This is the third in a series of blogs following the work of Workwell and allied exercise physiologists who are aiming to do nothing less than revolutionize the way chronic fatigue syndrome / myalgic encephalomyelitis (ME/CFS) is viewed.
- The Disability Defenders: The Workwell Foundation, Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia
- How Physical Therapists are Getting it About Chronic Fatigue Syndrome (ME/CFS): The Workwell Foundation Pt. I
The first word in the first sentence of the paper says it all:
Concise methodological directions for administration of serial cardiopulmonary exercise testing (CPET) are needed for testing of patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).
Why concise? Because Workwell asserts that in the universe of diseases known to man, ME/CFS is so different when it comes to exercise that it needs a place all its own. It needs its own concise methodology, and above all it needs to be understood differently.
This methodology paper, then, is an attempt by the exercise physiologists at Workwell (Staci Stevens, Mark Van Ness, Chris Snell, Jared Stevens) and Betsy Keller to spread the word that something very different, something perhaps even unique in the annals of medicine, is occurring in people with chronic fatigue syndrome when they exercise.
Very Popular Paper (!)
Someone, it seems, is listening. This dry, seemingly obscure methodology paper (“Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome“) has proven to be a surprise hit. In the two months since its publication it’s been viewed by over 7,400 people spread across the globe. More than two months after its publication, Frontiers reports the paper is still receiving more views than 91% of the articles published in the Frontiers journals. (Add to the total by viewing the paper here.)
Much of the interest has probably been driven by the 194 tweeters (!) that Altmetrics states have linked to the article. People in Ecuador, Saudi Arabia and Malaysia have read this paper. (Check out the demographics here.)
The paper’s focus is on cardiopulmonary exercise testing (CPET). In heart disease, CPETs are used to assess disease severity and functionality and can even predict mortality outcomes. In ME/CFS, they’re used to assess functionality and energy production as an objective way to stress ME/CFS patients’ bodies and provide guidelines for safe exercise.
For people who need objective evidence of impaired functionality for disability, these tests can make all the difference. Their ability to provide physiologically based assessments of functionality in ME/CFS and FM destroys any ideas about malingering.
The Deconditioning Dilemma
When done correctly, CPET tests can cut through the mistaken idea that malaise and malingering cause this disease, something that has shrouded the ME/CFS field in controversy for decades.
There’s a danger, though. The same tests done incorrectly or used for the wrong purpose can produce more trouble than help. While one-day CPET tests provide an excellent way to objectively stress one’s system, they have also been used as evidence that deconditioning causes ME/CFS and that people with the disease are malingerers.
That’s because the reduced peak oxygen levels that often show up in ME/CFS during one-day CPETs can be taken as a sign of deconditioning. That finding – which makes sense in other diseases but not ME/CFS – has given the biopsychosocial crowd a reason to emphasize graded exercise therapy (GET) and cognitive behavioral therapy (CBT) as treatments.
Not so fast, Betsy Keller and the exercise physiologists from Workwell say. It’s impossible, they assert, to say anything about deconditioning in ME/CFS without doing a two-day exercise test. The reason is simple: ME/CFS is so different from other diseases that the traditional rules do not apply.
Studies indicated that people with all sorts of disabling diseases can exercise to exhaustion two days in a row, and, surprisingly, generate the same amount of energy on the second day as they did on the first.
Take pulmonary hypertension (PH), a very serious disease (about 50% of patients die within five years) which can cause exercise intolerance. PH causes a narrowing of the blood vessels in the lungs that makes it difficult for the heart to push blood through them. Yet people with PH can hop on a bike, exercise until they can go no further, and then the next day do the same, with no diminishment of their ability to exercise.
The same is true for people with heart failure, end-stage renal disease, cystic fibrosis, COPD and/or stroke. The fact that they can do so is a testament to the incredible robustness of our energy production systems.
Those people don’t need a 2-day test to demonstrate their functional status: a one-day test works just fine – for them. It only makes sense to assume that people with chronic fatigue syndrome would be able to do the same. But they can’t.
A Unique Disease?
Cardiopulmonary exercise testing can provide helpful insights into this disease by better characterizing the unique post-exertional pathology of the illness. The authors
The ME/CFS community lucked out when an exercise physiologist named Staci Stevens got ill. She realized that exercise was making her symptoms worse (post-exertional malaise or PEM) and making her weaker to boot. When she tested herself on a metabolic cart two days in a row she found that the first exercise bout had indeed inhibited her ability to produce energy. She had gotten ”pemmed”.
The finding intuitively made sense, but intellectually it was an astonishing moment. Her mentors, after all, had ground into her that anyone – even people with serious illnesses – can reproduce their exercise test results. She was an anomaly and so are many of the hundreds of ME/CFS patients that she and the exercise physiology group at Workwell have tested over the past 20 years. Their findings indicate that as exercise greatly exacerbates patients’ symptoms, it’s also whacking away at their ability to aerobically produce energy.
The protracted symptom flare following exertion (post-exertional malaise) is such a dramatic feature of ME/CFS that a term new to medicine, “post-exertional malaise or PEM”, was created to explain it.
The Somatic Hypervigilance / Deconditioning Trap
ME/CFS is not alone in its struggle to get past the deconditioning issue. Because deconditioning occurs in any disease that severely limits movement, it is, of course, present in diseases like ME/CFS and POTS. The difference between the deconditioning that results from disease and the deconditioning that causes disease is critical, though. The consequences of not convincing the medical profession that the deconditioning found in ME/CFS and POTS is caused by the disease has been immense.
