A systematic review of mitochondrial abnormalities in ME/CFS/SEID

Posted on 08/16/2020 by wames

A systematic review of mitochondrial abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome/systemic exertion intolerance disease, by Sean Holden, Rebekah  Maksoud, Natalie Eaton-Fitch, Hélène Cabanas, Donald Staines & Sonya Marshall-Gradisnik in Journal of Translational Medicine vol 18, no: 290 (2020)[doi.org/10.1186/s12967-020-02452-3]

 

Review abstract: 

Background:
Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or Systemic Exertion Intolerance Disease (SEID) present with a constellation of symptoms including debilitating fatigue that is unrelieved by rest. The pathomechanisms underlying this illness are not fully understood and the search for a biomarker continues, mitochondrial aberrations have been suggested as a possible candidate. The aim of this systematic review is to collate and appraise current literature on mitochondrial changes in ME/CFS/SEID patients compared to healthy controls.

Methods:
Embase, PubMed, Scopus and Medline (EBSCO host) were systematically searched for articles assessing mitochondrial changes in ME/CFS/SEID patients compared to healthy controls published between January 1995 and February 2020. The list of articles was further refined using specific inclusion and exclusion criteria. Quality and bias were measured using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies.

Results:
Nineteen studies were included in this review. The included studies investigated mitochondrial structural and functional differences in ME/CFS/SEID patients compared with healthy controls. Outcomes addressed by the papers include changes in mitochondrial structure, deoxyribonucleic acid/ribonucleic acid, respiratory function, metabolites, and coenzymes.

Conclusion:
Based on the included articles in the review it is difficult to establish the role of mitochondria in the pathomechanisms of ME/CFS/SEID due to inconsistencies across the studies. Future well-designed studies using the same ME/CFS/SEID diagnostic criteria and analysis methods are required to determine possible mitochondrial involvement in the pathomechanisms of ME/CFS/SEID.

Posted in News | Tagged , , , , , , , | Comments Off on A systematic review of mitochondrial abnormalities in ME/CFS/SEID

Clinically accessible tools for documenting the impact of Orthostatic Intolerance on symptoms & function in ME/CFS

Posted on 08/14/2020 by wames

Clinically accessible tools for documenting the impact of Orthostatic Intolerance on symptoms and function in ME/CFS, by Jihyun Lee, Pelle Wall, Chris Kimler, Lucinda Bateman, Suzanne D Vernon in Work vol. 66, no. 2, pp. 257-263, 2020 [doi: 10.3233/WOR-203169]

 

Research abstract:

Background:

Clinical observations have indicated that hours of upright activity (HUA) reported by Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients correlated with orthostatic symptoms and impaired physical function. This study examined the relationship between HUA and orthostatic intolerance (OI).

Methods:

Twenty-five female ME/CFS subjects and 25 age and race matched female healthy controls (HCs) were enrolled. Subjects reported HUA (defined as hours per day spent with feet on the floor) and completed questionnaires to assess the impact of OI on daily activities and symptoms. ME/CFS patients were categorized into those with <5 HUA and ≥5 HUA and analyzed by employment status. Data analysis used one-way ANOVA.

Results:

ME/CFS patients had fewer HUA, worse symptoms and greater interference with daily activities due to OI than HCs. The <5 HUA ME/CFS subjects had more severe OI related symptoms than ≥5 HUA ME/CFS subjects even though OI interfered with daily activities similarly.

Only 33% of ME/CFS subjects were employed and all were ≥5 HUA ME/CFS subjects with an average HUA of 8.

Conclusions:

ME/CFS subjects experienced more frequent and severe OI symptoms, higher interference with daily activities, and reduced ability to work than HCs. Reported HUA and assessment of OI using standardized instruments may be useful clinical tools for physicians in the diagnosis, treatment and management of ME/CFS patients.

