Occupy CFS

Exercise is an issue for every CFS patient, and there is no shortage of advice on whether and how to do it. On January 14th, the CDC hosted a conference call as part of its Patient Centered Outreach and Communication Activity (PCOCA) efforts. Dr. Nancy Klimas and Dr. Connie Sol presented their exercise advice for people with ME/CFS. I’ve seen some sharp criticism of the presentation, so I thought it would be helpful to compare their advice to the recommendations from Dr. Christopher Snell’s group at the Pacific Fatigue Lab. Dr. Snell and his collaborators (Staci Stevens, Todd Davenport, Mark Van Ness) have done the most work on exercise capacity in CFS, and published a conceptual model for safe exercise in 2010. You can learn more about their work in this webinar they gave last year.

Why Do It?

It’s common knowledge that exercise is an important part of preventing heart disease, diabetes, and osteoporosis. And I think most CFS patients would be eager to exercise if it did not make us sick. On Monday, Dr. Klimas said that deconditioning explains much of the dysautonomia seen in CFS. I think she may have overstated it because there are physically fit people who develop POTS, NMH or other orthostatic conditions, but deconditioning certainly wouldn’t help. Dr. Klimas described herself as the “perfect advocate to talk about exercise” because of her decades of research and clinical experience focused on biomarkers and immune function. She does not believe exercise is the only possible treatment for the disease (unlike proponents of the psychosocial model), but she also does not think it should be ignored.

I should note that while Drs. Klimas and Sol use exercise to provoke PEM so they can measure the gene expression cascade that follows, they have published no papers on exercise physiology in CFS. Snell and his group have published multiple papers on the topic, including a study that shows deconditioning is not the cause of PEM. Despite showing that there is metabolic dysfunction unique to CFS, Snell and many other experts recommend being as active as is safely tolerated. Stronger muscles will lead to less pain. Being as physical fit as possible will improve our chances with heart disease and other long-term consequences. If we can safely tolerate a certain kind or level of activity, we should do it. The emphasis must be on the word SAFE, and activity should be tailored to each individual patient’s capacity.

Identifying a Target Heart Rate

My articles on PEM and exercise explain the body’s energy systems and the importance of heart rate in detail. For purposes of this post, I can say that both Klimas and Snell agree that heart rate at the anaerobic threshold is the limit for safe activity in CFS. So how do we identify the correct heart rate?

Dr. Sol uses a single test in which the patient exercises to exhaustion. Multiple measurements help identify the heart rate at the anaerobic threshold, and then that heart rate is used to design an individualized exercise protocol. Dr. Snell and Staci Stevens use a two day maximum exercise test to do the same thing. That second test is critical because CFS patients’ metabolic function declines significantly after the first test. In my own case, my heart rate at the anaerobic threshold went from 105 on day one to 95 on day two. Under Sol’s system, 105 beats per minute would be my maximum heart rate, but that would be too high on any day that I was not well rested. My personal view is that by skipping the second test, Sol and Klimas are at risk for setting the safety limits too high for most patients.

Not everyone can take a two-day exercise test (for a variety of reasons), so there is a simple calculation for guessing at your heart rate at the AT. Klimas and Sol recommended: 220 minus your age times 60%. In my case, (220 – 44) x 60% = 105.6 bpm (matching my AT on day one).  Stevens recommends 50%, or (220 – 44) x 50% = 88bpm (lower than my AT on day two). Here’s the problem with the calculation: a bedridden patient would not have the same limit as me (housebound) or a friend of mine (who can leave the house every day). We’re all sick with CFS; we all have metabolic dysfunction. But it’s unlikely that our heart rate limits are identical.  Patients must be cautioned that the calculation is a guess only; careful experimentation is necessary to establish your safe level.

Defining Safe Activity

Both Sol and Stevens agree that the safe level of activity is the level that does not produce symptoms. Dr. Sol said that she knows she has prescribed the right level of activity when the patient reports that he/she feels no difference. Stevens has said that any symptom flare that lasts more than a few hours is too much and that activity must be scaled back.

What qualifies as exercise? Both Sol and Stevens agree that activities of daily living should be seen as exercise. The effort required to cook a meal or shower can raise your heart rate too high, and may need to by modified to stay in the safe zone. They both agree patients should examine the activities that make them tired, and try to adapt and pace those activities. Dr. Klimas said that these methods will lead to a more even, reliable supply of energy; Dr. Snell has said the same thing.

Beyond activities of daily living, Sol suggested yoga or non-weight bearing activities such as water exercises. She recommended starting with a minute or two of activity followed by a few minutes of rest, repeated five times once a week to start. In contrast, Stevens recommends a more modest starting point of stretching and range of motion exercises. Patients should advance to low intensity, short duration activity only if the stretching is well tolerated. For Snell and Stevens, heart rate is not the only indicator of capacity. Patients must pay attention to their perceived level of effort, and avoid activities (or activity duration) that feels “somewhat hard.”

Severely Ill

There is no question that there are CFS patients who are too sick to come to a lab and pedal a bike for eight minutes. Accordingly, these patients have not been studied for metabolic dysfunction and exercise capacity. Drs. Klimas and Sol made no comment on Monday about what these patients could or should do. I interviewed Staci Stevens as part of the research for my article on exercise, and based on her advice I wrote:

A bed bound patient may need assistance to turn in bed or complete basic activities such as showering, but heart rate biofeedback can help identify the appropriate pace and duration of these activities. Bed bound patients can also try deep diaphragmatic breathing, perhaps six deep breaths at a time. Deep breathing will lower heart rate, and also work the large muscles of the diaphragm. Severely ill patients might begin with passive stretching, where a physical therapist or caregiver moves the patient’s limbs slowly and carefully to gently stretch muscles and try to improve flexibility.

This must be done very cautiously. There is simply no published data that investigates the metabolic dysfunction in bedridden CFS patients or that explains what they can do safely. The cost of trial and error can be high, so patients should be very careful.