For one thing, it’s enabled biopsychosocial researchers to attempt to explain ME/CFS by throwing deconditioning together with something called “somatic hypervigilance”. That hypothesis has caught many POTS, ME/CFS and fibromyalgia patients in its snare.
We can get an excellent view of what’s going on by looking at other diseases such as orthostatic intolerance (POTS), in which exercise seem to indicate that deconditioning plays a major role. One exercise study concluded that 90% of people with orthostatic intolerance had some form of deconditioning.
One lecture (“POTS versus deconditioning: the same or different?”) concluded, using the results of a one-day exercise test, that what people with POTS and ME/CFS really need to do is exercise.
“In this context, the physiological responses to exercise appear remarkably normal in many patients with chronic fatigue syndrome, but there is a mismatch between the perception of effort and objective measures of the physiological stress. These results seem analogous to the somatic hypervigilance seen in patients with POTS. In other words, normal physiological responses are perceived very differently in these patients.
“It is important that the medical community retain their empathy for patients with unusual conditions, but at the same time perhaps we should send a firm but empowering message about physical activity to them.” Joyner and Mazuki
There’s no doubt that exercise, when properly done in POTS, can often times be helpful. A 2015 review flatly stated that, “the tachycardia (increased heart rate upon standing) seen in POTS is due to reduced stroke volume, which can be ameliorated or even eliminated by exercise”. A three month graded exercise program, which started off with supine exercise, found that after 3 months about 50% of the participants no longer met the criteria for POTS.
That was clearly a positive finding, but then again, 50% of the study participants still met the criteria for POTS, those who didn’t meet the criteria weren’t necessarily cured, and the physiological results – blood volume increases of 6%, end-diastolic volume increases of 8% – weren’t exactly staggering. In fact, despite all the exercise – which by the end of the study was being done several times a week and included weight-lifting – neither the heart rate nor stroke volume of the POTS patients reached the normal levels found in sedentary, healthy individuals.
Two researchers who had clearly tired of what they believed was an over-emphasis on deconditioning in POTS recently penned an editorial. They acknowledged that deconditioning is present in POTS while asserting it is not primary. Noting that 60% of POTS patients fail to complete graded exercise studies, they bemoaned the emphasis the medical profession now places on deconditioning in POTS.
“Most (POTS) patients undergo extensive, noninvasive cardiac testing and are often told that their symptoms are secondary to deconditioning, given a common finding of poor exercise tolerance on an exercise stress test.”
Of course, people with ME/CFS have been dealing with this scenario for decades. The entire graded exercise therapy (GET) edifice is built upon the idea of deconditioning, false beliefs and somatic hypervigilance. If you can just get people with ME/CFS moving again, the original GET proponents felt, the disease should resolve itself. That hasn’t proven to be true, but the idea has burrowed into many doctors’ heads.
The Antidote to the Deconditioning Dilemma
There is an antidote, though, to the deconditioning/somatic hypervigilance issue and it’s called a two-day exercise test.
Staci Stevens and Workwell have tried to get the need for two-day CPETs in ME/CFS across for over a decade. It’s a measure of the strength belief systems (i.e dogma) can have that the idea has received considerable pushback. It’s really no surprise; Workwell is, after all, trying to overturn decades of perceived wisdom, and they’re using a controversial disease to do it.
Rather than believe their results, some exercise physiologists simply assume Workwell’s metabolic cart is not working properly. Workwell’s response to that is to do the most rigorous calibrations possible, including using a technique called biological validation which many exercise physiologists probably haven’t even heard of.
The two-day exercise test occupies an important and even unique position in ME/CFS’s research armory: not only does it make clear, in a way that no other test can do, that too much exertion reduces functioning in ME/CFS – the core issue in this disease – but it does so in a way that demonstrates how unique this disease is. It comes as no surprise that a test which objectively demonstrates the energy problems in ME/CFS is going to overturn accepted dogma.
The opportunities the two-day exercise test provides have made it all the more puzzling to me, at least, why two-day studies have been rather rare in ME/CFS. The tests, of course, aren’t easy on patients. Most recover within a week but others can take much longer.
A large two-day exercise study could, though, at one stroke both legitimize this disease, demonstrate its uniqueness, and point a finger straight at energy production problems and arouse tremendous interest in that vital area of research.
I asked Staci which, if any, studies employing this test were underway.
The most exciting for us is the Cornell’s ENID NIH CRC 2 day CPET study. Workwell will be providing testing as the west coast arm of the study. I’m thrilled when I hear of any study using 1 or 2 day CPET. There are several groups – the NIH Intramural Study, Columbia ME/CFS CRC, Nova, Cortene and Mike VanElzakker come to mind – who have opted for a 1 day CPET instead of submaximal testing and this is huge progress for the field.
Workwell has been giving two-day CPETs for years. I asked Staci if the drop in energy production seen in an exercise test given one day after a previous test was really unique in ME/CFS. Her answer demonstrated just how much we have to learn.
Clinically we have seen patients with more than 30 different fatiguing conditions including POTS and fibromyalgia. ME/CFS is unique but more research is needed to determine ME/CFS CPET subsets and if other conditions have abnormal test 2 responses.. Our clinical patients often have comorbid conditions, so this makes it more difficult to sort out. That said, several distinct subsets of abnormal responses are emerging. We have a case series on this very topic comparing fatiguing conditions with ME/CFS which will be published soon.