 

Excerpts:

Orthostatic intolerance (OI) is defined as the development of symptoms upon assuming and maintaining upright postures that are alleviated by recumbency . “Symptoms of orthostatic intolerance are those caused primarily by

  1. cerebral under-perfusion (such as lightheadedness, near-syncope or syncope, impaired concentration, headaches, and dimming or blurring of vision), or
  2. sympathetic nervous system activation (such as forceful beating of the heart, palpitations, tremulousness, and chest pain), and
  3. other common signs and symptoms of orthostatic intolerance such as fatigue, a feeling of weakness, intolerance to low-impact exercise, nausea, abdominal pain, facial pallor, nervousness, and shortness of breath.”

Symptoms of OI are exacerbated by prolonged periods of upright posture and various daily experiences such as exercise, warm environments or large meals. Circumstances in daily life that can easily exacerbate OI include standing in line, grocery shopping, hot weather, overheated rooms, hot showers or baths and even sitting to eat a meal.

Clinicians should document patients’ symptoms and function in order to determine the impact of illness on the performance of daily activities and occupational responsibilities.

…Our clinical experience with over 1,000 ME/CFS patients has indicated that their disease severity can be gauged by hours of upright activity which we define as time with feet on the floor over a 24-hour period. Severely ill ME/CFS patients reported 0 to 4 hours with their feet on the floor while moderately ill patients reported having their feet on the floor for 5 to 8 hours. This observation led us to explore which ME/CFS symptoms were associated with an upright activity.

In this study, subjects were asked to report hours of upright activity (HUA) by estimating the hours per day spent in the following 4 positions over the past week:

  1. hours upright (standing, walking, running),
  2. hours sitting with feet on the floor,
  3. hours reclining or sitting with feet elevated and,
  4. hours lying down (includes sleeping).

We also used a standardized orthostatic questionnaire to evaluate how being in upright positions affected daily activities and the severity of symptoms. We found that both assessment tools can be easily administered and are effective at documenting the impact of orthostatic intolerance on symptom severity and daily activities in ME/CFS patients.

Posted in News | Tagged , , , , , , , , , | Comments Off on Clinically accessible tools for documenting the impact of Orthostatic Intolerance on symptoms & function in ME/CFS

Environmental, neuro-immune & neuro-oxidative stress interactions in CFS

Posted on 08/13/2020 by wames

Environmental, neuro-immune, and neuro-oxidative stress interactions in Chronic Fatigue Syndrome, by Geir Bjørklund, Maryam Dadar, Lyudmila Pivina, Monica Daniela Doşa, Yuliya Semenova & Michael Maes in Molecular Neurobiology (2020) [doi.org/10.1007/s12035-020-01939-w]

 

Review abstract:

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS) is a complex, multisystem disease that is characterized by long-term fatigue, exhaustion, disabilities, pain, neurocognitive impairments, gastrointestinal symptoms, and post-exertional malaise, as well as lowered occupational, educational, and social functions.

The clinical and biomarker diagnosis of this disorder is hampered by the lack of validated diagnostic criteria and laboratory tests with adequate figures of merit, although there are now many disease biomarkers indicating the pathophysiology of CFS.

Here, we review multiple factors, such as immunological and environmental factors, which are associated with CFS and evaluate current concepts on the involvement of immune and environmental factors in the pathophysiology of CFS. The most frequently reported immune dysregulations in CFS are modifications in immunoglobulin contents, changes in B and T cell phenotypes and cytokine profiles, and decreased cytotoxicity of natural killer cells. Some of these immune aberrations display a moderate diagnostic performance to externally validate the clinical diagnosis of CFS, including the expression of activation markers and protein kinase R (PKR) activity. Associated with the immune aberrations are activated nitro-oxidative pathways, which may explain the key symptoms of CFS.

Fig. 1 The pathogenesis of
CFS due to
exposure to infections, metals,
& environmental factors

This review shows that viral and bacterial infections, as well as nutritional deficiencies, may further aggravate the immune-oxidative pathophysiology of CFS. Targeted treatments with antioxidants and lipid replacement treatments may have some clinical efficacy in CFS. We conclude that complex interactions between immune and nitro-oxidative pathways, infectious agents, environmental factors, and nutritional deficiencies play a role in the pathophysiology of CFS.

