Hyperactive brain in CFS – neurometabolites in anterior cingulate cortex

Posted on 11/07/2017 by wames

Research abstract:

Neurometabolites in anterior cingulate cortex in chronic fatigue syndrome: a magnetic resonance spectroscopy study at 7 Tesla, by Chi Chen, [Master’s Thesis, Oxford University Sep 2017]

Background:
Chronic fatigue syndrome (CFS) is a disorder characterized by prolonged physical and mental fatigue that cannot be explained by another established medical diagnosis. The anterior cingulate cortex (ACC) and putamen are two regions involved in frontal-striatal neural circuitry, which may be related to the pathophysiology of CFS. The aim of this study was to investigate the concentrations of neurometabolites, including glutamate, gamma-aminobutyric acid (GABA) and glutathione, in  the ACC and putamen, using magnetic resonance spectroscopy (MRS) at 7 Tesla (7T). In addition, this study also aimed to evaluate resting-state functional connectivity in CFS with functional magnetic resonance imaging (fMRI).

Methods
This study involved 12 patients who met the Oxford criteria for CFS and 25 healthy controls. Participants rated themselves on the Chalder Fatigue Questionnaire (CFQ) and the Beck Depression Inventory (BDI). All participants had a single proton (1H) MRS and resting-state fMRI scan with a 7T Siemens MAGNETOM scanner (Siemens, Erlangen, Germany) with a Nova Medical 32 channel receive array head coil. Spectra were measured
from voxels in the ACC (20x20x20 mm), putamen (10x16x20 mm) and occipital cortex (20x20x20 mm). Spectra were analysed with LCModel to obtain absolute concentrations of the neurochemicals. Differences in functional connectivity between CFS and healthy participants were tested using multivariate exploratory linear optimized decomposition into independent components (MELODIC) and dual regression.

Results
Concentrations of putamen glutamate and glutamate+glutamine (Glx) were increased in CFS while that of ACC GABA was decreased. Putamen Glx and ACC glutamine were negatively associated with the severity of self-reported fatigue. There were main effects of CFS diagnosis on glutathione (GSH) and total creatine, indicating decreases of these
neurometabolites in all the regions studied in CFS patients. In addition, the CFS patients demonstrated elevated functional connectivity between the default mode network and right supracalcarine cortex, precuneus cortex and dorsolateral prefrontal cortex.

Conclusions
The increased putamen glutamate, decreased ACC GABA and elevated resting state functional connectivity of the default mode network suggest a hyperactive brain status in CFS. The global decrease of GSH and total creatine also suggest that CFS patients may have an abnormal bioenergetic status with higher oxidative stress.

Posted in News | Tagged , , , , , , , , | Comments Off on Hyperactive brain in CFS – neurometabolites in anterior cingulate cortex

Blood cells in CFS are drained of energy

Posted on 11/06/2017 by wames

New Scientist article, by Andy Coghlan, 3 Nov 2017: Blood cells in chronic fatigue syndrome are drained of energy

Blood cells in people with CFS seem as listless as it can make people feel

Thirteen years ago, Cara Tomas was rendered bedbound with chronic fatigue syndrome. It came on suddenly, she says, without warning signs. Even now she has good days and bad days due to the lingering effects of the disease. “A lot of people dismiss it as a psychological disease, which is a big frustration,” she says.

Tomas knows more about CFS than most. A PhD student at Newcastle University in the UK, she has just published a paper demonstrating that white blood cells in people with the disease are as listless as the people themselves often feel. “Now we’ve shown there’s a physiological difference, it could explain the whole-body fatigue shown by patients,” she says.

The finding adds to mounting evidence that the disorder has a biological explanation, and raises the prospects for new treatments and diagnostic tests.

For many years, arguments have raged over whether CFS — also known as myalgic encephalomyelitis, or ME — has a physiological or psychological basis. But the latest research comparing samples of peripheral blood mononuclear cells (PBMCs) from 52 people with the condition and 35 without has reinforced the case for a biological explanation.

