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.

 

Preliminary Results from Synergy Trial Released

May 14, 2015

The long-awaited preliminary results from the K-PAX Synergy Trial are out. While both the patient group and control groups showed improvements, the difference between the two was not statistically significant. The Synergy Trial was designed to produce an FDA-approvable treatment for Myalgic Encephalmyelitis/Chronic Fatigue Syndrome. The double-blinded, placebo-controlled trial evaluated the safety and efficacy of methylphenidate (generic Ritalin), combined with a mitochondrial support nutrient formula over 12 weeks. The outcome measurement tool used in the study was the Checklist Individual Strength (CIS), a patient-reported symptoms questionnaire specifically developed to evaluate CFS symptomatology.prescription-300x199

Per-Protocol Analysis: The Per-Protocol analysis included all study subjects who completed the 12-week study and were at least 75 percent compliant with taking the study treatment:

  • The patients in the KPAX 002 Treatment Group experienced an average 22-point decline in their CIS total symptoms score.
  • The patients in the Placebo Group experienced an average 13-point decline in their CIS total symptoms score.

The company says that, although the KPAX 002 group experienced almost twice the improvement as the patients taking placebo, the difference between the two groups did not achieve statistical significance, primarily due to the relatively small sample size—87—of the Per-Protocol population.

Intent-to-Treat Analysis (ITT): The ITT analysis included all study subjects who were randomized, took at least one dose of the treatment, and completed at least one post-baseline evaluation. This group included both study dropouts and non-compliant patients and is a much more rigorous analysis:

  • The patients in the KPAX 002 Treatment Group experienced an average 17-point decline in their CIS total symptoms score.
  • The patients in the Placebo Group experienced an average 13-point decline in their CIS total symptoms score.

The company says that due to the large improvement seen in the placebo group, the difference between the two groups did not achieve statistical significance.

Previous Methylphenidate Alone Study

Only one prior study has been performed for the treatment of CFS using the same dosage of methylphenidate (without mitochondrial support nutrients) and using the same outcome variable (CIS total score). This study was published in 2006 by Blockmans and colleagues in the American Journal of Medicine.

  • The patients in the Treatment Group of this study demonstrated an average 11-point decline in their CIS total symptoms score.
  • The patients in the Placebo Group of this study demonstrated an average 3-point decline in their CIS total symptoms score

Next Steps

Overall, K-PAX says it is encouraged by the substantial decline in patient symptoms and the treatment’s significant safety profile. The company says it will continue to review the more than 2,000 pages of additional data and secondary analyses and share additional information from the clinical trial as it becomes available.The company also will be collaborating with the study’s investigators to publish the full study results in a peer-reviewed medical journal.

To have your name added to the Synergy Trial update list, send a request to ask@KPAXpharm.com

To read a description of the Synergy Trial for CFS, go to www.thesynergytrial.org

SMCI Co-Hosts Research Roundtable in Boston

May 8, 2015

Mass CFIDS BannerThe Solve ME/CFS Initiative co-hosted a Research Roundtable May 2 with the Massachusetts CFIDS/ME & FM Association.

At the event, which was held at Newton Wellesley Hospital, Dr. Suzanne Vernon, Scientific Director of the Solve ME/CFS Initiative, provided an update on the research being conducted through SMCI’s Research Institute Without Walls by some of the brightest investigators from the best medical institutions. Dr. Vernon also described the exciting work currently being conducted through the SolveCFS BioBank™.

Following Dr. Vernon’s presentation, she and SMCI President Carol Head took part in a question and answer session in which they fielded questions on a wide range of topics related to research funding and developments, treatment options and implications from the February Institute of Medicine report.

To view the PowerPoint presentation from the event, go here  Boston Research Roundtable May 2015-PDF

Dr. Ledia Martinez Assumes CFSAC Designated Federal Officer Post

May 7, 2015

From the CFSAC listserv, posted May 6, 2015

With the retirement of Barbara James, we are pleased to announce that Ledia Martinez, MD, MPH has been appointed as the designated federal officer (DFO) of the Chronic Fatigue Syndrome Advisory Committee. Dr. Martinez joined the Office on Women’s Health (OWH) in 2008 and has worked as the Regional Women’s Health Liaison, coordinating programs and activities among regional and central office staff to improve the health and wellbeing of women and girls across the US. In addition to her success at leading the Regional Women’s Health Coordinators, Dr. Martinez has substantial experience coordinating meetings for OWH, including a yearly three-day in-person meeting for regional staff and coordination and chair of the 2011 OWH national meeting, which brought to Washington, D.C., more than 200 women’s health leaders.

