Valganciclovir is potential treatment for CFS subset

Posted on 09/02/2013 by wames

Research abstract 

There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV-6) and Epstein–Barr virus (EBV) have been proposed as infectious triggers.

Method:

Thirty CFS patients with elevated IgG antibody titers against HHV-6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double-blind, placebo-controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI-20) and Fatigue Severity Scale (FSS) scores, self-reported cognitive function, and physician-determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels.

Results:

VGCV patients experienced a greater improvement by MFI-20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders (P = 0.029). In the VGCV arm, monocyte counts decreased (P < 0.001), neutrophil counts increased (P = 0.037) and cytokines were more likely to evolve towards a Th1-profile (P < 0.001). Viral IgG antibody titers did not differ between arms.

Conclusion:

VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted.

Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome by JG Montoya et al in J. Med. Virol. 9999:1–9, 2013.

 

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A dozen different diseases? Prof Stephen Holgate calls for radical change in ME/CFS research

Posted on 09/02/2013 by wames

ME/CFS probably isn’t one disease, or even a few different ones – but could be as many as fifteen. So said Professor Stephen Holgate, Chair of the UK Research Collaborative (CMRC), when he addressed the Forward ME Group in the House of Lords on 2nd July. He also argued that a radical New Science was needed to tackle ME/CFS and said patients must be partners in research.

…To have any hope of identifying many different diseases (or causative pathways) within the umbrella definition, a lot of patients are needed; and there are early plans for a study involving a 5,000-strong cohort of patients. The idea is to explore everything: phenotypes, genotypes, gene expression, cells, cytokines, metabolites and more. Some of these individual features have been researched before, but not all together: and never on such a scale. High quality scientists would then have to be involved to look at applying the new technologies to the data generated from patients. But there has to be a multi-disciplinary approach, and nurses, for example, would be just as important as mathematicians in this operation.

New computer technology would be used to probe the mass of data, with the aim of finding distinct groups of patients who ‘cluster’ together with similar features, which should make it easier to home in on different causal molecular pathways in different types of patients. It is identifying causal pathways that will lead to a much deeper understanding of ME/CFS and, hopefully, provide targets for drug therapy too.

Stephen Holgate’s vision for ME/CFS research requires a radical change. The majority of research funded in the UK to date assumes that whatever triggers ME/CFS, it is perpetuated by patients’ flawed beliefs and behaviours. The new approach focuses instead on differences between patients, to see what this might reveal about different underlying causal mechanisms.

[Excerpts from Simon McGrath’s article in Phoenix rising]

Minutes of the Forward ME group July 2013

Report of Prof Holgate’s talk in Phoenix Rising 

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Paralysis in ME

Posted on 08/30/2013 by wames

Study abstract

Paralysis is a symptom that is rarely highlighted in the literature for ME, yet is found amongst the most severely ill ME population and even some of those not so severely affected. My wife has experienced it for almost two decades, without adequate exploration, alongside exposure to denial and dismissal, ignorance and neglect as well as harmful treatment.

We wanted to find out if there was anyone else with a similar experience to my wife’s or if she was a rare and very severe case. We wanted to highlight the seriousness of this symptom and ask why it is being ignored and down played not only by the medical profession, with its inappropriate focus on fatigue and the psychosocial response, but also by the main charities, none of whom, flag it up as a main symptom.

This qualitative research study indicates that there are significant others experiencing apparently similar paralysis and that my wife is not unique. It begs the question why are they being neglected and why is there not urgent research into the understanding and alleviation of this devastating physical symptom? What is the mechanism, are there different mechanisms at play and are there any possible ways to treat it?

Greg Crowhurst

Paralysis, a qualitative study of people with Severe Myalgic Encephalomyelitis

Stonebird website: The Lived experience of Severe ME

 

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Self-management can improve fatigue

Posted on 08/30/2013 by wames

Research abstract

Objective:

To assess the efficacy of brief fatigue self-management (FSM) for medically unexplained chronic fatigue (UCF) and chronic fatigue syndrome (CFS) in primary care.

Methods:

A randomized controlled design was used wherein 111 patients with UCF or CFS were randomly assigned to two sessions of FSM, two sessions of symptom monitoring support (attention control; AC), or a usual care control condition (UC). Participants were assessed at baseline and at 3 and 12 months after treatment. The primary outcome, the Fatigue Severity Scale, measured fatigue impact on functioning. Analysis was by intention to treat (multiple imputation) and also by per protocol.

Results:

A group × time interaction across the 15-month trial showed significantly greater reductions in fatigue impact in the FSM group in comparison with the AC group (p < .023) and the UC group (p < .013). Medium effect sizes for reduced fatigue impact in the FSM group were found in comparison with the AC group (d = 0.46) and the UC group (d = 0.40). The per-protocol analysis revealed large effect sizes for the same comparisons. Clinically significant decreases in fatigue impact were found for 53% of participants in the FSM condition, 14% in the AC condition, and 17% in the UC condition. Dropout rates at the 12-month follow-up were high (42%–53%), perhaps attributable to the burden of monthly telephone calls to assess health care use.

