Do MS & ME/CFS co-exist in the same patients?

Posted on 10/05/2014 by wames

Research abstract

INTRODUCTION:
Fatigue is a major cause of disability and handicap in Multiple Sclerosis (MS) patients. The management of this common problem is often difficult. Chronic Fatigue Syndrome (CFS/ME) is another common cause of fatigue which is prevalent in the same population of middle aged females commonly affected by MS.

AIM:
This report aims at examining the potential coexistence of MS and CFS/ME in the same patients.

METHOD:
This is a retrospective study examining a cohort of MS patients referred for rehabilitation. The subjects were screened for CFS/ME symptoms.

RESULTS:
Sixty-four MS patients (43 females) were screened for CFS/ME. Nine patients (14%) with a mean age 52 (SD 9.7) who were all females fulfilled the Fukuda criteria for diagnosis of CFS/ME. Their symptoms, including muscular and joint pain, malaise and recurrent headaches, were not explained by the pattern of their MS.

DISCUSSION:
MS and CFS/ME are two common conditions with increased prevalence in middle aged females. As the diagnosis of CFS/ME is clinical with no positive clinical signs or investigations; it can be made with difficulty in the presence of another clear explanation for the disabling fatigue. Our results suggest that the two conditions may co-exist. Considering CFS/ME as a potential co-morbidity may lead to more focused and appropriate management.

When two common disorders collide by TA Gaber, WW Oo, H Ringrose
NeuroRehabilitation. 2014 Sep 18. [Epub ahead of print]

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Reduced pro-inflammatory cytokines in the CSF of CFS/ME

Posted on 10/05/2014 by wames

Research abstract

Objectives: Previous research has provided evidence for a dysregulation in cytokine levels in the periphery of patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). To date few studies have examined cytokines in the cerebrospinal fluid. The purpose of this research is to examine the role of cytokines in the symptom presentation of CFS/ME patients.

Methods: Cerebrospinal fluid (CSF) was collected from 18 CFS/ME patients and 5 healthy controls. The CSF samples were examined for the expression of 27 cytokines [interleukin (IL)-1ββ, IL-1ra, IL-2, IL-4, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17, basic FGF, eotaxin, G-CSF, GM-CSF, IFN-γγ, IP-10, MCP-1 (MCAF), MIP-1αα, MIP-1ββ, PDGF-BB, RANTES, TNF-αα and VEGF] using the bio-plex human cytokine 27-plex assay.

Results: Of the cytokines examined, only four were significantly reduced in the CFS/ME patients in comparison to the controls.

Conclusions: The results show a decrease in pro-inflammatory cytokines in the CSF of CFS/ME patients and this may contribute to the clinical disease progression.

The role of cytokines in the cerebrospinal fluids of patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), by Sonya Marshall-Gradisnik, Gunnar Gottschalk, Sandra Ramos, Ekua Brenu, Don Staines, Dan Peterson

 

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2 Age peaks in the incidence of CFS/ME in Norway

Posted on 10/05/2014 by wames

Research abstract (provisional)

Background: The aim of the current study was to estimate sex- and age-specific incidence rates of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) using population-based registry data.
CFS/ME is a debilitating condition with large impact on patients and their families. The etiology is unknown, and the distribution of the disease in the general population has not been well described.

Methods: Cases of CFS/ME were identified in the Norwegian Patient Register (NPR) for the years 2008 to 2012. The NPR is nationwide and contains diagnoses assigned by specialist health care services (hospitals and outpatient clinics). We estimated sex- and age-specific incidence rates by dividing the number of new cases of CFS/ME in each category by the number of person years at risk. Incidence rate ratios were estimated by Poisson regression with sex, age categories, and year of diagnosis as covariates.

Results: A total of 5,809 patients were registered with CFS/ME during
2008 to 2012. The overall incidence rate was 25.8 per 100,000 person years (95% confidence interval (CI): 25.2 to 26.5). The female to male incidence rate ratio of CFS/ME was 3.2 (95% CI: 3.0 to 3.4). The incidence rate varied strongly with age for both sexes, with a first peak in the age group 10 to 19?years and a second peak in the age group 30 to 39?years.

