Deciphering Post Exertional “Malaise”
PEM? – Cook asserts it’s compulsory in ME/CFS: no PEM – no ME/CFS….
In the last blog we found that the “fatigue” in chronic fatigue syndrome and multiple sclerosis (MS) were very different. While exercise knocked the ME/CFS patients into a new sphere of suffering, it had only temporary and moderate effects on the MS patients. Upregulated genes clearly linked with the exertion problems in ME/CFS that were unchanged in MS. These are two very different disorders – when it comes to exercise.
Now, taking advantage of Dane Cook’s recent Solve ME/CFS Initiative (SMCI) webinar, we take a look at two more studies that further underscore the perhaps unique post-exertional malaise problems found in ME/CFS.
A “Defining, Compulsory and Cardinal Feature”
Cook called post-exertional malaise a “defining, compulsory and cardinal feature” of chronic fatigue syndrome. (Dr. Unger would disagree, but most ME/CFS experts and doctors would agree.) Cook noted that PEM is a horrible term that in no way reflects the extent of the debility it causes in ME/CFS.
A Short Digression – the Malaise of It All
The word malaise is clearly the issue here. According to Wikipedia malaise, a French word in use since the 12th century, refers to “a feeling of general discomfort or uneasiness, of being “out of sorts” … [that is] often the first indication of an infection or other disease”. Medline says it refers to “a generalized feeling of discomfort, illness, or lack of well-being”.
Cook is right: PEM is another powder-puff term that somehow has gotten latched onto, whoops, another powder-puff term, “chronic fatigue syndrome”.
“Malaise” – another medical term that fails to do justice
Somebody came up with the term “post-exertional malaise” – but who and when? And is it exclusive to ME/CFS? A PubMed search indicates it first shows up in a medical abstract in a review paper on chronic fatigue syndrome in 1993 by none other than, whoops again, Dr. Anthony Komaroff, who has regretted his part in bringing the name chronic fatigue syndrome into existence for twenty years or so. Did he also help bring PEM into existence? He appears to be off the hook on this one.
Ramsey does not appear to have used it in his ME definition, but PEM was listed as a minor criterion in the 1988 Holmes Definition of CFS. It has become one of eight key symptoms in the Fukuda criteria, was not mentioned in the Oxford criteria, was retained in the Empirical Criteria, and was made a cardinal symptom for the first time in the Canadian Consensus Criteria. In the International Consensus Criteria PEM was transformed into PENNE.
After 1993, the next research reference to PEM in PubMed is fifteen years later in 2008. The Workwell exercise studies probably brought PEM to the fore, and since then it’s been referred to fairly frequently. All of the 25 references to PEM in PubMed involve chronic fatigue syndrome. It is apparently a term developed for and exclusively used to refer to ME/CFS.
Onward with the Webinar
What is PEM? Depending on how you look at it it can mean many things. These studies will add another dimension.
But what is PEM? Depending on how you’re looking at it, PEM could refer to the increased pain and fatigue people with ME/CFS experience after exercise, reduced aerobic energy production during exercise, an earlier entry into anaerobic energy production, reduced cognitive results on tests, impaired pain regulation, increased activation of the complement system, increased oxidative stress, and finally changes in gene expression – the topic Cook addressed next.
[It’s no surprise the SolveME/CFS Initiative (SMCI) funded Cook’s exercise/gene expression and cognition study. The SMCI, then the CFIDS Association of America, provided seed money for the pilot studies that helped get both the two-day exercise test studies and the Lights’ gene expression work started. Exercise studies now permeate ME/CFS research and the Lights have received several big NIH grants to continue their work. That’s a lot of bang for your buck and it demonstrates how powerful the pilot study approach can be.]PEM Study #1: Replicating and extending the Lights’ work
ME/CFS patients and controls performed maximal exercise test to exhaustion (legs won’t go any more) and had blood collected before and after exercise. This was a little different from the first Light study where the participants engaged in moderate exercise for a longer period of time. This study, which was published in 2013, found startling changes in several receptors. These included an adrenergic (sympathetic nervous system) receptor and the NR3C1 receptor that binds with cortisol. A receptor that regulates ATP production (P2X) tanked at 48 hours and then basically disappeared at 72 hours in the ME/CFS patients. The opposite pattern prevailed in the healthy controls.
Cortisol – Again!
“There is a lot of information about cortisol and ME/CFS, but very few answers to its biological significance.” – Dane Cook
The research community glommed onto cortisol early on in ME/CFS and has never let go. Low cortisol makes sense given the problems with energy regulation and immune functioning found in this disorder.
Dane Cook on Deciphering Post Exertional Malaise
Easily the single most studied biological factor in this disorder, it appears, after decades of inconsistent results, that a consensus is finally being reached that salivary wakening cortisol is mildly low in ME/CFS, but other aspects of it may be normal (at least in a significant percentage of patients).
Cortisol just keeps popping up
Brodericks homeostatic model of ME/CFS suggests women with ME/CFS inhabit an altered homeostatic state characterized by hypocortisolism, high estradiol, and a shift towards Th2 activation. Abnormalities in cortisol genes have been found in ME/CFS.