Conclusion:

A brief self-management intervention for patients with UCF or CFS seemed to be clinically effective for reducing the impact of fatigue on functioning.

Chronic Fatigue Self-Management in Primary Care: A Randomized Trial in Psychosomatic Medicine August 6, 2013, by Fred Friedberg, PhD et al

 

 

 

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Eye movement dysfunction in ME/CFS

Posted on 08/30/2013 by wames

Research abstract

Background:

People who suffer from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often report that their eye movements are sluggish and that they have difficulties tracking moving objects. However, descriptions of these visual problems are based solely on patients’ self-reports of their subjective visual experiences, and there is a distinct lack of empirical evidence to objectively verify their claims. This paper presents the first experimental research to objectively examine eye movements in those suffering from ME/CFS.

Methods:

Patients were assessed for ME/CFS symptoms and were compared to age, gender, and education matched controls for their ability to generate saccades and smooth pursuit eye movements.

Results:

Patients and controls exhibited similar error rates and saccade latencies (response times) on prosaccade and antisaccade tasks. Patients showed relatively intact ability to accurately fixate the target (prosaccades), but were impaired when required to focus accurately in a specific position opposite the target (antisaccades). Patients were most markedly impaired when required to direct their gaze as closely as possible to a smoothly moving target (smooth pursuit).

Conclusions:

It is hypothesised that the effects of ME/CFS can be overcome briefly for completion of saccades, but that continuous pursuit activity (accurately tracking a moving object), even for a short time period, highlights dysfunctional eye movement behaviour in ME/CFS patients. Future smooth pursuit research may elucidate and improve diagnosis of ME/CFS.

Characterising eye movement dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome, in Graefe’s Archive for Clinical and Experimental Ophthalmology August 2013, by Stephen P. Badham, Claire V. Hutchinson

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Human herpesvirus-6 infection can be inherited

Posted on 08/18/2013 by wames

HHV-6 has been found in people with ME.

Abstract

Human herpesvirus-6 (HHV-6)A and 6B are ubiquitous betaherpesviruses viruses with lymphotropic and neurotropic potential. As reported earlier, these viruses establish latency by integration into the telomeres of host chromosomes. Chromosomally integrated HHV-6

(CIHHV-6) can be transmitted vertically from parent to child. Some CIHHV-6 patients are suffering from neurological symptoms, while others remain asymptomatic. Four patients with CIHHV-6 and CNS dysfunction were treated with valganciclovir or foscarnet. HHV-6 replication was detected by reverse transcriptase polymerase chain reaction amplification of a late envelope glycoprotein.

In this study we also compared the inherited and persistent HHV-6 viruses by DNA sequencing. The prevalence of CIHHV-6 in this cohort of adult patients from the USA suffering from a wide range of neurological symptoms including long-term fatigue were found significantly greater than the reported 0.8% in the general population.

Long-term antiviral therapy inhibited HHV-6 replication as documented by loss of viral mRNA production. Sequence comparison of the mRNA and the inherited viral genome revealed that the transcript is produced by an exogenous virus.

In conclusion, the data presented here document that some individuals with CIHHV-6 are infected persistently with exogenous HHV-6 strains that lead to a wide range of neurological symptoms; the proposed name for this condition is inherited herpesvirus 6 syndrome or IHS.

Persistent human herpesvirus-6 infection in patients with an inherited form of the virus, by N Shara et al in J. Med. Virol. first published online: 25 Jul 2013

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Delayed recovery in CFS can affect exercise testing results

Posted on 07/03/2013 by wames

Research abstract

Objectives  –  Reduced functional capacity and post-exertional fatigue following physical activity are hallmark symptoms of chronic fatigue syndrome (CFS) and may even qualify for biomarker status. That these symptoms are often delayed may explain the equivocal results for clinical cardiopulmonary exercise testing among individuals with CFS.

Test reproducibility in healthy subjects is well documented. This may not be the case with CFS due to delayed recovery symptoms. The objectives for this study was to determine the discriminative validity of objective measurements obtained during CPET to distinguish individuals with CFS from non-disabled sedentary individuals.

Methods –  Gas exchange data, workloads and related physiological parameters were compared between 51 individuals with CFS and 10 control subjects, all females, for two maximal exercise tests separated by 24 hours.

Results –  Multivariate analysis showed no significant differences between controls and CFS for Test 1. However, for Test 2 the individuals with CFS achieved significantly lower values for oxygen consumption and workload at peak exercise and at the ventilatory/anaerobic threshold. Follow-up classification analysis differentiated between groups with an overall accuracy of 95.1%.

Conclusions  –  The lack of any significant differences between groups for the first exercise test would appear to support a deconditioning hypothesis for CFS symptoms. However, results from the second test indicate the presence of a CFS related post-exertional fatigue. It might be concluded that a single exercise test is insufficient to reliably demonstrate functional impairment in individuals with CFS. A second test may be necessary to document the atypical recovery response and protracted fatigue possibly unique to CFS, which can severely limit productivity in the home and workplace.