I asked Staci what was next for Workwell. She reported that research will be ramping up and several publications are in the works including the CPET case report series, heart rate responses in ME/CFS and more on PEM. Plus, Workwell will be producing a continuing education program on ME/CFS in partnership with MedBridge, which will be aimed at health care providers, including physical and occupational therapists, nurses and athletic trainers, and is expected to launch in 2019. Her hope is to educate health care providers and provide resources for patients.
A Guide to Giving a Two-Day Exercise Test in ME/CFS – The Methodology Section
The methodology section of the paper gives exacting instructions on how to give a two-day exercise test. Some are given below.
The pre-test preparations should begin as early as 2-3 weeks prior to the test and basically include ways to minimize stress on the patient. Alcohol, caffeine, exercise and food restrictions prior to CPET are given. Physician consent and a completed cardiovascular disease risk questionnaire is required. If a plane trip is required, resting after the flight for a day or two is suggested. The patient should not drive after either exercise test.
Following 5 min. of supine rest at the facility, baseline measurements (resting heart rate, blood pressure, O2 saturation, body temperature, and monitor electrocardiogram) are taken. Water should be provided throughout the testing and after the second exercise test electrolyte replacement drinks may be helpful. A saline infusion at that time can also be helpful.
The test should be devised so that the patient is on the bike (treadmills are not recommended) at least 8 min. but no more than 12 min. Depending on the physical condition of the patients, Workwell gives different workload increments that can be used. (The pressure on the pedals starts off at basically zero and then is ramped up (workload increments) over time.)
The protocol is as follows:
- START: 3 min seated rest on cycle—monitor ECG, VO2, and record BP and O2saturation at min 2.
- EXERCISE PROTOCOL: first minute exercise stage—begin at 0 watts (no prior warm-up) and increase 10–15 watts per min, or as appropriate.
- DURING EXERCISE: Measure BP/O2saturation/RPE every 2 min (e.g., @ 15W, 45W, 75W, etc.).
- PEAK EXERCISE: Obtain RPE, HR, BP at peak or immediate post exercise.
- POST EXERCISE: Recovery measures of BP, HR/ECG, O2 sat @ minutes 1, 3, 5, etc. until recovery when HR is within 20 bpm above pretest HR, close to pretest BP, normal ECG, asymptomatic.
Special emphasis is placed on ensuring that the exercise physiologist accurately report that a maximal effort has been given.
“Even when automated system calibration appears accurate, results may be erroneous.”
Workwell has long emphasized the need to ensure that the twitchy metabolic carts are properly calibrated. They assert that it’s essential to calibrate the machine prior to and following each CPET and then go beyond normal guidelines to assert that monthly “biological validation” of the metabolic cart is essential as well.
That includes having a human being (usually a staff member) with known values test the machine monthly. Biological validation can identify errors not detected by the automatic calibration of the machine.
Biological validation of the metabolic cart is particularly important for ME/CFS patients because the carts tend to read high; i.e. make the patient appear healthier than they are, when biological validation is not done.
The group also provides recommendations for software, frequency of sampling, data display, etc. Finally, the group asserts that one-day CPETs should only be used as stressors in studies seeking to understand how exercise impacts the immune system, gene expression, etc. Because they provide an objective measure of effort, they’re ideal for this purpose.
One-day CPETs should never be used, however, to assess aerobic capacity, functionality, etc. Two CPETs are needed to assess functionality and the impact of exercise on energy production.
A two-day maximal exercise (CPET) is not an easy test for someone with ME/CFS to take but it can be stunningly effective in demonstrating the apparently unique effect exercise has on energy production in this disease. The fact that one-day maximal exercise tests do accurately assess functioning in people with other serious disabling diseases unfortunately has had negative consequences for ME/CFS. This is because the low values people with ME/CFS often post on one-day tests suggest deconditioning is present. Two-day exercise tests reveal, however, that the low values are primarily due to problems with energy production.
Few fields are receptive to findings that overturn dogma and the exercise physiology field has proven to be no exception. The field, in general, has resisted Workwell’s and other’s findings indicating that exercise affects people with ME/CFS differently than people with other diseases.
The evidence, though, is starting to add up, and Workwell’s recent CPET methodology paper will make it harder for exercise physiologists and others to keep ignoring the obvious. Not only do studies suggest that exercise affects people with ME/CFS far differently than people with other diseases, but it also asserts that a rigorous methodology unique to ME/CFS is needed to successfully do these tests. That by itself should open some exercise physiologists’ eyes, change some minds, and hopefully spark more interest.
More on Workwell From Health Rising
- The Disability Defenders: The Workwell Foundation, Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia
- How Physical Therapists are Getting it About Chronic Fatigue Syndrome (ME/CFS): The Workwell Foundation Pt. I
- The Workwell Foundation Resource Page for Chronic Fatigue Syndrome
PEM is nothing exceptional. Everyone with a common flu has it and thats why I think ME is a brain infection.
Interesting – certainly suggests that ME/CFS is a immune mediated disease but we need much more information on other diseases. Workwell is going to come out with a case series which describes their findings in HIV and other diseases vs ME/CFS. Hopefully we’ll get to the point where statistical analyses can be done.
One study did find more fatigue in multiple sclerosis and much less PEM than in ME/CFS – suggesting that something very different is going on MS. Jarred Younger found neuroinflammation in ME/CFS but not in the rheumatoid arthritis – another fatiguing disease – suggesting that something is going on there as well.
My guess is the PEM is going to be found in some conditions (certainly FM and POTS and biliary cirrhosis) to a smaller degree than ME/CFS. The ME/CFS community invented the term PEM for a reason – it’s fundamental in this disease.
