Solve ME/CFS Initiative 2014 Webinar Series

July 8, 2014

Workplace-WebinarBeginning in July and continuing through year-end, the Solve ME/CFS Initiative (SMCI) will be bringing you a free, monthly webinar series. Anyone that is interested can RSVP to participate live. Each webinar will be recorded and posted to our website and YouTube channel within a week of the live date, so if you miss it, don’t worry! You can still have access to the great content at your convenience.

Read more about the series and RSVP today!

 

Suzanne

Research Institute Without Walls – Progress and Promise

HELD on Thursday, July 31, 2014
Video Link

Suzanne D. Vernon, Ph.D., scientific director of the Solve ME/CFS Initiative will provide an update on the work being conducted through our Research Institute Without Walls. Participants can also expect to learn more about how the SolveCFS Biobank works and is attracting some of the brightest investigators from the best institutions to ME/CFS research.  You will leave with an understanding of what makes the SolveCFS BioBank unique, how to get enrolled and what to expect when you participate.  Vernon will also provide a sneak peek at some of the types of research being conducted on samples using the SolveCFS BioBank.

 

McGowan

Investigator Report: Epigenetics of ME/CFS

Thursday, August 21, 2014
2-3:00pm Eastern (1pm Central/Noon Mountain/11am Pacific)

Space is limited –  RSVP to Reserve Your Slot – Click HERE

Patrick O. McGowan, Ph.D., is one of the Solve ME/CFS Initiative 2011 funded investigators.  McGowan is an assistant professor in the Department of Biological Sciences, University of Toronto at Scarborough.  He will talk about his latest results from our grant funding.  McGowan used blood samples from the SolveCFS BioBank to identify the chemical modifications (e.g., methylation) to the DNA that is different in ME/CFS patients compared to healthy people.  This type of research will help explain the immune dysfunction of ME/CFS.

 

Dane-Cook

Investigator Report: Deciphering Post-Exertional Malaise

Thursday, September 18, 2014
2-3:00pm Eastern (1pm Central/Noon Mountain/11am Pacific)

Space is limited –  RSVP to Reserve Your Slot – Click HERE

Dane B. Cook, Ph.D. is assistant professor of Kinesiology at the University of Wisconsin, Madison.  Cook is one of the Solve ME/CFS Initiative’s 2011 funded investigators.  Cook will describe the system biology approach his team is taking to provide a clear picture as to what causes post-exertional malaise.  This is critically important research for ME/CFS because as Cook notes, “You can’t begin to fix a problem like post-exertional malaise until you can understand its underlying cause.”

 

unutmaz

Investigator Report: Decoding the Human Immune Response

Wednesday, October 1, 2014
2-3:00pm Eastern (1pm Central/Noon Mountain/11am Pacific)

Space is limited –  RSVP to Reserve Your Slot – Click HERE

Derya Unutmaz, MD, is Professor of Microbiology, Pathology and Medicine at NYU Langone Medical Center.  Unutmaz is using samples from the SolveCFS BioBank to understand the “Good, Bad and Ugly” aspects of the immune response in ME/CFS.  Unutmaz hypothesizes that a disproportionate immune response leads to damage in ME/CFS.   He will describe what the immune signature of ME/CFS looks like compared to a healthy immune response.

 

PeterRoweInvestigator Report: Neuromuscular Strain in ME/CFS

Thursday, October 23, 2014
2-3:00pm Eastern (1pm Central/Noon Mountain/11am Pacific)

Space is limited –  RSVP to Reserve Your Slot - Click HERE

Peter Rowe, MD, who directs the Chronic Fatigue Clinic at Johns Hopkins Children’s Center, will describe some novel observations about restrictions in range of motion in the limbs and spine in those with ME/CFS. Many affected individuals have restricted movements and increased mechanical tension in nerves. Applying a further mechanical strain to the nervous system can provoke increased symptoms in some patients. These concepts are starting to help explain the pathogenesis of some symptoms and neurological abnormalities in the illness—not only how they might arise but also how we might treat them more effectively.

 

 

November and December webinars to be announced at a later date.

 

 

Same Mission | New Name

May 30, 2014

Solve ME/CFS Initiative

We’re delighted to announce that The Solve ME/CFS Initiative has a new name – the Solve ME/CFS Initiative.   While our name has changed, our mission steadfastly remains the same:  We will make ME/CFS understood, diagnosable and treatable.

Why the change?  We recognize the many changes in our organization and our illness space since the organization was first named so long ago in 1987.  While the name of our illness continues to be controversial, “ME/CFS” better reflects today’s understanding. And we believe that the word “initiative” (defined as ‘leading action’), expresses our strong commitment to funding ground-breaking research.

Since our organization was founded and named in 1987, we have been the leading organization focused on this illness.  Over the years, we’re proud of our remarkable advances regarding this controversial and misunderstood disease.

  • Under the 22-year leadership of Kim McCleary, the organization’s first CEO, the Association played an integral part in developing a policy ruling for the Social Security Administration that recognized CFS as a disabling condition.
  • We are the leading private funder of ME/CFS research, directly funding $5.5 million in ground breaking research which has been leveraged into more than $12 million in additional ME/CFS research.
  • The organization fought to create and continues to advocate to sustain a dedicated federal advisory committee on ME/CFS research and education (CFSAC).
  • We helped expose the misappropriation of $12.9 million in CDC spending, restoring these funds to ME/CFS research.
  • We led the first-ever public awareness campaign for ME/CFS, led lobbying events, organized Congressional briefings and regularly deliver testimony at numerous federal hearings and meetings.

Four years ago, guided by a desire to move into a new era of scientific progress on ME/CFS, the Association made a strategic decision to heighten its focus on research.  Our thinking was simple – the best way to use our precious dollars is toward solving this despicable illness.

