PHOENIX RISING

Bringing Opportunity to ME/CFS Patients

A GUIDE TO ME/CFS ADVOCACY

Some of the issues discussed in this meeting include:

● Why more women than men have chronic fatigue syndrome (ME/CFS).
● Which kind of community does Dr. Reeves’ data suggest places women at a higher risk of chronic fatigue syndrome (ME/CFS)?
● Where do more men than women have chronic fatigue syndrome (ME/CFS)?
● Where do the short-term attention problems possibly originate?
● Does child abuse play a big role in chronic fatigue syndrome (ME/CFS)?
● Is there a hormone/female connection?
● How might the Surgeon General get involved in this disease?

Dr. Reeves’ Report of the Center for Disease Control's (CDC's) program

Dr. Reeves’ report is always interesting and this section is always long because (a) there’s a lot going on at the CDC and (b) Dr. Reeves reports on it. There will be a distinct contrast between his report and Dr. Hanna’s report on the chronic fatigue syndrome (ME/CFS) program at the NIH later – of which just the opposite is true.

A Complex Disease - As he did at the last CFSAC meeting Dr. Reeves emphasized that chronic fatigue syndrome (ME/CFS) is a complex illness that represents changes in systems all across the body and is caused by a combination of factors which includes your genes and the things (i.e. ‘environmental factors’) that happen to you. Dr Reeves again hit on the notion, which to my understanding he alone has embraced publicly: that chronic fatigue syndrome (ME/CFS) is the kind of illness that leads to other diseases. He believes, in fact, that CFS research may help researchers elucidate common pathways that show up in other complex diseases. (Some other complex diseases include autism, diabetes, heart disease, etc.)

Obviously we’re getting only the tip of the iceberg with regard to Dr. Reeves’ concept of chronic fatigue syndrome (ME/CFS) here. His most recent presentation, though, fits in with the CDC’s ‘allostatic stress’ theory which posits - if I understand it correctly - that a poorly working stress response system results in basic aspects of ME/CFS patients’ physiology beginning to break down. The finding that chronic fatigue syndrome patients are usually adults appears to fit in with this scenario of problems slowly accumulating over time.

The Role Gender Plays (or Why Women Should Stay Out of Large Cities)! (?). Dr. Reeves then made what I thought was a rather startling statement; that the increased rate of chronic fatigue syndrome (ME/CFS) in women was probably due to gender not biology. This finding is based on the greatly increased prevalence of women in certain communities (metropolitan) vs. others (urban, rural) in the latest Georgia study. The Georgia study found that women living in the metropolitan (Atlanta) areas had enormously increased risk of ME/CFS while men there had a lower risk. In one part of Georgia (the rural areas) men had a greater risk of getting CFS than women (!).

This suggests that it’s not hormonal or immune or other differences that increase the risk of CFS for women, but sociological ones; i.e. society and gender collide to evoke CFS in more women in certain areas. This is the conclusion the facts support but the facts are so odd that one wonders if a mistake was made in the study. What after all would put women so much more at risk in a metropolitan area (Atlanta) as opposed to a smaller urban area (Macon). On the face of it it’s a very puzzling finding. One must wonder as well what role the empirical definition with its discounting of fatigue and its inclusion of emotional factors plays in building this particular group of CFS patients. It’ll be interesting to see if this finding is replicated in future studies.

CDC’s Laboratory Findings. The new Georgia study is apparently confirming what the Wichita study found; that chronic fatigue syndrome (ME/CFS) patients are 6 times more likely than healthy people to have suffered some sort of abuse (physical, emotional, sexual) and carry about six times the amount of stress-induced physiological loads (‘allostatic load’) than healthy people do. This suggests to him to that the maladaption to stress that CFS represents probably starts very early with some adverse incidents including childhood abuse, infections, surgery, injury, etc.

The Attention Problem: Dr. Reeves believes this shows up in several physiological ways. With regard to cognition there is ‘slowed movement time’ and problems with sustained attention, poorer spatial memory, etc. These differences are often quite subtle but they show up again and again and Dr. Reeves thinks they are quite significant. He believes they may involve problems in the neurocircuitry that link the basal ganglia and the frontal cortex.

While CDC studies have not found evidence of altered ‘sleep architecture’ (i.e. REM sleep, etc.) a spectral analysis indicated that two types of brain waves during sleep were reduced; alpha power which is associated with ‘quiet wakening’ and delta power which is associated with sleep homeostasis.

