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Repeat Test Reveals Dramatic Drop in ME/CFS Exercise Capacity

Hooked up for a CPET

Hooked up for a CPET

Simon McGrath reports on Dr Snell’s new study demonstrating that ME/CFS patients have a reduced capacity to exercise when they repeat a maximum exercise test one day on – unlike healthy controls.

One of the biggest problems of getting ME/CFS taken seriously is that often we ‘look’ normal, even though we feel lousy, and most lab tests produce ‘normal’ findings. How do we prove to the world that we are sick?

A defining feature of ME/CFS is Post-Exertional Malaise (PEM) and a couple of studies have clearly demonstrated PEM in patients [see box]. However, PEM is a subjective experience and one that can only be measured by patient self-report, which won’t satisfy everyone.

Dr Chris Snell, Staci Stevens, Dr Todd Davenport, and Dr Mark VanNess’s new study aimed to objectively demonstrate the problem of post-exertional malaise, by using a repeat Cardiopulmonary Exercise Test (CPET). As they formally hypothesized in their paper: “an exacerbation of symptoms following the first test would be reflected in physiological responses to the second”.

The study

The 51 CFS patients were all women, met Fukuda criteria and also reported PEM. Controls, also female, were similar in age and BMI, and were fairly sedentary. In fact, the results of the first CPET revealed that the controls were in the bottom 10% of published population norms and would count as deconditioned. CFS patients were barely different from controls so were also deconditioned, but, crucially, they were ill while controls were healthy, casting doubt on the idea that deconditioning is responsible for CFS.

CPET: Cardiopulmonary Exercise Testing explained

CPET is the Gold standard for measuring physical capacity, used by athletes wanting to measure the effectiveness of their training programs. It’s also used medically e.g. to diagnose cardiovascular, breathing and muscle disorders.

cPETb

The principle is to get someone to exercise to exhaustion, using a protocol that starts easy and gets increasingly difficult until the subject can do no more. The key measures for this study are the Volume of Oxygen consumed (VO2) and the amount of work done, measured in Watts on the exercise bike.

Anaerobic/Ventilatory Threshold

A critical factor is the anaerobic threshold, the point at which the body has to supplement normal aerobic (oxygen-burning) metabolism with much less efficient anaerobic metabolism, creating lactic acid. This threshold is measured in CPET by finding the point where carbon dioxide (CO2) starts to be produced faster than Oxygen, and is called the Ventilatory Threshold, or VT (strictly, VO2 VT).

CPETaVO2 max versus VO2 peak

One challenge of CPET is detecting if the person is using maximal effort, as opposed to trying pretty hard. Data showed that CFS patients and subjects here all went deep into anaerobic exercise and met at least one other measure of high effort. However, as it’s almost impossible to be completely sure, the study reported ‘peak’ measures instead of maximum, e.g. VO2 peak, not VO2 max.

Note there are equivalent thresholds for work output, in watts: W max, W peak and W VT

More: Lannie’s blog on PR about her CPET at Pacific Fatigue Labs.

Day 2 results separated patients from controls

Day 2 CFS patient...

A Day 2 CFS patient…

The big differences between the groups emerged on the second maximal CPET test, 24 hours after the first. On average, controls did slightly better on Day 2 (something that has been observed in other studies too) while patients did substantially worse. Interestingly, VO2 peak did not differ significantly between patients and controls, but peak Watts output was significantly lower, as was VTO2 . The biggest difference of all was for Watts output at VT, down for the patient group by over half.

The study found the repeat test could separate CFS patients from controls in this sample with 95% accuracy (3 errors in total). They also used a statistical technique called ‘cross-validation’, which indicated the test would achieve a 90% accuracy in an independent sample (though see issue with convenience sample below).

This ability of a 2-day repeat test to discriminate healthy but sedentary controls from CFS patients is critical. In theory, doctors can manage this easily enough without a CPET test. However, where there is doubt about the reality of symptoms, as can happen with disability insurance claims, an objective test can demonstrate that a patient really is sick. As Workwell Foundation notes, it’s useful in legal or medical disputes; the reduced performance on VT is “impossible to fake”, adds Dr Snell.

“the post-exertional state in CFS is characterized by objectively measurable deficits in submaximal metabolism and workload that would be nearly impossible for patients to fabricate”

In some ways the findings are unexpected, as it was the same group’s earlier finding of a substantial drop in VO2 max on the second test that caused such a buzz amongst patients. And the big drop in output at VT wasn’t seen in a study (albeit a small one) by a separate research group, though a smaller drop was seen for VT, and VO2 max in a study presented at an IACFS conference. I asked Chris Snell if he was surprised by the finding. “No”, came the reply: the initial study was small making the findings less robust, and he said that a much bigger effect on VT than VO2 max has been seen in the clinic too.