Prior to her work with OWH, Dr. Martinez worked at the HIV/AIDS Bureau, Health Resources and Services Administration as the Acting Branch Chief for the AIDS Education and Training Centers. She also worked with planning councils for the Ryan White grants to resolve issues related to the treatment and care of HIV/AIDS patients. Among her previous positions, she worked at the national headquarters of the American Red Cross leading a national and international health program for Hispanics, where she developed training curricula and trained more than 1,000 community leaders. While working at the Colorado Department of Education, she developed and provided training for school personnel on health issues related to HIV/AIDS, STDs and drug and alcohol use among others.

She holds a bachelor’s degree from the University of Puerto Rico, a medical degree from the Eastern Central University at the Dominican Republic, and a Masters of Public Health from The George Washington University in Washington, D.C.

Dr. Martinez is assuming the DFO responsibilities immediately.

To join the CFSAC email list, go to: http://www.hhs.gov/advcomcfs/cfsac_email_list.html

SMCI Comment on the Institute of Medicine Report—Part 5

April 30, 2015

Orthostatic Intolerance and Cognitive Impairment
By Suzanne D. Vernon, PhD, SMCI Scientific Director

This is fifth and final post from our blog series to break down the Institute of Medicine (IOM) report, “Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness.” This blog focuses on cognitive impairment and orthostatic intolerance, one or both of which are required for an ME/CFS/SEID diagnosis, according to the IOM’s recommended criteria.

A diagnosis of a patient with ME/CFS requires functional impairment accompanied by debilitating fatigue, post-exertional malaise (PEM), unrefreshing sleep and at least one of these: cognitive impairment and orthostatic intolerance. Let’s take a look at cognitive impairment first.

Cognitive Impairment

Cognition is a suite of interrelated conscious and unconscious mental activities and processes including learning, memory, attention and processing speed. At one time, it was thought that these abilities and processes were located in discrete regions of the brain. With the help of powerful imaging technologies we now know that the brain is more like a highly sophisticated, multidimensional circuit board with wires traversing the brain to help ensure coordinated neural communication and function.

Patients describe the effect of ME/CFS/SEID on their brain as “brain fog,” “confusion,” “disorientation,” “hard to concentrate, can’t focus,” “inability to process information,” “inability to multitask” and “short-term memory loss.”  Neuropsychological research, which is research aimed at understanding the structure and function of the brain in people with disease, has shown that the cognitive impairment experienced by ME/CFS is due to slowed information processing.

Processing speed is defined as, “The rapidity with which a cognitive operation is undertaken successfully. Although this is usually related to the speed of information processing, it may also apply to the speed of retrieval. Processing speed affects performance in many tasks and is operationally related to reaction time.1

Impairment of processing speed is a common feature of other neurological diseases including Parkinson’s disease. Recent evidence published after the IOM report indicates changes in brain structure2, brain inflammation3 and immune activation4 in the brain and likely explains the cognitive dysfunction that occurs in ME/CFS/SEID patients.

The IOM committee concluded that there was sufficient evidence to show that slowed information processing was common in patients with ME/CFS and recommended that doctors ask the following questions to assess processing speed:

  1. Do you have problems doing the following activities:
    • Driving
    • Watching a movie
    • Reading a book or magazine
    • Completing complex tasks under time constraints
    • Following or participating in conversation; doing more than one thing at a time?
  1. Compared with before your illness, how is your performance at work or school?

The committee indicated neuropsychological testing could be used to provide objective data on slowed information processing. It should be noted that a neuropsychologist or someone with the appropriate expertise should administer formal neuropsychological tests. Physicians could also use questionnaires to obtain information on cognitive impairment including the Wood Mental Fatigue Inventory, Checklist Individual Strength Questionnaire, and the Cognitive Failures Questionnaire.

Orthostatic Intolerance

Orthostasis means standing upright. Orthostatic intolerance is “the development of symptoms while standing upright that are relieved by lying down.” The research evidence was strong that symptoms of orthostatic intolerance are common in ME/CFS patients. The IOM committee concluded the following:

“Sufficient evidence indicates a high prevalence of orthostatic intolerance in ME/CFS, as measured by objective heart rate and blood pressure abnormalities during standing or head-up tilt testing or by patient-reported exacerbation of orthostatic symptoms with standing in day-to-day life. These findings indicate that orthostatic intolerance is a common and clinically important finding in ME/CFS.”