Discriminative validity of metabolic and workload measurements to identify individuals with Chronic Fatigue Syndrome  in Physical Therapy July 2013, Volume 93, Issue 7 (published online ahead of print) Christopher R. Snell, Staci R. Stevens, Todd E. Davenport, J. Mark Van Ness  P

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Treatment of sleep disorder may not improve fatigue in CFS

Posted on 06/30/2013 by wames

Abstract

Chronic fatigue syndrome (CFS) is a disabling condition characterized by severe fatigue lasting for more than six months and the presence of at least four out of eight minor criteria. Sleep disturbance presenting as unrefreshing or nonrestorative sleep is one of these criteria and is very common in CFS patients.

Biologically disturbed sleep is a known cause of fatigue and could play a role in the pathogenesis of CFS. However, the nature of presumed sleep impairment in CFS remains unclear. Whilst complaints of NRS [non restorative sleep] persist over time, there is no demonstrable neurophysiological correlate to substantiate a basic deficit in sleep function in CFS.

Polysomnographic findings have not shown to be significantly different between subjects with CFS and normal controls. Discrepancies between subjectively poor and objectively normal sleep suggest a role for psychosocial factors negatively affecting perception of sleep quality.

Primary sleep disorders are often detected in patients who otherwise qualify for a CFS diagnosis. These disorders could contribute to the presence of daytime dysfunctioning.

There is currently insufficient evidence to indicate that treatment of primary sleep disorders sufficiently improves the fatigue associated with CFS. Therefore, primary sleep disorders may be a comorbid rather than an exclusionary condition with respect to CFS

Sleep in the chronic fatigue syndrome, by An N. Mariman, Dirk P. Vogelaers, Els Tobback, Liesbeth M. Delesie, Ignace P. Hanoulle, Dirk A. Pevernagie in Sleep Medicine Reviews, June 2013

 

 

 

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Flu vaccination alters gene expression in CFS

Posted on 06/21/2013 by wames

Research abstract

Vaccines have been shown to cause differential expression of genes and increase antibody titers against antigens.

Influenza vaccines may have an effect on unexplained disorders such as Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Immunological changes have been identified following immunization with trivalent influenza vaccine (TIV).

The objective of this pilot study was to examine the consequences of TIV on cytokine and cytotoxic genes in CFS/ME.

Peripheral blood mononuclear cells were preferentially isolated from whole blood of 7 CFS/ME patients and 8 controls. Following total RNA extraction and synthesis of cDNA, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of mRNAs for cytotoxic genes (perforin (PRF1), granzyme A (GZMA), granzyme B (GZMB) and cytokine genes.

GZMB was significantly increased overall in the CFS/ME patients compared to the controls. GZMA was significantly increased 28 days after vaccination while PRF1 was reduced prevaccination but increased 14 days post-vaccination in the CFS/ME patients. There were no significant changes in cytokine genes pre or post vaccination.

Administration of TIV may increase the expression of lytic genes in CFS/ME and this may contribute to the increase in cytotoxic activity we observed in these patients post vaccination.

Enhanced Gene Expression Following Vaccination in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis by Ekua W. Brenu et al International Journal of Clinical Medicine, March 2013

 

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Mitochondrial dysfunction differs in CFS and FM

Posted on 06/19/2013 by wames

Research abstract

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are complex and serious illnesses that affect approximately 2.5% and 5% of the general population worldwide, respectively. The etiology is unknown; however, recent studies suggest that mitochondrial dysfunction has been involved in the pathophysiology of both conditions.

We have investigated the possible association between mitochondrial biogenesis and oxidative stress in patients with CFS and FM. We studied 23 CFS patients, 20 FM patients, and 15 healthy controls.

Peripheral blood mononuclear cell showed decreased levels of Coenzyme Q10 from CFS patients (p<0.001 compared with controls) and from FM subjects (p<0.001 compared with controls) and ATP levels for CFS patients (p<0.001 compared with controls) and for FM subjects (p<0.001 compared with controls).

On the contrary, CFS/FM patients had significantly increased levels of lipid peroxidation, respectively (p<0.001 for both CFS and FM patients with regard to controls) that were indicative of oxidative stress-induced damage.

Mitochondrial citrate synthase activity was significantly lower in FM patients (p<0.001) and, however, in CFS, it resulted in similar levels than controls. Mitochondrial DNA content (mtDNA/gDNA ratio) was normal in CFS and reduced in FM patients versus healthy controls, respectively (p<0.001). Expression levels of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha and transcription factor A, mitochondrial by immunoblotting were significantly lower in FM patients (p<0.001) and were normal in CFS subjects compared with healthy controls.

These data lead to the hypothesis that mitochondrial dysfunction-dependent events could be a marker of differentiation between CFS and FM, indicating the mitochondria as a new potential therapeutic target for these conditions.

Could Mitochondrial Dysfunction Be a Differentiating Marker Between Chronic Fatigue Syndrome and Fibromyalgia? J Castro-Marrero et al  Antioxidants and Redox Signalling, 29 May 2013. [Epub ahead of print]

 

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