Tag: 2018

Cardiac sympathetic innervation associates with autonomic dysfunction in chronic fatigue syndrome – a pilot study

Despite hemodynamic abnormalities being well documented in chronic fatigue syndrome (CFS), it remains unclear the nature of the underlying autonomic nervous system problems that underpin these findings. Studies performed in subgroups of those with CFS suggest cardiac sympathetic denervation.

Meta-iodo-benzylguanidine (MIBG) imaging provides a quantitative measure of cardiac sympathetic innervation. Clinically, cardiac MIBG scanning is used to estimate local myocardial sympathetic nerve damage in heart disease and dysautonomia, particularly abnormalities arising due to sympathetic innervation [1,2]. In this study, we explored potential mechanisms that underpin the autonomic abnormalities seen in CFS using I125 MIBG participants that fulfilled Fukuda diagnostic criteria for CFS [3]. Participants were excluded if screened positive for a major depressive episode (Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders). Fatigue was measured using the Fatigue Impact Scale (FIS).

Read the rest of this article HERE.

Source: Petrides G, Zalewski P, McCulloch D, Maclachlan L, Finkelmeyer A, Hodgson T, Blamire A, Newton JL. Cardiac sympathetic innervation associates with autonomic dysfunction in chronic fatigue syndrome – a pilot study. Fatigue. 2017 May 4;5(3):184-186. doi: 10.1080/21641846.2017.1322235. eCollection 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5942146/ (Full article)

Childhood sleep and adolescent chronic fatigue syndrome (CFS/ME): evidence of associations in a UK birth cohort

Abstract:

OBJECTIVE/BACKGROUND: Sleep abnormalities are characteristic of chronic fatigue syndrome (CFS, also known as ‘ME’), however it is unknown whether sleep might be a causal risk factor for CFS/ME.

PATIENTS/METHODS: We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. We describe sleep patterns of children aged 6 months to 11 years, who were subsequently classified as having (or not having) ‘chronic disabling fatigue’ (CDF, a proxy for CFS/ME) between the ages 13 and 18 years, and we investigated the associations of sleep duration at age nine years with CDF at age 13 years, as well as sleep duration at age 11 years with CDF at age 16 years.

RESULTS: Children who had CDF during adolescence had shorter night-time sleep duration from 6 months to 11 years of age, and there was strong evidence that difficulties in going to sleep were more common in children who subsequently developed CDF. The odds of CDF at age 13 years were 39% lower (odds ratio (OR) = 0.61, 95% CI = 0.43, 0.88) for each additional hour of night-time sleep at age nine years, and the odds of CDF at age 16 years were 51% lower (OR = 0.49, 95% CI = 0.34, 0.70) for each additional hour of night-time sleep at age 11 years. Mean night-time sleep duration at age nine years was 13.9 (95% CI = 3.75, 24.0) minutes shorter among children who developed CDF at age 13 years, and sleep duration at age 11 years was 18.7 (95% CI = 9.08, 28.4) minutes shorter among children who developed CDF at age 16 (compared with children who did not develop CDF at 13 and 16 years, respectively).

CONCLUSIONS: Children who develop chronic disabling fatigue in adolescence have shorter night-time sleep duration throughout early childhood, suggesting that sleep abnormalities may have a causal role in CFS/ME or that sleep abnormalities and CFS/ME are associated with a common pathophysiological cause.

Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Source: Collin SM, Norris T, Gringras P, Blair PS, Tilling K, Crawley E. Childhood sleep and adolescent chronic fatigue syndrome (CFS/ME): evidence of associations in a UK birth cohort. Sleep Med. 2018 Jun;46:26-36. doi: 10.1016/j.sleep.2018.01.005. Epub 2018 Jan 31.  https://www.ncbi.nlm.nih.gov/pubmed/29773208

Dutch Health Council Advisory Report on Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: Taking the Wrong Turn

Abstract:

Recently, the Dutch Health Council published their advisory report on Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) which is meant to determine the medical policy with regard to ME in the Netherlands. The Health Council briefly discusses several diagnostic criteria and proposes to use new diagnostic criteria for “ME/CFS” in research and clinical practice in the future. The advisory report then summarizes organic abnormalities observed in the last decades and concludes that “ME/CFS” is a “serious, chronic, multisystem disease”.