A case series is exactly what we need. The problem with the 3 day CPET has never been sensitivity, its been specificity. The more that can be done to show the response is specific, the better.
I have seen no data to show PEM exists in common infections. There is a theoretical basis for it though. However a flu or most infections are time limited. They do not go on for decades.
Of course some viral and bacterial infections can be indefinite, but most of those are easily tested for. They might however present problems for those with such infections and ME, presuming that its right that infections might induce PEM.
Of course infections induce exercise intolerance a lot of the time. That is not the same thing as PEM at all.
I assert the fact that PEM IS exceptional and unless you have experienced it you will never believe it. That is why this study is so important. It proves the biological process involved and how absolutely unique it truly is.
PEM is a terrifying thing to have happen to you when you are healthy and actively exercising every chance you get. To be absolutely incompacitated INSTANTLY when doing nothing remarkable is terrifying and any person would immediately call their doctor or 911. I assumed that something was terribly wrong, but literally was unable to ask for help until after the PEM had passed. My doctor, who was looking at what appeared to be the 40 something year old woman he’d been treating since she was 14 years old believed my claims as I had proven to be trustworthy over the decades immediately began “the tests”. This scenario of me coming in making extraordinary claims of a recent “Event” after it passed, him running tests and referring me to specialists lasted for two years.
Then we came across the Canadian Consensus Criteria and It was an overwhelming “this is IT!” moment. My GP, Neurologist and Rheumatologist all agreed on a diagnosis of ME/CFS for me. At the time of diagnosis I was performing at 17% of normal for me. That was before the neurological symptoms began.
I worked my butt off trying to fix my physical strength problems.. I had the normal mindset that you get stronger when you exercise.. and since I had already been in good shape and exercising daily when I got sick I had no reason to suspect deconditioning.
Yet, in late October of 2007 while standing in the middle of a book store holding the highly anticipated and long-awaited release of the latest installment of Dean Koontz “Odd Thomas” series.. in hardback of course something unimaginable happened. One minute I was Standing there holding this source of joy for me.. envisioning everything I love about reading a good book while sipping cup after cup of tea from my favorite tea set with cozy lighting in my favorite warm pajamas under grandma’s afghan after when my daughter went to bed my legs gave out.
No warning signs. I felt fine. Better than fine.
But my legs had just suddenly turned into noodle legs. I was on the floor, in an awkward heap, stunned and shocked. When I was unable to stand back up, it was then that I became afraid.
I was 5’7″, weighed 140 lbs and was physically fit. My legs were strong. I had always had very strong legs and arms and I had no reason to expect anything so bizarre would happen to me.
THAT wasn’t even PEM. It was a symptom.
PEM is, for me, All 4 limbs becoming limp noodles. I feel severe pain body wide, I lose consciousness. Always. And when I surface I am often not able to open my eyes or move.. I can hear everything going on around me but I can’t communicate with them. then I sink into darkness again. When I finally wake fully I am extremely disoriented and cannot tell night from day literally. I have to be told the time using a weekday and a morning or evening reference. it’s very hard to adjust to those facts because my brain isn’t registering what I’m being told. I also find that I speak but my words make no sense to everyone else well they sound fine in my head and hearing as I talk. I can’t dial a phone, and often I can’t remember how to use it. the phone will ring and I answer the remote control instead. I lose the ability to write.
PEM is unlike anything I ever experienced before getting this disease. It’s absolutely in a class all its own and I firmly believe that.
“No warning signs. I felt fine. Better than fine. But my legs had just suddenly turned into noodle legs.”
This isn’t a typical description of PEM. The sudden onset makes me think of an allergic reaction – mast cells behaving badly, perhaps causing a big drop in blood pressure. Vasovagal syncope also comes to mind.
I’ve had a number of strange episodes over the years, including sudden-onset near-hypothermia caused by an apparent nut allergy. I know it sounds weird. I probably wouldn’t believe it either if I hadn’t experienced it myself and confirmed it with a thermometer.
Congratulations on finding a doctor that believes you. For many ME patients, that never happens.
My PEM never starts immediately after exercise. It comes gradually at about 3 hours after exercise. First I have a redness and hot flushes in the face and then the “acid starts to pour in the brain feeling” or “brain inflammation” or “brain flu” begins. I dont remember what it is like to be healthy, have fever and exercise (I have this mononucleosis beginning ME shit for 20.5 years), but I think what happens is similar to PEM: First after exercise with a flu and fever you feel better (inflammation suppression, endorphines) but then the infection strikes back. (But you recover from flu, ME is eternal. (I hope it is not.)
Totally agree with Jim Ellis that the legs going out is a mast cell activation disorder induced allergic reaction because the same thing happened to me about 6 months ago after I ate a wheat based product (cake or something).
I was a fitness trainer when I got this lovely, life altering ME/CFS/FM plus Anaphylaxis! I never had an allergy in my 50+ life, not even to hay fever, but my sisters did. I most certainly have MCAD though tryptase levels are too low and methylhistamine is always lower than WHO requires to meet criteria..ha, by 1 point even though I have every classic symptom. So, don’t be too destroyed if you never get a diagnosis for that, instead be proactive with elimination diets, get a dna test for the MTHFR gene and other genetic mutations (mine revealed the inability to absorb vitamins D and some Bs) find a functional MD who gets mast cell disorders (and can do a deeper analysis of a 23andme test) and try to be optimistic by looking at your fatigue days as “rest days” so you will have more energy later.