Expectations

Reasonable and realistic expectations are an important part of any rehabilitation effort. Snell and his group describe the goal as being as active as possible within toleration, and hopefully this will lead to a more predictable energy supply (eliminating the push-crash cycle). In contrast, Dr. Klimas said on Monday that patients will show improvement if they follow the program, and that when they stay below the AT they feel “much better.” Then Dr. Klimas claimed that some patients have been able to return to work or athletics. This is an extraordinary claim, especially in the absence of published data. How impaired were these patients to start with? How long did they follow the program, and was the program standardized across patients? Did these patients show objective improvement on subsequent exercise testing? How long did their improvement last?

Personally, I was very surprised to hear Dr. Klimas make this claim. She is quite familiar with the severity of the disease, the dearth of treatments, and the danger of false hope. In my opinion, claiming that pacing with a heart rate monitor and slowly progressing exercise is curative in the absence of published data is misleading, at best. The notion that exercise will make us all better is pervasive and potentially harmful to patients. Show me the data.

The Comparison

There are many similarities between the advice of Klimas and Sol on the one hand and Snell and Stevens on the other. Both sides agree that patients should be as active as they can safely tolerate. They agree that activities of daily living should be seen as exercise. Both recommend using a heart rate monitor to pace activity by staying under the anaerobic threshold. Both recommend starting very slow with exercise, and avoiding exercise that increases symptoms.

There are also some differences. The two groups calculate the safe zone differently, with Klimas and Sol potentially setting limits higher than patients’ anaerobic thresholds. Klimas and Sol offered no advice to bedridden or other severely incapacitated patients, while Snell and Stevens offer at least a little guidance. Finally, Snell and Stevens do not suggest that their program is curative in any way. They suggest a cautious but realistic goal of eliminating the push-crash cycle. In contrast, Dr. Klimas was quite expansive in her claim that her program had helped some patients return to work.

Despite their differences, both groups give the same basic advice to CFS patients: use a heart rate monitor to help you recognize when you are doing too much; ensure adequate rest; be as active as you can without triggering symptom flares or post-exertional malaise. This is a good starting point, but I hope that one day we will have access to physical therapists and others trained to help us navigate these limits. From my own experience, trying to apply this expert advice on my own has been unnecessarily frustrating.

One of the most frustrating aspects of coping with CFS is the lack of definitive data. A PubMed search for “chronic fatigue syndrome” yields 4,877 results (as of today), but as a patient on the front lines I have to make treatment decisions based on theory, supposition, and anecdotal evidence.

Case in point: I’m wearing a heart rate monitor and reducing my activity to stay below my anaerobic threshold based on a few studies that show CFS patients have disruptions in their energy metabolism. There is even a published case study showing that following this pacing method and short duration exercise leads to improvement in functional capacity and activity recovery. But because my anaerobic threshold is so low, I exceed my heart rate limit just by climbing 12 steps. An expert advised me to reduce my activity to stay below the heart rate limit, even if it meant stopping halfway up the steps to rest or using a shower chair. Another expert endorsed the use of beta blockers to lower my heart rate. That topic is worthy of a separate post, but there are patients who have benefited from this approach. Sue Jackson has written excellent posts about her experience doing just that, and she credits beta blockers with drastically improving her functional capacity. When I asked the first expert about beta blockers, the expert responded that beta blockers would not change my actual anaerobic threshold but would mask when I was exceeding my limit by lowering my heart rate.

So how do I decide what to do? Expert One advises significantly reducing my activity to obey the heart rate limit, and not using medication to lower the heart rate. Expert Two advises using the medication to lower heart rate in order to increase my activity levels. There is no research that definitively answers this question. There have been no case control studies or systematic long-term follow up. Both experts can support their theories with anecdotal patient data. Both experts can support their theories with sound reasoning. There is simply no data that answers the question: which method is better for my health?

Large treatment trials, longitudinal studies, and sophisticated research into etiology and disease course drive treatment decisions for many diseases and conditions. If I had breast cancer, detailed analysis of the tumor would tell my doctor which chemotherapy regimen to use and for how long. If I had a broken hip and a heart condition, a physical therapist would be able to prescribe a rehab program suitable for both conditions. If I was HIV positive, triple therapy would be prescribed and tightly monitored to make frequent adjustments.

But those of us with CFS are left flapping in the wind. I think even the best CFS expert doctors in the country would acknowledge that treating people with CFS involves a lot of trial and error, educated guesses, and fine-tuning. The CFIDS Association recently stated that CFS patients on Patients Like Me report trying over 800 different treatments. This is insane! It’s like throwing spaghetti at the wall to see how much will stick.

Making CFS treatment decisions should be like playing sudoku – there might be some trial and error, but there is inherent logic to the puzzle. Instead, making these decisions feels like the Sunday New York Times crossword on steroids, with incomprehensible clues and multiple right answers. No one can get all the right answers based on insufficient data. Should I take the beta-blockers, or should I buy a shower chair? Your guess is as good as mine. Literally.

Let’s play a game. Imagine you have a large puzzle that makes an Impressionist picture of a colorful cottage-style garden. You can put it together as long as you have the picture on the box. First you assemble the lower left corner, all lavender and yellow flowers. Another section of red roses sits somewhere in the middle. Near the upper right corner is a section of white and gray paving stones, and you also put together an area of green herbs although you are not sure where it goes yet. This puzzle will take a lot of time to solve, but with the finished image on the box you know that you’ll put it together eventually.

Now imagine the box is gone. All you have is a white/gray blob, and lavender/yellow section, the red rose section and another green blob. The rest of the pieces are all mixed up together, and while you can separate out some edge pieces and consolidate others by color, without the box you cannot even be certain what the final picture should look like. It’s frustrating, isn’t it, to have all those pieces on the table and not see how it fits together or even know for certain that you have all the pieces. That’s the feeling I got reading the American Family Physician’s article on Chronic Fatigue Syndrome: Diagnosis and Treatment. I dissected the AAFP patient information sheet on CFS in a recent post, but now I think it’s important to examine this review article by the same authors. The article attempts to present a finished picture of CFS for family practitioners, but so many pieces are missing that the paper bears little resemblance to the CFS I live with.