Today, led by President and CEO, Carol Head, the organization continues to drive its mission forward – to fund research that will make ME/CFS understood, diagnosable and treatable.  How do we do that? By providing more funding for high-quality ME/CFS studies, fostering increased collaboration among ME/CFS researchers and pushing the federal government to make ME/CFS research a higher priority.  We are working to leverage our experience, relationships and collective knowledge to propel the ME/CFS research field forward. We are a catalyst for scientific advances that translate into better care for ME/CFS patients. We are accelerating ME/CFS research.

As we continue our efforts to make ME/CFS widely understood, diagnosable, and treatable, it is fitting that we have a name that more accurately reflects who we are: The Solve ME/CFS Initiative. We trust that you will continue this journey with us as we work towards a day when ME/CFS is no more.

 

Research Digest – September 2014: Cortisol in ME/CFS

September 15, 2014

Cortisol is a hormone that is produced in the adrenal glands where it enters into the circulation to dampen inflammation. It does this by entering into the cytoplasm of cells, binding to the cortisol receptor (called the glucocorticoid receptor) and then moving into the cell nucleus to bind to DNA and regulate the expression of inflammatory molecules.

Cortisol is an essential hormone for immune function and many studies have shown that cortisol is low in ME/CFS patients – known as hypocortisolism.  Recent articles find increased cortisol receptor expression is associated with post-exertion malaise (PEM), low cortisol is associated with more severe PEM and a return of cortisol to normal levels is associated with recovery.

In this month’s research digest, we review three studies that look at the effect of cortisol on function and post-exertional malaise in ME/CFS.

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In a Solve ME/CFS Initiative funded study published in Fatigue: Biomedicine, Health & Behavior Jacob Meyer, a PhD candidate at the University of Wisconsin, worked with a team of investigators from the University of Wisconsin, Madison, Marshfield Clinic Research Foundation and the University of Utah to study gene expression using an exercise challenge.  Thirteen ME/CFS patients and 11 healthy controls had blood samples taken before and after a maximal exercise challenge.  Compared to controls, ME/CFS patients had increased expression of 2 genes – the glucocorticoid receptor and the adrenergic alpha 2a receptor.  This increased gene expression was associated with PEM symptoms.  The authors suggest that these finding, particularly as they relate to cortisol, may lead to an understanding of the biological mechanism of PEM.  http://www.tandfonline.com/doi/full/10.1080/21641846.2013.838444#.U9gd-qgox4I

 

A short communication titled “Stress management skills, cortisol awakening response, and post-exertional malaise in Chronic Fatigue Syndrome” was published online in the journal Psychoneuroendocrinology.  Daniel L. Hall and Michael Antoni from the Department of Psychology at the University of Miami together with Mary Ann Fletcher and Nancy Klimas from the Institute for Neuro Immune Medicine, Nova Southeastern University found that greater stress management skills was associated with higher cortisol levels upon wakening and less PEM severity.  The investigators recommend that similar research be conducted over longer periods of time to determine if by improving stress management skills, cortisol regulation improves and ME/CFS patients experience less PEM.
http://www.ncbi.nlm.nih.gov/pubmed/25049069

 

In another study published earlier this year in Psychoneuroendocrinology titled “The role of hypocortisolism in chronic fatigue syndrome”, investigators from the Netherlands examined cortisol levels in young ME/CFS patients participating in the FITNET (Fatigue In Teenagers on the interNET) trial.  FITNET, an internet-based cognitive behavioral therapy program for young ME/CFS patients. These investigators found that the cortisol levels in patients that improved after 6 months of treatment returned to normal levels.  ME/CFS patients that did not respond to treatment had slight increases in cortisol levels but still below normal.  The investigators conclude that the return of cortisol levels to normal is associated with treatment success and that poor functioning of the hypothalamic-pituitary-adrenal (HPA) axis that regulates cortisol levels plays a role in ME/CFS symptoms.  Understanding what contributes to HPA axis dysfunction could help improve ME/CFS treatment.
http://www.ncbi.nlm.nih.gov/pubmed/24636516

 

Guest Blog: Dr. Peter Rowe – Is The Physical Examination Normal in CFS? Part 3

September 11, 2014

In this 3rd piece of our three-part blog series Dr. Peter Rowe discusses range of motion in ME/CFS patients.

In the first post in the series, Dr Rowe discussed orthostatic heart rate and blood pressure changes. Read Part 1 HERE

In the second post, Dr Rowe discussed joint hypermobility. Read Part 2 HERE

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Postural dysfunctions and movement restrictions

Some of those with joint hypermobility also have postural abnormalities that are thought to be a consequence of the effect of gravitational loading of the spine, including a head-forward posture, a rounded appearance of the thoracic spine, and increased lumbar curvature. My physical therapist colleague, Rick Violand, had originally identified a number of associated areas of reduced movement of the spine and limbs during his examination of those with CFS. These observations describing adverse neural tension (also termed neurodynamic dysfunction) have been reported elsewhere.1-3 During the clinical care of patients over the last decade, we had been struck by how many individuals with CFS had focal areas of restricted range of motion, and how adding an elongation strain to nerves and soft tissues could aggravate their typical CFS symptoms. With other co-investigators, we recently published a large study showing that reduced range of motion of the limbs and spine was significantly more common in adolescents and young adults with CFS than in carefully matched controls, and that adding a longitudinal strain to the nerves and soft tissues was another way of provoking common CFS symptoms.18 These examination abnormalities can be detected most readily by physical therapists and other manual practitioners. Physicians and nurse practitioners can become adept at screening for these problems if provided with extra training.

Why does the detection of movement restrictions matter? Our experience leads us to believe that the areas of adverse neural tension are treatable. In clinical care we have noted that improvement in the range of motion is usually accompanied by improvement in daily function for those with CFS. Much more work needs to be done to characterize these abnormalities further, to determine whether the same changes are also present in adults with CFS, and to identify the optimal treatment approaches. These observations open up new avenues for understanding the pathogenesis of CFS symptoms, and for further individualized approaches to treatment. We hypothesize that treating the movement restrictions first using gentle manual therapy techniques will help the most impaired CFS patients begin to tolerate exercise better.