Less mighty mitochondria
Across almost all measures of energy capacity, the cells from people with CFS were weaker compared with their healthy counterparts. If other cells are equally compromised, it could explain why people with the condition are often bed- or wheelchair-bound for months, and struggle with even modest physical exertion.

Read more

See also: Science alert blog post, by Mike McRae, 7 Nov 2017: People With Chronic Fatigue Syndrome Are Exhausted at a Cellular Level, Study Shows

Posted in News | Tagged , , , , , , | Comments Off on Blood cells in CFS are drained of energy

Norwegian Rituximab studies update

Posted on 11/03/2017 by wames

Helse Bergen blog post, 29 Sep 29017: RituxME

B-lymphocyte depletion using the anti-CD20 antibody rituximab (Mabthera®) in Myalgic Encephalopathy/Chronic Fatigue Syndrome (“RituxME”)

​RituxME is a multicentre study conducted in five study centres in Norway: the Oncology Department at Haukeland University Hospital, the ME/CFS Centre at Oslo University Hospital (Aker), the Dept of Medicine at Notodden Hospital, the Dept. of Pain and Complex Disorders at St. Olav’s Hospital in Trondheim, and the Division of Rehabilitation Services at the University Hospital of North Norway in Tromsø.

The purpose of the study is to confirm or disprove the results from two smaller phase II studies, which have indicated improvement in symptoms in a subgroup of ME patients after rituximab treatment.

The study is randomized, double-blind and placebo controlled. This means that out of 152 participants, half will receive treatments with rituximab and the other half will be treated with placebo (saline). The treatments are allocated at random, and neither patient nor doctor is informed of which intervention group the patient is allocated to.

All participants receive six intravenous treatments during one year, followed by one year of regular consultations and blood tests. The participants complete examinations and tests before and after treatment, and they submit regular reports on any changes in symptoms and physical function.

The clinical study also encompasses three substudies:

  • Endothelial function in ME/CFS – at Haukeland University Hospital and Notodden Hospital
  • Ergospirometry in ME/CFS – at Haukeland University Hospital, Notodden Hospital and Oslo Universitety Hospital.
  • Irritable Bowel Syndrome and functional dyspepsia in ME/CFS – at Haukeland University Hospital.

Status, RituxME
All patient treatment and follow-up has been completed according to schedule in September 2017. The placebo and rituximab groups will be revealed to the scientists in October, and all participants will receive a letter informing them of which treatment group they were allocated to. We will then start working on the analysis of results, and expect to publish the results of the study in a medical journal during the first half of 2018.

Note: Senior Consultant Øystein Fluge and Professor Olav Mella supervise the ME/CFS research group at the Dept. of Oncology and Medical Physics at Haukeland University Hospital.

Read more about ME/CFS Research at Haukeland Hospital

Posted in News | Tagged , , , , , | Comments Off on Norwegian Rituximab studies update

Unrest film now available for download!

Posted on 11/02/2017 by wames

Jennifer Brea’s film Unrest is now available for download.

It will also be available on DVD in December.

Proceeds from the sale of Unrest will be reinvested into the Time For Unrest campaign, helping to bring the film to medical schools, policymakers, and research centres around the world.

Help bring Unrest to more people and raise awareness of ME:

  • buy via iTunes and get Unrest to the top of the iTunes chart! This is one of the best ways to make sure the film gets on the radar of millions of new viewers
  • talk to WAMES about helping to organise a screening in your area #TimeForUnrestWales campaign
  • share the order link and trailer on social media with the hashtag, #TimeforUnrest to join the conversation.