Nobody believes cortisol is “it” in chronic fatigue syndrome, but reduced cortisol does appear to be associated with increased fatigue and pain. Some studies suggest reduced cortisol is a secondary factor that occurs later in the illness than other components of ME/CFS. Salivary cortisol levels were not different early in the disorder between adolescents who came down with ME/CFS after infectious mononucleosis and those who did not. Just to confuse the issue more, CBT has normalized mildly lower cortisol levels in several studies.
The NRC31 receptor
NRC31 is the receptor to which cortisol and other glucocorticoids (steroid hormones such as hydrocortisone, prednisone, and prednisolone) bind. This receptor is found in the cytoplasm of the cell. After cortisol flows through the cell wall and attaches to it, it’s transported into the nucleus where it affects a variety of genes.
Found in almost every cell in our bodies, NRC31 turns on or off genes involved in metabolism and immune functioning. Glucocorticoids turn the immune system down by upregulating anti-inflammatory and downregulating pro-inflammatory cytokine levels. According to Wikipedia, NRC31 also appears to play a major role in regulating the effects of stress on the brain. Cortisol also spares glucose in response to exercise.
This was the first time gene expression of the cortisol receptor had been studied in response to exercise. The increased levels of inflammation expected with an upregulation of this receptor are what we would expect to find in ME/CFS.
The significant increases in this receptor seen after exercise in the ME/CFS patients could reflect an attempt to make more glucose available for energy or, perhaps more likely, reflect an attempt to reduce inflammation induced by the exercise.
Sympathetic Nervous System
Increased levels of the AD2 receptor are consistent with the sympathetic nervous system upregulation in both chronic fatigue syndrome and fibromyalgia. The one-two combination of the upregulated sympathetic nervous system and cortisol/inflammatory receptors was intriguing given Dr. Klimas’s gene expression findings (unpublished) suggesting that the sympathetic nervous system kicks off an immune cascade that causes the symptoms associated with PEM. [The Solve ME/CFS study did not measure gene expression during exercise.]
It is important that the changes in gene expression seen were correlated with the symptom flares experienced by the ME/CFS patients; increases in the cortisol receptor, for instance, mirrored increases in the fatigue reported by the people with ME/CFS.
Take away Points
Cook documents some gene expression changes found during exercise in the first Light study and adds the ubiquitous cortisolreceptor to the mix.
PEM Study II – the Uber Post-Exertional Malaise Study
“It’s clear to me that post-exertional malaise affects both the immune system and the brain.”
The Cook/Light/Broderick Solve ME/CFS study underway Cook talked about next is the kind of complicated multi-system study Solve ME/CFS loves to fund. No other studies have tried to tie PEM to so many aspects of ME/CFS.
Exercise is the constant. It’s hard on the ME/CFS patients, but Cook noted that nothing reveals the biological abnormalities in the disease better.
First they collected blood and had the ME/CFS and healthy controls do mentally fatiguing cognitive tasks while examining their brain functioning using a fMRI. Then they hit them with exercise (“moderate” exercise for thirty minutes) and then examined their gene expression, lactate levels, symptoms, cognitive functioning and brain activity 24 hours later using fMRI, all the while measuring their symptoms.
This is an important study. If Cook et al. can show that even moderate exercise hammers ME/CFS patients’ ability to think and messes up the way their brain functions at the same time, he’ll have built a powerful case for how destructive PEM is.
Many Pathways
PEM may be unique to ME/CFS, but that doesn’t mean it doesn’t require further refinement. Cook’s closer look at PEM revealed that it inhabits a complex world into itself. An analysis of the symptoms elicited by the exercise revealed a remarkably heterogeneous group. Memory and concentrations were highlighted in some people while headaches were the biggest component in others. One unfortunate person suffered from headaches, chills, and muscle pains. Muscle pains were almost the sole issue for one person, while another person’s joint pains improved markedly. While most people got worse, a few people actually got a bit better – one person’s joint pain improved markedly. Exercise clearly has very different effects in different people with ME/CFS.
The whole issue of symptom expression is complicated by the fact that many peoples’ symptoms, even at baseline, are already near the top of the charts. Even though they feel much worse after exercise, according to the charts they can’t get much worse! This “ceiling effect” complicates assessing symptom changes after exercise.
Cognition
If you feel that you’re, well, stupider after exercise, you’re right. If you feel you get stupider the more you exert your brain, you may be right as well. Your brain should get better after exercise and after engaging in difficult cognitive tests, but the ME/CFS patients’ brains behaved diametrically opposite to the healthy brains in the all the cognitive tests.
Practice Does Not Make Perfect – in ME/CFS
As the ME/CFS patients brains got more fatigued they did worse and worse on the cognitive tests.. and then came the exercise session
The cognitive tests were given three times at baseline and three times 24 hours after exercise. At baseline, while the controls got better and better on the cognitive test each time they took it, the people with Chronic Fatigue Syndrome – demonstrating that practice does not make perfect in ME/CFS – actually got worse and worse. The difficult cognitive tests appeared to be producing their own kind of post-exertional malaise or relapse. Every time the ME/CFS patients took them, their brains took a hit.