According to the Health Council there are no curative treatments for “ME/CFS”, due to lack of knowledge, but specific medication could bring symptomatic relief. The Health Council recommends conducting more research, to (re)educate medical professionals about “ME/CFS”, to appoint three academic expertise centres, which will install a care network for patients, and to fairly judge the limitations (disability) of patients when they apply for a disability income, medical aid and care. The advisory report was welcomed by many patients, because it puts an end to the dominance of the (bio)psychosocial explanatory model and seems to offer a perspective of improving the situation of patients. However, the starting point of the advisory report, a new definition of “ME/CFS”, will have serious (long-lasting) consequences for patients and researchers.

Source: Twisk F. Dutch Health Council Advisory Report on Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: Taking the Wrong Turn. Diagnostics (Basel). 2018 May 16;8(2). pii: E34. doi: 10.3390/diagnostics8020034. http://www.mdpi.com/2075-4418/8/2/34 (Full article)

Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

Non-restorative sleep is a hallmark symptom of chronic fatigue syndrome/myalgic encephalomyelitis. However, little is known about self-reported sleep disturbances in these subjects. This study aimed to assess the self-reported sleep quality and its impact on quality of life in a Spanish community-based chronic fatigue syndrome/myalgic encephalomyelitis cohort.

A prospective cross-sectional cohort study was conducted in 1,455 Spanish chronic fatigue syndrome/myalgic encephalomyelitis patients. Sleep quality, fatigue, pain, functional capacity impairment, psychopathological status, anxiety/depression and health-related quality of life were assessed using validated subjective measures. The frequencies of muscular, cognitive, neurological, autonomic and immunological symptom clusters were above 80%.

High scores were recorded for pain, fatigue, psychopathological status, anxiety/depression, and low scores for functional capacity and quality of life, all of which correlated significantly (all p < 0.01) with quality of sleep as measured by the Pittsburgh Sleep Quality Index. Multivariate regression analysis showed that after adjusting for age and gender, the pain intensity (odds ratio, 1.11; p <0.05), psychopathological status (odds ratio, 1.85; p < 0.001), fibromyalgia (odds ratio, 1.39; p < 0.05), severe autonomic dysfunction (odds ratio, 1.72; p < 0.05), poor functional capacity (odds ratio, 0.98; p < 0.05) and quality of life (odds ratio, 0.96; both p < 0.001) were significantly associated with poor sleep quality.

These findings suggest that this large chronic fatigue syndrome/myalgic encephalomyelitis sample presents poor sleep quality, as assessed by the Pittsburgh Sleep Quality Index, and that this poor sleep quality is associated with many aspects of quality of life.

Source: Castro-Marrero J, Zaragozá MC, González-Garcia S, Aliste L, Sáez-Francàs N, Romero O, Ferré A, Fernández de Sevilla T, Alegre J.  Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Sleep Res. 2018 May 16:e12703. doi: 10.1111/jsr.12703. [Epub ahead of print]  https://www.ncbi.nlm.nih.gov/pubmed/29770505

The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure

Abstract:

Chronic or persistent fatigue is a common, debilitating symptom of several diseases. Persistent fatigue has been associated with low-grade inflammation in several models of fatigue, including cancer-related fatigue and chronic fatigue syndrome. However, it is unclear how low-grade inflammation leads to the experience of fatigue. We here propose a model of an imbalance in energy availability and energy expenditure as a consequence of low-grade inflammation.

In this narrative review, we discuss how chronic low-grade inflammation can lead to reduced cellular-energy availability. Low-grade inflammation induces a metabolic switch from energy-efficient oxidative phosphorylation to fast-acting, but less efficient, aerobic glycolytic energy production; increases reactive oxygen species; and reduces insulin sensitivity. These effects result in reduced glucose availability and, thereby, reduced cellular energy.

In addition, emerging evidence suggests that chronic low-grade inflammation is associated with increased willingness to exert effort under specific circumstances. Circadian-rhythm changes and sleep disturbances might mediate the effects of inflammation on cellular-energy availability and non-adaptive energy expenditure.

In the second part of the review, we present evidence for these metabolic pathways in models of persistent fatigue, focusing on chronic fatigue syndrome and cancer-related fatigue. Most evidence for reduced cellular-energy availability in relation to fatigue comes from studies on chronic fatigue syndrome. While the mechanistic evidence from the cancer-related fatigue literature is still limited, the sparse results point to reduced cellular-energy availability as well.

