal development and migration whereas the second was related to androgen-mediated activation of NF-κB.These exploratory results suggest an over-expression of known exercise response mechanisms as well as illness-specific changes that may involve an overlapping stress-potentiated neuro-inflammatory response.

From the Journal of Internal Medicine, 4 December 2012.[Epub ahead of print].

Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome.

Lewis I, Pairman J, Spickett G, Newton JL.
Institute for Ageing & Health, Newcastle University, Newcastle, UK.



A significant proportion of patients with chronic fatigue syndrome (CFS) also have postural orthostatic tachycardia syndrome (POTS). We aimed to characterise these patients and differentiate them from CFS patients without POTS in terms of clinical and autonomic features.


A total of 179 patients with CFS (1994 Centers for Disease Control and Prevention criteria) attending one of the largest Department of Health-funded CFS clinical services were included in the study.

Outcome measures were: (i) symptom assessment tools including the fatigue impact scale, Chalder fatigue scale, Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS-A and -D, respectively), (ii) autonomic function analysis including heart rate variability and (iii) haemodynamic responses including left ventricular ejection time and systolic blood pressure drop upon standing.


CFS patients with POTS (13%, n=24) were younger (29±12 vs. 42±13 years, P<0.0001), less fatigued (Chalder fatigue scale, 8±4 vs. 10±2, P=0.002), less depressed (HADS-D, 6±4 vs. 9±4, P=0.01) and had reduced daytime hypersomnolence (ESS, 7±6 vs. 10±5, P=0.02), compared with patients without POTS.In addition, they exhibited greater orthostatic intolerance (OGS, 11±5; P<0.0001) and autonomic dysfunction.A combined clinical assessment tool of ESS ≤9 and OGS ≥9 identifies accurately CFS patients with POTS with 100% positive and negative predictive values.CONCLUSIONSThe presence of POTS marks a distinct clinical group of CFS patents, with phenotypic features differentiating them from those without POTS.A combination of validated clinical assessment tools can determine which CFS patients have POTS with a high degree of accuracy, and thus potentially identify those who require further investigation and consideration for therapy to control heart rate.

From Neuromuscular Disorders, December 2013.

The relationship between muscle pain and fatigue.

Mastaglia FL.
Australian Neuro-Muscular Research Institute and Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Queen Elizabeth II Medical Centre, Perth, WA, Australia.


Pain and fatigue may occur together during sustained exhausting muscle contractions, particularly as the limit of endurance is approached, and both can restrict muscle performance. Patients with neuromuscular disorders may have chronic myofascial pain (e.g. fibromyalgia) or contraction-induced pain (e.g. in metabolic myopathies). In some patients these two types of pain may coexist and both may inhibit central motor drive during exercise.

Little is known about the central motor adaptations that occur in patients with neuromuscular disorders and how the effects of pain are mediated.

Transcranial magnetic brain stimulation has made it possible to investigate the changes in excitability of the central motor pathway during fatiguing muscle activity and have thrown light on the mechanisms of fatigue in normal subjects and individuals with chronic fatigue syndrome and multiple sclerosis, but there have been few studies in patients with neuromuscular disorders.

Repetitive magnetic brain stimulation protocols can now be used to modulate the excitability of the motor system during exercise to delay the onset of peripheral fatigue, and to reduce chronic pain.

The possible application of these techniques in patients with neuromuscular disorders warrants further investigation.

From Neuromuscular Disorders, 1 December 2012.

Fatigue and exercise intolerance in mitochondrial diseases. Literature revision and experience of the Italian Network of mitochondrial diseases

M. Mancuso, C. Angelini, E. Bertini, V. Carelli, G.P. Comi, C. Minetti, M. Moggio, T. Mongini, S. Servidei, P. Tonin, A. Toscano, G. Uziel, M. Zeviani, G. Siciliano
The Nationwide Italian Collaborative Network of Mitochondrial Diseases


Fatigue and exercise intolerance are common symptoms of mitochondrial diseases, but difficult to be clinically assessed.

New methods to quantify these rather common complaints are strongly needed in the clinical practice. Coenzyme Q10 administration and aerobic exercise may improve exercise intolerance, but more definite studies are still pending.