Conclusions: Early etiological clues can sometimes be gained from examination of disease patterns. The strong female preponderance and the two age peaks suggest that sex- and age-specific factors may modulate the risk of CFS/ME.

Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: A population-based registry study from Norway
2008-2012, by Inger J Bakken, Kari Tveito, Nina Gunnes, Sara Ghaderi, Camilla Stoltenberg, Lill Trogstad, Siri E Håberg and Per Magnus
in BMC Medicine 2014, 12:167

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Staphylococcus vaccine as immunomodulating drug in ME?

Posted on 10/01/2014 by wames

In videos published Sept 29, 2014 Carl-Gerhard Gottfries (professor emeritus) talks about his experiences of treatment of patients with ME with a vaccine against Staphylococcus.

He thinks the effect of the Staphylococcus vaccine is immunomodulatory. The drug has been shown to work in a small clinical trial, and the clinical experience is that it is a working treatment for a significant proportion of patients.

Unfortunately the drug is no longer available on the market, so the clinical research is stopped, and patients can not benefit of it. Gottfries has saved vaccine for his own use. He takes the drug/vaccine once each month, and he believes this has enabled him to continue working.

The videos have the titles:
1 Background and Vaccine
2 Experience and The Clinic
3 The Clinic and Urgent Needs
4 Continued Research
5 Wishes For The Future

Carl-Gerhard Gottfries is head of a clinic for ME and fibromyalgia patients in Gothenburg (Göteborg) in Sweden. The clinic is also involved in research.

Gottfries Clinic

 

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MicroRNA hope for CFS/ME biomarker

Posted on 09/24/2014 by wames

Research abstract

Background:

MicroRNAs (miRNAs) are known to regulate many biological processes and their dysregulation has been associated with a variety of diseases including Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). The recent discovery of stable and reproducible miRNA in plasma has raised the possibility that circulating miRNAs may serve as novel diagnostic markers. The objective of this study was to determine the role of plasma miRNA in CFS/ME.

Results:

Using Illumina high-throughput sequencing we identified 19 miRNAs that were differentially expressed in the plasma of CFS/ME patients in comparison to non-fatigued controls. Following RT-qPCR analysis, we were able to confirm the significant up-regulation of three miRNAs (hsa-miR-127-3p, hsa-miR-142-5p and hsa-miR-143-3p) in the CFS/ME patients.

Conclusion:

Our study is the first to identify circulating miRNAs from CFS/ME patients and also to confirm three differentially expressed circulating miRNAs in CFS/ME patients, providing a basis for further study to find useful CFS/ME biomarkers.

High-Throughput Sequencing of Plasma MicroRNA in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, by Ekua W. Brenu et al in PLoS ONE 9(9): e102783 Sep 19, 2014

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SNPs in CFS/ME genes could lead to diagnostic test for CFS/ME subtypes

Posted on 09/24/2014 by wames

Research abstract

Aims

We have reported gene expression changes in patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and the fact that such gene expression data can be used to identify subtypes of CFS/ME with distinct clinical phenotypes. Due to the difficulties in using a comparative gene expression method as an aid to CFS/ME disease and subtype-specific diagnosis, we have attempted to develop such a method based on single-nucleotide polymorphism (SNP) analysis.

Methods

To identify SNP allele associations with CFS/ME and CFS/ME subtypes, we tested genomic DNA of patients with CFS/ME (n=108), patients with endogenous depression (n=17) and normal blood donors (n=68) for 504 human SNP alleles located within 88 CFS-associated human genes using the SNP Genotyping GoldenGate Assay (Illumina, San Diego, California, USA). 360 ancestry informative markers (AIM) were also examined.

Results

21 SNPs were significantly associated with CFS/ME compared with depression and normal groups. 148 SNP alleles had a significant association with one or more CFS/ME subtypes. For each subtype, associated SNPs tended to be grouped together within particular genes.