As for exercise…I agree and disagree. Of course I feel worse on the 2nd day like everyone else after anything strenuous BUT I had a doctor who told me “..even if you feel like you are dying, get up and walk anyway” and I live by that philosophy, I believe because of it I have a lot more good days than most. With a small farm with horses and dogs that MUST be fed and turned out no matter how badly I feel, I swear, having to get up when I would rather sink into a void of oblivioun, aka my bed, makes me feel better and stronger, not always, but most of the time.
I am glad you have a supportive physician and wish you well on this interesting and frustrating journey. Thank goodness for Cort and this forum..another source of optimism!
PEM is considered the hallmark of CFS and that if you don’t have PEM you don’t have CFS/ME, according to some CFS/ME paper I read but can’t remember by whom.
Another well written blog Cort. Thanks!
As for the 2 day exercise test I believe it could be interesting to add the following:
* buy an infrared camera; about 10k$.
* dress patients in “standard clothing” an hour before the test (in order to get better comparison between patients and control group, not influenced by obscuring thick clothing) and get them to stay in a room with either controlled or measured temperature and air humidity.
* Take an (hole body) IR picture before the test.
* Take several IR pictures during and after the test; ideally take several IR images with half hours difference during several hours after the test.
* A bit more difficult (requires hospital stay) but take a series of IR pictures at night when the patient is sleeping. When having a PEM my body temperature at night often initially tanks and is often followed by cold sweats. Even better would be to start taking IR pictures the night before the first exercise test for reference.
* Do the same the second day.
* Do the same with healthy control group.
I’m not sure, but my gut feeling says it could be a cheap and effective way to convince the skeptics that there is really something odd going on in ME.
It would be very hard to argue with a strong statistical (chance of error < 1%) difference in body temperature or body temperature distribution as that would be a simple mathematical processing.
It could even lead to a simple and effective way to prove GET is dangerous to a large part of the ME/CFS population, leading to abolishing its blanket use.
As always De Jurgen very creative thinking. It seems to me like you try to understand the problem from inside out – a very effective way to approach something.
I still very well remember what happened when I had the worst crash in my entire life.
That day I temporary lost my ability to speak in single words. Every single step I had to take to let my parents in, who I called by phone while only making weird sounds, was as exhausting as walking 40 kilometers (about 27 or so mile) in my prime. Doing so I felt pain far beyond anything I could imagine.
When I arrived that hot summer evening in ER, the medic toke my temperature. It was still in range. But it’s near always higher in the evening and the PEM cascade just started. The next hot summer morning the nurse took my temperature: 33.5 °C. She called it plain impossible and blamed it to those unreliable digital thermometers.
As nurses have a tight schedule and I clearly had no fever she decided to not go and grab a mercury thermometer to check. However the next morning the thermometer stated I had 34.5 °C. She didn’t go and grab a mercury thermometer neither. I just thought it was plain wrong to use that same dysfunctional thermometer with over a dozen patients the day before but stayed silent.
That day I did a very light exercise/functionality test. Walking the first 5 meters between bars required focus and dedication but I could manage. Going back I failed. I had the first episode of hyperventilation ever and boy I went all the way. I made sounds and movements resembling a total panic attack. However, 10 minutes later my mind was calm and clear. I felt no shame as I knew it was my body being in utter despair.
I left the hospital a few days later with “CFS flare up; no abnormal medical signs found” and “patient had a panic attack” on different forms.
Later on I discovered I regularly had hypothermia in the morning, so the impossible temperature wasn’t impossible.
And the so called panic attack was very likely me having a very extreme case of air hunger.
Everything below 35°C=95°F is hypothermia and requires emergency treatment. My temperature dipped to 33.5°C=92.3°F on a hot summer day in a poorly cooled room.
If the nurse and doctors would have realized that my temperature was that low they’d had me sent immediately to the ER.
My limbs and legs are however hit disproportionately hard by low temperature. If they would have had an IR image of my body at that time and would have known how to compare it to a healthy IR image, then they would have forbidden me to take a single step. Maybe an inexperienced doctor or nurse might have had a panic attack themselves.
It’s hard to argue with calibrated IR images even for the most stubborn denier.
ps Cort: if you’d think it’s a good idea to add in future research protocols, feel free to forward. They will value your opinion more then mine as you are well known and respected. I’d think if successful it could easily yield another NIH research grand.
What a story. My god, the things that happen. Stories like that make me think – on the optimistic side – just how fascinating this disease is going to be to the medical community when it finally gets accepted and the proper research.
So an infrared camera would do something similar or result in something similar to what Jarred Younger is doing with his brain scans?
Off topic, but comments to the “Anaerobic Thresholds” topic are dying out so you might miss it:
Diane linked the requested info and it seems a fit. Confidence in the high value of the combined ATP recycling/NADPH recycling/glutathion idea grows strong.
So to your recent request to write a blog on the NADPH idea: no thanks. The combined ATP recycling/NADPH recycling/glutathion idea is growing far beyond the sum of its components IMO. So yes, I’ll let it sink in for another two weeks but feel confident my opinion will remain the same:
I’m ready to go forward, build and present a complete model of an elaborate energy blocking mechanism including extensive detailed biochemical processes if you (writing and selecting key information to present) and others (fact checking and questioning validity) are up to it. It’ll be no small task, but if the idea remains valid it’ll be reshaping the ME field.
“So an infrared camera would do something similar or result in something similar to what Jarred Younger is doing with his brain scans?”