While exercise appears to have stimulated the healthy controls brains – they continued to get better and better at the tests – ME/CFS patients continued to tank on the tests. By the last test they were making almost twice as many errors as in the first test done at baseline.
Brain Drain
That’s pretty good evidence that exercise is messing up cognition in ME/CFS, but would Cook be able to show it was messing up ME/CFS patients’ brains as well?
He would.
Functional MRIs taken during the cognitive testing showed reduced activity in a part of the brain devoted to sustained attention – the parietal cortex – as well as increased activity in three areas of the brain involved in executive functioning: the anterior cingulate, the hippocampus, and the frontal cortex.
It appears that the ME/CFS patients’ inability to maintain sustained focus on a task (parietal cortex) put more pressure on other parts of the brain (frontal cortex, anterior cingulate, hippocampus) involved in executive functioning… and that was just at baseline.
As exercise sapped the sustained attention area of the brain the errors on the cognitive test mounted
Twenty-four hours after exercise – plenty of time one might think for the brain to recover – the situation was much worse for the ME/CFS patients. Those splotches of color in the fMRI indicating differences in brain functioning in the ME/CFS patients were now much larger. (One can only imagine what they would look like after two exercise tests.) Cook explained that they indicate how much harder a person with ME/CFS has to work to accomplish the same task as a healthy person.
Put the exercise and cognitive tests and the fMRI all together and you have a brain that was already having problems sustaining attention on a task before exercise getting worsening cognitively and functionally after exercise.
People with ME/CFS say it’s hard, really hard, to think, particularly after exercise, and this study helps explain why. Sustained attention was already poor at baseline, but it takes an even bigger hit after exercise. Other areas of the brain work extra hard to compensate – making cognition more effortful – but the effort largely fails and the errors mount and mount. By the end of the test the ME/CFS patients were making about double the errors of the healthy controls. Plus their symptoms – whether it’s headaches and chills in one patient or muscle pain and trouble concentrating – are sky high.
Gene expression was apparently also part of the this study but the results were not announced. [We also await the results of the big Enlander exercise test underway.]
Take Away Points
A reduced ability to think after exercise is documented and tied to changes in brain functions. Reductions in the ability of ME/CFS patients ability to sustain attention stand out, as does the need to engage more regions of the brain than usual to do mental exercises. People with ME/CFS also get worse, not better over time, when they engage in mentally fatiguing exercises.
Healthy people react in the opposite manner at all points; in contrast to the people with ME/CFS they do better over time and after exercise at mental tests.
Cook essentially documents and expands on the debilitating effects of exercise on ME/CFS.
Great writeup, Cort! This says it all.
So does this mean we shouldn’t exercise or that we should just exercise lightly? I have severe depression which exercise is supposed to help…not that I have the energy to do much anyway…feeling so horribly discouraged and hopeless. I live in the MidWest where NO one seems to take this debilitating illness very seriously and am SO sick of being so ill! I had 2 months of Transcranial Magnetic Therapy which seems to have done very little if anything to help…That was just about my last hope…altho at this point I’m ready to do acupuncture or ANYthing to have my life back. Feels like my functional life is over and I’m not even 60 yet…
Dear Fellow Sufferer,
I’m sorry to hear how down you are right now and I’m sure all of us can relate to how you feel because most of us have felt the same way too. I hope you check into things that can help like the book “How To Be Sick” written by a woman with our illness whose name escapes me this moment. I encourage you to follow up on anything that you think can help you get better and/or cope better.
Something did help me which was treatment of my gut issues with Xifaxan which you can read about here if you have similar symptoms.
I recently moved to Nashville which doesn’t have a single doctor who treats either ME/CFS or Fibromyalgia. I know how frustrating it can be to deal with doctors who have no clue and/or don’t take your illness seriously both from earlier days and now.
I’ve been fortunate that I’ve had knowledgeable doctors in CA for a number of years and am able to see them when I visit. But even they are unable to offer a cure at this time. Research results, however, are starting to come more quickly in recent years as evidenced by this article so I encourage you to put your hope in breakthroughs that are beginning to emerge recently. And to try to learn to accept your present situation as best you can. Help is on the way…
I too am waiting for breakthroughs to help my ME/CFS, but what is going to occur first, the breakthrough or the end of my life span?
My ME/CFS seems to have been triggered by a very stressful layoff from work in a job and place that I was very happy with. That was in October 1997. Now ME/CFS is a way of life.
Does acupuncture help?
Exercise lightly or rather exercise as much as you can without getting worse – which generally means quite lightly. These were exercise sessions that few people with ME/CFS would be able to tolerate without symptoms. Sorry to hear that the magnetic therapy didn’t help…
Hi Cort,
First of all, this was a great article! Especially for those of us unequipped to grasp science from lack of background. Thanks so much!
I am waiting to see if my insurance will renew my Rx for Xifaxan now but would appreciate any information from others as to where to get it as cheaply as possible. I’ve awakened a sleeping giant and they may decide not to continue coverage which may have been granted in error.