The IOM committee recommended that doctors ask the following questions:

  • How do you feel when you have been standing still for more than 1-2 minutes?
  • What happens to you after you get up rapidly after sitting for a long time?
  • How long can you stand before feeling ill? For example, can you do the dishes? Can you stand in line for a bus or movie? Are you able to grocery shop or be at a mall for more than a few minutes? Can you take a hot shower or hot bath without feeling tired and lightheaded? Do you have to sit down or lie down after a shower? Have you fainted or felt like you were going to faint while standing?
  • Do these symptoms get worse in hot weather?
  • Do you study in a reclining or prone position?
  • Do you prefer to sit with knees to your chest or legs under you?

Looking Ahead

The Institute of Medicine’s landmark report has comprehensively and single-handedly redefined ME/CFS and brought new attention to its legitimacy. The report is also a huge leap forward in helping patients get diagnosed, which in turn will create more potential research participants. As the IOM committee found, “remarkably little research funding has been made available to study the cause of ME/CFS.” In the months and years ahead, the historic IOM report will help to inform the patient-centered research SMCI conducts through our Research Institute Without Walls and our SolveCFS BioBank.

Citations

1. Millan MJ, Agid Y, Brüne M, et al. Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nature Reviews Drug Discovery. 2012 Feb 1;11(2):141-68.

2. Zeineh MM, Kang J, Atlas SW, Raman MM, Reiss AL, Norris JL, Valencia I, Montoya JG. Right arcuate fasciculus abnormality in chronic fatigue syndrome. Radiology. 2015 Feb;274(2):517-26.

3. Nakatomi Y, Mizuno K, Ishii A, Wada Y, Tanaka M, Tazawa S, Onoe K, Fukuda S, Kawabe J, Takahashi K, Kataoka Y, Shiomi S, Yamaguti K, Inaba M, Kuratsune H, Watanabe Y. Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study. Journal of Nuclear Medicine. 2014 Mar 24;55(6):945-950.

4. Hornig M, Gottschalk G, Peterson DL, Knox KK, Schultz AF, Eddy ML, Che X, Lipkin WI. Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome. Molecular Psychiatry. 2015 Mar 31.

“White Matter Fibers, HCP Dataset Red Corpus Callosum,” courtesy of the Laboratory of Neuro Imaging and Martinos Center for Biomedical Imaging, Consortium of the Human Connectome Project: www.humanconnectomeproject.org

SMCI Comment on the Institute of Medicine Report—Part 4 of 5

April 28, 2015

Sleep
By Suzanne D. Vernon, PhD, SMCI Scientific Director

This is Part 4 of 5 of a blog series that breaks down the Institute of Medicine (IOM) report, “Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness.” This post focuses on unrefreshing sleep, the third diagnostic criteria recommended by the IOM committee.

Sleep is essential to recovery and rejuvenation of every system in the body—immune, nervous, muscular, etc. It is the time when our body builds up and replenishes the molecules that are essential for the body to function when awake. Yet sleep disorders and diseases are very common and almost everyone experiences disturbances, including problems falling and staying asleep, waking up early, sleeping all day and staying awake all night. We now know that left untreated, severe and chronic sleep disorders increase the risk of developing other chronic diseases such as heart and cardiovascular diseases.

Unrefreshing sleep, which is described as “feeling as tired upon waking as before going to bed,” is one of the most common symptoms reported by ME/CFS/SEID patients. The graph below is from a study conducted by DePaul University of SolveCFS BioBank participant responses to the DePaul Symptom Questionnaire1. The black portion of each bar corresponds to responses from ME/CFS patients; the gray portion from healthy control patients. Unrefreshing sleep and fatigue are the two most common symptoms in more than 90 percent of ME/CFS/SEID patients.

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Click on image to see full-size.

There has been research on unrefreshing sleep in ME/CFS, but like other research, ME/CFS/SEID sleep studies have suffered from small size, different designs and measures and including different patients defined by various case definitions. In general, in studies that used polysomnography to find possible causes of the unrefreshing sleep, ME/CFS patients had normal sleep study. Therefore, whether unrefreshing sleep is a cause or a consequence is unknown.

But since sleep is required for the body to rejuvenate and recover and since ME/CFS/SEID patients have chronically poor sleep that does not replenish their bodies, clearly this puts ME/CFS patients at significantly increased risk for a number of other diseases such as heart disease. Chronic unrefreshing sleep causes fatigue, brain fog, increased pain sensitivity, irritability and depression. Research has not identified the cause(s) of unrefreshing sleep in ME/CFS, and it is not clear if unrefreshing sleep may be the root cause of ME/CFS.