Read full paper

Posted in News | Tagged , , , , , , , , , , , , | Comments Off on Environmental, neuro-immune & neuro-oxidative stress interactions in CFS

Exercise alters brain activation in Gulf War Illness & ME/CFS

Posted on 08/12/2020 by wames

Exercise alters brain activation in Gulf War Illness and Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, by Stuart D Washington, Rakib U Rayhan, Richard Garner, Destie Provenzano, Kristina Zajur, Florencia Martinez Addiego, John W VanMeter, James N Baraniuk in Brain Communications, Vol 2, Issue 2, 2020, fcaa070 [doi.org/10.1093/braincomms/fcaa070] Published: 10 August 2020

 

Research abstract:

Gulf War Illness affects 25–30% of American veterans deployed to the 1990–91 Persian Gulf War and is characterized by cognitive post-exertional malaise following physical effort. Gulf War Illness remains controversial since cognitive post-exertional malaise is also present in the more common Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

An objective dissociation between neural substrates for cognitive post-exertional malaise in Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome would represent a biological basis for diagnostically distinguishing these two illnesses.

Here, we used functional magnetic resonance imaging to measure neural activity in healthy controls and patients with Gulf War Illness and Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome during an N-back working memory task both before and after exercise. Whole brain activation during working memory (2-Back > 0-Back) was equal between groups prior to exercise.

Exercise had no effect on neural activity in healthy controls yet caused deactivation within dorsal midbrain and cerebellar vermis in Gulf War Illness relative to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients. Further, exercise caused increased activation among Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients within the dorsal midbrain, left operculo-insular cortex (Rolandic operculum) and right middle insula.

These regions-of-interest underlie threat assessment, pain, interoception, negative emotion and vigilant attention. As they only emerge post-exercise, these regional differences likely represent neural substrates of cognitive post-exertional malaise useful for developing distinct diagnostic criteria for Gulf War Illness and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

 

The Science Times: Chronic Fatigue Syndrome and Gulf War Illness Distinguished by Brain Activity

The functional magnetic resonance imaging (fMRI) results showed that the brain activity of Gulf War veterans behaved differently from CFS patients after exercise and memory tasks. GWI patients had lower brain activity in the part of the brain that processes pain (periaqueductal gray) as well as in the cerebellum. The cerebellum controls motor skills, cognition, and emotions.

The opposite was found in patients CFS, with increased activity in the two brain areas which increased attention and vigilance. Despite no changes in brain activity, CFS still suffered several physical symptoms and episodes of brain fog. Previous evidence has shown how the molecular structure of the cerebrospinal fluid in patients of both conditions alter after moderate exercise.

Medical Express: Gulf War illness, chronic fatigue syndrome distinct illnesses, study suggests

The two illnesses share many symptoms, including cognitive and memory problems (often described as “brain fog”), pain, and fatigue following mild to moderate exercise. Some medical institutions, including the U.S. Department of Veterans Affairs (the VA), list CFS as a symptom of GWI (called chronic multisymptom illness associated with service in the Gulf War by the VA).

“Our results strongly suggest that GWI and CFS represent two distinct disorders of the brain and therefore CFS is not a symptom of GWI,” says Stuart Washington, Ph.D., a post-doctoral fellow and first author on the study. “Combining of two different disorders could lead to improper treatment of both.” Washington works in the laboratory of James Baraniuk, MD, professor of medicine at Georgetown.

 

Posted in News | Tagged , , , , , , , , , , , , , , , | Comments Off on Exercise alters brain activation in Gulf War Illness & ME/CFS

Orthostatic Intolerance explained – videos from Bateman Horne Center

Posted on 08/11/2020 by wames

What is orthostatic intolerance (OI)?

 

Two videos from the Bateman Horne Center in Utah, USA set out to explain orthostatic intolerance for health professionals and it’s role in ME/CFS.