Evidence of Post-Exertional Malaise from subjective studies

As well as the objective evidence from this new paper, PEM has been shown by self-report measures too. A 2010 study from Pacific Fatigue Labs found that only 1 of 25 female CFS patients recovered from a maximal exercise test 48 hours later while all 23 sedentary controls did. Another study using a moderate exercise test found that fatigue and pain increased in the 48 hours after exercise in CFS patients – while it returned to normal in that time for both healthy controls and Multiple Sclerosis patients.

Committed to Maximal CPET

Given that it’s hard enough for people with ME/CFS to do one maximal test, let alone two, these results create the temptation to just run the second test as far as the Ventilatory Threshold and forget about VO2 max. But Chris Snell stressed that the Workwell Foundation remains committed to the repeat-maximal approach. First, VT can’t be measured on the fly so they wouldn’t know when to stop the test. And perhaps more importantly, the post-exertional effect appears to differ by patient, with some showing a greater effect on peak measures and others at VT.  Dr Snell suggested that varying post-exertional responses may well reflect different underlying pathologies.

Unique to ME/CFS?

Is this the killer test that uniquely identifies CFS patients? Dr Snell has reported that their clinic has tested patients with numerous illnesses including Multiple Sclerosis and Congestive heart failure, but have only seen the problem in ME/CFS patients. Published studies show normal repeat CPET performance for sarcoidosis, angina, Chronic Airflow Obstruction, Pulmonary Hypertension and heart disease. I’ve seen no studies showing failure to reproduce CPET results in other illnesses, but it’s probably too soon to say if this is unique to ME/CFS, or just very unusual.

What might cause the exercise problems?

The authors suggest that a synergy of small effects across multiple systems could be responsible for the poor exercise performance of the individuals with CFS. Lower oxygen carrying capacity could result from low blood volume, while low oxygen consumption could also result from autonomic dysfunction and reduced ventilation. But research into the causes is needed.

No study is perfect…

  • There were only 10 controls, though as the repeatability of CPET results is firmly established (with 94% reliability between tests), in some ways controls mainly serve to demonstrate that the protocol is working properly.
  • The CFS patients were a convenience sample, rather than, for example, consecutive referrals to a secondary clinic. This, and the fact that patients had agreed to a repeat maximal exercise test, means the results might not generalize to the patient population as a whole.
  • The earlier study by this group, and the other studes from independent groups, didn’t find the dramatic changes with workload at the ventilatory threshold, so further replication would help to confirm the nature of the changes.

These findings, which make visible the hallmark ME/CFS problem of post-exertional malaise, have potentially huge importance. Replication of this study, perhaps with a more representative sample of CFS patients and some sick controls, should in my view be a priority for the research community. Stage two of the huge CDC multi-clinic study could provide the perfect opportunity for this.

Simon McGrath tweets on ME/CFS research:

 

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{ 155 comments… add one }

  • SOC August 1, 2013, 1:50 pm
    urbantravels

    The worst crash symptoms actually did not fully set in until four days after the test. I actually felt OK on the second day in terms of general malaise symptoms – better than I expected. In fact, I got home OK (short flight Sacramento –> Los Angeles, accompanied by my dad) and was all settled in for my recovery period before I started feeling really sick.

    I found this particularly interesting. In the days when I was still doing the push-crash thing, my delay was 4 days, which seems longer than most people are reporting. I usually hear of people crashing 24-48 hours after over-exertion. I did wonder if the 2-day CPET would catch my more delayed reaction, but it sound like it did for you, which is promising.

    That was a clear and complete description of your reaction to the test. Thanks for that! Your description of a shorter "acute" phase of PEM, followed by a longer phase where you get back to baseline resonates with me. It's very much the way my (now rare) crashes work, but I've never described it that clearly.

  • SOC August 1, 2013, 2:08 pm
    urbantravels

    I'm not sure what deathly things could happen to you once you are done with the test and are recuperating at home that would require specialist medical intervention. I think people often imagine a huge risk of permanent damage from taking the exercise test and I just don't see that happening. But the only way to know for sure would be to do long-term follow-up on a group of patients.

    I'm thinking of things like viral reactivations or some kind of resurgence of infections. That seemed to happen to me with crashes when I had a pack of chronic infections. Antivirals and abx might be helpful under those circs. I'm also wondering if some people have some kind of autonomic crash after overexertion that could be alleviated with, I dunno, IV saline or meds…?