The autonomic nervous system - which is one branch of the stress response – is altered. Four findings; increased heart rate, reduced heart rate variability, lower blood aldosterone and higher norepinephrine suggest that the ‘fight or flight’ branch of the ANS (the sympathetic nervous system) is overly activated and the ‘rest and digest’ branch (parasympathetic nervous system) has been turned off to some extent.

Women and Hormones – An ME/CFS Connection? An opposite situation appears to be occurring on the other side of the stress response, the HPA axis. Cortisol, the main adrenal hormone, is turned down. Interestingly the CDC’s recent data shows this is true only in women and in those ME/ CFS patients (male or female apparently) who’ve experienced childhood trauma. This suggests that low cortisol may be a pre-existing factor and suggests there may be a distinct low cortisol/childhood trauma subset in ME/CFS.

When and how cortisol levels drop in CFS is one of the big mysteries of this disease; does the HPA axis ramp up and then ‘burn out’, or do pre-existing low cortisol levels predispose one to getting CFS, or do cortisol levels drop later on in the disease? We may have an answer to this sooner rather than later. Dr. Taylor is examining adolescents as they lapse into CFS following infectious mononucleosis and she’ll be charting cortisol levels.

The CDC’s genetic data continues to implicate the adrenal gland. Dr. Reeves emphasized the HPA (hypothalamus-pituitary-adrenal) axis’s role, in particular the hypothalamus. He noted that different stressors are processed in different ways with ‘neurogenic stressors’ (such as anticipating something negative and fear) being processed through the frontal lobes and physical stressors (cold, heat, infection, dehydration) being processed through the brain stem. Both meet at the hypothalamus and hypothalamic dysfunction appears to be a key part of a complex model that involves neurotransmitters and immune agents.

Here we have a meeting of the minds between Dr. Reeves and physician/researchers such as Dr. Holtorf and Dr. Teitelbaum. Both groups emphasize the HPA axis and locate a main dysfunction in or around the hypothalamus.

Emory University (A Future Center of Excellence for CFS?) –– Dr. Reeves has cultivated close ties with Emory University and is collaborating with them on a large, complex NIH/CDC funded project called ‘Pathophysiologic Mechanisms of CFS: Neuroimaging, Neuroendocrinology and Genomics’. This project, began in Jan/Feb of this year, finds the CDC moving into brain imaging in a big way. It involves a three day visit to a hospital to do the following:
1. Functional MRI tests to identifies abnormalities in brain regions (primarily the basal ganglia) that play a role in mental fatigue, cognitive function and autonomic nervous system functioning (heart beat, blood flow, breathing rate, immune regulation).

Intersection: Chaudhuri and Behan suggested the basal ganglia played a key role in fatigue in ME/CFS in 2001.

2. During memory stress tests brain imaging scans will capture changes in psychomotor speed (response time) sustained attention, etc. Researchers will apparently chart changes in the brain as ME/CFS patients show increased response time, inability to sustain their attention and problems with short-term memory. They will also be looking at indicators to see if the stress response (cortisol, heart rate variability, heart rate) as well as immune system (cytokines) is responding abnormally when CFS patients engage in these memory stress tests.

3. A different stress test will monitor many of the same components plus respiration, galvanic stress response and gene expression (to see if ME/CFS patients show altered gene activity.) These studies will constitute the most thorough examination of the stress response yet done in CFS.

Epidemiology – Another large project will look at ME/CFS prognosis, economic impact, prevalence, and quality of life. Projects which quantify the impact ME/CFS has on a population are very important for elucidating the need for more funding.

Pilot Registry – In June/July a registry of patients in Macon, Georgia will be created that Emory University and Mercer Medical School can use in their studies of ME/CFS patients. They’ll scour HMOs, private practice physicians, psychiatrists, endocrinologists, infectious disease specialists as well as physical therapists, acupuncturists, homeopathists, herbalists, etc. for ME/CFS patients.

This registry will presumably be used to compare CFS patients from clinics with those gathered during the CDC’s random sampling surveys.

The CDC will then target the area for a public awareness campaign about ME/CFS and see how effective it is in driving previously undiagnosed patients to these practitioners and in increasing physician awareness.

Conclusion: All told an exciting spate of activity that promises much. It’s encouraging to see a well-respected University get involved. Dr. Reeves has stated Emory would love to house a Centers of Excellence Program on CFS.

Q and A with Dr. Reeves

Dr. Hanna, the director of the NIH’s CFS program at the Office for Research For Women’s Health, went off on what I thought was a somewhat bizarre tangent. She noted that the CDC excluded from their studies alcoholics who otherwise met the criteria for ME/CFS and then stated that if Dr. Reeves had submitted his project to the NIH for approval it wouldn’t have been funded because he didn’t have that other group (alcoholics with CFS) in there.