There is sufficient evidence to suggest a high prevalence of orthostatic intolerance (OI) exists in those with ME/CFS. OI is measurable, and the ability to identify and manage OI can greatly improve patient outcomes and daily functioning.

Video 1: Defines OI, and discusses the physiology and testing for OI.

Video 2:  Describes findings of reduced cerebral blood flow. Treatments include hydration, compression clothing and medications. Possible causes of OI in ME/CFS are listed. [Duration 6 minutes each]

Posted in News | Tagged , , | Comments Off on Orthostatic Intolerance explained – videos from Bateman Horne Center

Mapping of pathological change in CFS using the ratio of T1- & T2-weighted MRI scans

Posted on 08/11/2020 by wames

Mapping of pathological change in chronic fatigue syndrome using the ratio of T1- and T2-weighted MRI scans, by Kiran Thapaliya, Sonya Marshall-Gradisnik, Don Staines, Leighton Barnden in NeuroImage: Clinical Vol 28, 2020, 102366 [doi.org/10.1016/j.nicl.2020.102366]

 

Research highlights

  • We showed increased T1w/T2w in ME/CFS in contrast to other neurodegenerative diseases.
  • Higher T1w/T2w occurred in basal ganglia and white matter tracts.
  • Increased T1w/T2w indicates increased myelin and/or iron levels.
  • T1w/T2w regressions vs clinical measures were abnormal in cingulate cortex and white matter foci.

Research abstract:

Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) subjects suffer from a variety of cognitive complaints indicating that the central nervous system plays a role in its pathophysiology.

Recently, the ratio T1w/T2w has been used to study changes in tissue myelin and/or iron levels in neurodegenerative diseases such as multiple sclerosis and schizophrenia.

In this study, we applied the T1w/T2w method to detect changes in tissue microstructure in ME/CFS patients relative to healthy controls. We mapped the T1w/T2w signal intensity values in the whole brain for forty-five ME/CFS patients who met Fukuda criteria and twenty-seven healthy controls and applied both region- and voxel-based quantification. We also performed interaction-with-group regressions with clinical measures to test for T1w/T2w relationships that are abnormal in ME/CFS at the population level.

Region-based analysis showed significantly elevated T1w/T2w values (increased myelin and/or iron) in ME/CFS in both white matter (WM) and subcortical grey matter. The voxel-based group comparison with sub-millimetre resolution voxels detected very significant clusters with increased T1w/T2w in ME/CFS, mostly in subcortical grey matter, but also in brainstem and projection WM tracts. No areas with decreased T1w/T2w were found in either analysis. ME/CFS T1w/T2w regressions with heart-rate variability, cognitive performance, respiration rate and physical well-being were abnormal in both gray and white matter foci.

Our study demonstrates that the T1w/T2w approach is very sensitive and shows increases in myelin and/or iron in WM and basal ganglia in ME/CFS.

Posted in News | Tagged , , , , , , , , , , | Comments Off on Mapping of pathological change in CFS using the ratio of T1- & T2-weighted MRI scans

Genetic risk factors of ME/CFS: a critical review

Posted on 08/10/2020 by wames

Genetic risk factors of ME/CFS: a critical review, by in Human Molecular Genetics, ddaa169, 3 Aug 2020 [doi.org/10.1093/hmg/ddaa169]

 

Review abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex multisystem illness that lacks effective therapy and a biomedical understanding of its causes.

Despite a prevalence of approximately 0.2–0.4% and its high public health burden, and evidence that it has a heritable component, ME/CFS has not yet benefited from the advances in technology and analytical tools that have improved our understanding of many other complex diseases.

Here we critically review existing evidence that genetic factors alter ME/CFS risk before concluding that most ME/CFS candidate gene associations are not replicated by the larger CFS cohort within UK Biobank. Multiple genome-wide association studies of this cohort also have not yielded consistently significant associations.

Ahead of upcoming larger genome-wide association studies we discuss how these could generate new lines of enquiry into the DNA variants, genes and cell-types that are causally involved in ME/CFS disease.