The IOM committee relied largely on patient-reported information to decide on unrefreshing sleep as one of the ME/CFS diagnostic criteria. After a review of the data and peer-reviewed biomedical evidence, they concluded:

“Despite the absence of an objective alteration in sleep architecture, the data are strong that the complaint of unrefreshing sleep is universal among patients with ME/CFS when questions about sleep specifically address this issue. While PSG (polysomnography) is not required to diagnose ME/CFS, its use to screen for treatable sleep disorders when indicated is appropriate. Diagnosis of a primary sleep disorder does not rule out a diagnosis of ME/CFS.”

The IOM committee recommended that medical providers ask about unrefreshing sleep when taking the medical history diagnosis. Example questions to ask include:

  • Do you have any problems getting to sleep or staying asleep?
  • How do you feel in the morning or after you’ve slept?
  • Do you need too much sleep?
  • Do you need to take more naps than other people?

Questionnaires that can be used to determine the frequency and severity of unrefreshing sleep include the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale. Certain medications, diet and behavioral changes can be used to treat sleep disorders and have been shown to help ME/CFS symptoms.

The fifth and final blog post in this IOM series will address the final two “either/or” diagnostic criteria: orthostatic intolerance and cognitive impairment. To ensure you receive notification of each future blog post as it is published, simply sign up for notifications in the grey and blue “Sign Up” box on the top right of this page.

Citation

1. Jason LA, Sunnquist M, Brown A, Evans M, Vernon SD, Furst J, Simonis V. Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis. Fatigue. 2014 Jan 1;2(1):40-56.

SMCI Comment on the Institute of Medicine Report—Part 3 of 5

April 24, 2015

Post-Exertional Malaise (PEM)
By Suzanne D. Vernon, PhD, SMCI Scientific Director

This is the third of our five-part blog series to break down the Institute of Medicine (IOM) report titled, “Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness.” As covered in the second blog post of this series, the IOM committee proposed specific criteria that focused on the central symptoms to make a diagnosis of ME/CFS.

This blog focuses on the second of the IOM-recommended diagnostic criteria and what we know to be the cardinal symptom of ME/CFS: post-exertional malaise (PEM). PEM is defined as an exacerbation of some or all of an individual’s ME/CFS symptoms that occurs after physical or cognitive exertion and leads to a reduction in functional ability.1 Patients have long known that PEM is a characteristic feature of their disease and individuals have described it as “crash,” “debility” and “hitting the wall.” The description by Dr. Larry Baldwin, a general surgeon and ME/CFS patient, is telling of the profound physiological effect of PEM:

“This pattern (of symptoms) is specific and vastly different from any post-exertional experience I had as an athlete, surgery resident or while practicing surgery. While training for marathons I was able to run through the ‘wall’ that many runners experience. Now I experience a similar wall after minimal exertion and have not been able to train through or push through this wall.”

Dr. Baldwin described his post-exertion symptoms as post-exertional debility because the consequences of too much physical or cognitive exertion are much more than malaise, which is a general feeling of discomfort and an inadequate term. As you can see in the chart below, Dr. Baldwin tracked the symptoms he experiences and how these increase in severity with increasing physical or cognitive workload.

Note that symptoms of fatigue, brain fog and sleep disturbance appear after minimal exertion. Other symptoms like gastrointestinal and neurological symptoms occur after higher levels of exertion. Nasal congestion and impaired thermoregulation symptoms occur but do not increase in severity. Tracking PEM symptom patterns can help patients understand what triggers PEM and what the individual physiological effects are. Importantly, this will help the individual convey their PEM experience to their doctor.

Caption: Dr. Larry Baldwin submitted this chart detailing his PEM symptom pattern to the IOM committee.

Caption: Dr. Larry Baldwin submitted this chart detailing his PEM symptom pattern to the IOM committee.

If the above is an example of the PEM experience for the individual, what does PEM look like in a research setting? Dr. Dane Cook, one of SMCI’s funded investigators, uses an exercise challenge in an attempt to obtain physiological assessment of PEM as well as standardized questionnaires that assess symptoms. Cook finds that the symptoms experienced by ME/CFS patients are quite variable.

The chart below, which shows how patients report on the symptoms and severity they are being asked about, displays results from 12 ME/CFS patients that went through an exercise challenge and then reported their symptoms 24 hours later. Patients 3, 6 and 11 had increased severity of many of the same symptoms. Patient 9 had increased chills. Interestingly, the symptoms for patients 4, 7, 8 and 10 decreased or diminished in severity following the exercise challenge as evidenced by negative values.