If it’s true that exercise only makes us mildly worse, I’m wondering whether it would be a good idea to try it again in some mild form. I know I am deconditioned and my muscle strength is poor and getting worse as I age and I also have balance problems. I’d love to hear what is working and not working for others.
For others with gut issues, please check out my story on Health Rising to learn about my dramatic improvement on Xifaxan which I started and have used for 3 years now and hope to be able to get to continue using it. Namaste and Shalom, Esther
I too have been down in the dumps lately and losing hope. I’m 41 and have 3 girls under the age of 5, but have the abilities of a 95 year old. I feel like I’m missing them grow up. I tried acupuncture in the beginning and it made me worse, but everyone is different on what helps them. I have done about 15 minutes of floor gentle yoga daily from the beginning as I have POTS and can’t stand. I believe it has helped give me energy and kept my muscles somewhat active. I’ve tried doing exercise bands and sometimes notice I don’t sleep that night, but I can’t be sure if it was the exercise or something else, so I have been hesitant on keeping them up….I live in the Midwest and went to one of the big research hospitals and gave them a lot of money and they were no help at all. They diagnosed me with post viral syndrome and fibro and told me to exercise. I did not listen as at that time, I couldn’t even walk across the room. I now go to a lyme doctor in Missouri. I have been bitten by many ticks, so I wanted to explore that avenue as well. My western blot actually came back cdc positive despite doctors saying we have no lyme in our state. After 6 months of treatment I’m not really much better, but i have heard treatment can take years. A friend of mine here also tested positive and is back to 90 percent of herself after 1 year of treatment. So, there is hope. I don’t know if we all have tick borne infections, but I’m guessing we all have many virus / bad bacteria that our immune system can no longer handle. I know I also had a terrible entereovirus when my health came tumbling down that was transported here from Asia which caused 75 deaths there. They are seeing fatigue with the entereovirus 68 and ebola, maybe there will be research into that…
Acupuncture is pseudoscience. It does not work, at all. I am sick of quacks profiting off CFS sufferers. They are part of the reason our suffering is not taken seriously!
my doctor found that amphetamine works for some of us & fortunately it has worked for me, maybe you too? best wishes
For some, physical and emotional relief may be found in the Biomodulator device patented by Dr. Jerry Tennant based on very upgraded Soviet space station technology. The premise, on which he has done extensive clinical research, is that all replication of healthy cells for improved whole-body functioning takes place in an intracellular environment in which the millivoltage of each cell is in a certain range conducive to keeping the enormous volumes of potentially bad pathogens, etc. dormant. The new healing paradigm (since the old once seems to have failed most of us) is “Healing is voltage.” This has been measured; no room to go into details, but much can be found on his Synergy medical website and the Tennant website. One of these devices was given to me and is the daily go-to for an energy booster, mental clarifier, pain reliever, inflammation reducer and even a detoxer (if certain substances are taken along with its use). This is by no means a primitive TENS device (info on sites), but something that uses the highest known frequency technology to date. Energy medicine has much to offer people who have exhausted conventional means. Not everything works for everyone, and not everything works all the time, but this is a great thing for me. It is worth the sacrifice to obtain one and be trained in its use. Acupuncture works along the same principle of upleveling the millivoltage of cells, but over time it can be slow with chronic disease, can cost well over the cost of the Biomod., and the Biomod. can be used as a cell energy booster 24/7. When I was without it for a while, the drop in overall wellbeing was marked. It just seems to allow the body to heal itself better. Getting all the toxic cleaning products, building materials and carcinogenic substances in my home (into a toxic waste facility) over a period of years has helped much also. The 23andme genetic test identified many dietary issues, including that of eliminating high oxalate foods, which are in progress, this seems to be producing good results for many.
This is an ad for pseudoscience.
Do you have to travel somewhere to use the Tenant device? I don’t have that much energy.
I was a strong runner, which can not be the case now with CFS. However, I found that when I began walking every other day, my baseline/tolerance gradually built up. I have discovered that building mild aerobic exercise up gradually helps me feel better. If I attempt any anerobic exercise, I am back to an episode. I highly recommend walking to eventually get your life back.
Fantastic thanks Cort. We need more of this exercise/cognition testing. I count PEM as the main symptom/problem and the whole ‘practise doesn’t make perfect’ hits the nail on the head.
Hey, fantastic blog of a complex area. Makes complete sense to me. “Practise makes perfect” comment said it all to me. I’ve been trying to understand why repetition or practise doesn’t seem to work with me. A very clear example was when I made th ridiculous decision to try skiiing recently. I only managed 3 runs down an easy slope. I’d been before, pre ME, and the others I was with were complete beginners. First run I didn’t fall over and went well, but deteriorated rapidly over the next two while my companions improved hugely. Legs gave out completely on the 4th and literally stopped working. Had to slide myself down to be carried off. Then my brain was completely stoopid, slur words, no concentration etc for ages afterwards along with all the other lovely symptoms of pain, nausea, chills.
So so glad we are getting closer and closer to scientifically explaining this PENNE phenomenon which, for me, makes working impossible.