Jennifer Brea talks about her film Unrest in the UK media

“Moving. Astonishing.” – Mark Kermode for BBC Radio 5

“Unrest is … clever, fascinating, heartwrenching, and very frustrating. This portrait of a couple coping through extreme adversity … will chew you up and spit you backout again.” – The Upcoming

“Bracingly inventive and moving.” – The Observer

“Important for so many reasons.” – Cosmopolitan UK

Posted in News | Tagged , , | Comments Off on Unrest film now available for download!

Treating autism and ME/CFS: could one drug help both?

Posted on 11/01/2017 by wames

Open Medicine Foundation blog post, by Cort Johnson, 19 October 2017: Treating autism and ME/CFS: could one drug help both?

Autism is one of the most difficult conditions to treat. A neurodevelopmental disorder that typically strikes before the age of two, about a dozen different areas of the brain are affected.

Autism is characterized by social withdrawal, problems with both verbal and non-verbal communications and repetitive behaviors.  Autistic infants tend to smile less and have less eye contact with others than normal, have trouble in social situations, and are less verbal. The prognosis for autistic children is bleak with one study finding that only 4% ever achieve full independence.

Autism Spectrum Disorder (ASD) and ME/CFS
ASD is not chronic fatigue syndrome (ME/CFS) but some similarities exist. Both diseases affect cognition and sensory processing, cause problems with stimuli, cause significant social withdrawal, and are associated with increased levels of oxidative stress, reduced glutathione levels, and a Th2 immune response shift.

According to Dr. Naviaux, “ASD and ME/CFS are on the same biological spectrum.”  Dr. Naviaux has encountered teenagers with ASD who develop ME/CFS, and adults with ME/CFS who develop autism-like symptoms of mutism, social withdrawal, sensory hypersensitivities, and OCD-like symptoms.

Both, he believes, are caused by a failure of the cell danger response (CDR) to shut down normally after a chemical or biological injury has been healed or cleared. Both disorders lead to abnormalities in metabolism that he has characterized using a laboratory tool called mass spectrometry and metabolomics.  (The similarities in metabolism are illustrated in Figure 1.)

Some of the abnormalities shared by both disorders include disturbances in purines, sphingolipids (including sphingomyelins and ceramides), phospholipids, and the microbiome.  Depending on whether a person is still actively fighting a perceived threat like a virus, bacterium, or toxin, or whether they are trying to heal after the exposure, these pathways can be increased or decreased compared to normal.  The take-home message is that these are precisely the same pathways the cell uses normally for fight infection and recovery from injuries.

Read more

Posted in News | Tagged , , , | Comments Off on Treating autism and ME/CFS: could one drug help both?

Cellular bioenergetics is impaired in patients with CFS

Posted on 10/31/2017 by wames

Research abstract:

Cellular bioenergetics is impaired in patients with chronic fatigue syndrome, by Cara Tomas, Audrey Brown, Victoria Strassheim, Joanna Elson, Julia Newton, Philip Manning in PLOSone [Published: October 24, 2017]

Chronic fatigue syndrome (CFS) is a highly debilitating disease of unknown aetiology. Abnormalities in bioenergetic function have been cited as one possible cause for CFS. Preliminary studies were performed to investigate cellular bioenergetic abnormalities in CFS patients. A series of assays were conducted using peripheral blood mononuclear cells (PBMCs) from CFS patients and healthy controls.

These experiments investigated cellular patterns in oxidative phosphorylation (OXPHOS) and glycolysis. Results showed consistently lower measures of OXPHOS parameters in PBMCs taken from CFS patients compared with healthy controls.

Seven key parameters of OXPHOS were calculated: basal respiration, ATP production, proton leak, maximal respiration, reserve capacity, non-mitochondrial respiration, and coupling efficiency.

While many of the parameters differed between the CFS and control cohorts, maximal respiration was determined to be the key parameter in mitochondrial function to differ between CFS and control PBMCs due to the consistency of its impairment in CFS patients found throughout the study (p≤0.003).