Herein, we have revised “how to measure” and “how to treat” these symptoms of mitochondrial patients. Subsequently, we reviewed the clinical data of the 1164 confirmed mitochondrial patients present in the Italian nation-wide database of mitochondrial disease, with special regard to exercise intolerance.

We observed that more of 20% of mitochondrial patients complain of exercise intolerance. This symptom seems to be
frequently associated with specific patient groups and/or genotypes. Ragged red fibers and COX-negative fibers are more often present in subjects with exercise intolerance, whereas lactate levels could not predict this symptom. Multicenter efforts are strongly needed for rare disorders such as mitochondrial diseases, and may represent the basis for more rigorous longitudinal studies.

From Clinical and Experimental Immunology, 29 November 2012.

Altered functional B-cell subset populations in patients with chronic fatigue syndrome compared to Healthy Controls

A.S. Bradley, B. Ford, A.S. Bansal
Department of Immunology, St. Helier University Hospital NHS Trust, Carshalton, Surrey


Chronic Fatigue Syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterised by disabling fatigue, headaches, sleep disturbance and several other symptoms. The onset of CFS may follow a viral infection or period of stress. Patients with CFS do not have hypogammaglobulinaemia, predisposition to recurrent bacterial infections or symptoms of autoimmunity.

To date, defects in B-cell numbers or function have not been shown in the literature. However, treatment with anti-B-cell therapy using Rituximab has recently shown benefit to CFS patients. We therefore postulated that patients with CFS had a subtle humoral immune dysfunction, and performed extended B-cell immunophenotyping.

We undertook a detailed characterisation of the proportions of the different B-cell subsets in 33 patients with CFS fulfilling the Canadian and Fukada criteria for CFS and compared these with 24 age and gender matched healthy controls (HC).

CFS patients had greater numbers of naïve B-cells as a % lymphocytes – 6.3 % versus 3.9 % in HC (P=0.034), greater numbers of naïve B-cells as a % of B-cells – 65 % versus 47 % in controls (P=0.003), greater numbers of transitional B-cells – 1.8 % versus 0.8 % in controls (P=0.025) and reduced numbers of plasmablasts – 0.5 % versus 0.9 % in controls (P=0.013).

While the cause of these changes is unclear, we speculate whether they may suggest a subtle tendency to autoimmunity.

2 thoughts on “TGI Friday! Our weekly round-up of recently published research abstracts | 7 December 2012”

  1. These studies are a reflection of how chaotic research has become.

    It is not possible to create a computer model of a disease or test any treatment when those they are studying are grouped by nothing more than fatigue. Neither is it possible to create subgroups from such a group. There is simply no evidence that there are ME subgroups. This does not adhere to any subgrouping used for disease.

    ME is also clearly not sickness behaviour, the response everyone experienced when the body has to fight an infection. It is not logical to therefore suggest this process can be useful for diagnosis and management.

    There is evidence that ME patients have mitochondria dysfunction, but there is no evidence that it is the same type as those mitochondria patients studied above. Without testing mitochondria using validated assays it is dangerous to exercise ME patients, but continually patients are subjective to these dangerous practices in the NHS as if investigators have some sort of six sense to determine the biological response at a cellular level. Whereas the biology of ME already indicates that for patients exercise can be lethal.

    The B cells study is intriguing, however it is disingenuous of the authors to say that this could represent a subtle autoimmune response when the number of B cells is almost twice that found in healthy controls. This finding however is also supportive of retroviruses. MuLVs for instance infect B cells leading to autoimmunity. To propagate they encourage the B cells to divide, making an exact copy of themselves and thus increasing the number of B cells.

  2. This is what the experts say about mitochondria diseases which refutes the 20% claim above.

    “Exercise intolerance is a hallmark characteristic of mitochondrial disease (Mito). Adults and children with Mito typically are unable to withstand intense physical activity, and often require more rest, oxygen, carbohydrates, and fluids following any physical activity. In other words, even low-impact or small amounts of exercise can leave a Mito patient feeling “wiped out”, complaining of fatigue, shortness of breath, weakness and an increased heart rate (tachycardia). As a result, for years doctors have recommended maintaining a low activity level to their Mito patients.”

    Most mitochondria diseases show no evidence of red ragged fibres.

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