Perhaps feeling defensive about the lack of ME/CFS research the NIH is funding, she then said “that’s why it’s more difficult to get studies funded when they’re peer reviewed’. Suggesting Dr. Reeves’ study would not have passed a more stringent peer review process could only have raised his hackles. Dr. Reeves shot back that his upcoming study wouldn’t have passed peer review ‘because the review panel would say that it was too ambitious”; i.e. suggesting that the review panels at the NIH are inherently too cautious to provide real breakthroughs in CFS.

Rebecca Artman, the patient advocate on the panel from PANDORA, raised a concern about the large number of exclusionary conditions the CDC uses to winnow down its sample to more or less ‘pure’ CFS patients. Dr. Reeves didn’t directly answer this question but chose to emphasize that a very significant percentage of ME/CFS patients do, in fact, have other problems that are missed and can and should be treated. This struck a chord with Dr. Oleske who jumped in noting that almost every condition a ME/CFS patient presents is under-treated because every symptom is blamed on ME/CFS. He’s seen numerous cases of ME/CFS patients, for instance, with untreated asthma (!).

Child Abuse Or Not? Questions have been raised whether the CDC was seeking to ‘psychologize ME/CFS’ through its findings of increased rates of child abuse in CFS. Given that context it was startling to read Dr. Klimas report that she had found much (much) higher rates of child abuse in ME/CFS than even the CDC reported (!).

Dr. Jason then jumped in to state that his prevalence studies had not shown greatly increased levels of childhood trauma and then transitioned to the one of the great questions facing ME/CFS; how was the empirical definition – the controversial ‘new’ definition created by the CDC – changing the types of patients seen in the CDC’s studies?

Dr. Reeves went back over the need for a new definition – which no one and certainly not Dr. Jason, who helped advise the CDC on the new definition - would deny. He basically defended the new definition, saying that because it quantifies fatigue and disability symptoms, that he knows for the first time, what kinds of patients show up in his studies. He didn’t address the question whether they might be the wrong kinds of patients.

CFS Interventions (i.e. treatments) – In response to a question from Dr. Klimas Dr Reeves stated that a workshop in Spring was going to discuss ME/CFS treatments and that funding levels were slightly less than last year (which were significantly less than the year before).

National Institutes of Health CFS Research Program

Now we move to the other arm of the government’s CFS research effort, the NIH. The CFS research effort there is led by Dr. Eleanor Hanna based at the Office of Research For Women’s Health. Her report is, typically, quite a bit shorter.

‘Painting the Pig’ - Dr. Hanna and the NIH CFS Program:

The NIH’s big effort of the past year was to produce a Grantsmanship Workshop that explored ways ME/CFS researchers could obtain research funding from other sources than the ME/CFS research program. Dr. Hanna characterized it as ‘extremely successful’ but it clearly was not; despite a good turnout from the Institutes of the NIH, very few CFS researchers attended. Hence the title of this section –we will see Dr. Hanna repeatedly try to pretty up the pig; i.e. dress up the NIH’s accomplishments during her presentation. The poor turnout at the Workshop couldn’t have been surprising. As NIH budgets remain static or decline and the search for grant moneys gets more competitive, CFS researchers who can’t get funded from their own program in the NIH obviously have trouble believing they have much of a chance of getting money from other programs.

A big obstacle is simply the lack of researcher interest, much of which can be laid directly at the NIH’s feet. Researchers will not take on controversial subjects unless they have an expectation that they’ll have continued funding, but the NIH’s actions suggest they have very little interest in funding CFS. Their one big effort of the past five years – a relatively small grant for research into neuro-immune issues in ME/CFS – took years to get together and ultimately failed, not because the research community didn’t respond, but because the NIH failed to fund many proposals.

What’s needed is to commit to a sustained research effort, i.e. research centers or Centers of Excellence. Dr. Hanna’s big announcement – the creation of a program looking not at ME/CFS but at multiple pelvic pain disorders – underlines what pitiful shape the CFS research is in.

Dr. Hanna is obviously trying; the Grantsmanship workshop, the inclusion of CFS in the Multi-Pelvic-Pain Disorder program and her announcement that National Institute of Aging and NIDDK will be members of the Chronic Fatigue Syndrome Working Group (CFSWG) are testaments to Dr. Hanna’s creative capabilities in a difficult situation, but they also underscore the astonishingly little support CFS receives at the NIH. Diseases that cause tens of billions of dollar a year in losses shouldn’t have to try to shoehorn their researchers into other diseases in order to get funding. Dr. Hanna and Dr. Pinn and the ORWH have utterly failed in their most essential mission; to create a viable CFS research program at the NIH.