Generally Speaking

“Chronic Fatigue Syndrome: Diagnosis and Treatment” by Dr. Joseph Yancey and Dr. Sarah Thomas gives an overview of CFS for family physicians. They review the Oxford and Fukuda criteria, the basic lab workup recommended by CDC, and a list of exclusionary conditions. In a section on etiology of CFS, the authors quickly cover the immune system, genetics, psychosocial, adrenal system, and sleep/nutrition. Finally, the treatment section focuses on cognitive behavioral therapy (they say it works), graded exercise therapy (this works too), nonpharmacological (nothing really helps) and pharmacological treatments (these don’t work either).

In the authors’ defense, there are significant space limitations in the American Family Practitioner journal: 1,500 to 1,800 words in the case of clinical review articles like this one. There is no way to include all the information about CFS that family doctors need in such a limited space. It also appears that neither Yancey nor Thomas are CFS experts, based on the very limited information I could find online. I emailed Dr. Yancey, the corresponding author for the paper, on October 24th with a few questions but to date I have not received a response.

Method Madness

Drs. Yancey and Thomas describe their research methods as follows:

A PubMed search was completed using the MeSH term chronic fatigue syndrome. The search included randomized controlled trials and clinical trials in English from the past 10 years. We also searched the Cochrane database, Essential Evidence Plus, the National Institutes for Health and Clinical Excellence guidelines, and the Centers for Disease Control and Prevention Web site. Search date: August 26, 2011.

This methodology accounts for some of the missing pieces. First, anything published after August 26, 2011 was not captured in the search. That includes the IACFS/ME Primer, NCI’s paper on the risk of cancer among elderly CFS patients, the ME-ICC criteria, and the Rituximab trial. But before we forgive the authors’ oversight of these papers based on the date of their literature search, consider a curiosity I found in the paper references. The authors cite one paper published after August 26, 2011: The FITNET trial of internet based CBT for adolescents with CFS is included as reference Number 27. Does that strike you as odd? If the authors truly limited themselves to the references found on August 26, 2011 then this paper should not be included. Furthermore, of all the papers published after August 2011 to include in a review of CFS treatment and diagnosis, why was a CBT paper the one cherry-picked by the authors?

Even within the boundaries of the search methodology, the authors missed some papers that would have been helpful in their overview sketch of CFS. I attempted to recreate the authors’ search in PubMed, and found more than 1,300 clinical study papers alone. These include all of the letters critical of the PACE study and Tom Kindlon’s many letters and papers on the potential harms and inaccuracies in CBT/GET studies. Other important papers such as the spinal fluid proteome by Schutzer, et al., the differential gene expression post-exercise paper from Light, et al., and the cytokine network modeling by Broderick, et al. were captured in the PubMed search but did not make it into this review paper.

Finally, there are several seminal papers that are not returned in the PubMed search. The Journal of Chronic Fatigue Syndrome published the Canadian Consensus Criteria by Caruthers, et al., in 2003. This case definition is gaining broad acceptance among policy makers and researchers, but it does not show up in a PubMed search because the journal was never indexed in Medline. Another example is the Van Ness, et al. study showing the significance of two-day exercise testing in differentiating CFS patients from controls. This is a critical paper, suggesting a possible diagnostic test (albeit an extremely unpleasant one) for CFS. But because the journal was never indexed, these papers do not show up in a PubMed search and so non-experts like Yancey and Thomas never see them.

Cognitive Bias

I do not know what Dr. Yancey and Dr. Thomas believe about CFS, including whether they believe the illness is primarily psychological in origin. After reading this paper, however, I fear this may be the case. I can best illustrate this through examples.

In the opening paragraph of the article, the authors say “CFS is often mentally and emotionally debilitating, and persons with this diagnosis are twice as likely to be unemployed as persons with fatigue who do not meet formal criteria for CFS.” What about physically debilitating? If the authors recognized the physical disability experienced by many CFS patients, and the physical suffering of all of us, wouldn’t they mention it in this paragraph? This simple omission is a very subtle way to communicate that people with CFS are not physically ill.

There is a brief discussion of the case definition in the paper. According to the authors, the 1988 CDC definition focused on physical symptoms, and the 1991 Oxford definition “emphasize mental fatigue over physical symptoms.” But the criteria, printed as Table 1 in the article, require fatigue to be “severe, disabling, and affects physical and mental functioning.” I’m no fan of the Oxford definition, but even I can see the requirement of physical disability. Again, Yancey and Thomas gloss right over the fact that CFS has serious, physical symptoms.

In discussing the biopsychosocial model of CFS etiology, the authors say: “CFS is often associated with depression, which has led many physicians to believe that CFS is a purely psychosomatic illness. Evidence supporting this conclusion is lacking.” Fair enough. But then they say, “Strong evidence suggests that childhood trauma increases the risk of CFS by as much as sixfold.” Sigh. I covered this in my dissection of the patient information sheet. Childhood trauma may have physical systemic affects, but I am not aware of any evidence showing that CFS patients have higher rates of trauma compared to patients with other illnesses like MS or lupus or diabetes or cancer. In my opinion, it is misleading to single out childhood trauma as a risk factor for CFS in the absence of such evidence.

The authors devote space and attention to CBT and GET studies, and this is understandable given the fact that CBT and GET treatments have received the most study in CFS. CBT “can help persons with CFS recognize how their fears of activity lead to behaviors that ultimately cause them to feel more fatigued and disabled.” It is true that CBT can help patients correct activity avoidance behavior, but in my experience this is a very small minority of patients. Even the CDC, target of so much criticism, does not describe CBT this way. The CDC says: “CBT can be useful by helping them pace themselves and avoid the push-crash cycle in which a person does too much, crashes, rests, starts to feel a little better, and then does too much once again.” This is a more appropriate description of CBT that acknowledges the importance of self-management and the prevalence of the push-crash cycle, as opposed to the activity avoidance highlighted by Yancey and Thomas.

Graded exercise therapy is very controversial for CFS patients, mainly because traditional GET uses a scheduled increase process as opposed to a patient-driven increase process based on symptoms. Not surprisingly, this issue is not discussed in the paper. The authors do mention that a heart rate monitor can be used to avoid overexertion during exercise, but there is no mention of the body of evidence on CFS exercise testing and pacing methods. They even cite a study that suggests improvements in GET do not correlate with increases in exercise capacity, suggesting that GET may actually work by “decreasing symptom-focusing behavior in persons with CFS.” Pacing, the only behavioral technique that truly helps CFS patients, is not mentioned by name, although the authors do say:

Patients should be encouraged to take rest periods as necessary, and to practice relaxation techniques. Although there is no evidence these modalities are effective, they are unlikely to be harmful and may be helpful.