AIM SNPs indicated that 4 subjects were of Asian origin while the remainder were Caucasian. Hierarchical clustering of AIM data revealed the relatedness between 2 couples of patients with CFS only and confirmed the overall heterogeneity of all subjects.

Conclusions

This study provides evidence that human SNPs located within CFS/ME associated genes are associated with particular genomic subtypes of CFS/ME. Further work is required to develop this into a clinically useful subtype-specific diagnostic test.

Use of single-nucleotide polymorphisms (SNPs) to distinguish gene  expression subtypes of chronic fatigue syndrome/myalgic encephalomyelitis  (CFS/ME), by  Nana Shimosako, Jonathan R Kerr in J Clin Pathol Published 19 September 2014,

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Recovery rates from CFS following CBT

Posted on 09/23/2014 by wames

Research Abstract

Highlights

  • This study investigates recovery from CFS in a routine practice.
  • Approximately 18% of people with CFS recover after CBT.
  • The study of CBT in routine practice demonstrated recovery rates akin to RCTs.

Cognitive behavioural therapy (CBT) is one of the treatments of choice for patients with chronic fatigue syndrome (CFS). However, the factors
that predict recovery are unknown.

The objective of this study was to ascertain the recovery rate among CFS patients receiving CBT in routine practice and to explore possible predictors of recovery.

Recovery was defined as no longer meeting Oxford or CDC criteria for CFS measured at 6 months follow-up. A composite score representing full recovery additionally included the perception of improvement, and normal population levels of fatigue and of physical functioning.

Logistic regression was used to examine predictors of recovery. Predictors included age, gender, cognitive and behavioural responses to symptoms, work and social adjustment, beliefs about emotions, perfectionism, anxiety and depression at baseline.

At 6 months follow-up 37.5% of the patients no longer met either the Oxford or the CDC criteria for CFS while 18.3% were fully recovered. Multivariate analyses showed that worse scores on the work and social adjustment scale, unhelpful beliefs about emotions, high levels of depression and older age were associated with reduced odds for recovery.

Recovery rates in this routine practice were comparable to previous RCTs. There was a wide spectrum of significant predictors for recovery.

Prevalence and predictors of recovery from chronic fatigue syndrome in a routine clinical practice, by Elisabeth Floa, Trudie Chalder in Behaviour Research and Therapy Volume 63, December 2014, Pages 1–8

NB  This research relates to recovery from CFS as defined by CDC and Oxford, not ME as defined by Canadian criteria.

 

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Tryptophan depletion in CFS

Posted on 09/22/2014 by wames

Research abstract (provisional)

Background
Chronic fatigue syndrome (CFS) is still an enigmatic disorder. CFS can be regarded as a complex disorder with tremendous impact on lives of CFS-patients. Full recovery without treatment is rare.

A somatic explanation for the fatigue is lacking. There is clinical and experimental evidence implicating enhanced serotonergic neurotransmission in CFS. Genetic studies and imaging studies support the hypothesis of upregulated serotonin system in CFS.

In line with the hypothesis of an increased serotonergic state in CFS, we performed a randomised clinical trial investigated the effect of 5-HT3 receptor antagonism in CFS. No benefit was found of the 5-HT3 receptor antagonist ondansetron compared to placebo.

To further investigate the involvement of serotonin in CFS we performed a placebo controlled cross over pilot study investigating the effect of Acute Tryptophan Depletion.

Findings

Five female CFS-patients who met the US Center for Disease Control and Prevention criteria for CFS were recruited. There were two test days, one week apart. Each participant received placebo and ATD. To evaluate the efficacy of the ATD procedure tryptophan and the large neutral amino acids were measured. The outcome measures were fatigue severity, concentration and mood states.

ATD resulted in a significant plasma tryptophan to large neutral amino acid ratio reduction of 96%. There were no significant differences in fatigue-, depression and concentration between the placebo- and ATD condition.

Conclusions
These first five CFS-patients did not respond to the ATD procedure. However, a much larger sample size is needed to draw final conclusions on the hypothesis of an increased serotonergic state in the pathophysiology of CFS.