Conclusion    

These three related areas of dysfunction—circulatory disturbances, joint hypermobility, and movement restrictions—emphasize that there is much to be gained from the performance of a careful clinical examination in those with CFS. Given that aspects of each abnormality are treatable, their identification has the potential to improve the daily symptoms and function for those with CFS. We recommend the more widespread adoption of maneuvers to ascertain for these abnormalities in the clinical and research evaluation of those with CFS.

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 As medicine becomes more and more dependent on sophisticated technology, the physical exam is in danger of becoming a lost art.  As Dr. Peter Rowe, Johns Hopkins University, has laid out in this three-part series, there is much to be learned in a physical exam in CFS. Our hope is that this information will be of great value to both you and your doctor. We believe it clearly illustrates the value of laying on of hands in the physical examination of ME/CFS.

Suzanne D Vernon, PhD
Solve ME/CFS Initiative Scientific Director

 

References

  1. Rowe PC, Fontaine KR, Violand RL. Neuromuscular strain as a contributor to cognitive and other symptoms in chronic fatigue syndrome. Frontiers in Integrative Physiology 2013; Front Physiol 2013;4:115. doi: 10.3389/fphys. 2013.00115
  2. http://www.research1st.com/2013/01/25/manual-therapy-1-of-2/
  3. http://www.research1st.com/2013/02/01/manual-therapy-2-of-2/
  4. Rowe PC, Marden CL, Flaherty M, Jasion SE, Cranston EM, Johns AS, Fan J, Fontaine KR, Violand RL. Impaired range of motion of limbs and spine in chronic fatigue syndrome. J Pediatrics 2014 (in press).

 

Guest Blog: Dr. Peter Rowe – Is The Physical Examination Normal in CFS? Part 2

September 9, 2014

In the 2nd part of this three-part blog series on physical examination in ME/CFS, Dr. Peter Rowe discusses joint hypermobility.  You can read the first blog post in the series where Dr Rowe discussed orthostatic heart rate and blood pressure changes HERE.

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Joint hypermobility

Some patients meeting the criteria for CFS have a genetic disorder of connective tissue known as Ehlers-Danlos syndrome (EDS). Those with EDS have stretchy skin, very loose, hypermobile joints that often dislocate easily, along with delayed wound healing, fragile skin, and a tendency to develop an early onset of varicose veins. Those with EDS have chronic fatigue and widespread pain of uncertain cause, which of course overlaps with the central features of CFS.

We first drew attention to this association in 1999, noting that those with CFS and orthostatic intolerance had a much higher prevalence of EDS than expected.1 We then went on to examine whether those with CFS had a higher prevalence of joint hypermobility. Although we might expect less flexibility in a population that has had at least 6 months of reduced activity, in that study, 60% of new adolescent patients with CFS met criteria for joint hypermobility, compared to just 24% of healthy controls.2

Slide2Slide1

The assessment of joint hypermobility takes only a couple of minutes, and can easily be performed using a goniometer for accurate measurement of joint angles. The most commonly used series of maneuvers is the 9 point Beighton score, as shown in the pictures above. It should be noted that the Beighton score does not do a good job of evaluating for laxity in the hips and shoulders, but it is a useful screening tool.

CFIDS PE article Fig 4

Other findings on the examination in those with EDS can include increased extensibility of the skin, abnormally widened and thin (“papyraceous”) scars, easy eversion of the eyelids, and stretch marks (striae) even in the absence of excessive changes in weight. Examples of these findings are shown in the pictures to the right.

Since the publication of these results, a number of studies have confirmed that those with joint hypermobility have more orthostatic symptoms and a reduced tolerance of upright posture,3 and that fatigue is a prominent contributor to lower quality of life in EDS.4 New work from investigators in Belgium confirms that those with hypermobile EDS have high rates of autonomic symptoms, abnormal heart rate responses to upright posture, and other features of autonomic dysfunction.5,6

Why does the assessment for joint hypermobility matter? Joint hypermobility is associated with other co-morbid disorders such as temporomandibular joint dysfunction, and the laxity in ligaments often contributes to arthralgias and myalgias. Better ascertainment of these problems can lead to more focused therapy directed at pain, and physical treatments directed at biomechanical dysfunctions.7 Beyond the effects on joints, connective tissue laxity also affects the blood vessel walls. The increased distensibility in blood vessels may be a factor in the early development of varicose veins in those with EDS. Vascular stretch also is thought to allow increased blood pooling in the dependent circulation during upright posture, leading to diminished blood return to the heart, and thus to orthostatic intolerance symptoms. Given the high prevalence of skin and joint laxity in those with CFS, and the contribution of connective tissue abnormalities to the development of orthostatic intolerance, we recommend that all those with CFS undergo screening with a Beighton score, and that clinicians look carefully for the skin changes of EDS in their patients with CFS.

 

References

  1. Rowe PC, Barron DF, Calkins H, Maumenee IH, Tong PY, Geraghty MT. Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome. J Pediatr 1999;135:494-9.
  2. Barron DF, Cohen BA, Geraghty MT, Violand R, Rowe PC. Joint hypermobility is more common in children with chronic fatigue syndrome than in healthy controls. J Pediatr 2002;141:421-5.
  3. Gazit Y, Nahir AM, Grahame R, Jacob G. Dysautonomia in the joint hypermobility syndrome. Am J Med 2003;115:33-40.
  4. Voermans NC, Knoop H, van de Kamp H, et al. Fatigue is a frequent and clinically relevant problem in Ehlers-Danlos syndrome. Semin Arthritis Rheum 2010;40:267-274.
  5. de Wandele I, Calders P, Peersman W, et al. Autonomic symptom burden in the        hypermobile type of Ehlers-Danlos syndrome: a comparative study with two other EDS types, fibromyalgia, and healthy controls. Semin Arthritis Rheum 2014 (in press).
  6. de Wandele I, Rombaut L, Leybaert L, et al. Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome. Semin Arthritis Rheum 2014; (in press).
  7. Simmonds JV, Keer RJ. Hypermobility and the hypermobility syndrome, part 2: assessment and management of hypermobility syndrome: illustrated via case studies. Man Ther 2008;13:e1-e11.