Neither CBT nor GET is curative because it does not target the underlying mechanism of illness. CBT is not curative for cancer or heart disease either, for the same reason. Drawing the conclusion that these therapies are not curative because of the patient is a fallacy, but this is the conclusion that Yancey and Thomas suggest:

Despite the positive results of CBT and graded exercise therapy, the effects are usually moderate and rarely lead to resolution of CFS. Patients with poor social adjustment, a strong belief in an organic cause for fatigue, or some sort of sickness benefit (i.e. financial incentive) tend to have worse responses to therapy. Unlike with many other illnesses, membership in a CFS support group was associated with worse outcomes.

The study cited by the authors in support of these statements is this one from 2002. That study points out its own limitations: it uses the Oxford definition, lost 17% of the patients to follow-up, and did not actually measure the exercise capacity of the patients. But this is the kind of evidence that is sufficient for Yancey and Thomas.

The overall tone, selective quotation, and reference choices give me the impression that the authors believe CFS to be a psychological condition, at least in part. I do not know this for a fact, but if I read only this article about CFS and nothing else, I would believe that it is an emotional problem. It’s not just the amount of space devoted to the psychosocial research. The authors focus on the psychological elements to the exclusion of discussion of physical disability, post-exertional malaise, and the well-documented physiological findings in this illness.

Missing Pieces

There are huge gaps in this paper. Orthostatic intolerance, an issue for most CFS patients, is not mentioned at all. Post-exertional malaise is not explained, and no CFS exercise studies are referenced. The importance of medications and other treatments in managing sleep and pain issues is ignored, and pain is barely discussed at all.

This article illustrates a few pieces of the puzzle, mainly CBT, GET and the psychosocial model of CFS. A family physician reading only this article would not be able to separate chronic fatigue from CFS patients, and would understand almost nothing about the complexity of CFS. I found the tone to be generally hopeless: try therapy and exercise but it probably won’t help you much. Maybe a motivated physician would visit the CDC website (and this illustrates the importance of fixing problems in those materials).

No one will be able to assemble the CFS puzzle using the pieces in this article. Too much evidence is ignored, too much emphasis is placed on the psychosocial pieces, and there is very little information about how to manage the other symptoms of the illness. I know the full picture exists and I can identify the gaps. But a family physician who does not have the picture of the box will not recognize all that is missing and will never be able to assemble the pieces in a way that will help CFS patients.

I fear that doctors will rely on this article to provide the same kind of advice I received from doctors in 1994: keep going to the gym, staying in bed is the worst thing you can do, get some counseling, there is nothing else we can do to help you. This bad advice and hopelessness did not help me, and may have even hurt me by keeping me much more active than my body could tolerate. It was years before I found and received adequate care for pain, sleep, and orthostatic intolerance, and even more years before I found expert help for pacing and activity management. This article will do nothing to change the way doctors treat CFS, and will reinforce the destructive pattern already in place.

I’m on the verge of tearing my hair out, and I suspect I’m not the only one. The American Academy of Family Physicians published a review article about CFS (paywall) on Monday, accompanied by a patient information sheet. From the very first sentence, this information sheet is a disaster. It packages harmful misinformation for family doctors to share with patients. Let’s take a look:

Chronic fatigue syndrome (CFS) is a disorder that causes you to be very tired.

NO! No it does not! A person with sleep apnea is tired. A nursing mother is tired. A perfectly healthy person studying for the bar exam is tired (ask me how I know). CFS does not make me tired. CFS causes prostration, a medical term that means a collapse from complete physical or mental exhaustion. Using the word “tired” is not only medically inaccurate, it falsely minimizes the severity of my disease and my experience.

People with CFS may have other symptoms, such as poor sleep, trouble with remembering things, pain, sore throat, tender lymph nodes, or headaches.

Can you spot what’s missing? Post-exertional malaise! The generally accepted hallmark symptom of this disease is not on the list. It is the first symptom on the Fukuda criteria list of accompanying symptoms. But it’s not listed here and not explained to the patient.

Not everyone with CFS has all of these symptoms.

I know hundreds of CFS patients. Every single one of us has experienced these symptoms for extended periods of time, if not daily, over the course of years. While it is technically correct that the Fukuda criteria do not require all of those symptoms, it is an oversimplification to simply say we don’t have all the symptoms. And of course all the other symptoms and overlapping conditions are not mentioned at all.

Childhood trauma (for example, physical or sexual abuse) may raise the risk of getting it.

I am aware of two studies that showed a higher prevalence of childhood trauma among CFS cases compared to healthy controls (this one and this one). Here’s the problem: childhood trauma may raise the risk of many disorders later in life. Without comparing the prevalence rate of trauma among other illness groups, there is no way to know if the association with CFS is unique. Are there studies comparing the incidence of childhood trauma among people who develop multiple sclerosis, rheumatoid arthritis, cancer, hepatitis, heart disease or  . . . oh, that’s right. Doing that kind of study in those illnesses might be offensive because those illnesses are real. But we can do those studies in CFS with no problem.

Two treatments can help with CFS: cognitive behavior therapy (CBT) and graded exercise therapy. With CBT, a therapist teaches you about how your thinking affects how you feel and act. With graded exercise therapy, you slowly increase your physical activity, which hopefully increases your function.

You know where this is going, right? Setting aside the arguments about whether CBT and GET studies actually show a benefit, and setting aside how this sort of statement plays right into the mental illness meme, let’s talk about GET. Will GET increase CFS patients’ functional ability? Maybe some patients, but it should be pursued with extreme caution and prejudice. As the work of the Pacific Fatigue Lab and my own exercise testing results show, the energy metabolism systems of CFS patients are severely impaired. We do not make or use energy, or recover from activity, the way other people (including other illness groups) do. Graded exercise must be undertaken very carefully because it takes very little activity to push a patient into a severe crash.