The lower maximal respiration in CFS PBMCs suggests that when the cells experience physiological stress they are less able to elevate their respiration rate to compensate for the increase in stress and are unable to fulfil cellular energy demands. The metabolic differences discovered highlight the inability of CFS patient PBMCs to fulfil cellular energetic demands both under basal conditions and when mitochondria are stressed during periods of high metabolic demand.

Health rising: Cellular Energy Production Takes Big Hit in Chronic Fatigue Syndrome (ME/CFS) Study

New Scientist: Blood cells in chronic fatigue syndrome are drained of energy

Science alert blog post, by Mike McRae, 7 Nov 2017: People With Chronic Fatigue Syndrome Are Exhausted at a Cellular Level, Study Shows

ME Association: We hear from Cara Tomas about her about her recent study on cellular bioenergetics deficiencies in ME/CFS

Posted in News | Tagged , , , , , , , , , , , | Comments Off on Cellular bioenergetics is impaired in patients with CFS

Grey and white brain matter differences in CFS

Posted on 10/30/2017 by wames

Research abstract:

Grey and white matter differences in Chronic Fatigue Syndrome – a voxel-based morphometry study, by Andreas Finkelmeyer, Jiabao He, Laura Maclachlan, Stuart Watson, Peter Gallagher, Julia L. Newton, Andrew M. Blamire in NeuroImage: Clinical, Volume 17, 2018, Pages 24-30 [Preprint Available online 28 September 2017]

Objective:
Investigate global and regional grey and white matter volumes in patients with Chronic Fatigue Syndrome (CFS) using magnetic resonance imaging (MRI) and recent voxel-based morphometry (VBM) methods.

Methods:
Forty-two patients with CFS and thirty healthy volunteers were scanned on a 3-Tesla MRI scanner. Anatomical MRI scans were segmented, normalized and submitted to a VBM analysis using randomisation methods. Group differences were identified in overall segment volumes and voxel-wise in spatially normalized grey matter (GM) and white matter (WM) segments.

Results:
Accounting for total intracranial volume, patients had larger GM volume and lower WM volume. The voxel-wise analysis showed increased GM volume in several structures including the amygdala and insula in the patient group. Reductions in WM volume in the patient group were seen primarily in the midbrain, pons and right temporal lobe.

Conclusion:
Elevated GM volume in CFS is seen in areas related to processing of interoceptive signals and stress. Reduced WM volume in the patient group partially supports earlier findings of WM abnormalities in regions of the midbrain and brainstem.

ME Association comment: MEA Review: Grey and white matter differences in chronic fatigue syndrome

Posted in News | Tagged , , , , , , , , , , , , | Comments Off on Grey and white brain matter differences in CFS

Sleep quality in adolescents with CFS/ME

Posted on 10/26/2017 by wames

Research abstract:

Sleep quality in adolescents with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), by EK Josev, ML Jackson, B Bei, J Trinder, A Harvey, C Clarke, K Snodgrass, A Scheinberg, SJ Knight in J Clin Sleep Med. 2017 Sep 15; 13(9):1057-1066

 

Study objectives:

Little is known about the type and severity of sleep disturbances in the pediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) population, compared with healthy adolescents. Using a range of objective and subjective measures, the aim of this study was to investigate sleep quality, the relationship between objective and subjective measures of sleep quality, and their associations with anxiety in adolescents with CFS/ME compared with healthy controls.

Methods:

Twenty-one adolescents with CFS/ME aged 13 to 18 years (mean age 15.57 ± 1.40), and 145 healthy adolescents aged 13 to 18 years (mean age 16.2 ± 1.00) wore actigraphy watches continuously for 2 weeks to collect a number of objective sleep variables. The Pittsburgh Sleep Quality Index was used to obtain a subjective measure of sleep quality. Anxiety was measured by the Spence Children’s Anxiety scale.