What is on the ORWH’s CFS research team’s plate for the upcoming year? Nothing. They’ll continue to fund the few studies they are funding. They’ll probably add a study or two. They’ll update their Program Announcement. (Program announcements detail which subjects the NIH is interested in funding.)

Committee Questions: The committee is obviously not pleased at the state of CFS research at the NIH. They have asked for Centers of Excellence/Research Centers and have been rebuffed. Again Dr. Klimas asked how about funding COE’s and again Dr. Hanna said the Institutes will not fund them for CFS and that the research is there yet. Maybe Dr. Hanna once again suggested, after the RFA grants finish we’ll be able to get the support.

Let’s take a look at this idea: Dr. Hanna has several times suggested that once we get these grants done THEN maybe we can really build some support for research centers. The RFA funded four grants on CFS. Those grants will be finished in four years and it’ll take at least another year to write and publish their results. So Dr. Hanna is saying a) expect the status quo – very little activity – for at least five more years and b) pin your hopes that a very small number of studies will somehow cause the NIH to rear up and take notice of CFS. It’s a ludicrous argument that I’m not clear why the committee accepts at face value.

Dr. Willis-Fridinger then posed a type of question that I find unsettling; how does the NIH allocate funding? It’s a very basic question that indicates Dr. Fridinger may know almost nothing about this subject – something I find troubling in a member of federal advisory committee on CFS.

Dr. Jason then stepped in with an excellent question: why was the NIH able to fund three CFS Research Centers in the mid 1990’s, when we knew much less about the disease, but now can’t find the money to fund any?

Dr. Hanna gave what is becoming her usual answer to these types of questions “It’s above my pay grade”. She felt that the some of the Centers ‘rested on their laurels’ and noted that the NIAID, which was funding the Centers, recommended that they not fund them anymore apparently because they were getting tired of funding a lot of non-immune research. At that point it was incumbent on the other Institutes to step up and fund CFS research, but they failed to do so.

Dr. Hanna basically laid the blame for that on the Centers, stating they wouldn’t give the Institutes a ‘good accounting of what they had’, which suggested they couldn’t be bothered to answer questions about their programs when their fate was on the line – something which stretches one’s imagination. Dr. Natelson, who is reportedly still furious about the closing of his New Jersey Center, which became the most prolific CFS research program ever, would surely disagree.

Unfortunately the conversation died before we could get to the most important question; why are the big neurological, immune, cardiovascular, musculoskeletal institutes refusing to contribute to Centers now? What do they mean when they say the ‘research is not there yet’? How will we know when it is ‘there’? It would require a pittance money-wise in the medical research field to do so. As one explanation, Dr. Hanna did say the NH was moving away from having Centers. If so they’re not moving very fast – they currently fund over 1,500 of them.

Since I have the podium, I’ll state what I believe the Committee should do; they should ask the Institute representatives to appear before them and explain why CFS is not worthy of real funding and what benchmarks the research field needs to meet before they start spending even a little money on this disease. While they’re at it the Committee could also ask them if they feel comfortable presiding over a program that is responsible for uncovering the cause of a disease that strikes a million Americans and yet has funded only 8 new grants in the last five years.

Education Subcommittee Report

The Surgeon General and CFS? - The Education Subcommittee has been busy. They’re trying to get the Surgeon General (SG) to provide a letter to health care providers about CFS and they’ve had several meetings with the SG’s office. While they said the acting SG was receptive and sympathetic (they’re all sympathetic!) they bumped a number of basic issues that dog ME/CFS. Basically they’re issues of believability – something we’d hoped we’d gotten beyond by now – but we clearly haven’t. They included how to get someone (themselves?) to believe in a disease that does not have a biomarker.

They countered that question with a list of diseases that don’t have biomarkers but are still considered diseases. Then the acting SG retired! So they started over again. While the new SG was again ‘sympathetic’ he essentially gave them the brushoff stating he wanted to focus on his ‘major initiatives’ right now. They protested that the drafting of a single letter was hardly a ‘major issue’ but the staff said it was a major issue since the letter could result in the SG being ‘deluged’ with requests to carry the banner of CFS and speak and attend events regarding it.

While they didn’t get a positive result they did successfully reach into the Surgeon General’s Office. The SG did not just brush off the proposal; they had meetings with the entire senior staff and the proposal was apparently carefully considered. That sounds like considerable progress.