I shudder to think about how family doctors will use this information sheet, and what it will do to the patients who receive it. What is truly remarkable about it is that it bears only a passing resemblance to the full review article and the AAFP’s patient education page on CFS. But this watered down, oversimplified summary of misinformation about CFS will undoubtedly be used, and it is likely to make things worse for patients, not better.

So does anyone – journalists, doctors, policymakers, or other observers – wonder why the CFS Advisory Committee and patient advocates have been begging CDC to fully revise its website and remove the harmful content that filtered into this information sheet?

This is why.

Does anyone wonder why the CFSAC  recommended that the CDC remove its Toolkit from the CDC website?

This is why.

Does anyone wonder why an alliance of organizations and patients wrote a lengthy and heavily referenced position paper in support of that recommendation?

This is why.

Does anyone wonder why there was such vigorous disagreement at the CFSAC meeting about whether professional societies like the AAFP should be invited to participate in revising the CFS case definition?

THIS. IS. WHY.

Update November 2, 2012: Author Toni Bernhard published a great article about the AAFP patient information sheet.

Update October 31, 2012: I’ve also published a detailed analysis of the AAFP review article on CFS.

Pacing is . . . actually, my descriptions of pacing generally involve expletives that are not appropriate for this blog, so we’ll stick with “Pacing is challenging.” One positive side effect of my pacing efforts, though, is that I am still celebrating my birthday one month after the fact.

Last week, I went out for a birthday lunch with Friend K. We’ve been friends for 22 years now, and K knew me for four years before I got sick. We went to law school and took the bar exam together, and undertook a mammoth road trip together. When I started dating my husband, K was the first friend I asked to check him out. Hanging out with K is great because she really gets the illness, and so I don’t have to talk about it but I can if I want to. She told me the latest stories about her sons, and generally made me laugh my ass off. For a few hours, I felt like a normal person having lunch with her best friend, and it was glorious.

I also went out for a birthday dinner last week with Friend M. I met M soon after I got sick, and she is another rare gem: a friend who gets it. M and her husband read a prayer at our wedding, and she is one of the most loyal and giving people I know. For my birthday, M took me to one of my favorite local restaurants for dinner and we closed that place down. The meal was sublime, but having M’s undivided attention for four hours was even better. She told me some great stories about her eight year old daughter, including the “court proceedings” in which M has been accused of posing as the tooth fairy. I felt just like the women at the table next to ours, enjoying a girls’ night out with one of my closest friends. These moments of normalcy, of interacting with the world the way I used to, are so rare and precious.

And then there was the payback. The day after that dinner, I was crashed but I didn’t care. It was totally worth the pain and post-exertional relapse. I was still high on the joy of being with my friends. But then I was crashed for two more days, and I started to question the price of normalcy.

My attempts to implement stricter pacing techniques have challenged me far more deeply than I expected. I’m questioning everything now. Before the exercise testing, I was absolutely convinced that having occasional episodes of normalcy was worth the crash days. Outings like these feed my spirit and make me so happy. But now I wonder if it’s the right thing to do. Do I have to give up the last few remnants of my healthy life in order to cope with my sick life? How do I strike the right balance between accommodating my physical limitations and hanging on to who I am? What else do I have to give up in order to live crash free?

I feel like these are deep, existential questions. For 18 years, I have sacrificed my body in order to enjoy occasional outings with my friends, to participate in CFS advocacy, and to take care of my family. If pain and crashing was the price of continuing to participate in my life, I paid it gladly. But is this the right way to balance the equation? Is having dinner with a friend worth three days in bed? Facing that consequence is not fair, and I don’t want my life to be this way. But this is my reality. I need some kind of owner’s manual to tell me how to figure this out. Do I punish my body by exceeding my physical limits? Or do I punish my soul by living within those limits? It’s a no-win situation, and I don’t know how to answer these questions any more.

The largest pool of money available for investigator-initiated CFS research grants is the NIH. Although miniscule relative to other areas of research, $6 million a year is the largest annual research investment in CFS from any source. Given the significance of this investment, advocates and NIH representatives routinely disagree over how the money is spent and whether it is going to the right projects. Looking at one year of research, as I did with the NIH’s spending on CFS in 2011, is interesting, but year to year comparison is important as well. Is funding getting better each year? Are the projects actually investigating CFS? And what effect did XMRV have on CFS funding? I’ve examined the data available for 2008 – 2011, and the answers are complicated.

Here’s the broad view comparison to start out:

Several things stand out in that table. First, the percentage of funding for both psychological and orthostatic intolerance studies has dropped since 2008. Second, the amount of money going to non-CFS grants appears to have dropped. Third, while the percentage spent on neuroendocrine immune studies has generally risen, this category has never received as much as half of the NIH spending. Finally, XMRV represents an enormous share of the funding, and I’ll examine that in greater detail below. First, let’s drill down into each year and see whether the money went.

In 2008, NIH reported spending $3,503,942 on CFS research. The total includes a study by Dr. David Williams examining pain processing in interstitial cystitis and fibromyalgia. It is true that there is tremendous overlap between CFS and pain conditions such as fibromyalgia and interstitial cystitis, but the study does not include CFS patients and so the relevance to CFS is by inference only. I don’t think it makes sense to count this funding as “CFS research.” And it’s not an insignificant amount of funding; this study received $328,680 or 9.3% of the total. The remaining research breaks down as follows:

• Psychological studies – $747,470 (21.3%). This includes a study by Dr. Friedberg examining the effectiveness of two sessions of CBT, and a study by Dr. Antoni evaluating telephone based CBT. Another study evaluates CBT for insomnia in CFS. There is also a tiny amount ($940) to Dr. Friedberg examining psychiatric comorbidity in CFS but this appears to be a subproject of a much larger grant.
• Orthostatic intolerance – $1,153,528 (33%). This includes studies by Drs. Stewart and Freeman discussed in the post on 2011, as well as a study by Dr. Biaggioni.
• Neuroendocrine immune studies – $1,274,264 (36.3%). This includes studies by Drs. Fletcher, Baraniuk, and Huber. The mysterious Viagra study is included at $19,164.  Another grant ($188,125) went to Dr. Hartz examining the impact of complementary alternative medicine on chronic fatigue, with CFS as a subset. The diagnostic criteria are not specified in the abstract. There is also a grant to Dr. Mathew ($14,840) looking at neurometabolites in CFS but it is the subset of a much larger grant and no abstract is available.