If at least a decent sub population has the same “thermal characteristics” as I do/did then yes, but on a budget. And I’d anticipate it would improve understanding of ME a lot, create links with FM and improve patient care in small but simple and cheap ways if my results based on it would work for others in the subgroup as well.
This research gives me hope! I have always believed that ME/CFS is caused by abnormal thermoregulation. Our body temperature fluctuates in the wrong direction. It drops when it should actually rise. Everybody knows that people are encouraged to exercise because it increases metabolism, health and well being. It also increases body temperature. For me, it drops my temperature and I quickly become vasoconstricted. It is a case of the more I do, the lower it goes, the longer it stays down, the sicker I get. I do not shiver, I sweat, so it is not a visual malfunction. It is not only exercise that does it, any work load placed on my body causes my temperature to drop when it should have risen. My body temperature is normal at rest only if I have not eaten.
Infrared camera’s may not be necessary, if only they would keep monitoring our body temperature whilst conducting the exercise tests. I think what they discover would be mind blowing.
De Jurgen, your story of extremely hot weather causing you to be hypothermic is a common one with me, there was nothing wrong with the thermometers they used, but they would have taken it more seriously if they had bothered to check by getting another thermometer. Being so aware of my abnormal body temperature, during hot weather I do as little as possible in order to keep my temperature as close to normal as I can.
Much of what you say does sound familiar to me too (safe for the sweating, I lost that “ability” after some failed medication). It does probably sound familiar to a large subgroup of (mainly 3+ year sick?) patients.
I do tend to believe however it is not the main cause of our problems, but rather a protection mechanism. I’ll write and detail about it in the future. Of coarse when it hit extremes the protection mechanism becomes dangerous itself. Kinda like driving into a wall in order to stop a car with broken brakes.
The thermometer (preferable an IR one, about 50$, so they could also monitor for example belly or leg temperature) would be sufficient to see if the idea is worth investing in.
The IR camera is because in my experience as a former researcher I know that such complete images have far more convincing power then a “simple” thermometer reading.
Seeing a healthy patient with red/orange temperature levels on the head and yellow on the legs next to the image of a patient with the same red/orange temperature levels on the head and dark blue on the legs (with same color scheme) hits the mind like a grenade far more then a table with temperatures can do. Just being practical ;-).
Thanks for sharing your experience.
Hi De Jurgen,
I agree one hundred percent that body temperature phenomenons are far more understandable in images rather than on tables of numbers. I just thought thermometers would be cheaper than thermal imagining.
To me, the drop in body temperature is to quick to be a protective mechanism. As an example: if my grown up daughter and I take our dogs for a walk, within 15 minutes my temperature has drop at least one degree and hers has risen a degree. So to me it appears to be spontaneous, my hypothalamus is intentionally signalling the body temperature to drop instead of rise.
I look forward to reading any information you post on the protection mechanism.
“within 15 minutes my temperature has drop at least one degree”
That’s were the IR images drop in. I think those would show that your head temperature hasn’t dropped a lot in temperature at all compared to the rest of the body. At least my experience is that when I got hypothermia my head didn’t feel cold.
If that is so, then it basically says the head would be overheating if the body wasn’t that cold.
Why? Because the blood constantly circulates from the cold body to the head and back and takes heat from the head to release it in the cold body. Yet despite this large transfer of heat the head stays warm. That means that locally the head must be producing more then normal amounts of heat.
Without this “cooling mechanism” by having a cold body to dump the heads heat in, the head would likely overheat. And heat is pretty bad for increasing inflammation.
Low grade brain inflammation is already supposed to be a good candidate for many of our troubles. If so and up the brain temperature with 1 or 2 degrees and it would become disastrous. So the body halts energy production as much as possible in the body. That’s a very short and incomplete summary of this hypothetical protection mechanism.
Hi De Jurgen,
I’m really sorry, but I don’t see the logic in the protection mechanism. To me, body temperature is PRIMAL. After all, we are classified as warm blooded mammals. Our bodies have a set point from which the body temperature is supposed to rise, thereby increasing circulation and optimizing metabolism. We have the set point, but our, or maybe I should say my, body temperature drops, resulting in vasoconstriction, which is obvious because I always loose my radial pulse when I exert myself. This reduces circulation and therefore, has to impair metabolism. To date I have not been able to find anything that will cause my body temperature to rise. So to my way of thinking, it is the reduced blood flow to the brain that causes the inflammation.
For years I tried to get doctors to listen to me, but their anger and aggression left me traumatized! I know I’ll never understand why they don’t take our abnormal body temperature seriously. To me, it is a case of fix my body temperature and my body will to take of the rest!
“To me, body temperature is PRIMAL.”
To me, it is until it isn’t. When a healthy person gets an acute infection, it rises a lot. That’s part of a protection mechanism.
IF and WHEN the average head temperature is considerably above what is safe or what is safe under already present brain inflammation then the brain has to lower it’s own temperature with great priority.
That can be done by reducing brain activity, but if that is already bare minimum then further reduction is no option. Then it needs to find another way to decrease it’s temperature. The only reasonable option for the brain is to loose heat by letting cold blood flow through it to take away the heat.
From an engineering point of view, the head has very few surface area compared to it’s high power consumption, making effective cooling challenging. A reasonable way to make blood supplied to the brain drop temperature is to decrease power consumption in the rest of the body. And that is what can easily be observed.