I recently started doing around 15 to 30 minutes of very gentle yoga in the morning. I thought I would give it a try since I downloaded a new app onto my iPad for my husband who has arthritis in his back. (Which is awful since he’s only 39, the same age as me, and he’s had it since he was a teenager.) I found I could only start with the most gentle of the relaxation exercises. But, what felt strange to me was that for the first time in many years that when I did do the exercises I started feeling better. No other form of exercise has had this much of a positive effect. I have even added a few more poses to my original routine. I feel stronger.
Though to be fair my chronic fatigue is moderate, I haven’t been able to work much, but I can look after myself, do a set amount of housework and cook dinner almost every night ( I actually love cooking).
Admittedly I was surprised to find that doing yoga had benefits, I was so used to trying various forms of exercise, only to make myself sick. So I’m not sure if it is because yoga is best for my condition, or because I do a set amount of time and thus avoid overdoing it. Or even because I avoid an elevated heart rate.
Hope this helps.
Check out Dan Moricoli’s ME/CFS Knowledge Center for video’s on yoga. He’s done wonderfully on yoga. If you do it right it’s apparently more powerful than one might think. Then again it is at least partially about getting oxygen deep into the body and turning down the fight/flight response..thus enabling healing. He also very closely watched his heart rate. It was very important for him never to exceed it. He was also very careful about rest….He has a lot of discipline!
Glad to hear it’s helping.
Thanks, Cort, and thanks for the advice.
http://www.sciencebasedmedicine.org/yoga-woo/
This all fits in with Les Simpson’s observations that changes in the shape population of red blood cells is part of the picture – diminished oxygen delivery and metabolite removal in muscles, brain and endocrine system must play a role in all this.
And we need to recode exercise and rest. Rest, not trying to use muscles or the brain, does give our body the chance to address limited energy to whatever is needed to create the possibility for gradual improvement. Rest is as valuable as any medication we can take.
Exercise, on the other hand, as we constantly observe, acts like a poison, or an allergen, or something which stimulates whatever the agent is that is causing all this (latent virus? We don’t yet know.). But we need to reverse the mental habit of regarding exercise as doing us good – as the article shows, it doesn’t. Exercise is unavoidable in the course of everyday life, especially for anyone who has a physically demanding job, or is trying to run a home, let alone take care of children (the average mother of young children works 80 hours a week and gets more exercise than a coal miner). Doing extra exercise risks harm, makes our illness worse. Minimising exertion is what we need to go for.
Unfortunately, this goes absolutely against all that our fitness-mad culture teaches us – but if we want to have a chance of getting better, we need to make this shift in our thinking. We don’t offer people with a peanut allergy eating peanuts as a treatment, or make the goal of their treatment acquiring the ability to eat more peanuts.
I do think the right kind of “exercise” is generally helpful but that kind of exercise does not fit our conception of exercise and is certainly not the kind of exercise done in these studies.
Oddly enough, it takes discipline to rest properly and to not stop when one overdoes it…
Yes, this is so true. I was told to keep my heart rate under 104, and honestly, I have not been able to force myself to do that for even one full day. I just have this drive to do things, and get so frustrated by the boredom, and being deprived of the things I like to do, and then there are things that I need to do to take care of myself. Plus, on bad days, just standing up and brushing my teeth will get my heart rate to over 120. ME/CFS is like a prison, and I keep trying to break out, lol, which never works. I always get put right back into my cell, only more bruised and beaten up each time.
Postscript: It was Wessely, in the 1996 report, who contradicted Ramsay and Acheson’s unequivocal statements that complete rest from the beginning gave the best prognosis for patients with ME. Wessely said that rest should absolutely not be prescribed. And we know how much he has contributed to the well-being of people with ME!
I do have several recovery series in which rest and activity restriction were the main components..Absolute rest – minimal activity of any kind and a very slow ramping up of activity over time…It really works for some people.
Thanks, Nancy, the peanut story is such a great analogy!
I wonder if the term PEM came into being via another post-exertional problem people have – asthma. Post-exertional asthma is well known and I’m guessing the two terms arose within the medical community at large in early 1990s. I know about this because doctors briefly though I had post-exertional asthma. just a thought.
Could be. The first evidence in the literature I could find was Holmes in 1988 and he may have gotten it from somewhere else.
I am laughing at myself right now. I adore articles like this. I am constantly and desperately seeking validation … lol. And while I despise some of the sides of cortisone/Cortef, a tiny pinch during my worst ‘events’ of the day, keeps me from the ER. That and the fact that ER will make me more ill. No point in going….Six years ago, I could still get pharmaceutical grade bio-identical hormones, ie compounded DHEA, etc. That came to a screeching halt here. Not sure why. :Politics, I guess. So I haunt the health food store. But it isn’t the same….as having compounded hormones. And I can’t take them all the time for their side effects. Still it is better than chewing off my own hand to get free of whatever owns me when I am in deep dark painful, rigory ‘post-exertional’ haze.
Glad to hear it helps. We’re going to get more into hormones soon on the blog. It’s a fascinating topic…
I think this is the keydriver: ”Dr. Klimas’s gene expression findings (unpublished) suggesting that the sympathetic nervous system kicks off an immune cascade that causes the symptoms associated with PEM.” This must be the hallmark for a subgroup.