This illustrates that, even with a standardized exercise challenge in the controlled setting of a research laboratory, defining PEM is elusive. Further, standardized symptom assessments may not be adequate to capture the individual PEM experience, as evidenced by the symptoms that Dr. Baldwin experiences compared with those measured in research.

change
It is worth noting that the other IOM-recommended diagnostic criteria—functional impact of fatigue, unrefreshing sleep, orthostatic intolerance and cognitive impairment—can be objectively assessed in a clinical setting. But until we know how to objectively measure PEM, doctors will have to rely on eliciting information from the patient. The IOM recommended that clinicians use the following questions to diagnosis PEM:

  • What happens to you after you engage in normal physical or mental exertion?
  • How long does it take you to feel bad?
  • How long does it take to recover from physical or mental effort?
  • If you go beyond your limits, what are the consequences?
  • What types of activities do you avoid because of what will happen if you do them? (Consider asking patients to keep a diary for a week or two.)

These are actually very good questions that do not bias a patient toward a particular symptom, like fatigue or pain, but rather elicit the patient’s own, individual experience. Responses will give the doctor the information on exertion intolerance needed to make a diagnosis of ME/CFS and provide the symptom management and supportive care needed.

The need for research that objectively measures and defines PEM is even more paramount given the variability in the patients’ symptoms, experience and the complexity of PEM. Research on PEM has used the cardiopulmonary exercise test (CPET) to provoke and amplify the physiological disturbance that could be responsible for the post-exertion state. Individuals being challenged with one CPET test who have measures taken before and hours after the exercise challenge show changes in gene expression2, immune function3 and brain blood flow4. Administering two CPET tests—one 24 hours after the first—shows that ME/CFS patients cannot reproduce the physiological measurements from the first test indicating possible metabolic disturbances5. The source(s) of this metabolic disturbance has not yet been identified. Research that combines and correlates the CPET physiological results with the patients’ symptom experience will help zoom in on the possible causes of PEM, which could lead to objective diagnostic tests and treatment.

The next blog post in this IOM series will deal with the third IOM-recommended diagnostic criteria: unrefreshing sleep. To ensure you receive notification of each blog post as it is published, simply sign up for notifications in the grey and blue “Sign Up” box on the top right of this page.

Citations

1. Carruthers BM, Jain AK, De Meirleir KL, Peterson DL, Klimas NG, Lemer AM, Bested AC, Flor-Henry P, Joshi P, Powles ACP, Sherkey JA, Van de Sande MI. Myalgic encephalomyelitis/chronic fatigue syndrome: Clinical working case definition, diagnostic and treatment protocols (Canadian case definition). Journal of Chronic Fatigue Syndrome. 2003 11(1):7-115.

2. White AT, Light AR, Hughen RW, Vanhaitsma TA, Light KC. Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls. Psychosomatic Medecine 2012 Jan;74(1):46-54.

3. Sorensen B, Jones JF, Vernon SD, Rajeevan MS. Transcriptional control of complement activation in an exercise model of chronic fatigue syndrome. Molecular Medicine 2009 Jan-Feb;15(1-2):34-42.

4. He J, Hollingsworth KG, Newton JL, Blamire AM. Cerebral vascular control is associated with skeletal muscle pH in chronic fatigue syndrome patients both at rest and during dynamic stimulation. NeuroImage Clinical 2013 Jan 5;2:168-73.

5. Keller BA, Pryor JL, Giloteaux L. Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO₂peak indicates functional impairment. Journal of Translational Medicine & Epidemiology 2014 Apr 23;12:104.

SMCI Comment on the Institute of Medicine Report—Part 2 of 5

April 21, 2015

Defiant Fatigue
By Suzanne D. Vernon, PhD, SMCI Scientific Director 

The Institute of Medicine (IOM) convened a committee with expertise and experience in ME/CFS as well as other relevant medical and research domain experts. The committee was specifically charged with: 1) conducting a study to identify the evidence for various clinical diagnostic criteria for ME/CFS using a process with input from stakeholders, including practicing clinicians and patients; and 2) developing evidence-based clinical diagnostic criteria for ME/CFS for use by clinicians, using a consensus-building methodology. The result was the recommendation of new, evidence-based diagnostic criteria to diagnose ME/CFS. The new diagnostic criteria include the following three cardinal symptoms of ME/CFS, which the IOM proposed be renamed Systemic Exertion Intolerance Disease (SEID):

  1. A substantial reduction in activity

More specifically: A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social or personal activities that persists for more than six months and is accompanied by fatigue, which is often profound, is of new or definite onset—not lifelong—is not the result of ongoing excessive exertion, and is not substantially alleviated by rest;

  1. Post exertional malaise; and
  1. Unrefreshing sleep

AND one of these two:

  1. Cognitive impairment OR
  1. Orthostatic intolerance

Let’s start with the first recommended diagnostic criteria: “functional impairment that persists for more than six months along with fatigue.” Any attempt to study fatigue requires definition, measurement and interpretation. Yet for more than a century fatigue has defied definition and hence, effective measurement and interpretation. This is likely because fatigue is a subjective feeling or personal state. In fact, the International Classification of Diseases (ICD) classifies fatigue as a general, self-described symptom.