 

Figure Legends

Fig 3a: The Beighton score. Possible scores are 0-9, with scores ≥ 4 indicating joint hypermobility. On each side, score 1 point for > 90o of hyperextensibility of the 5th finger, 1 point for the ability to appose the thumb to the forearm, and 1 point for > 10o of hyperextensibility at the elbow.

Fig 3b: On each side, score 1 point for >10o of hyperextensibility at the knee, and 1 point for the ability to place the palms on the floor.

Fig 4: Other features of EDS: clockwise from the top left, stretch marks (striae) in a non-obese individual who has not had excessive weight change, easy eversion of the upper eyelids and Gorlin’s sign (the ability to touch the tongue to the tip of the nose, increased extensibility of the skin of the upper eyelid, and wide, thin scarring at the site of wound dehiscence after a simple laparoscopy incision.

 

Guest Blog: Dr. Peter Rowe – Is The Physical Examination Normal in CFS? Part 1

September 5, 2014

The Laying on of Hands: Recently I read with great interest a Medscape article titled, “Patients Lose When Doctors Can’t Do Good Physical Exams”.  You can read the article here: http://www.medscape.com/viewarticle/825442 but the crux is that as medicine becomes more and more dependent on sophisticated technology, the physical exam is in danger of becoming a lost art.

This Medscape article made me think about the experiences of our ME/CFS patient community and the frequency of physical examination. I reached out to Dr. Peter Rowe whose research we have funded that deals with neuromuscular strain and range of motion. This is the first in a series of blog posts from Dr. Peter Rowe of Johns Hopkins University titled “Is the physical exam in CFS normal?” We are certain that this information will be of great value to both you and your doctor and will clearly illustrate the value of laying on of hands in the physical examination of ME/CFS.

Suzanne D Vernon, PhD
Solve ME/CFS Initiative Scientific Director

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Is the physical examination normal in CFS?

Papers in the early 1990s described a low yield of physical examinations in patients with chronic fatigue and CFS.1 Although there were some notable counter-arguments made by Komaroff—describing sore throat and swollen lymph nodes, as well as a 10-20% prevalence of abnormal Romberg tests (Romberg test is a neurological exam that assesses balance while standing)2—most reviews of CFS included statements like the one that appeared in the 2002 Australian CFS Guidelines: “Characteristically, there are no abnormal physical findings in people with CFS.”3

The absence of abnormalities on the physical examination, especially when contrasted with the profound functional impairment in CFS, was often interpreted to be consistent with a largely psychosomatic origin of the illness. Research in the past 20 years, however, provides a decidedly different view.  In this three-part blog post, Dr. Peter Rowe will describe three groups of abnormalities found on physical examination.

Orthostatic heart rate and blood pressure changes

One of the most readily apparent abnormalities on the examination of those with CFS is that heart rate and blood pressure abnormalities are present, sometimes at rest, and more consistently during relatively brief periods of upright posture. In response to standing or upright tilt table testing, individuals with CFS have a higher prevalence of neurally mediated hypotension (NMH) and postural tachycardia syndrome (POTS), or both (Figure 1). The prevalence of these and other blood pressure and heart rate abnormalities is higher in adolescent than in adults, but even in the absence of objective changes in blood pressure or heart rate, orthostatic (upright) stress in individuals with CFS of all ages provokes characteristic daily symptoms of increased fatigue, lightheadedness, mental fog, or headache. In adolescents, all published controlled studies have shown a numerically higher prevalence of orthostatic intolerance in CFS than in healthy individuals (4 of 5 reporting statistically significantly differences), and all studies looking at autonomic tone show a sympathetic predominance of heart rate variability, especially in response to orthostatic stress.

Slide1   Slide2

NMH occasionally can be provoked by a brief standing test, but more commonly requires a more prolonged head-up tilt table test. The median time to provoke a drop in blood pressure in our tilt laboratory in the mid-1990s was 28 minutes,4 although symptoms are usually exacerbated shortly after the patient is tilted upright.

The diagnosis of POTS in adults requires a ≥ 30 beat per minute (bpm) increase in heart rate (HR) during 10 minutes upright when compared to baseline supine values, or a HR increase to ≥ 120 bpm, together with the reproduction of typical orthostatic symptoms. Normative data on healthy young people showed that the adult HR criteria overdiagnosed POTS, so in adolescents the diagnosis now requires a ≥ 40 bpm HR increase in the first 10 minutes of head-up tilt or standing, or a HR ≥ 120 bpm.5 Some individuals with POTS at an early point of tilt testing subsequently develop a more profound drop in BP, consistent with delayed orthostatic hypotension or with NMH.

CFIDS PE article Fig 2Along with the changes in heart rate and blood pressure, a striking physical finding among those with CFS and orthostatic intolerance is a purple discoloration in the dependent limbs termed acrocyanosis (Figure 2). Acrocyanosis is readily apparent if the patient is examined in shorts, seated on the examination table, with the legs hanging down. This finding can be differentiated from Raynaud’s phenomenon by the absence of blanching of the fingers or toes, and by the fact that hands and feet are diffusely discolored.