In 2009, NIH reported spending $4,844,044 on CFS research. Once again, the Williams study on interstitial cystitis and fibromyalgia is included for $328,680. There is a very small grant ($2,692) entitled “Effects of Aerobic Exercise on Cognition, Mood and Fatigue After TBI” but no abstract is available. Combined, these two non-CFS grants total $331,372 (7%). The remaining funding breaks down as follows:

• XMRV – $701,821 (14%) There is only one grant for XMRV in 2009, and it was internal to NIH. The abstract is confusing because it is about developing gene therapy, and only a few sentences relate to the genotyping of RNASEL and its relevance to XMRV in CFS.
• Psychological studies – $573,822 (12%). This includes the grants to Drs. Friedberg and Antoni.
• Orthostatic intolerance – $1,208,968 (25%). In addition to Stewart, Freeman and Biaggioni, there is a new grant to Dr. Ocon.
• Neuroendocrine immune studies – $2,028,061 (42%). This includes work by Drs. Fletcher, Baraniuk, Huber, Mikovits, Hartz, and Spencer. Another grant ($35,000) supported a researchers’ meeting entitled “From Infection to Neurometabolism: A Nexus for CFS.”  Once again, the Viagra study is included ($1,587).

In 2010, NIH reported spending $6,194,042 on CFS research. The Williams study is included once again. There is also a study by Dr. Juan Yepes examining the stress response in temporomandibular disorders and fibromyalgia. As with the Williams study, there is overlap between CFS, fibromyalgia, and temporomandibular disorders but these studies apply to CFS only by inference. The funding totaled $407,210, or 6.5% of the reported total. Here’s the breakdown of the rest of the money by research category:

• XMRV – $1,807,792 (29.3%). This included Dr. Hanson’s study (also funded in 2011), but the big item here was $1,538,297 for NIH research into the possible source animal for XMRV and testing gibbons in zoos for XMRV and another gammaretrovirus, GALV. The study did not examine CFS patients or any aspect of the possible relationship between XMRV and CFS.
• Psychological studies – $764,552 (12.3%). Again, this includes the Antoni and Freidberg studies.
• Orthostatic intolerance – $837,534 (13.5%). These are the same studies as were funded in earlier years (Stewart, Freeman, and Ocon).
• Neuroendocrine immune studies – $2,376,953 (38.3%). This includes studies by Drs. Fletcher, Schutzer, Huber, Mikovits, Theoharides, Klimas, and Spencer. This also includes the Viagra study ($83,644).

More details on the 2011 spending can be seen in my earlier post. The quick breakdown is as follows:

• XMRV – $1,743,776 (27.5%). This included Dr. Hanson’s study, as well as studies by Drs. Roth and Maldarelli. The big ticket item ($1,043,040) was the Lipkin study.
• Psychological studies – $857,397 (13.5%) was spent on the Antoni and Friedberg studies.
• Orthostatic intolerance – $856,346 (13.5%) spent on studies by Drs. Stewart, Freeman and Ocon.
• Neuroendocrine immune studies – $2,888,629 (45.5%) including new grants to Drs. Light, Natelson, and Saligan.

The XMRV Effect

The investigation of XMRV had a large impact on NIH funding for CFS. As I said in my earlier post and my post about the Lipkin study, there is no question that the connection between XMRV and CFS had to be investigated. However, the numbers show that XMRV funding artificially inflated the amount of CFS spending and as noted above, a great deal of the XMRV spending is actually on basic research that did not involve CFS samples or disease mechanisms.

Between 2008 and 2009, CFS spending increased $1,340,102 or 38%. That looks impressive, but 52% of the increase ($701,821) was for XMRV (and a basic science grant, at that). The effect is even more dramatic in 2010. That year, overall CFS spending reportedly increased $1,349,998 or 28%. But XMRV spending increased $1,105,971 over 2009. That means that 82% of the overall CFS increase in 2010 was an increase in XMRV spending. As detailed above, most of the XMRV spending allocated to the CFS category in 2010 was spent on a grant looking for an animal source of XMRV in zoos, as opposed to research on CFS patients. It’s not until 2011 that this effect disappears. In 2011, overall CFS spending increased by only $152,106 or 2.5% but XMRV spending decreased by $64,016. In contrast to 2009 and 2010, most of the XMRV spending was actually used in CFS studies as opposed to basic science.

Are we better off?

Comparing funding numbers is complicated because there are so many ways to crunch the data. I’ve identified grants that should not be counted as CFS funding, such as the Williams study on interstitial cystitis and fibromyalgia. Not all of the XMRV funding can be fairly categorized as CFS spending, either. There is overlap with gene therapy, genetics, infectious disease, and cancer research – and in fact, the grants are included in those categories as well. If every basic science grant that could be related in some way to CFS by inference or hypothesis was included in the CFS category, our funding numbers would be impressive indeed. And there is the difficulty of how to categorize the psychological studies which are offensive to many patients, but which do study CFS cohorts.

Here is my bottom line snapshot. I excluded the non-CFS grants, the XMRV funding for basic research, and the Lipkin study since it was awarded outside the usual applications process. I included the psychological spending, despite my misgivings about it. Here’s what was left:

I was surprised to see the increases hold up, although it’s much more modest than when XMRV is included. Spending for 2012 is projected to be $6 million. If all of that money is actually spent on CFS studies, it will represent a significant increase over 2011 because the Lipkin study funding would be shifted to other CFS studies. That would be a significant win for CFS patients. It will be interesting to see if NIH meets that projection. The CFS Special Emphasis Panel met to review grants on June 25-26, 2012, and hopefully there will be new CFS grants announced soon.

I feel like I am getting close to baseline, the state I was in prior to the exercise testing. It’s taken almost seven weeks, and in that time I have left my house a total of seven times – 5 doctor appointments and 2 social outings in my wheelchair. It has been a hard slog back to normalcy, and I’m getting close.