Fatigue is likely to be identified as a problematic symptom only when the individual is unable to obtain complete recovery through the normal processes of rest and sleep. In a 1940 address to the Omaha Midwest Clinical Society, which was published in the journal Psychosomatic Medicine, Wendell Muncie, M.D., of Johns Hopkins University explained that chronic fatigue was singly or in combination related to post-infectious states and endocrine-metabolic states.

Attempts at physiologic measures of fatigue have been inconclusive, and no specific measures have as yet been identified. Perhaps the only variable unique to fatigue is time. As C. Cameron wrote in a 1973 volume of Ergonomics: “Severity of fatigue is most effectively measured by the time required for the body to recover to homeostasis between exposures to the circumstances suspected of producing fatigue.”

This description puts severe fatigue in a context of time and homeostasis, or the ability of our body to monitor and regulate function. The IOM recommended that fatigue should be diagnosed using both time and impact on function:

“Conclusion: There is sufficient evidence that fatigue in ME/CFS is profound, not the result of ongoing excessive exertion and not substantially alleviated by rest. This fatigue results in substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social or personal activities and persists for more than six months.”

To illustrate the impact of fatigue on function in ME/CFS, the IOM committee compared vitality across a number of diseases. Vitality is one of the scales on the SF36, a standardized assessment instrument that assesses energy and fatigue by asking for responses to four questions: 1. “How much of the time during the past four weeks did you have a lot of energy?;” 2. “… have you felt full of life?;” “… did you feel worn out?;” and 4. “… did you feel tired?” The committee’s comparison clearly illustrated the profound effects of ME/CFS on vitality; the table below shows some of the vitality scores for healthy people, a few diseases and ME/CFS/SEID.

 

Vitality Score 

Healthy people 

60-70

Congestive heart failure 

29

Chronic hepatitis C patients 

48

Rheumatoid arthritis 

43-52

ME/CFS

15-20

Other research using the SF36 has shown that physical activity and social functioning are also impacted in ME/CFS. While the IOM noted the extensive use of the SF36 in research, it did not recommend it as a tool for doctors to use because it is complicated to score. However it seems reasonable that an app could be developed for use in a doctor’s office; in fact, a SF36 app already exists in the iTunes App Store, though it is not in English.

The stark differences in vitality scores between ME/CFS and a number of other diseases that are readily diagnosed and taken seriously indicates the importance of fatigue as one of the four criteria to diagnosis ME/CFS.

We will address the remaining criteria in subsequent blog posts, providing additional context and implications around them. The final post in this series will discuss how the scientific community can use these clinical diagnostic criteria to advance ME/CFS research.

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Suzanne D. Vernon Steps Down from Scientific Director Post

April 8, 2015

Eight years after joining the Solve ME/CFS Initiative (SMCI), Suzanne D. Vernon, PhD, will be stepping down as Scientific Director in late June. She will continue with the organization in a consultancy role. SMCI has begun an international search for a Research Director.

As the organization’s first Scientific Director, Vernon played a key role in transforming SMCI into a patient-centered research organization—one that translates donor-funded research into tangible results and progress.

Shortly after joining SMCI in 2007, Vernon tapped into her professional network to spark interest in ME/CFS research. Her efforts resulted in more than 10 new investigators becoming engaged in ME/CFS research. “ME/CFS is a blank slate, and for scientists this represents a great opportunity for discovery,” says Vernon.

Suzanne D. Vernon, PhD

Suzanne D. Vernon, PhD

During her time with the organization, Vernon established the SolveCFS BioBank, which is one of the few biobanks focused on ME/CFS. “Our SolveCFS BioBank puts patients as partners in the research pipeline,” says Vernon. This patient-centered research approach engages patients in being part of the solution.

Vernon’s contributions to SMCI have left the organization well-positioned to continue its leadership role in funding forward-thinking investigators from the best institutions. The Solve ME/CFS Initiative is one of the largest private funders of ME/CFS research.

Vernon is excited about the opportunities that are ahead of her. She is considering a return to her infectious disease roots, as well as embarking on quantified self research in the chronic disease space.

“Suzanne has made an indelible contribution not only to our organization, but also to the field of ME/CFS research broadly,” says Solve ME/CFS President Carol Head. “Her efforts will continue to bear fruit for many years to come.”