Why does recognition of orthostatic physical examination findings matter? Open treatment studies show that people with CFS can enjoy improved function with standard measures to manage orthostatic intolerance. That management involves lifestyle adjustments, compression garments, and increased salt and fluid intake, along with judicious use of medications. These treatments provide another avenue for a pragmatic, individualized approach to symptoms in those with CFS.

Studies by MacLean and Allen in the 1940s had drawn attention to the similarity between the symptoms of neuromyasthenia (an older term for what we now call CFS) and the symptoms of patients who experienced orthostatic tachycardia and hypotension after assuming an upright posture. Most of the latter group experienced orthostatic exhaustion, blurring of vision, weakness on exercise, and syncopal episodes,6,7 familiar problems for those with CFS. Although these observations were neglected for several decades, the weight of the evidence now suggests that all subjects with CFS deserve careful assessment of their heart rate, blood pressure, and symptomatic responses to at least 10 minutes of quiet upright posture. The British NICE guidelines that strongly recommend against the routine use of orthostatic testing8 need to be revised in light of the available and compelling data.

 

References

  1. Lane TJ, Matthews DA, Manu P. The low yield of physical examinations and laboratory investigations of patients with chronic fatigue. Am J Med Sci 1990;299:313-318.
  2. Chronic fatigue syndrome: clinical practice guidelines—2002. Medical J Australia 2002; 176:S24.
  3. Komaroff AL, Buchwald D. Symptoms and signs of chronic fatigue syndrome. Rev Infect Dis 1991;13(Suppl 1): S8-11.
  4. Bou-Holaigah I, Rowe PC, Kan J, Calkins H. Response to upright tilt testing in 100 consecutive patients with chronic fatigue syndrome. Circulation 1995;92(8S): I-414.
  5. Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 2011;21:69–72
  6. MacLean AR, Allen EV. Orthostatic hypotension and orthostatic tachycardia: with the “head-up” bed. JAMA 1940;115:2162-7.
  7.  MacLean AR, Allen EV, Magath TB. Orthostatic hypotension and orthostatic tachycardia: defects in the return of venous blood to the heart. Am Heart J 1944;27:145-63.
  8. National Institute for Health and Clinical Excellence. Clinical guideline CG53. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management. London, NICE, 2007. http://guidance.nice.org.uk/CG53.

 

Figure Legends

Fig 1a. NMH. The hemodynamic response to upright tilt testing in an individual with CFS. Note the early onset of orthostatic symptoms of lightheadedness (LH) and pallor, without early HR elevations, following at a relatively early point by profound hypotension and relative bradycardia, consistent with NMH.

Fig 1b. POTS. The hemodynamic response to quiet standing in an individual with CFS. Note the normal supine heart rate and the dramatic 51 beat per minute change in heart rate with standing, accompanied by lightheadedness, fatigue, and headache, without major changes in blood pressure.

Fig 2: Acrocyanosis (left) and delayed capillary refill (right) appearing within 5 minutes of quiet standing in an adolescent with chronic fatigue syndrome and low orthostatic tolerance.

P2P Workshop – Registration Now Open

September 3, 2014

P2P_title Registration is now open for the Pathways to Prevention workshop for Advancing the Research on ME/CFS. Interested individuals may register to attend live or participate via webcast. It is our hope that many stakeholders will participate in this process in order to ensure the patients have a strong presence and a voice.

To register to attend live click HERE 

To register for the webcast click HERE

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More About the P2P: The National Institutes of Health (NIH), through the Office of Disease Prevention (ODP) has a program called the Pathways to Prevention. The goal is to host workshops that identify research gaps in a selected scientific area, identify methodological and scientific weaknesses in that scientific area, suggest research needs, and move the field forward through an unbiased, evidence-based assessment of a complex public health issue.

You can read more about the P2P Workshop for ME/CFS HERE

In June of 2012, the NIH launched the process of including ME/CFS in the P2P program. Several departments within the federal government came together to recommend ME/CFS for a P2P workshop. In November of 2012, the ODP received the recommendation to consider ME/CFS and approved the submission of a full proposal in December of 2012 based on “necessity, urgency and the identification of ME/CFS as a serious unmet medical need and a public health issue and that proposal was accepted then later approved. The workshop will take place on December 9 & 10, 2014.

Topics for the two-day workshop agenda were defined by questions that formed the evidence review. Speakers have been recruited for the workshop for each question/agenda item. The speakers are all to be experts in ME/CFS and are able to speak to their personal experience and expertise as a patient, caregiver, researcher, etc. The evidence review is a concise presentation of the ‘evidence’ and literature in ME/CFS (that relates to the study questions), boiled down and presented to the panel. There is opportunity for the P2P panel to review unpublished data as well. The Solve ME/CFS Initiative submitted additional evidence for their review, as well as encouraged our funded investigators, colleagues and peers to do the same.

The P2P panel will review the evidence-based report in advance of the meeting and the report will be released to the public at that time. There will be opportunity to comment and offer feedback on this report. We anticipate the report’s release in early October and will alert you to its publishing as soon as we hear more.

At the two-day workshop, the P2P panel will hear from the expert speakers and be able to ask clarifying questions in a town-hall-like Q&A that will take place after each session during the meeting.  The P2P Panel will be made up of experts in areas or topics that have relevance to ME/CFS and the evidence based report, but they are not to be ME/CFS experts by design – an effort to avoid bias and produce a report based on the facts presented in the evidence-based report and through the speakers. We do not know if patients in the gallery will be able to engage in the Q&A.

The day after the P2P meeting, the P2P Panel will write a draft report which will be published and the public will have time for comment. Originally the comment period was slated for 15 days. SMCI, along with other organizations and advocates, reached out to the P2P and asked that this comment period be extended in order to accommodate patient’s needs. We have received word that the comment period will be lengthened, but the exact length of the extension has yet to be announced. Once the comment period closes, the report will be finalized and NIH will organize a robust plan to disseminate it widely.