Posted in News | Tagged , , , , , , , | Comments Off on Genetic risk factors of ME/CFS: a critical review

It’s still ME – Kara Jane’s album launched for Severe ME Day

Posted on 08/08/2020 by wames

Kara Jane’s album launch – It’s still M.E.

 

At last I can say it – my album, It’s Still M.E., is out now! Please, please share the news with everyone you know. My story is told today on the BBC News site.

Where to buy my album

It’s Still M.E can be downloaded and streamed from major platforms.

My story

I’m seriously ill with a severe form of ME. I’ve been bed bound for many years and am dependent on oxygen and 24 hour nursing care. I’m frequently admitted to hospital with serious infections, and a few years ago doctors warned me that my life expectancy could be very limited.

From this place of suffering and despair, my album was born.

I began writing music to express my pain, and a family friend helped me to record the songs from my bed.  As I’m too ill to sing more than a line or two at a time, completing the vocals took a couple of years.

Recording from my bed

In May 2020, a BBC appeal resulted in over 100 musicians and producers coming forward to offer their help in completing the album.  An amazing team have dedicated the last few months to working on my music.  Thanks to them, my dream of releasing an album has now come true.

I’m aiming to raise £100,000 for research into severe ME. (More information here.)

How you can help

There are several ways that you can support me.

1 – Buy my album!  Every penny raised will go towards research into the severest cases of ME.    It will also help raise awareness of just how serious this illness can be.

2 – Donate to my fund.  If you wish to make a donation in addition to purchasing the album, please visit my Just Giving page.

3 – Spread the word about my album, on social media and in person.  (All my social media links are at the bottom of the page.) The more people we can reach, the greater the success of the project.

Album taster

 

Posted in News | Tagged | Comments Off on It’s still ME – Kara Jane’s album launched for Severe ME Day

Severe ME resources for health and social care professionals

Posted on 08/08/2020 by wames

New WAMES website page for severe ME resources

 

A new page has been added to the professionals section of the website:

Severe ME Care Resources

The page highlights the need for a compassionate approach to care for a group of patients who are extremely hypersensitive to their environment and vulnerable to harm.

The Videos, books and information come from experienced sources such as Stonebird, Dialogues from ME, Dr Nigel Speight, Emily Collingridge etc.

Posted in News | Comments Off on Severe ME resources for health and social care professionals

Severe ME Day – 8 August 2020

Posted on 08/08/2020 by wames

A day to remember everyone who is suffering or who has ever suffered from Severe and Very Severe Myalgic Encephalomyelitis.

 


Severe ME Understanding & Remembrance Day :

This day aims to bring public attention to the illness for the sake of all those presently suffering from Severe Myalgic Encephalomyelitis and to remember all those who have died from ME.

A day to honour the strength of spirit of all those who have endured and continue to endure decades of suffering and profound physical dysfunction and yet receive little, or no recognition or help, but rather continue to experience gross misrepresentation and misinterpretation of their illness and profound disability.

 

What’s the significance of 8th August?

This is the birth date of Sophia Mirza.  Sophia was bed-bound with severe Myalgic Encephalomyelitis and was a victim of medical abuse.  Her doctors did not believe that Myalgic Encephalomyelitis was a physical disease and so she was forcibly taken from her bed/home by social workers, police officers and doctors, and kept in a psychiatric facility where she received inappropriate treatment and care.  Sophia subsequently died of ME at the age of 32.  Her post-mortem revealed widespread inflammation in the spinal cord.  This same inexcusable abuse still goes on.

 

We remember all those died of ME/CFS in Wales, and those who gave up the fight:

  • Annabel Senior , 2003 – first known person in the UK to have CFS on the death certificate
  • Sarah Ann Tyler, 2017
  • Dr Martin Rhisiart, 2017

Please let us know if you’d like someone’s name to be added to the list.

Posted in News | Tagged | Comments Off on Severe ME Day – 8 August 2020