Head adds that this is an exceptional time for research into ME/CFS, given the impetus of the Institute of Medicine report. “We look forward to building on the current research momentum, which is beginning to bring clarity to this complex, insidious disease,” Head says.

 

Solve ME/CFS Initiative Hosts IOM Briefing in D.C.

April 2, 2015

On March 25, the Solve ME/CFS Initiative hosted a briefing in Washington, D.C., on the Institute of Medicine’s report on myalgic encephalomyelitis/Chronic Fatigue Syndrome.

The briefing gathered congressional representatives, reporters, government officials and researchers in the ninth-floor rotunda at 101 Constitution Ave. More than 300 also viewed the event through a live webcast, which can be viewed on the Solve ME/CFS YouTube channel. Mary Sue Perpich, daughter of the late Gov. Rudy Perpich, helped to organize the event.

Speakers included:Morgan_DrClayton_Carol

  • Dr. Ellen Wright Clayton, chair of the IOM committee on ME/CFS;
  • Morgan Fairchild, actress, activist and former ME/CFS patient;
  • Carol Head, president of the Solve ME/CFS Initiative

Dr. Clayton began her presentation with some background on the landmark report and the unanimity the committee members experienced over the 18-month period. “It really was an amazing, dynamic process,” said Clayton, who has chaired or co-chaired five other IOM committees. After providing an overview of the report’s key recommendations, she offered her own thoughts about the next steps that need to be taken now that the committee’s work is done.

“It is my sincere hope that people will use this report, which clearly demonstrates the seriousness of this illness for advocacy with policy makers,” she said. “It is time to fund more research into this disease’s causes, defining subtypes and effective treatments. This will require stronger advocacy in—and outside—the government.”

Clayton added: “We opened the door. The challenge now is to go through that door.”

In her remarks, Solve ME/CFS president Carol Head made a forceful case for the need for dramatically more government funding for the disease. Through a series of slides, Head demonstrated that the funding for ME/CFS ranked 232 of the 242 National Institutes of Health spending categories in 2014.

“In actual dollars, the spending on ME/CFS is less than what our government spends on hay fever,” Head said. She also showed that, given the prevalence of ME/CFS, the NIH funding is a mere $5 per patient, compared with, say, $255 per multiple sclerosis patient and $2,482 per HIV/AIDS patient.

Given the disparity of federal funding, as well as the $17 to $24 billion dollar economic burden on the country from ME/CFS, Head called for three things to take place:

  1.  Provide funding for biomedical research and studies commensurate with the disease burden. Head said that based on disease prevalence, NIH funding should be roughly $250 million annually.
  2. Resolve the organizational and institutional barriers within the federal departments. “We need a strategic and tactical plan and commitment to solving this disease across agencies, perhaps even an ME/CFS czar.”
  3. Accelerate educate of the nation’s medical professionals since “patients cannot wait.”

Morgan_0n_Mic2Morgan Fairchild led off her remarks with a question. “I know a lot of you are wondering, why is Morgan Fairchild talking about this disease?,” she said. “It’s because Morgan Fairchild has had this disease.”

Fairchild explained that she had always been interested in science and research and had read a fair amount about ME/CFS in the 1980s. In 1989, after returning to L.A. from a movie shoot in Portland where it had been cold and rainy, she went to see her doctor who told her she tested positive for Epstein-Barr virus. “Suddenly, CFS wasn’t just a fascinating case study; I was one of the cases,” she said. While Fairchild didn’t suffer from fatigue at the time of diagnosis, she says, “When it hit me, it hit me like a ton of bricks.”

She was fortunate on a number of fronts: She had a mild case, she was diagnosed early, and she had a doctor who didn’t think she was “nuts.”

Fairchild said she learned how to pace herself and save herself for her work, which was manageable since movies require work in spurts with long down times in between, when she could rest. While the brain fog made it harder to learn her lines—something that had always come easily to her—she “was able to muddle through and keep making a living.” She knows this is not the case for most ME/CFS patients.

“I was very lucky, Carol was very lucky,” she said. “We got past it.”

Fairchild says she’s committed to making the path easier for others.

“Real pain and devastation exist because of this disease,” she told the in-person and webcast audiences. “We need the powers that be to give us focus and funding because, honey, the science ain’t free.”

Access the PowerPoint presentations and Carol Head’s comments from the briefing HERE

 

 

SMCI Comment on the Institute of Medicine Report – Part 1 of 5

April 1, 2015

Redefining an Illness

By Suzanne D Vernon, Ph. D, SMCI Scientific Director

IOM_ReportCover

 

On February 10, 2015 the Institute of Medicine (IOM) issued the long awaited report on diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) titled, “Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness”.  This 304-page landmark report is remarkably thoughtful, highly informative and an accessible evidence-based document that succeeded in providing medical providers a much-needed framework for diagnosing ME/CFS (SEID).