Results:

On average over the 2-week period, adolescents with CFS/ME were found to have (1) significantly longer objective sleep onset latency, time in bed, total sleep time, and a later rise time (all P < .005), and (2) significantly poorer subjective sleep quality (P < .001), compared with healthy adolescents. The CFS/ME patient group displayed higher levels of anxiety (P < .05), and in both groups, higher levels of anxiety were significantly related to poorer subjective sleep quality (P < .001).

Conclusions:

This study provides objective and subjective evidence of sleep disturbance in adolescents with CFS/ME compared with healthy adolescent controls.

 

Posted in News | Tagged , , , , , | Comments Off on Sleep quality in adolescents with CFS/ME

Can physical assessment techniques aid diagnosis in people with CFS/ME?

Posted on 10/25/2017 by wames

Research abstract:

Can physical assessment techniques aid diagnosis in people with chronic fatigue syndrome/myalgic encephalomyelitis?  A diagnostic accuracy study, by Lucy Hives, Alice Bradley, James Richards, Chris J Sutton, James Selfe, Bashkar Basu, Kerry Maguire, Gail Sumner, Tarek Gaber, Annice Mukherjee, and Raymond Perrin, Raymond in BMJ Open, October 2017 [Preprint].

Objective:
To assess 5 physical signs to see whether they can assist in the screening of patients with CFS/ME, and potentially lead to quicker treatment.

Methods:
This was a diagnostic accuracy study with inter-rater agreement assessment. Participants recruited from 2 NHS hospitals, local CFS/ME support groups and the community were examined by three practitioners on the same day in a randomized order. Two Allied Health Professionals (AHPs) performed independent examinations of physical signs including;
postural/mechanical disturbances of the thoracic spine, breast varicosities, tender Perrin’s point, tender coeliac plexus and dampened cranial flow. A physician conducted a standard clinical neurological and rheumatological assessment, whilst looking for patterns of illness
behaviour. Each examination lasted approximately 20 minutes.

Results:
Ninety-four participants were assessed, 52 CFS/ME patients and 42 non-CFS/ME controls, aged 18-60. Cohen’s kappa revealed agreement between the AHPs was substantial for presence of the tender coeliac plexus (kappa=0.65, p<0.001) and moderate for postural/mechanical disturbance of the thoracic spine (kappa=0.57, p<0.001) and Perrin’s point (kappa=0.56, p<0.001).

A McNemar’s test found no statistically significant bias in the diagnosis by the experienced AHP relative to actual diagnosis, (p=1.0) and a marginally non-significant bias by the newly trained AHP, p=0.052. There was however, a significant bias in the diagnosis made by the physician relative to actual diagnosis, (p<0.001), indicating poor diagnostic utility of the clinical neurological and rheumatological assessment.

Conclusions:
Using the physical signs appears to improve the accuracy of identifying people with CFS/ME and shows agreement with current diagnostic techniques, however the present study concludes that only 2 of these may be needed. Examining for physical signs is both quick and simple for the AHP and may be used as an efficient screening tool for CFS/ME. This is a small single centre study and therefore further validation in other centres and larger populations is needed.

Posted in News | Tagged , , | Comments Off on Can physical assessment techniques aid diagnosis in people with CFS/ME?

North Wales Draft Plan for health & social care services – do you agree?

Posted on 10/24/2017 by wames

Draft North Wales Local Area Plan

Following the publication of the regional population needs assessment on 1st April 2017, it is a requirement to publish a (North Wales) Local Area Plan by 1 April 2018.

The first draft of the regional plan is now out for consultation here

The plan explains how authorities will work together across North Wales to deliver health and social care services.

There are some gaps in the plan where more information is needed about what is happening at the moment and suggestions for what needs to happen.

Your help is invited –  Please could you complete the online survey or send any additional information to sarah.bartlett@denbighshire.gov.uk by 31 October 2017.

Posted in News | Tagged , , | Comments Off on North Wales Draft Plan for health & social care services – do you agree?