There is also mounting evidence that behavioral-energy expenditure exceeds the reduced cellular-energy availability in patients with persistent fatigue. This suggests that an inability to adjust energy expenditure to available resources might be one mechanism underlying persistent fatigue.

Source: Lacourt TE, Vichaya EG, Chiu GS, Dantzer R, Heijnen CJ. The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure. Front Behav Neurosci. 2018 Apr 26;12:78. doi: 10.3389/fnbeh.2018.00078. eCollection 2018.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932180/ (Full article)

OMF-Funded Research Overview 2018

From Open Medicine Foundation.

I am proud to share with you the new and expanding research projects that we are funding this year. As we have recently shared, research is quickly expanding. We look forward to continuing to share updates with you about our exciting Collaborative Research Centers at Stanford and Harvard and all of our research projects. We invite you to continue to support our efforts to fund these teams of expert scientists pursuing our common goal: End ME/CFS.

We are confident that our research is leading us to answers. To keep this momentum growing, we count on your support. Whether you can donate $5, $500, or $5,000, every gift makes a difference in supporting research and delivering hope. Please donate today.

And please help us to grow by spreading our news. Forward this email to your family and friends and invite them to personally sign up to receive our news in their inbox to stay informed.

I am looking forward to seeing all who are attending the Invest in ME Research International Conference next week in London. I will be attending the Conference and the Biomedical Research into ME Colloquium along with 6 of our scientific advisory board members. If you are attending, please come visit us at our table on June 1st so that we can say hello in person.

With hope for all,

Linda Tannenbaum
CEO/President
linda@omf.ngo

ME/CFS COLLABORATIVE RESEARCH CENTER AT STANFORD

OMF is continuing to fund the ME/CFS Collaborative Research Center at Stanford. These are the projects currently underway:

  • T cells and immunology Michael Sikora, in collaboration with Mark Davis, PhD, Lars Steinmetz, PhD, and Ron Davis, PhD, at Stanford University, will examine the role of T cells and immune-related genes in ME/CFS. This may help address the outstanding question of whether ME/CFS is an autoimmune or infectious disease, or simply an activation of the immune system. Click here to read more about the plans for this study.
  • Extended big data study in families Fereshteh Kenari Jahaniani, PhD, in collaboration with Mike Snyder, PhD, and Ron Davis, PhD, of Stanford University, are generating multiple large datasets (genomics, gene expression, metabolomics, proteomics, and cytokines) in a cohort of patients and their families. By comparing patients to healthy blood relatives, we are more likely to understand what genes cause or contribute to the development of ME/CFS. This data will also be integrated with the Severely ill Patients (Big Data) Study (SIPS) , providing important validation and extension of those findings. Read and watch more about the multi-omics approach.
  • Diagnostic and drug-screening technology development Four technologies are being developed that could provide a biomarker for ME/CFS. Dr. Davis’s team is dedicated to developing these into inexpensive tests that can be easily used in a doctor’s office. In the future, all patients will be measured on all of these diagnostic platforms, enabling us to compare their efficacy and determine what combination of them will be most useful to export for diagnostic testing. Click here to read more about the plans for this study.
    1. Nanoneedle: Rahim Esfandyarpour, PhD, in collaboration with Ron Davis, PhD, is validating and further developing the nanoneedle biosensor platform, which has shown promise as a blood-based diagnostic for ME/CFS. This is a nanofabricated device that measures electrical impedence from a drop of blood. Thus far, this test is able to distinguish ME/CFS patients from healthy controls. The technology will be optimized for easy clinical adoption and scaled up so that numerous FDA-approved drugs can be simultaneously screened as potential treatments. Click here to read more about why a blood-based diagnostic could be a game-changer.
    2. Magnetic Levitation Device: Gozde Durmus, PhD, in collaboration with Ron Davis, PhD, has been developing a magnetic levitation device. This device uses a ferrofluid in a glass capillary surrounded by permanent magnets. This generates a density gradient and cells move to their respective densities in the capillary. Their position is imaged by a camera from a smart phone. It was discovered that white blood cells from ME/CFS patients are less dense than healthy controls. One patient was followed for several months, consistently showing a light density. It was further observed that there was a correlation between the lightness of the cells and the severity of symptoms. This could be a very inexpensive diagnostic test, and more patients will be tested in 2018.
    3. Red Blood Cell Deformability Test: Mohsen Nemat-Gorgani, PhD, of Stanford University, and Anand Ramasubramanian, PhD, of San Jose State University, in collaboration with Ron Davis, PhD, are developing a micro-fluidic device that measures blood flow and deformability of red blood cells. In preliminary results, the red blood cells of ME/CFS patients and healthy controls differ in their time of entry into a capillary, rate of movement through the capillary, and the extent of deformation of the cell in the capillary. This has the potential to be yet another biomarker that would only require a drop of blood. (More)
    4. Mitochondrial Function Test: Julie Wilhelmy, in Dr. Davis’s lab, has developed a protocol using the Seahorse instrument that measures mitochondrial function. This protocol reveals a significant difference between activated T-cells of ME/CFS patients and healthy controls. The instrument is commercially available, which will allow other laboratories to easily reproduce our results.
  • Metabolic Trap Dr. Robert Phair, PhD, of Integrated Bioinformatics, Inc, has been working with Dr. Davis’s team at Stanford. He has found a metabolic pathway in ME/CFS patients that he hypothesizes to be stuck in a “trap” in an unhealthy state. His metabolic trap hypothesis emerged from genetic and metabolomics data from the Severely ill Patients Study (SIPS) combined with published enzymatic kinetics using mechanistic computational modeling. Dr. Phair and the team are eager to test this hypothesis as fast as possible, as it could be the underlying cause of ME/CFS and lead to effective treatment. (More) Read Health Rising’s article about the Metabolic Trap