Tryptophan depletion in chronic fatigue syndrome, a pilot cross-over study, by KH Gerard et al in BMC Research Notes 2014, 7:650

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The Basal Ganglia, inflammation and fatigue in ME/CFS

Posted on 09/22/2014 by wames

Cort Johnson discusses the research of Dr Andrew Miller, a psychoneuroimmunologist who is interested in how immune activation affects symptoms and behaviour.  His research has mostly focused on the biological roots of depression and the effects an immune agent called interferon alpha (IFN-a) given to fight hepatitis A patients has on their symptoms and behaviour.

Miller and others have been exploring the role the basal ganglia, found in the limbic system in the brain, plays in the producing the fatigue and other symptoms found in ME/CFS and other disorders.

Read more: Unrewarding Reward: The Basal Ganglia, Inflammation and Fatigue In Chronic Fatigue Syndrome

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Man with ME calls for cannabis to be legalised

Posted on 09/19/2014 by wames

ITV news story: Calls for medicinal cannabis to be legalised to help people now turning to the streets for their pain relief

He’s been threatened, his home has been attacked, and he lives in fear of going to jail for possession of cannabis.

But he says he has no choice. The man says he’s forced to use cannabis illegally

He suffers from ME, or Chronic Fatigue Syndrome, and he spoke exclusively with ITV News Central to describe how being denied legal cannabis-based medication has meant he is forced to turn to the streets for his pain relief.

It comes as the government’s Crime Prevention Minister called for medicinal cannabis to be legalised – telling ITV News Central he believes it is wrong to deny people a product which could help.

See the video report from Charlotte Cross

Home Officer Minister Norman Baker told ITV News Central that he had spoken to people suffering from conditions including cancer, epilepsy, and multiple sclerosis who all said they used cannabis as they could not find any other medication which worked.

He said he had written to the Department of Health to ask them to consider the issue, and wanted a cross-party review into it. “It’s been quite clear to me for some time, as the government’s drugs minister, that there is a case for making available more easily cannabis-based products to help particular medicinal conditions.

I think it’s wrong that we’re actually preventing people having access to something which will help their health, and in the process potentially criminalising them for obtaining it.”

The ME patient, who struggles to walk much of the time, told ITV News Central he has repeatedly tried – and failed – to get his local NHS trust to pay for Sativex, which is the government’s first legal, licensed cannabis-based medication.

So now, he said, he regularly has to trawl the back streets of Birmingham and deal with violent crooks to get something which helps.
“I have to go crawling the back streets late at night, dealing with gangs to buy small bags of weed off them. And sometimes it’s not very nice, and I get very very scared and feel intimidated.

I do feel awful about the illegal side of it, and I worry about it all the time, because it’s not nice to be breaking the law. But what choice do you have when you’re so ill?

I don’t know what magic ingredient there is in cannabis, but it’s how I get through my day. And just trying to survive and manage my illness makes me a criminal. It’s absolutely absurd.”

While Sativex is usually prescribed for people with multiple sclerosis, health bosses have said it can be used for other conditions including ME – but only if local NHS trusts decide to fund it.

A spokesman for Birmingham CrossCity Clinical Commissioning Group said they could not comment specifically on individual cases, but added:
Sativex is not routinely commissioned for the treatment of ME, however clinicians can apply for funding of a treatment if they can demonstrate exceptional medical circumstances for a patient.

A Home Office spokeswoman said there were “no plans” to review how cannabis is classified. “This government has no plans to legalise cannabis or to soften our approach to its use as a medicine.

There is clear scientific and medical evidence that cannabis is a harmful drug which can damage people’s mental and physical health.

Our cross-government strategy on drugs remains clear. We must prevent drug use in our communities, support users through treatment and wider recovery and ensure law enforcement agencies tackle the organised criminals behind the drugs trade.”

And a spokeswoman for the MHRA – the body responsible for licensing new medicines – said they could not confirm or deny whether there were any other applications in place for cannabis-based medication due to “commercial sensitivity”.

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