The goal, as we understand it, is to have a report that contains a set of recommendations based on the totality of the evidence, in the hopes of having said recommendations carried out by Federal partners in one-nine months. These recommendations are aimed at improving the robust nature of the research being conducted in ME/CFS.

The Solve ME/CFS Initiative will pass along additional information as it is received and when the opportunity for public comment is scheduled, we will report that and share the means by which you can effectively participate.

 

Research Digest – August 2014: More Results from the SolveCFS BioBank

August 22, 2014

The Solve ME/CFS Initiative established the SolveCFS BioBank in 2010.  Over the past 4 years clinical information and samples from the first 240 ME/CFS patients and 87 controls have been used by more than ten researchers – most new to ME/CFS research.   Right after we established the SolveCFS BioBank, Science magazine published the results that described a new virus in ME/CFS patients called XMRV.  This research caught the attention of many scientists and the pharmaceutical industry – immediately investigators needed samples to try to further these XMRV results.

The timing was perfect for the then-new SolveCFS BioBank.  In collaboration with GlaxoSmithKline (GSK) and four expert ME/CFS physicians, the SolveCFS BioBank collected information and samples from ME/CFS patients and healthy controls.  We are pleased to now report the publication of this SolveCFS BioBank “founding” study and some of the results from the first study of epigenetics in ME/CFS. Both used the clinical information and samples that were collected in 2010 through the SolveCFS BioBank.

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The study that helped us establish the SolveCFS BioBank titled No association found between the detection of either xenotropic murine leukemia virus-related virus (XMRV) or polytropic murine leukemia virus and chronic fatigue syndrome in a blinded, multi-site, prospective study by the establishment and use of the SolveCFS BioBank was recently published in the open access journal BMC Research Notes. The authors are from GSK, the Solve ME/CFS Initiative and several ME/CFS clinics – a great example of partnership and collaboration.  Like the many studies that have been published following the initial description of XMRV in ME/CFS, this research also found that the XMRV was found in both ME/CFS patients and healthy controls.  XMRV was detected in 6.7% (5/72) of ME/CFS patients and 5.4% (2/37) healthy controls.  Since these detection rates were so similar, it indicated that XMRV was a contaminant rather than a virus associated with the disease.  By comparing the XMRV detected here to the XMRV described in other studies, it was clear that XMRV was a contaminant from a reagent(s) used in the laboratory test. The finding that XMRV is a “contaminant” in the reagents we use in these very sensitive laboratory tests was an important discovery and has improved the way we test for viruses and interpret results.  This study was also the only one related to XMRV that used a biobank and collaborated with a patient-centered research organization.
You can read the full text of this open access article here: http://www.ncbi.nlm.nih.gov/pubmed/25092471

 

 

Wilfred de Vega, PhD candidate at the University of Toronto and his mentor Dr. Patrick McGowan together with Suzanne D. Vernon, scientific director of the Solve ME/CFS Initiative and the SolveCFS BioBank conducted the first ME/CFS epigenetic study. The results have just recently been published in the open access and highly regarded journal PLOS ONE.  The title of this paper is “DNA methylation modifications associated with chronic fatigue syndrome”.  Methylation modifies DNA without changing the genetic sequence and this chemical change affects the way the gene is expressed.  Lots of methylation corresponds to less gene expression – possibly even silencing the gene; less or no methylation corresponds to increased expression.  de Vega and his team found genes important for the immune response had different methylation patterns in ME/CFS patients compared to matched healthy controls.  Many of the methylation differences were in parts of the gene important for regulating gene expression.  These novel findings provide further evidence of immune response abnormalities contributing to ME/CFS pathophysiology.
You can read the full text of this open access article here: http://www.ncbi.nlm.nih.gov/pubmed/25111603

Read more about this study in a recent blog post HERE 

And watch McGowan’s webinar on this topic HERE

 

CFSAC Charter Up for Renewal

August 21, 2014

The Solve ME/CFS Initiative is involved in advocacy efforts aimed at improving the research landscape for the early detection, objective diagnosis and effective treatment of ME/CFS.  As part of this effort, we work to validate the burden of illness imposed by ME/CFS in agencies where national policy is made and executed.

The Chronic Fatigue Syndrome Advisory Committee (CFSAC) provides advice and recommendations to the Secretary of Health and Human Services (HHS) through the Assistant Secretary for Health on issues related to myalgic encephalomyelitis and chronic fatigue syndrome (ME/CFS).  In addition to sitting on the CFSAC as a non-voting liaison member, SMCI has been involved in the CFSAC through encouraging patient involvement in meetings, by providing public testimony, and through serving on various sub-committees.

Every two years, the charter for the CFSAC must be renewed. With the last renewal being filed September 5, 2012, the charter is again up for renewal. SMCI understands the importance of having a federal advisory committee focused on issues related to ME/CFS and so on August 1, 2014 we wrote to the Secretary of Health and Human Services urging her to renewal the CFSAC charter.

We will keep you posted on the results of this request, a copy of which is posted below.

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CFSME_logomain_fkacfids

 

 

 

Sylvia Mathews Burwell
Secretary of Health and Human Services
U.S. Department of Health and Human Services
200 Independence Avenue, SW
Washington, D.C. 20201

August 1, 2014

Dear Secretary Burwell:

We are writing to urge you to renew the charter and fully fund the Department of Health and Human Services (DHHS) Chronic Fatigue Syndrome Advisory Committee (CFSAC). The charter is set to expire on September 5, 2014.

The CFSAC was established to provide evidence-based advice and recommendations to you and the Assistant Secretary of Health on issues related to chronic fatigue syndrome (CFS). The issues can include factors affecting access and care for persons with CFS; the science and definition of CFS; and broader public health, clinical, research and educational issues related to CFS.