OTHER EXCITING PROJECTS FUNDED BY OMF:

ME/CFS COLLABORATIVE RESEARCH CENTER AT HARVARD

OMF has newly awarded a grant totaling $1.8 million to establish a new ME/CFS Collaborative Research Center at Harvard. The new Harvard Center will be led by OMF Scientific Advisory Board members Ronald G. Tompkins, MD, ScD, and Wenzhong Xiao, PhD, and will work synergistically with the ME/CFS Collaborative Research Center at Stanford led by Ronald W. Davis, PhD, of Stanford University, also funded by OMF. All science funded by OMF continues to be under the overall direction of our Scientific Advisory Board, directed by Ron Davis. Click here for more information.

Stanford ME/CFS Data Management and Coordination Center

OMF is also funding the expansion of the Stanford Data Center for the Severely Ill Patients (SIPS) Study to encompass all the data from the Stanford and Harvard ME/CFS Collaborative Research Centers, as well as data from any other research we are funding. The clinical results from the SIPS are currently already open to researchers with access via our website. This expanded data center will give researchers quick access to massive amounts of research data.

Analyzing Patient Data Study

This retrospective study aims to analyze the clinical records and test results of thousands of patients from 9 ME/CFS specialists. (More)

Hormones, Proteins, Autoantibodies

Jonas Bergquist, MD, PhD, is validating his autoantibody findings, as well as measuring proteins and steroid hormones in plasma and cerebrospinal fluid. (More)

Metabolomics Validation Study

Robert K. Naviaux, MD, PhD’s 2016 ME/CFS metabolomics study is being expanded to include additional validation studies with Oliver Fiehn, PhD, and his team at the West Coast Metabolomics Center (WCMC), University of California, Davis (UCD). (More)

Second Annual Collaborative Team Meeting on the Molecular Basis of ME/CFS at Stanford University

This year our collaborative team meeting will be expanded to three days, September 26-28. The first two days will allow for in-depth scientific discussion of recent ME/CFS research results. On the third day we will establish collaborations and discuss the most effective path forward to expedite ME/CFS research. At this groundbreaking scientific conference, over 30 international researchers will share unpublished data and ideas. Sharing unpublished data is a very effective way to accelerate the research because scientists can consider these results without waiting for publication. This interdisciplinary team of experts in numerous fields, including Nobel laureates, and several members of the National Academy of Sciences, will discuss genetics, metabolism, immunology, data integration, related diseases, drug discovery, and lessons from these and other fields for ME/CFS research.