I note you say dr melvin Ramsey did not use the term PEM, he did though write muscle fatiguability following minimal activity plus delayed recovery “is the dominant factor and without it a diagnosis should not be made”.
Sorry I have this blasted side bar cover half of the comment box on my ipad screen nd can’t get rid so forgive any mistakes.
Yes, he was ahead of the curve with the idea (just not that particular term) and he was obviously right. Thanks for providing his exact words; i.e. “without a diagnosis should not be be made. It’s taken the research world a couple of decades to catch up with his insights – but it is occurring 🙂
I note you say dr melvin Ramsey did not use the term PEM, he did though write muscle fatiguability following minimal activity plus delayed recovery “is the dominant factor and without it a diagnosis should not be made”.
Sorry I have this blasted side bar cover half of the comment box on my ipad screen and can’t get rid so forgive any mistakes.
Hi Esther,
In response to your request for info on Xifaxan. If you google Xifaxan coupons you will see there are 75% off ones that come up. This is what I used as my insurance denied coverage. It was still very expensive but a lot better with the discount. See if a local pharmacy will honor one of the coupons. I actually took all the coupons I found online and they added them together. (I’m in California). Also for future possibility, I read that the FDA is considering Xifaxan approval for treatment of IBS in 2015. If approved it would be covered by insurance for us as SIBO and IBS go hand in hand. So who knows maybe help is on the way. And lastly I am now using the “herbal protocol” for my SIBO and after one month on Xifaxan it IS working as well as the antibiotics did. If you can’t continue with the Xifaxan its worth a try for you. Dr Pimintel at Ceder Sinai I am told is using the herbs as well for some of his patients. I am working with the folks at the SIBO center in Oregon and they have helped me enormously.
Great article Cort, as always. I cannot tell you the number of rheumatologists that I have actually paid money to, one in particular that told me that I needed to start getting out of bed,get a job,and start exercising,all while examining my leg muscles to point out the fact that I am losing my muscle tone. Thankfully, I was far along enough in my illness not to just burst out in tears, but instead point out to her that she had only known me for five minutes before making assumptions about my refusal to work or exercise, that prior to my illness I obsessively worked out at the gym a minimum of four to five days a week, plus worked two jobs, and was a single mom. So like the others above stated, validation itself is sometimes the most gratifying thing, but of course I pray for all of us that suffer with this illness and other invisible chronic illnesses that we see a cure in our lifetime. I also believe at that point, there is a whole bunch of doctors that owe the CFS/fibro suffers a HUGE apology for the way we have been treated. We won’t get it, but just my way of venting for today, sorry. 🙂
Greetings EveryOne,
In addition to yoga, which is the best, I have a rebounder that I enjoy using. It can be used for a very short time or longer as you like and it is handy in my living room so I don’t have to go anywhere to use it. Always reminds me of jumping on the bed as a child. Fun!
I’d like to get a rebounder but they take up so much floor space. Has anyone found a smaller one?
I am just beginning to chek out your site so forgive me if I ask something that seems obvious or silly. I was diagnosed with lupus about 15 yrs. ago after many yrs of mostly joint pain & rashes, along with a few other things. When I described the symptoms & progression (leaving out somethings that I didn’t know we’re connected) the rheumatologist said I had made his job very easy & had given a text book description. A couple of months later when I asked about something that didn’t seem to go with everything else he just said that’s your fibromyalgia. As if we had discussed it. It was the first time he’d said it to me. Since then bld work has gone from pos to neg but my family Dr who I now see says even with neg tests I seem to have symptoms that go with Fibro & symptoms that definitely seem like Lupus. Now I’ve been told that the severe fatigue could be considered CFS. Do you think that’s true? I have not had positive effects from exercise, I try walking-the last year the walking I can do has greatly decreased. I’ve done stretches, very basic yoga. 2 yrs ago a physical therapist that I saw after my Dr sent me to be evaluated by a physiatrist told me no exercise bike, (I was thinking of trying) after evaluating me using it & after. No stretching, walking in easy amounts & to basically stick to ROM exercise. Any thoughts or ideas? Thanks
This edition of all your hard work really got to my symptom experience, letter by letter. I appreciate the studies that are going on, and we are getter there.
I wish to note that my bed days are either 2 up to 4 to recover from a stimulus.
It used to be that the emotional stimulus hit harder. Now the physical stimulation is becoming the same.
For me, the best resting is staying in bed and listening to a book or my Satellite radio. This listening activity along with the resting helps shorten the resting in my particular recovery swing.
Now, I am experiencing more confusion and forgetfulness. I keep a calendar in front of me when out of bed to list 2 or 3 things to do, plus reminders. Have to note when to check meds. I create a map for myself at a pace I can handle hoping to prevent a relapse of the need to rest so much.this map means my chores and appointments. I have 2 days with a helper that saves me.
Thank all of you working so hard on this disease. Very grateful.