Chronic Fatigue Syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a complex and severely debilitating chronic illness that affects up to 4 million Americans, according to the CDC. ME/CFS is now recognized by most authorities, including CDC and NIH, as a severe and debilitating disease. Unrelenting exhaustion, widespread muscle and joint pain, cognitive impairments (particularly problems with memory and concentration), unrefreshing sleep, sore throat, headache, and a constellation of other symptoms are debilitating enough to dismantle careers and destroy active lifestyles. Its hallmark, post-exertional malaise, is a return or worsening of all symptoms following even modest physical or mental activity which can last for days or weeks.

Alarmingly, less than 20 percent of ME/CFS patients have been diagnosed, yet early detection and symptom management have been shown to improve the patient’s long-term outlook. The high prevalence of ME/CFS, its low rate of diagnosis and the annual economic toll of up to $25 billion demonstrates the need for increased public and policy-maker awareness and a more potent research effort.

Meetings of the CFSAC provide a vital opportunity for experts selected by the Department to listen to and exchange information with representatives of DHHS agencies, including the National Institutes of Health, Centers for Disease Control and Prevention, Health Resources and Services Administration, Agency for Healthcare Research & Quality, Food and Drug Administration and Social Security Administration. The CFSAC meetings also provide opportunities for patients and advocates to express support for or concerns about ME/CFS programs through public testimony. The CFSAC allows for greater transparency and accountability for ME/CFS programs, helping to ensure the most effective policies and utilization of federal resources dedicated to ME/CFS.

We urge you to renew the CFSAC charter before its September 5, 2014 expiration and to fully support its important work. We appreciate your consideration and look forward to receiving your response.

Sincerely,

Carol E Head
President and CEO, Solve ME/CFS Initiative

 

cc: Dr. Nancy C. Lee, Deputy Assistant Secretary for Health – Women’s Health
Designated Federal Officer for CFSAC

 

Guest Blog: Roger Dodd, PhD – Retrovirus Testing in Retrospect

August 21, 2014

On August 13, 2014, Suzanne D. Vernon Ph.D., Scientific Director for the Solve ME/CFS Initiative (SMCI), held a webinar that provided an overview of the work done through SMCI’s Research Institute Without Walls and SolveCFS BioBank, as well as a glimpse of what’s ahead.  (Watch it HERE) During the Q&A portion of that webinar she received a question from someone concerning XMRV, wondering if they should be concerned that they tested positive. Realizing that others may have similar lingering questions or concerns about XMRV, she reached out to Roger Dodd, PhD, Vice President of Biomedical Services Research and Development at the American Red Cross, and asked him to provide this guest post on the topic.

“I met Roger in 2010 when I was asked to be on the Blood XMRV Scientific Research Working Group. The situation with XMRV was being taken very seriously and companies like Gen-Probe were developing the most sensitive diagnostic tests to detect the virus.  Roger told me a story about HIV testing that I asked him to share with you, as it applies to our XMRV situation.  It is a great example of the rigor needed for diagnostic tests.”, says Suzanne.

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Dodd2-249x300Guest Blog – Retrovirus Testing in Retrospect
By Roger Y. Dodd, PhD
Vice President of Biomedical Services Research and Development at the American Red Cross
Member of SMCI’s Research Advisory Council

Around the world, donated blood had been tested for HIV antibodies since 1985 – in the US alone, about 400 million tests – and we still have not perfected the process.  Certainly, there is essentially no risk of transmission of HIV by transfusion, but thousands of blood donors are uncertain about their test results even though we now use the most sensitive and specific tests available, from top flight manufacturers, intensively regulated by the FDA.  How can this be?  Simply put, it is a result of complexity, caution and simple mathematics.

The term complexity covers a tremendous range of issues, but suffice it to say that developing a test for antibodies to retroviruses is not at all simple.  The virus itself has many components that can react with antibodies, but it also has proteins that are similar to human proteins (human antigens).  Originally, the virus used to develop tests was grown in cells in the lab and some of the components of these cells were carried over into the test.  Also no retrovirus is totally unique and may share antigens with other retroviruses that humans may be exposed to but which do not cause any problems.    The tests themselves might react in unexpected ways – for example, some human antibodies react with the plastics in the test kits.  Not all of these complex issues are understood, and the outcome is that a test may give a result that looks positive, but has nothing to do with HIV infection.  This kind of event is called a false positive.  The term “specificity” is a measure that defines how often false positives occur (although its definition is actually the proportion of negative results when the test is used on people who are absolutely negative for the virus).  The ideal value for specificity is 100%, of course.  Because false-positives occur, it is always important to check reactive test results using a different test method, but even this is not perfect.

Caution has been a very important component of testing programs for HIV.  This caution is expressed in two directions: firstly, as pointed out to be sure that results are confirmed, but more importantly in the ways in which uncertainties have been handled.  So, even though a false positive result may be identified by a second test, no blood is used if the first test gives reactive results after the test is repeated.  So donors may be told that they cannot give blood, but that additional testing indicates that they are not infected.  Not a very encouraging message.

Where does simple mathematics fit into the equation?  It is a matter of understanding what the actual meaning of a reactive result is.  In collecting blood, very few of our donors are infected with HIV (actually, about 3 in every 100,000).  The test that we use has a specificity of about 99.9%.  That means that there is one false positive result for every 1000 donations tested.  So, in 100,000 donations, there might be three people with HIV and 100 with a false positive.  So a positive result with the very good test that we use only has one chance in about 33 of being right.  No wonder we have to do careful confirmatory tests and scrupulous counseling of our donors.  All of this with the very best of retrovirus tests used and refined over 30 years. Imagine how difficult it was in 1985.