Does it have drawbacks: sure! When the person tries to do any exertion regardless then the poor blood flow increases inflammation during exertion and some time after (note that too high brain temperature increase brain inflammation 24/7 by contrast). But to me that’s a bowl like curve:
* right from the optimal setting point: lower body temperature is causing more extra inflammation then it reduces
* left from the optimal setting point: higher brain temperature is causing more inflammation then the amount of inflammation you loose by having better temperature of the rest of the body (and better blood flow).
Regardless of it being a protection mechanism or not, thermal images of the body plus head could reveal a lot a give a clear clue as to which of both is most likely.
I’m a mild/moderate case, but I typically have a morning oral temperature of around 96.8 (degrees F)– not hypothermic, but of concern. Subjectively, I seem to feel better when my temperature is in >98, but that’s rare. I get cold hands quite easily.
The IR camera data could give researchers a new direction of inquiry.
Thank you Cort for your amazing updates. You give me hope!
Thank! Happy Thanksgiving to you. 🙂
Cort, Thank you as always for making these reports comprehensible to those of us without a medical degree. Question — I was surprised to see this paper published under the heading of “frontiers in Pediatrics.” I do not see age-specific criteria for Workwell’s CPET. Why did a Pediatrics journal publish this paper when it does not appear to be geared towards children?
I didn’t even notice that… That journal has published other ME/CFS studies and articles but they seem to be on Pediatrics…I do know that it took some time to find a journal which would publish it. This is, unfortunately, apparently not unusual for ME/CFS.
Thank you for this report Cort!
I must say, although these studies deal with physical exercise, I notice in myself, a substantial decline in energy the following day after ANY stress provoking use of energy. I wonder if ones autonomic dysfunction can play a part in this, in addition to muscle and cardio/pulmonary function.
I also suspect I have POTS (very common in EDS), or at least dysautonomia, as my blood pressure and heart rate is all over the place–regardless of the appropriateness of the situation. I think it probable that I would have this effect simply by having to take an exercise test–kind of like ‘white coat syndrome.’ I wonder if others might have the same issue and thereby influence the results.
Regarding de-conditioning vs. ME/CFS, the truth is probably somewhere in the middle, in that for some of us, small amounts of exercise can be very beneficial–until it surpasses our ‘energy envelop.’ For the severely ill, that is probably not the case.
At least this study is shining light on some previous misconceptions!
Even Workwell finds that extremely careful exercise can often be beneficial, though the benefit is very small and takes a long time to manifest. They set very careful limits on exercise though, because as soon as there is too much energy demand it does more harm than good.
Anything inducing increased energy demand is enough to crash us according to the anecdotal evidence. We need alternative PEM tests to validate this. Even if it turns out that PEM is not unique to ME, it will be a great help to validated it without an exercise test. Bed bound patients who are too sick to even move could be tested with something that does not require exercise.
One candidate is the nanoneedle test, which stresses blood cells and shows an abnormal response to energy demand. If validated this only requires a drop of blood.
It is a fine line, isn’t it? The fact that carefully done, heart rate monitored exercise can be quite helpful for some could be used to assert that exercise is what we need.
That’s way too simplistic, though. There’s this tendency to to try to find simple answers to complex issues.
Workwell, as you note, has never said that heart-rate based exercise is curative at all. It’s just helpful in keeping one as fit as possible. In the case below it helped her stop slipping and improve some of her cardiovascular results but – and this is the big but – her aerobic energy production system was still broken.
This is great research and hopefully will be helpful in getting CFS/ME recognised and understood better.
But I very much agree with Alex Young.
Even if done carefully, any test that has a risk that the subject will have a relapse as a result is NOT A GOOD IDEA!
We really need a test that doesn’t pose a risk to patients.
A bit more on that last comment –
No Doctor would expect an asthma sufferer to ‘prove’ they have the condition by triggering an asthma attack would they?
Would a Doctor agree to a test for diabetes that required the patient to overload on sugar?
Would you test for deafness by requiring someone to do a dangerous task with only spoken instructions?
These are ludicrous ideas. Yet, for some reason, those with ME/CFS are experimented on until they relapse – and sometimes we never recover. But if it helps research it’s OK??!
Do the 2 day stress test by increasing heart rate in the sauna. I have found I can’t match my first day max heart rate on the second day in the sauna.
I would be shocked if the autonomic nervous system wasn’t playing a role in most people with ME/CFS.
I suspect that for the vast majority of us the kind of “exercise” we can safely do hardly deserves the name.
Sauna therapy. It “exercises ” the heart without the work.
Hi Cort. The link to the article is bad. Do you know the correct one, or can you tell me where to find the paper?
This is the broken link. (“Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome“)
Darn! I tried to put that link in twice (and failed both times). Here is the correct link – https://www.healthrising.org/blog/2013/08/13/heart-rate-monitor-program-improves-heart-functioning-in-chronic-fatigue-syndrome-mecfs/
I think there seems to be difficulties levels of PEM. Like people who have just increased fatigue/lethargy after exercise for a few days, but they don’t seem to get the flu like sickness and hangover symptoms that I would assume is more suited to the name ‘Post Exertional Malaise’.
They are linked, as I used to have mild to moderate ME/CFS for 25 years and rerely got the flu/hangover PEM symptoms. Unfortunately it severely worsened 3 years ago and I feel these vile symptoms 50% of my life now. it’s utterly awful. But what I’m wondering, is do the ‘very severe’ patients (like Ron Davis’s son) suffer from PEM permanently? If so that would be a living nightmare!
Workwell has a paper coming out on the different stages of PEM; from what I gathered muscle pain and fatigue is the first stage followed by flu-like symptoms. That fits my experience, when it’s really bad I get the dreaded flu-like symptoms
“But what I’m wondering, is do the ‘very severe’ patients (like Ron Davis’s son) suffer from PEM permanently?”