Thanks so much for this article, Cort! It is only with Ritalin that I am actually able to read through this. Although I do have a verifiable ADD diagnosis, I know the ME is exacerbating things (which has been apparent more recently)…. as the fMRI study pointed out.
This is such important information, and I am happy to see a study is actually being funded. I agree with what someone above said, grateful that there is more and more validation.
I think my daily self care routine is my exercise. I do need a power chair when I go out into the world, but I also use a cane at different times to walk as well. I am on the push-crash spectrum, (maybe part of being an ADDer) so being mindful of my limits is clearly key.
This article makes me wish for a larger interdisciplinary research collaboration between the ME front-running docs. All this kind of physiologic validation is still fairly young, so maybe in 10 years’ time there will be more collaboration amongst researchers. And, funding. And, hopefully treatments.
Thanks again.
The results of the methylphenidate/immune supplement Synergy trial are going to be interesting…I think we hear early next year.
Hey Cort, Yes indeed. The only big huge difference for me, personally, is that I’m not taking a special vitamin/amino acid concentrate/supplement. I think that makes a huge difference. People on Ritalin actually have to be careful with supplements (I speak from experience). It can throw off the Ritalin’s function for focus and calmness. But, yes, it’ll be nice to see the final results.
I won’t buy what’s on the market as the pseudo form of their supplement formula, because the one that anyone can buy has glutamate in it. That will make the brain on Ritalin go “off kilter”. Speaking from personal experience.
Vyavanse, a sister drug of Aderol, has helped me substantially. It increases blood flow to the brain, which I belive helps a struggling brain. I started taking it before i realized what i was sick with was cfs. When my memory and concentration got so bad in my 20’s, with what i later discovered was cfs, somebody suggested maybe I was ADD. The Vyavanse helps my cfs!!
Good to hear – thanks for that Rachel. For others here’s a blog done on a Vyvanse study and ME/CFS – http://www.cortjohnson.org/blog/2012/12/28/26/
I’ve long said that with this illness “practice makes stupid”. So, I found this article particularly relatable. However, I still don’t think it captures how significantly many of us are cognitively challenged. Because, the research indicated that by the last test, ME/CFS patients “were making almost twice as many errors as in the first test done at baseline”. My experience is much worse.
A few years after diagnosis, I decided to study music theory and write my exams so my theory credentials would better match the level of my actual playing — pre-illness, that is. This was a significant challenge, because I soon realized that while doing both the learning exercises, and later the practice exams, my brain shut off at about the 20 minute mark. I consistently went from getting every answer correct, to getting every answer incorrect, with no realization that I was struggling. So, my errors went from 0 to 100 percent very rapidly. In order to overcome this problem, I pencilled “cheat” notes at the top of the exam paper as soon as I started (while my brain was still working), and learned to work so quickly I was able to finish a one-hour exam in 20 minutes or less. The examiner was surprised I was finished so quickly; and yes, I got 100 percent! Of course, it is impossible in everyday life to anticipate all of the challenges we will encounter, and find/practice tricks to overcome them. The fact that we can do so occasionally, and for a few tasks, probably contributes to our looking “normal” to the outside world.
I started learning to play the piano 50 years ago, and had many years of lessons while healthy. You’d think by now I’d have a large repertoire of challenging pieces. Instead, there is not a single piece of music I can play with music — not a single bar of music I can memorize. I still try from time to time, but the more I practice, the worse I sound.
I’d love to know what fMRI tests would show after minimal cognitive effort every day for a period of a few weeks. I wouldn’t be at all surprised if the results would be the same as for tests performed after maximal exercise.
What a great example of cognitive deficits. This disorder is so interesting! (I keep saying that). To think that you’ve lost the ability to memorize music is astonishing given how deeply embedded in your brain those “music pathways” must have been….
Hi this is such an interesting article and great to read others experience of PEM !! Three specialist have mentioned GET / cbt again only this last few weeks !! It makes me do angry the misinformation and lack of awareness of how moderate daily movement let alone exercise affects us
Hi Cort,
Re: Ramsay
I have his book here somewhere but am not able now to access it, however I am pretty sure this is correct and he certainly does refer to ‘PEM’ in his own way. I aslo found it online and believe it to be correct:
“Muscle fatigability, whereby, even after a minor degree of physical effort, three, four or five days, or longer, elapse before full muscle power is restored and constitutes the sheet anchor of diagnosis. Without it I would be unwilling to diagnose a patient as suffering from ME, but it is most important to stress the fact that cases of ME or mild or even moderate severity may have normal muscle power in a remission. In such cases, tests for muscle power should be repeated after exercise.”
http://www.cfids-me.org/ramsay86.html
He goes on to say (bottom of this page) that a person is ‘dogged by… a general sense of feeling awful’ [i.e. Malaise] among other things, should they not recover.
Agreed, while he didn’t say the word “PEM” that was what he was referring to.
Just a small note on the terminology change in ICC: It’s PENE, not PENNE. Penne’s good too, though, perhaps with a white sauce. 😉
I have been excersising slowly and increasing over the last 6 years since I was diagnosed. I am still able to work part time and am up to 2 miles walking. I do still suffer when I overdo things, and it doesn’t always seem to be right away or make sense. Am I making myself progressively worse?
