TGI Friday! | Our weekly round-up of recently published research abstracts | 12 June 2015

June 12, 2015

From Neuromuscular Disorders, 23 April 2015.[Epub ahead of print]

Perceived fatigue is highly prevalent and debilitating in patients with mitochondrial disease.

Gorman GS(1), Elson JL(2), Newman J(3), Payne B(4), McFarland R(3), Newton JL(5), Turnbull DM(3).
1) Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Institute of Ageing and Health and NIHR Biomedical Research Centre for Ageing, Newcastle University, Newcastle upon Tyne NE4 5PL, UK. Electronic address:
2) Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
3) Wellcome Trust Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Institute of Ageing and Health and NIHR Biomedical Research Centre for Ageing, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
4) Institute of Ageing and Health and NIHR Biomedical Research Centre for Ageing, Newcastle University, Newcastle upon Tyne NE4 5PL, UK; Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
5) Institute of Ageing and Health and NIHR Biomedical Research Centre for Ageing, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.


Perceived fatigue is a prominent symptom in patients with mitochondrial disease but to date its prevalence, impact and aetiology are poorly understood. Our aim was to determine the prevalence and assess for comorbidities associated with clinically relevant fatigue in patients with mitochondrial disease.

A cross-sectional postal survey of patients with mitochondrial disease was undertaken using a
validated self-completion, patient-reported outcome measures (response rate: 60%; n = 132).

The prevalence and perceived functional impact of experienced fatigue were assessed using the Fatigue Impact Scale.

Other putative biological mechanisms were evaluated using the Hospital Anxiety Depression scale and Epworth sleepiness scale.

Data were compared with those for healthy control subjects and patients with Myalgic Encephalopathy/Chronic Fatigue Syndrome matched for age and gender. Sixty-two per cent of patients with mitochondrial disease reported excessive symptomatic fatigue (Fatigue Impact Scale ≥ 40); whilst 32% reported severe, functionally limiting fatigue symptoms (Fatigue Impact Scale ≥ 80) comparable to perceived fatigue in patients with Myalgic Encephalopathy/Chronic Fatigue Syndrome.

Fatigue is common and often severe in patients with mitochondrial disease irrespective of age, gender or genotype. Future evaluation of causal factors in mitochondrial disease-associated fatigue is warranted with the potential to guide future treatment modalities.

From Lupus, 1 June 2015

Autoimmune markers and autoimmune disorders in patients with postural tachycardia syndrome (POTS)

S Blitshteyn
Department of Neurology, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, USA



In recent years, there have been a number of studies suggesting that POTS may have an autoimmune etiology. This study examined whether the prevalence of antinuclear antibodies (ANA), other markers of autoimmunity and co-morbid autoimmune disorders is higher in patients with POTS than in the general population.


Medical records of 100 consecutive patients with POTS evaluated at our clinic were reviewed.

In this cohort (90% females, mean age 32, range 13–54 years), 25% had positive ANA, 7% had
at least one positive aPL antibody and 31% had markers of autoimmunity. When compared to the general population, patients with POTS had a higher prevalence of ANA (25% vs. 16%, OR 1.8, CI 1.1–2.8, p < 0.05), aPL antibody (7% vs. 1%, OR 7.5, CI 3.4–16.1, p < 0.001) and co-morbid autoimmune disorders (20% vs. highest estimated 9.4%, OR 2.4, CI 1.5–3.9, p < 0.001).The most prevalent autoimmune disorder was Hashimoto’s thyroiditis (11% vs. up to 2%, OR 6.1, CI 3.2–11.3, p < 0.001), followed by RA (4% vs. up to 1%, OR 4.1, CI 1.5–11.2, p < 0.01) and SLE (2% vs. up to 0.12%, OR 17, CI 4.1–69.7, p < 0.001). The prevalence of CVID was very high (2% vs. 0.004%, OR 510.2, CI 92.4–2817.8, p < 0.001), while celiac disease showed a nonsignificant trend toward increased prevalence.CONCLUSIONPatients with POTS have a higher prevalence of autoimmune markers and co-morbid autoimmune disorders than the general population. One in four patients have positive ANA, almost one in three have some type of autoimmune marker, one in five have a co-morbid autoimmune disorder, and one in nine have Hashimoto’s thyroiditis.

From The Cochrane Database of Systematic Reviews, 5 June 2015.[Epub ahead of print].

Selective serotonin reuptake inhibitors for fibromyalgia syndrome.

Walitt B, Urrútia G, Nishishinya MB, Cantrell SE, Häuser W.
Academic affiliations not found



Fibromyalgia is a clinically well-defined chronic condition with a biopsychosocial aetiology. Fibromyalgia is characterized by chronic widespread musculoskeletal pain, sleep
problems, cognitive dysfunction, and fatigue. Patients often report high disability levels and poor quality of life.