The blood bank community took XMRV seriously, but were fully aware of the pitfalls of retrovirus tests and found little to encourage them about the validity of the XMRV testing that was being offered to the public.  What works in the research lab is not appropriate for mass testing without extensive validation and a clear, proven rationale.  XMRV itself was a laboratory artifact, and the so-called antibody tests were not credible.  This means the test that was being used to test the blood samples that ME/CFS patients sent to the testing laboratory were false positive.  If you were one of those who received a report indicating you tested positive for XMRV, you should rest assured that you are not. It is to be hoped that nobody carries lingering concern about XMRV and any test results associated with it.

CDC Stakeholder Call – Open Invitation

August 18, 2014

CDCIn the fall of 2012, the U.S. Centers for Disease Control and Prevention (CDC) began a new series of conference calls to update stakeholders about ME/CFS-related research activities and other topics of interest. Information on the next call, scheduled for Tuesday, September 9, 2014, is provided below from their listserv and website.  

There is no need to RSVP for this call, simply dial in. To join the listserv, please send an email message directly to CDC at  CFSPCOCACall@cdc.gov

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MARK YOUR CALENDARS

Tuesday, September 9, 2014

3:00 pm - 4:00 pm EDT

CDC CFS Patient-centered outreach and communication activity (PCOCA) Conference Call

Call number: 1-800-857-5128

Participant Code: 4459244

Please mark your calendars for the next CDC Chronic Fatigue Syndrome (CFS) Patient-Centered Outreach and Communication Activity (PCOCA) Conference Call.

 

Meeting Agenda

3:00pm    Welcome and Telephone Overview

3:05pm   Updates from CDC – Elizabeth Unger, PhD, MD

Branch Chief, Chronic Viral Diseases Branch

Centers for Disease Control and Prevention

 

3:15pm  “Can ME/CFS and FM Sleep Research Help You Sleep?”

Lucinda Bateman MD

Director, Fatigue Consultation Clinic

Adjunct Assistant Professor, Anesthesiology – Operations, University of Utah

Adjunct Instructor, Family and Preventive Medicine, University of Utah

3:45pm   Questions from CFSPCOCACall Mailbox for Guest Speaker and CDC

 

 Disclaimer: Although the content of calls is directed to patients, caregivers, health care professionals, and other interested parties, CDC has no control over who participates on the conference call.  Therefore please exercise discretion on sensitive content and material, as confidentiality during these calls cannot be guaranteed. 

 

Please note that questions for the Guest Speakers and CDC can be submitted only via email at CFSPCOCACall@cdc.gov. This mailbox cannot respond to inquires received and is in use only for the scheduled CFS PCOCA calls. If you would like to be added to the call list, please send an email to CFSPCOCACall@cdc.gov.

 

Contact for CFSPCOCA Conference Call: CFSPCOCACall@cdc.gov

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For some additional resources and information on the biology of sleep, CLICK HERE

 

 

Breaking News: Chemical Changes in Immune Cell DNA from ME/CFS Patients

August 12, 2014

SMCI Funded Research Results Announced!

We are pleased to announce the first study to report epigenetic modifications throughout the genome in female ME/CFS patients compared to a matched sample of healthy controls.  This research conducted in partnership and funded by the Solve ME/CFS Initiative (SMCI) was published today in the high impact and open access journal PLOS ONE (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0104757).

McGowanThe Solve ME/CFS Initiative launched our Research Institute Without Walls in 2010 and Dr. Patrick McGowan was one of our first grantees to use this innovative infrastructure. Together with his graduate student, Will de Vega and SMCI’s Scientific Director, Suzanne D. Vernon, they found evidence of distinct epigenetic profiles in immune and other physiologically relevant genes in a selected group of female ME/CFS patients. Will de Vega, who performed much of the work, is a PhD candidate in the department of Cell and Systems Biology at the University of Toronto. His thesis research concerns how environmental factors and ME/CFS impact immunological processes, and their effects on clinically relevant phenotypes. 

Epigenetic modifications affect the way genes are turned on or off without changing the inherited gene sequences. “Knowledge about the epigenetics of ME/CFS could potentially lead to alternative treatment options for sufferers, from targeted lifestyle interventions to new pharmacological treatments”, notes McGowan. There were many epigenetic modifications in and around immune genes that affect the way these genes are regulated and expressed. These types of changes would be expected to affect immune cell function in ME/CFS patients. “This is the first in a series of exciting results coming from McGowan’s lab at the University of Toronto”, says Suzanne D. Vernon. “By understanding these epigenetic differences in the immune cells of ME/CFS patients, we can begin to decipher the molecular mechanisms of the immune dysfunction that we suspect is at the root of ME/CFS”.

McGowan started this ME/CFS epigenetic research in 2012. His quick success is a testament to the power of patient-centered research approach used by the Solve ME/CFS Initiative. “Our study would not have been possible without the funding provided by the Solve ME/CFS Initiative, patient samples from the SolveCFS BioBank, and the collaborative support of the Initiative’s scientific director Dr. Suzanne D. Vernon” says McGowan.

The Solve ME/CFS Initiative will continue to partner with McGowan and his team at the University of Toronto to further this exciting work of epigenetics and ME/CFS. This field of research holds promise for identification of diagnostic biomarkers and potential treatment and interventions for ME/CFS. For right now it is further demonstration of the indisputable biological basis of ME/CFS.

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Learn More about McGowan’s work and results through our Webinar Series

Investigator Report: Epigenetics of ME/CFS

Thursday, August 21, 2014
2-3:00pm Eastern (1pm Central/Noon Mountain/11am Pacific)

Space is limited –  RSVP to Reserve Your Slot - Click HERE

Patrick O. McGowan, Ph.D., is one of the Solve ME/CFS Initiative 2011 funded investigators.  McGowan is an assistant professor in the Department of Biological Sciences, University of Toronto at Scarborough.  He will talk about his latest results from our grant funding.  McGowan used blood samples from the SolveCFS BioBank to identify the chemical modifications (e.g., methylation) to the DNA that is different in ME/CFS patients compared to healthy people.  This type of research will help explain the immune dysfunction of ME/CFS.