Dr. Reeves has not been impressed by the idea of the letter to the Surgeon General and he several times pressed the Committee about just what the letter was going to accomplish, and if it was going to accomplish something, how anyone could tell. Dr. Snell rightly pointed out that any public letter from the Surgeon General provides gives CFS advocates another arrow in their quiver; its adds some ‘gravitas’ to their efforts.

The CFIDS Association of America Backs Out of the CDC Continuing Education Program - The subcommittee is also working on the provider education project and the CME (Continuing Medical Education?) program for doctors. The CAA’s withdrawal from the program after several years obviously raised questions.

Kim McCleary, President and CEO of the CAA, stated they withdraw because they wanted to include more clinic-derived information – i.e. advice from doctors – in the program. The CDC, taking a more conservative bent, however, wished to continue to restrict the program to research-derived information – i.e. treatment information derived from research studies.

The Research Subcommittee Chaired by Dr. Jason

The research subcommittee has been quite dynamic under Dr. Jason’s leadership and is raising several important questions. The subcommittee wants to do three things.

Accountability: First and foremost they want to get an accurate accounting of federal research funding on ME/CFS. This a laudable goal given the Committee’s responsibilities; if they are to advise the Secretary of Health on the federal response to CFS they need to know just what the federal response is and how it has changed from year to year. Past CFSAC committees have not been particularly interested in these facts but I believe knowing them is vital if the Committee is to make a difference. If, for instance, they can show a downward trend in funding then they can make the case the program is not succeeding in its present state and request changes.

CFS and Medical Texts: They’re poring over medical texts to see what medical students are learning about ME/CFS. They’re looking to see a) if ME/CFS is portrayed and if so, b) how it’s being portrayed. This data could presumably be used to ask the government for more outreach to medical schools.

Judging the Competence of the Panels That Review ME/CFS Grant Applications – The makeup of the panels that review CFS grant proposals has been a source of frustration for many years now. It’s an important problem; if CFS researchers don’t believe they’ll get a fair shot before the review panel they won’t apply. Indeed it appears that not many researchers are applying for CFS grants, and when they do, very few are getting accepted.

Dr. Glaser stated that an examination of the review panel for CFS found that only 15% of reviewers had ‘worked on anything related to CFS’. Note this figure doesn’t refer to work on CFS, they had trouble finding reviewers who had worked ‘on anything’ even ‘related’ to CFS.
He stated “the whole field doesn’t move forward not because there’s no money, but because of the nature of the study sections (review process)”. This was a strong statement – the strongest yet by a CFSAC member on this issue. This is the first time that I remember a CFSAC member actually quantifying the lack of expertise on the panel.

Dr. Hanna’s only comment was that there were complaints about the review panel for the RFA but look how well that turned out. The RFA had the potential to turn the NIH’s CFS program into a dynamic entity but out of a projected $4 million dollar windfall only $1 million was spent and several significant grant proposals were rejected. Out of approximately 30 grant proposals, only 4 (on CFS) were accepted. It’s unfortunate to see Dr. Hanna get away with comments like this.

Dr. Hanna is viewed as a champion for ME/CFS by most in the community but her answers before the CFSAC committee make one wonder. It may be that because she has so little positive to report she’s constantly on the defensive. At times I wonder why CFSAC members don’t take her to task more. She has dealt with these complaints for years and has basically stood behind the review panels.

As it happened the Deputy Director of the Center for Scientific Review (CSR), Dr. Cheryl Kitt gave a presentation. The CSR is in charge of the review panels.

Dr. Cheryl Kitt's Presentation

Dr. Cheryl Kitt's presentation was typical – very general and lengthy – and addressed nothing germane to the CFS community’s complaints. These types of presentations – which simply review the workings of whatever agency is under discussion are absolutely useless and I wonder why the CFSAC permits them. Instead of being informative what they manage to do is use up most of an official’s allotted time. The CFSAC should request presenters to submit their presentation to the panel beforehand to read and then go directly to questions.

When asked about the review panel situation, Dr. Kitt replied that there were few researchers primarily focused on CFS and they’d communicated with them all and they basically couldn’t get anyone. Dr. Glaser replied that the IACFS/ME (Association of CFS professionals) has sent ‘large lists of potential reviewers’ to the CSR for five years now.

It wasn’t so surprising to see Dr. Glaser lead the way on this issue. He is an established researcher who has, apparently, been unable to get his grant proposals funded. An Epstein-Barr Virus researcher he couldn’t have been happy to find only 1 (maybe) reviewer with immune research experience in two years of review panel members. Dr. Glaser is currently being funded by the CFIDS Association of America (CAA).

Dr. Kitt gave no ground and the conversation quickly died.

Patient Presentations

 Several patient presentations were given including my own. You can find them on the CFSAC website.