I’ve been wearing a heart rate monitor for 18 days, and have the alarm set to go off when I go over 95 beats per minute. It does not take much to put me over that line. I’ve been so frustrated that it goes off when I climb a flight of stairs or laugh or walk through my yard. But that alarm has forced me to pace much more than I normally would. I am walking slower. I’m making different choices about what I try to accomplish in the house. And that alarm has stopped me from doing things I would normally have pushed to do, like weeding for even 5 minutes or planting flowers in the yard. I have done far far less than I was inclined to do.

Has it made any difference in my symptoms? Perhaps. I have not had a crash day since strapping on the monitor. But my fatigue, pain, and cognitive symptoms all persist. Nothing is off the charts, but none of it is gone, either. On the other hand, I have been coming back to baseline and I think it makes sense to attribute that progress to the careful pacing forced by the monitor.

Today I raised the limit on my heart rate monitor to 105 beats per minute. This was my anaerobic threshold on the first day of the exercise tests. Now that I am feeling closer to normal, I thought it made sense to experiment with the higher limit. If I can sustain that without crashing, perhaps it will be a sign of progress. So far today, I have been able to climb the stairs and water some plants in the yard without setting off the monitor for more than a couple of beats.

The anaerobic threshold is not the only barrier I am trying to avoid. There is what I am calling the crazy threshold (CT) to manage as well. The crazy threshold is that point at which I can’t take being isolated in this house for another minute. The past few days have been ok. My husband was home for most of the holiday weekend instead of running in several directions at once. We went out for ice cream at the dairy right by the house. And my parents came for a visit too. I’ve had enough human interaction that I don’t feel perilously close to the CT.

This week, I am in self-imposed seclusion and house arrest. We have a wonderful family event to attend on Saturday that will also involve a car trip. It will be a big outlay of energy, and I cannot WILL NOT miss it. I don’t think I will be resentful of the heart rate monitor if careful pacing gets me to and through this family celebration without a crash. Too much to hope for? We’ll see.

Now that my exercise tests are finished and I have the results, it’s time to figure out what to do about it. I’m relying on the work of Staci Stevens, Chris Snell and others at the Pacific Fatigue Lab who have done a great deal of work on CFS metabolic dysfunction and how to cope with it. Everything revolves around my heart rate at the anaerobic threshold.

The anaerobic threshold (AT) is the point at which most energy is derived through anaerobic processes (as opposed to using oxygen) and lactate begins to accumulate in the bloodstream. As people cross their ATs, they are not able to sustain activity for much longer and experience the rapid onset of fatigue. People with CFS seem to have lower than normal ATs due to metabolic dysfunction, although no one can yet pinpoint where the dysfunction is. While a healthy person can get through work and other activities of daily living without reaching the AT, people with CFS can reach it just by taking a shower. As a result, we experience fatigue much earlier than healthy people and we continue to build up that oxygen debt as we eat, sit, walk up stairs, and so on. Any activity has the potential to cross the AT, building up yet more need for rest. It’s no surprise that we end up prostrate in bed, unable to do anything at all.

Rest and oxygen are necessary for recovery after crossing the AT, but people with CFS do not recover normally. Here’s an example that Staci Stevens gave in an article I wrote in 2010:

An athlete can climb two flights of stairs without fatigue or shortness of breath. A sedentary overweight person might climb the same two flights of stairs and feel out of breath, but will recover completely after a brief rest. A person with CFS may struggle to climb the stairs, and experience severe fatigue and PEM. In other words, the CFS patient reaches the AT after much less exertion than a healthy person, and requires a longer period of time to recover.

People with CFS end up in trouble from two directions. On the one hand, we cross our ATs abnormally early. And on the other hand, it takes us abnormally long to recover. It’s a vicious cycle, and I suspect that many of us spend large chunks of time over our ATs. I saw that in my own test results. One day two, I crossed my AT before I started biking and then biked for 11.5 minutes – all over the AT!!!

Common sense says that if something is bad for you, don’t do it. So the first step is to avoid crossing the AT. Obviously, we can’t spend our days hooked up to EKG and ventilation equipment to carefully monitor our ATs. But we can use heart rate as a proxy for the AT. My heart rate at the anaerobic threshold on day one was 105 beats per minute, and 93 beats per minute on day two. I am now wearing a heart rate monitor (this one) with the alarm set to go off when my heart rate goes over 95 beats per minute.

When the alarm sounds, I am supposed to sit down and rest until my heart rate drops back down. I’m also keeping notes on my activities so I can begin to pinpoint my true limits. If I can avoid my AT, I should be able to avoid taxing my body and triggering post-exertional malaise. Heart rate is not the perfect proxy. For example, my heart rate as I write this blog post is 79 beats per minute, and I will still be fatigued afterwards. But heart rate can at least help get my physical activity more in line with my capacity.

It’s been very surprising to see what activities push my heart rate over 95 beats per minute. Here’s a sample:

• Walking from the back of my yard up an incline to the house
• Rolling an empty trashcan up the driveway
• Pulling weeds for two minutes
• Walking up stairs at my normal pace
• Standing at the reception desk at a doctor’s office
• Laughing really hard (I’m giving my self a break on that one)

The first goal is to get my activity under control. Sometimes I won’t have a choice about going over the AT, like when I go to the doctor this week. But there are a lot of things I would normally be trying to do – weeding, laundry, going to our small farmer’s market – that I am not doing because it sets off the heart rate monitor. It will take some time to see if this really does help minimize my crashes.

Three weeks ago, I had my exercise stress tests. A friend had cautioned me that it could take three weeks to recover, and I think she was right although I did sabotage myself a little bit, as I’ll explain.

I was not prepared for how bad the post-test crash would be. I mean, I knew it would be bad but this was possibly the most intense crash I have ever had. I was completely bedridden for three days, and was unable to sit up longer than the time it took to eat (in bed). The pain was excruciating, especially in my legs. My brain was fuzzy, and I could not focus on anything. But it was the weakness that really shocked me. I felt like a Raggedy Ann doll, my limbs all floppy. When I stood, I felt like I should sit right back down. My arms tingled with that weird pins-and-needles feeling I get before I pass out, although I did not faint. I could not hold my head up for very long without support. To get to the bathroom, I had to resort to my old castigation mind-trick: “You are not paralyzed. There is nothing wrong with your muscles. You can’t wet the bed like an invalid. Get off your a** and walk to the bathroom.” (It occurs to me that I would never speak to a sick person this way, but that self-reflection probably merits its own post.)