I think it depends on how you’re feeling overall. If you can work up to 2 miles and are still doing OK then I would keep with it. Keep your fitness up is important. Remember the participants in this trial engaged in pretty hefty exercise – far more than walking.
I made myself better overall by walking. The gradual build increased my threshhold. On my first episode that started with a horrible flu and lasted over 2 years, I did not begin to improve until i started walking. I didn’t feel like walking, but since i had been an avid runner I missed the outdoors. The strolls began to build and I began to improve greatly. Eventually i built up to a marathon, but i crossed some threshhold line in the process and it set me way back to square one with a relapse. Now I just walk a few miles.
Very interesting research. Much appreciated. I’m a Canadian. I can’t find any Canadian research. Does anyone know if there anything happening here in Canada.
I was DX around 2002. I was referred to a rheumologist. All he did was poke me on the tender points. Then he sent me to get blood work done. He also gave me a pamphlet on fibro. That’s all he did. I haven’t been able to work since June 2004.
My doctor at the time gave me Oxycodine and Percocet for break through pain. My life quickly turned into a nightmare. Thank goodness I had two friends that worked in another town. I phoned one of them and told him what was happening to me. He and my other friend that was a doctor. They arranged for me fly to where they worked. I had to be detoxify. Thank goodness for them otherwise I wouldn’t be alive today.
I started to see a good doctor there. I used to have acupture on my ears. I also saw an amazing Counselor who would do Reiki. When I saw both these amazing women I could actually be so relaxed that I’d go back to my hotel room and would fall asleep. Unfortunately the doctor I saw moved away. And my Counselor passed away suddenly from a food allergy.
Since then I was referred to another doctor who is a real sweetheart. And I have a wonderful Counselor. The doctors were I live are absolute idiots. So I have to fly to another city to see them. Thank goodness my Hubby works for the government so my flights, hotel rooms, ground transportation and meals are covered. For the last number of years I have to have an escort as I get very confused and forgetful. My escort’s expenses are also covered.
I am blessed that my meds are also covered. Otherwise I wouldn’t be able afford them.
I also developed Type 2 diabetes. Turns out that I’m allergic to Methformin. My primary doctor referred me to the doctor who specializes in alternative medicine for diabetes.
Before I became sick I was a trained Social worker and worked as the Student Counselor. I absolutely loved my job. Now I feel like my brain has turned to mush.
I should state that I live in a very small community of approximately 2500 people in the Northwest Territories, Canada. So our health care system is free for everyone. People with chronic illnesses don’t have to pay for their medication. My husband is employed by the Territorial government as an Associated Warren at our jail. Our facility is for special needs inmates. Part of the benefits include a very good health care package. Hence the reason my flights, etc are covered.
I saw a physiotherapist for a while. It just made me more ill and extremely sore. Before I became sick I never thought twice about how far I walked. Now I have to think twice about leaving the house.
My one doctor has given me a RX for vitamin B 12 shots. I’m at the point where I’ll try almost anything. Has anyone taken vitamin B 12 shots and did they help?
I’ve tried a chiropractor without any real success.
I’ve been on so many different medications these 11 years without any success.
I keep getting so depressed. I’ve been on different medication for depression with no success.
I can’t do very much housework which drives me crazy. Even after all these years I still can’t deal with this disease.
It doesn’t help that my one sibling who’s been an RN for about 30 years doesn’t understand or believe that I have fibro. We used to be very close – not anymore. My other sibling could care less. My other sibling is 5 years older but since I’ve gotten sicker we’ve become closer.
Thank goodness my Hubby loves me and always tells me to relax and not to overdo it. Our one daughter has moved back to where I live in order to help me as much as possible. The rest of our kids really don’t understand what I’m dealing with but love me anyways. The rest of our kids don’t live close enough to help.
My Hubby and I got married in 2002 so we have a blended family of 8 adult children and 13 grandchildren. My Hubby and I have known each other since high school. So we’ve been friends since then. We ended up marrying different people so our lives took other paths. Our kids all knew each other before my Hubby and I decided that we belonged together.
Sorry for the extremely long and off track post. It’s wonderful for me to learn I’m not alone. I’m grateful to learn what is happening with research. I pray that a cure is found before it’s too late for me and others. I turned 63 last August. I want my life back.
I’d like to know if there is any research being done to learn how to repair the defective genes. I need relief desperately.
This is also interesting because after my mono at 13 with enlarged spleen and liver ( sometimes my alt & ast still comes up high) I have further testing because of my liver enzymes and no hepatitis of any kind. Only thing it shows is a previous EBV test negative but high VCA- and EBNA IGG tests levels in 500’s but lab says maternal exposed? anyway I’m off point ever since the mono I could not run a block with loss of oxygen, couldn’t ride bike, Rollerblade etc. it was so embarrassing for me, and one time I walked a mile and half straight and that’s when I ended up on holt monitor saying heart rate slows down at times to 50 beats a minute. I have to think its that because I can feel a lack of oxygen. Do I make any sense? Cort please show my email address in case anyone has similar issues, if its okay? Rita/Sis