Second Annual Community Symposium on the Molecular Basis of ME/CFS at Stanford University – September 29

The Community Symposium will take place on Saturday, September 29. At the Community Symposium, the scientists will update patients and any interested members of the public on the latest research and our progress towards understanding the molecular basis of ME/CFS and our plans for the future. Come hear from our amazing team in person. If you can’t attend, the symposium will be livestreamed. Registration information for the Community Symposium will be coming out soon.

​M.E. highlighted at the 71st World Health Assembly

Press Release: Action for ME, May 23, 2018

The need for accelerated biomedical research, and training and education for health professionals has been highlighted at the first-ever World Health Assembly side event focused on M.E.

Taking place last night in Geneva and held by the International Alliance for M.E. (IAFME), led by Action for M.E. and hosted by the Union for International Cancer Control (UICC), the aim of the event was to raise awareness and understanding of M.E. among international policy-makers, and to build connections with other public health organisations and individuals who support the IAFME’s goal of achieving a global public health response to M.E.

Those attending were visibly shocked by a short screening from Jen Brea’s award-winning documentary Unrest, showing the devastating impact of M.E. on people across the world. Afterwards, panel members Sonya Chowdhury, Prof Chris Ponting, Greg Perry and M.E. patient Steven offered their view on the challenges facing people affected by M.E., and those that support them, and the steps that must be taken to address these.

“It is not OK that people with M.E. are being told there is nothing wrong with them, whether that’s one person, 100 people, or 35 million people – which is the latest estimated number of people with M.E., using data from a new research due to be published,” said Sonya Chowdhury, Chief Executive, Action for M.E. “The universal health coverage championed by the World Health Organisation must include coverage for every single person. They must not turn their backs on one person with M.E., let alone 35 million.”

Steven, who lives on the French-Swiss border, described the difficulties he faced in getting a diagnosis, and we also heard, via video, from Dr Nina Muirhead, a UK surgeon living with M.E. “It is true of most hospital doctors that they do not know about, or understand, M.E./CFS,” she said. “This was the case for me before I got ill in 2016.” You can watch Nina’s video on the IAFME Facebook page.

Turning to the urgent need for accelerated biomedical research, Prof Chris Ponting, University of Edinburgh, suggested four key areas of focus: a large-scale genome-wide association study that will help us understand the genetics of M.E.; cheap, longitudinal, population-scale immune system surveys; molecular and physiological measurements of people with M.E. following exercise; and taking action to ensure that case-control studies use more appropriate control cohorts with individuals with sedentary lives. He was also emphatic about the need to bring more new and established scientists into the field.

Our final speaker was Greg Perry, Assistant Director General, International Federation of Pharmaceutical Manufacturers and Associations. “I am struck by the fact that M.E. has been around for a long time, but there has still not been any real progress ,” he said. “I do think that the World Health Organisation is a hub of innovate thinking, so there are great opportunities here to focus on this neglected disease.”

During a lively discussion, moderated by Alexandra Heumber, Head of International Advocacy and Coordinator of the IAFME, based in Geneva, the panel heard from people directly affected by M.E., and from those working within global health policy. They reinforced the need for global leadership from the World Health Organisation in setting-up a framework, at global level, that guides and supports policy-makers and health professionals whose decisions impact the lives of those with M.E.

We are hugely grateful to Dr Cary Adams, Chief Executive, UICC, for hosting this event, and for everyone who contributed, particularly those affected by M.E.

Love Means Never Having to Say … Anything

By Jamison Hill, New York Times, May 25, 2018

After dating Shannon for several months, I needed to say something to her, but I couldn’t. It’s not that I was nervous or unsure of the phrasing. It’s that I couldn’t speak. My lungs and larynx couldn’t create the air pressure and vibrations needed to say the words floating around my mind.

This is our reality. I can’t talk to Shannon about anything — not the weather or her day or how beautiful she is. Worst of all, I can’t tell her I love her.

You can read the rest of this moving essay HERE.

_____________________________

About the author: A graduate of Sonoma State University, Jamison Hill is a former bodybuilder, model, and fitness instructor. He has written for, among others, The Washington Post, Men’s Journal, The Los Angeles Times, Vox, Quartz, VICE and The New York Times. Jamison appeared in the documentary, Forgotten Plague, and his story is featured in an upcoming Netflix documentary about mysterious diseases. He writes about living with Chronic Fatigue Syndrome and Lyme disease at JamisonWrites.com. Jamison is currently finishing his memoir, When Force Meets Fate.