At my worst year I wasn’t even close to what Ron’s son was, but it was hell.
I could compare the average day during that year with the single worst day before I got ill. It was a day I had the real flue and had nearly 41°C=105.8°F of fever. During much of the day it felt like my bed was spinning quickly beneath me (like at a rate of about 10 full spins per minute). I spread my arms and legs so I good grab the edge of the bed “to not fall off”. I still vaguely had the notion that probably the bed wasn’t really spinning but that it was just my impression.
That single day had comparable quality of life as the !average! day during my worst year. The many bad days were a lot worse. Utter hell were they!
Now that I improved a lot since then I can’t even recall well how I felt back then as it is just too intense to relive that. I more recall the description in words then the actual feeling. It’s beyond my imagination how the worst affected must feel but I doubt it’s easy to find anything worse on earth given it’s not just an instant but a lifetime of this extreme suffering.
Dejurgen, You are one of the few ones that I have heard of who have actually improved from a worse state. What, specifically, did you do to improve your symptoms? Right now, all I do is pace my activities so that I can avoid crashes, but there’s got to be more that I can do.
The two day CPET test is an objective method to determine an energy defect and unique for ME. But it is hard to do for many patiënts. I don’t understand why this test is still not accepted.
It kind of boggles my mind as well. It boggles my mind that the ME/CFS researchers haven’t made doing a large two-day exercise study a priority either. It is hard on patients but most recover within a week. Others, unfortunately, take longer.
When I first heard about the two-day exercise test years ago I thought this is it! This is going to change everything. It’s taking longer than I thought!
To her immense credit Maureen Hanson is using the two-day test extensively in her studies at her NIH research center. It apparently has been dropped from the NIH Intramural study.
Why has it not caught hold? Remember the ulcer story – data on bacterial origin of ulcers had been around for quite a while before that caught on.
Plus there are some other hurdles: controversial disease and Workwell is a small group based in a small University. Even as they were reporting these incredible findings they were getting kicked out of the Pacific Fatigue Lab at the University.
I think Hanson’s study will be very helpful but it’s going to take five years and quite frankly, we could really use a big, rigorous study before then.
Thanks for sharing the great work – it really gives me hope! When I was on a GET/CBT program they told me the POTS was from deconditioning and not CFS which I found it a little hard to believe. I was still walking over 6000 steps a day, so by that logic should’t half the office workers in the world have POTS? and how come my POTS varied so much from day to day, surely my level of fitness shouldn’t swing that wildly in 24 hours?! (wink wink)
You might be interested to know that similar fitness testing is being done at a university in New Zealand http://www.massey.ac.nz/massey/about-massey/news/article.cfm?mnarticle_uuid=8D4B673B-BF30-718A-4363-5BE878DD08C3. Awesome that Workwell are sharing information so others can replicate findings and expand our knowledge of ME/CFS.
Wow. I didn’t know about that fascinating study. I am trying to get in touch with Dr. Hodges to get a copy of it. Thanks!
I am 99% bedridden and severely ill. how could I do the 2 days excercise test? 30 years ago, when I wass stil better, I could have done that, but I went worse and worse. In the beginning I had crashes, now it feels like a continu crash.
You couldn’t Konjin! Workwell would never subject you to that but think of this – others can do it for you and produce the results we need so that you and everyone else can get the funding we need.
If it helps any, konijn, to know that someone else is severely affected, I, too, suffer greatly. Bedridden for over 10 years. But my point is, I’m here with you.
1. Post-exertional sickness (yeah, I call it sickness rather than amorphous “malaise”) is a well established fact by now that I don’t think it needs further proving. Maybe 2-day CPET test could serve as a useful diagnostic tool?
2. Researchers should focus more on moderately ill patients rather than solely on the severely ill. The severely ill patients are in a constant state of PEM (“just walking from bedroom to bathroom causes a crash”), that CFS looks like some sort of infection, hibernation, metabolic, psychosomatic etc.
3. I wish someone like Workwell would study the relationship between the intensity/duration and PEM. Walking at 1 m/sec requires 10-15 watts and reducing it by 5-10%, or incorporating a break, allows you to walk twice as far. Squatting that requires 1-2 kw, on the other hand, only takes 2-3 reps to bring about PEM the next day. Studying this kind of relationship could eventually lead to the the underlying causes of CFS and PEM.
The two day test is very interesting. How does it compare to the invasive CPET done by Dr. Systrom? I had that done, and it found significant problems with my venous blood pressure, with the suggestion that that’s caused by some form of disautonomia. No one told me that my problem was de-conditioning (although that was obviously present as well).
Glad you had Systrom’s test done. The invasive CPET digs deeper and provides more information while the two-day provides a kind of iron clad assessment of how exercise impacts one’s functioning and ability to produce energy.
I would love to take this 2-day CPET for a variety of reasons, but haven’t been able to find anyone near me that even knows what it is, much less somebody who is able to administer it!
Does anyone have tips on how to find a testing facility?
it’s demoralizing…3 years into a pandemic proliferating the crap out of this disease and…we’re at the same status quo basically!
Sodium Chloride helps. 3 to 6 Grams a day with a good amount of fluids. O.T.C adrenal support.
Technically, just because a two day test provides evidence of PEM does not mean graded exercise therapy-you will not be effective. Even fit individuals when they are pushed hard experience overtraining. Overtraining results in a drop in peak performance the day after the hard workout.