Since there is no specific treatment that alters the pathogenesis of fibromyalgia, drug
therapy focuses on pain reduction and improvement of other aversive symptoms.


The objective was to assess the benefits and harms of selective serotonin reuptake inhibitors (SSRIs) in the treatment of fibromyalgia.


We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 5), MEDLINE (1966 to June 2014), EMBASE (1946 to June 2014), and the reference lists of reviewed articles.


We selected all randomized, double-blind trials of SSRIs used for the treatment of fibromyalgia symptoms in adult participants. We considered the following SSRIs in this review: citalopram, fluoxetine, escitalopram, fluvoxamine, paroxetine, and sertraline.


Three authors extracted the data of all included studies and assessed the risks of bias of the studies. We resolved discrepancies by discussion.


The quality of evidence was very low for each outcome.

We downgraded the quality of evidence to very low due to concerns Nabout risk of bias and studies with few participants. We included seven placebo-controlled studies, two with citalopram, three with fluoxetine and two with paroxetine, with a median study duration of eight weeks (4 to 16 weeks) and 383 participants, who were pooled together.

All studies had one or more sources of potential major bias.

There was a small (10%) difference in patients who reported a 30% pain reduction between SSRIs (56/172 (32.6%)) and placebo (39/171 (22.8%)) risk difference (RD) 0.10, 95% confidence interval (CI) 0.01 to 0.20; number needed to treat for an additional beneficial outcome (NNTB) 10, 95% CI 5 to 100; and in global improvement (proportion of patients who reported to be much or very much improved: 50/168 (29.8%) of patients with SSRIs and 26/162 (16.0%) of patients with placebo) RD 0.14, 95% CI 0.06 to 0.23; NNTB 7, 95% CI 4 to 17.

SSRIs did not statistically, or clinically, significantly reduce fatigue: standard mean difference (SMD) -0.26, 95% CI -0.55 to 0.03; 7.0% absolute improvement on a 0 to 10 scale, 95% CI 14.6% relative improvement to 0.8% relative deterioration; nor sleep problems: SMD 0.03, 95 % CI -0.26 to 0.31; 0.8 % absolute deterioration on a 0 to 100 scale, 95% CI 8.3% relative deterioration to 6.9% relative improvement.SSRIs were superior to placebo in the reduction of depression: SMD -0.39, 95% CI -0.65 to -0.14; 7.6% absolute improvement on a 0 to 10 scale, 95% CI 2.7% to 13.8% relative improvement; NNTB 13, 95% CI 7 to 37.

The dropout rate due to adverse events was not higher with SSRI use than with placebo use (23/146 (15.8%) of patients with SSRIs and 14/138 (10.1%) of patients with placebo) RD 0.04, 95% CI -0.06 to 0.14.

There was no statistically or clinically significant difference in serious adverse events with SSRI use and placebo use (3/84 (3.6%) in patients with SSRIs and 4/84 (4.8%) and patients with placebo) RD -0.01, 95% CI -0.07 to 0.05.


There is no unbiased evidence that SSRIs are superior to placebo in treating the key symptoms of fibromyalgia, namely pain, fatigue and sleep problems. SSRIs might be considered fortreating depression in people with fibromyalgia.

The black box warning for increased suicidal tendency in young adults aged 18 to 24, with major depressive disorder, who have taken SSRIs, should be considered when appropriate.

From PLoSOne (open access journal), 26 May 2015

Hyperbaric Oxygen Therapy Can Diminish Fibromyalgia Syndrome – Prospective Clinical Trial

Shai Efrati(1,2,3,4), Haim Golan(3,5), Yair Bechor(2), Yifat Faran(6), Shir Daphna-Tekoah(6,7), Gal Sekler(8), Gregori Fishlev(2,3), Jacob N. Ablin(3,9), Jacob Bergan(2,3), Olga Volkov(3,5), Mony Friedman(2,3), Eshel Ben-Jacob(1,4,8,10), Dan Buskila (11)
1) Research and Development Unit, Assaf Harofeh Medical Center, Zerifin, Israel
2)The Institute of Hyperbaric Medicine, Assaf Harofeh Medical Center, Zerifin, Israel
3) Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
4) Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel
5) Nuclear Medicine institute, Assaf Harofeh Medical Center, Zerifin, Israel
6) School of Social Work, Ashkelon Academic College, Ashkelon, Israel
7) Social Work Department, Kaplan Medical Center, Rehovot, Israel
8) School of Physics and Astronomy, The Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University, Tel-Aviv, Israel
9) Institute of Rheumatology, Tel Aviv Sourasky medical center Israel, Tel- Aviv, Israel
10) Center for Theoretical Biological Physics, Rice University, Houston, Texas, United States of America
11) Department of Medicine H, Soroka Medical Center, BGU University of the Negev, Beer Sheva, Israel



Fibromyalgia Syndrome (FMS) is a persistent and debilitating disorder estimated to impair the quality of life of 2–4% of the population, with 9:1 female-to-male incidence ratio. FMS is an important representative example of central nervous system sensitization and is associated with abnormal brain activity. Key symptoms include chronic widespread pain, allodynia and diffuse tenderness, along with fatigue and sleep disturbance. The syndrome is still elusive and refractory. The goal of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on symptoms and brain activity in FMS.