I’ve had a day or two of crashing as severe as this many times over the last 17 years. But this crash went on for days. I’ve never gone as long as a week with that floppy spaghetti-noodle weakness in my limbs. I started to get a little scared. What if the exercise test broke something in me? What if this never got better? Both my friend and Dr. Betsy Keller had said that some patients benefited from IV fluids after the exercise tests. I’ve never tried it before now, but after five days I was feeling desperate to try anything to break the pattern. My doctor agreed, and I went to his office for the infusion. Another first: I have never used a wheelchair to get to his office before. He even ran the line himself, and I received 2 liters of IV saline over the course of three to four hours. After the nurse hooked up the second bag and increased the drip rate, my head started to clear a little bit. Then the floppy feeling started to dissipate. By the time my Mom brought me home, I did feel a little better, despite the energy expenditure of going to the office.

I felt like I turned a corner after that. I still could not be out of bed for very long. Standing at the sink for five minutes was too much. Getting up to put away a couple books brought on the now-familiar weakness. But I could sit up in bed and read, focus on a movie, or knit for awhile. That was a huge improvement. Then came the Hot Water Heater Episode, and I had a setback. I was back to being bedridden for a couple days, unable to stay upright without support. But by the end of week two, I did experience a little improvement. The pain in my legs was back down to pre-test levels. I no longer felt like I might pass out. And I started to feel a little bored, always a good sign for me. There is no doubt I was still crashed, but I started to think I might actually climb out of this one.

Then I sabotaged myself, a little. Long before my exercise test was scheduled, my parents had purchased handicapped-accessible tickets for my husband and I to accompany them to a baseball game. I still wanted to go. In fact, when my husband and I discussed whether I was physically able to go, I told him I couldn’t handle the emotional consequences of not going to the game. I was scared, unsure what the outing would do to my recovery and how bad the setback might be. But I threw caution to the wind and went anyway. I am so very glad I did! We had a blast, and it is always such a gift to get out in the world after a prolonged relapse. I’m sure that it has added days to my recovery. I’ve spent these last few days “resting aggressively.” Tomorrow is our 16th wedding anniversary, and I don’t know if I will be able to go out to dinner to celebrate.

My understanding is that a recovery time of more than one day after exercise testing is considered abnormal. In one study, none of the CFS patients recovered within 48 hours and 60% of CFS patients took more than 5 days to recover. That particular study only followed patients for 7 days post-testing, so it is likely that many of those patients took more than a week to recover. I think three weeks was a reasonable estimate for me. If I hadn’t indulged in the baseball game, I might be pretty close to baseline by now.

Instead, it’s three weeks out and I am writing this from bed. As soon as I publish this post, I will lie back down as I feel my head getting heavier – the concrete football helmet of fatigue. I won’t attempt anything more demanding than knitting for the rest of the day, and have some audiobooks to fill the time. Whether we go out to celebrate our anniversary will be a last minute decision, and I have already mentally allocated next week to more bed rest. I hope I can be back at baseline by the end of the week, but as anyone with CFS knows, I am ultimately not in control of whether I make that deadline.

Still waiting for exercise test results.

Still waiting for recovery from exercise tests.

Still waiting for the brain power to research and write some in depth blog posts I’ve been planning.

But life doesn’t give us many breaks, so cue complaint!

At 7am Sunday morning, we discovered that our hot water heater was leaking. A lot. Apparently, it sprung a leak overnight and proceeded to discharge gallons of hot water onto the basement floor. I won’t even go into the Basement Saga we have endured for the last 18 months or so, but suffice to say that this was not the first time my husband has cleaned up water from the basement floor. And that’s how he proceeded to spend his Sunday: cleaning up the spill, emptying the water heater out, discarding waterlogged stuff. We couldn’t get a new water heater installed until mid-day Monday, so we went about 36 hours without hot water.

If you have CFS, you know that stress is very very bad. I managed enough detachment to observe the cascade effect of this stress in my body. The adrenalin rush after we found the leak hit my gut first, with spasms and pain, and triggered orthostatic intolerance symptoms of dizziness and weakness. Nausea and fatigue came next, and then anxiety about how we would find a way to deal with this mess. Deep breathing and emotional support helped calm the anxiety, but fatigue and post-exertional malaise swept in. I was flat on my back and out of commission.

I had a criminal law professor who liked to say, “If you believe that, you’ll never own your own home.” Sometimes I wonder if people with CFS should not try to own their homes. It’s nice to have control over your space, until something breaks and you have to be in control of that too. This kind of day-to-day stress is just unmanageable for me when I am in a crash. I am not capable of mopping the basement floor or carrying wet trash up the stairs. When I’m sick like I am in the wake of the exercise tests, I’m not capable of dealing with a contractor to get a new water heater installed. I’m really not in any kind of shape to make a cup of tea, let alone deal with the perfectly normal problem of a busted water heater.

End complaint. Cue gratitude.

I am so fortunate to have a home, when many CFS patients do not. We can afford to have the water heater replaced. I have a husband who is able to clean up the mess and work from home to deal with the contractor. My mom was staying with us to help with cooking, errands, etc. and she found the leak Sunday morning, hours before my husband would have himself. She helped him with the clean up. Nothing valuable was damaged. And compared to the water situation in most of the world, 36 hours without hot water is really not a big deal.

This episode was an annoyance, in the grand scheme of things, and we dealt with it. No lasting harm was done. What is most upsetting to me about the whole thing is that I could not have coped with it alone. Even on a good day, I am too disabled to manage this kind of homeowner responsibility by myself. This incident throws a spotlight on the fact that I could not live by myself, not without a great deal of assistance. It’s not fair, and both pisses me off and makes me sad. And it fills me with compassion for those of you with CFS who DO live alone, and find ways to cope.