In the weeks ahead, I will break down the report allowing a better understanding as to why the committee recommended these particular diagnostic criteria. There has been much discussion on the diagnostic criteria put forth in the IOM report, and debate on how this may affect clinical practice and research. It is important to begin with clarifying what is meant by “case definition” and “clinical diagnostic criteria”:

  • Case definitions are used in research to identify biomarkers and causes of diseases.  A case definition is an epidemiological tool used to establish whether a patient can be linked to an outbreak and to determine the number of people in the affected population – or “cases” involved in an outbreak.  (Epidemiology is the science that studies the patterns, causes, and effects of health and disease conditions in a specifics population.)  It is not recommended that case definitions be used to guide clinical practice. Case definitions should be designed to be simple and practical and are formulated to include the following components:
    • Time – a period of time “cases” are associated with an outbreak
    • Place – limiting “cases” to a geographical location
    • Person – personal characteristics (e.g., age, sex) as well as clinical and laboratory criteria that are hallmarks for the illness
  • Diagnostic Criteria are used by medical providers to help diagnose what is making an individual sick. People often present to their doctor with symptoms like pain and fatigue that are nonspecific.  Many medically unexplained diseases do not have objective diagnostic tests making diagnosis challenging.  Medical providers use many of the following types of information to make a diagnosis:
    • Intake history (the events that preceded the visit to the doctor)
    • Medical history
    • Family history
    • Physical examination
    • Diagnostic tests (e.g., blood tests, imaging procedures, etc.)

Perhaps the biggest difference is that “case definition” deals with populations of patients and “diagnostic criteria” focuses on the individual.

There are currently no diagnostic laboratory abnormalities or clinical tests that can be used to diagnose ME/CFS. The IOM committee was charged with developing evidence-based clinical diagnostic criteria for ME/CFS.  In other words, what could the IOM committee recommend with confidence that medical providers could use to diagnose ME/CFS in an individual who comes into their office.  The IOM committee did not limit themselves to the peer-review medical literature and in fact drew upon the extensive input from the patient community and also reviewed and evaluated unpublished data. The committee developed a process or diagnostic algorithm that providers could use to make an ME/CFS diagnosis.

Many case definitions put forward, such as the Canadian Consensus Criteria and Fukuda, have been a combination of research and diagnostic and have not been operationalized for a clinical setting. This has led to much confusion and a lack of adoption. We believe that the diagnostic criteria recommendations from the IOM are an important step in moving ME/CFS into the medical mainstream. It is clear that the IOM considered the Canadian Consensus Criteria in coming up with these evidence-base diagnostic criteria.  It was also clear that the IOM wanted criteria that could be more readily and easily used by physicians.

Another important aspect of the IOM report is that it declared that ME/CFS/SEID must no longer be a diagnosis of exclusion.  Patients can and must be diagnosed so that they can begin to receive the care that they need. This simple criteria will help move diagnosis and treatment forward. This flow diagram is the streamlined and systematic approach using specific diagnostic criteria that was recommended by the IOM committee:

diagnostic algorithm

This disease has been poorly defined, which means that diagnosis is difficult. That is not uncommon for a multisystem, complex disease, with symptoms that appear in other illnesses as well, and can be difficult to measure objectively. There is no simple blood test, or genetic test for diagnosis. The newly discovered biomarkers are few and cannot be done routinely in a doctor’s office. And as it is a genuinely complex disease and therefore can be difficult to diagnose. Doctors face an overwhelming amount of information to absorb, 15 minute appointment slots in their days, filled with both time and financial pressures. With new, clear diagnostic criteria as put forth, diagnosis is far less complicated and more readily deployed in the clinical setting. A simpler criteria, well deployed and utilized, will lead to better, faster diagnosis for millions of suffering individuals.

This represents the federal government clearly affirming that this is a serious, physical disease, not a syndrome. For the million Americans who have long suffered with skepticism and lack of care, this is deeply affirming.

Access the full clinicians guide HERE

This is but one piece of a very lengthy and thorough report. In the weeks ahead, we will put forth a series of blog posts, focused on a deeper dive into the evidence for each of the diagnostic criteria, one by one.  The final post in this series will discuss how the scientific community can use these clinical diagnostic criteria to advance ME/CFS research.

To ensure you receive notification of each blog post as it is published, simply sign up for notifications in the grey and blue “Sign Up” box on the top right of this page.