A prospective, active control, crossover clinical trial. Patients were randomly assigned to treated and crossover groups: The treated group patients were evaluated at baseline and after HBOT. Patients in the crossover-control group were evaluated three times: baseline, after a control period of no treatment, and after HBOT. Evaluations consisted of physical examination, including tender point count and pain threshold, extensive evaluation of quality of life, and single photon emission computed tomography (SPECT) imaging for evaluation of brain activity. The HBOT protocol comprised 40 sessions, 5 days/week, 90 minutes, 100% oxygen at 2ATA. Sixty female patients were included, aged 21–67 years and diagnosed with FMS at least 2 years earlier. HBOT in both groups led to significant amelioration of all FMS symptoms, with significant improvement in life quality. Analysis of SPECT imaging revealed rectification of the abnormal brain activity: decrease of the hyperactivity mainly in the posterior region and elevation of the reduced activity mainly in frontal areas. No improvement in any of the parameters was observed following the control period.


The study provides evidence that HBOT can improve the symptoms and life quality of FMS patients. Moreover, it shows that HBOT can induce neuroplasticity and significantly rectify abnormal brain activity in pain related areas of FMS patients.


From Metabolomics, 30 May 2015

Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients

Christopher W. Armstrong (1), Neil R. McGregor (2), Donald P. Lewis(3), Henry L. Butt(4), Paul R. Gooley(1).
1) Department of Biochemistry and Molecular Biology, Bio 21 Molecular Science and Biotechnology Institute, University of Melbourne, 30 Flemington Road, Parkville, VIC 3010, Ausatralia
2)Faculty of medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC 3010, Australia
3) CFS Discovery, Donvale Medical Centre, Donvale, VIC 3111, Australia
4) Bioscreen (Aust) Pty Ltd, 5 Little Hyde Street, Yarraville, VIC 3013, Australia
Correspondent: Paul R Gooley, prg@unimelb,edu,au


Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating long-term multisystem disorder with a central and inexplicably persistent fatigue symptom that is unable to be relieved by rest.

Energy metabolism and oxidative stress have been recent focal points of ME/CFS research and in this study we were able to elucidate metabolic pathways that were indicative of their dysfunction.

Blood and urine samples were collected from 34 females with ME/CFS (34.9 ± 1.8 SE years old) and 25 non-ME/CFS female participants (33.0 ± 1.6 SE years old). All samples underwent metabolic profiling via 1D 1H Nuclear magnetic resonance spectroscopy and quantitated metabolites were assessed for significance.

Blood glucose was elevated while blood lactate, urine pyruvate, and urine alanine were reduced indicating an inhibition of glycolysis that may potentially reduce the provision of adequate acetyl-CoA for the citric acid cycle.

We propose that amino acids are being increasingly used to provide an adequate carbohydrate source for the citric acid cycle. We suggest that this is via glutamate forming 2-oxoglutarate through an enzyme that deaminates it and subsequently elevates blood aspartate.

Dysfunctional energy metabolism appears to have impacted creatinine and its elevation in
urine suggests that it may be used as an alternative for anaerobic ATP production within muscle. A decrease in blood hypoxanthine and an increase in urine allantoin further suggest the elevation of reactiveoxygen species in ME/CFS patients.

These findings bring new information to the research of energy metabolism, chronic immune
activation and oxidative stress issues within ME/CFS.

2 thoughts on “TGI Friday! | Our weekly round-up of recently published research abstracts | 12 June 2015”

  1. The last study in “Metabolomics” looks very promising. Would a replication study in the UK be affordable and reasonably straightforward? Would the MEA be able to organise a replication study in the UK?

  2. This is very interesting. I would be very interested in whether these were ‘at rest’ blood tests? The lowered lactate levels seem to fly in the face of much of what I have read. I think even Dr Shepherd said somewhere that he himself had a positive stress lactate test when ill. Is it possible that people who are relying heavily on anaerobic metabolism (glycolysis) for any exertion have an increased rate of hepatic lactate “mopping up” at rest?

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