    For me, the one-day tests have not been bad. You described it quite well. No long-term effects. I never did one when I was in the bedbound stage, though, so I don't know what it might have done to me then. Still, having done one before I was bedbound, I don't think I would have been afraid of trying it when I was. It might have been miserable, but I've been miserable with this illness, so that's not a big deal. I wouldn't have expected any permanent damage.

  • Bob August 1, 2013, 2:33 pm
    SOC

    Good point. I was a bit too flip there with the "we get up, we move on".

    Yes, I had the feeling that you'd experienced worse crashes than it appeared from your comment.

    SOC

    I guess I was thinking of participating in research — I would plan ahead for a crash and do everything I could to ensure I had the opportunity to go into mega-rest mode for up to a couple of weeks afterward. This is what I've done for other important things — my mother's funeral, for example. Not exactly "we get up, we move on" :whistle:. More like, we sometimes do what we have to do.

    Yep, we all plan for big days, by resting before-hand etc., but a day visiting family, for example, is completely different to a maxed out exercise test. I've been through long periods of my illness where I only have to take a short walk and I crash severely. I can't think of anything worse for me than a maxed out exercise test!

    Obviously many patients might feel confident that an exercise test is OK for them to participate in. But we've all got to safely make that decision for ourselves.

    urbantravels

    I think people often imagine a huge risk of permanent damage from taking the exercise test and I just don't see that happening. But the only way to know for sure would be to do long-term follow-up on a group of patients.

    Each individual is different. A number of us here seem to be saying that an exercise test would be really bad for us. For myself, it could mean years of added distress if I had a bad crash. And it's very likely that I would have a bad crash if I exercised to the max, just once. Two days could be asking for a life time of hell. Remember that we're all different, and so the extent and severity of flare ups, in reaction to exertion, is different in all of us.

    I'd like to see this research taken forwards, but it's got to be done safely, and not every one will be suitable to get involved.

  • urbantravels August 1, 2013, 4:49 pm

    Well, then the reasonable question would be: for those who have had crashes lasting months or longer, how often have they started from baseline (i.e you were at your personal average level of unwellness, not already extra unwell) and been triggered by one single episode of over-exertion?

  • peggy-sue August 2, 2013, 10:52 am

    My worst "crash" was after a 3 month prolonged overdoing under severe stress, while my Dad was dying (in a hospital 70 miles away). I did not stabilise to a new, but lower baseline than I had been at before, for 6 years.

    I have just come home from a 6 day period of big overdoings – travelling a long way to cram as many friends and family members into the short space of 4 days (2 full days travelling).
    I got home early Tuesday am. (this is now Friday afternoon)

    I haven't crashed yet. I will monitor what happens and report. :)

    Normally, I try to ignore it as much as I can. I had a lot of fun and it was very mentally uplifting. I anticipate a bout of depression as part of it (getting happy has its costs:cry: ) But I most sincerely hope it does not happen.

    I generally find resting as much beforehand, taking a carnitine supplement daily while away, and carrying on with the carnitine supplement when I get back really does help to minimise suffering, and I have been doing that.

  • SickOfSickness August 2, 2013, 11:45 am

    I would like to see the results if they waited longer between tests… 36 hours, 48 hours, perhaps more.

    Some doctors are bound to say that the results can be faked. The terrible ones who think we want to be sick.

  • peggy-sue August 2, 2013, 12:15 pm

    SickofSickness said;
    "Some doctors are bound to say that the results can be faked. The terrible ones who think we want to be sick."

    You mean the ones that are already "faking" their results? Possible. They would, I'm sure, expect everybody else to be as deceitful as they are. :p

    However, I don't think these are the sorts of results that CAN be faked, SoS. Honestly! :)

  • urbantravels August 2, 2013, 1:16 pm

    It's important to define what information you are looking for and why. Since the two-day exercise test is cumbersome, expensive, stressful, and contraindicated for many people, I certainly don't want and don't expect it to become the standard diagnostic test to confirm the presence of ME/CFS…or at least the ONLY test available.

    A blood test for cytokines after a mild exercise challenge may become accepted as diagnostic. That would be quicker and cheaper and much more widely applicable. (Actually I've no idea how cheap it is to measure what the Lights are measuring, which is, as I understand it, activation of the genes that produce certain cytokines, not the cytokines themselves.)

    Here's one problem though, drawn from my personal experience, that goes beyond the need to diagnose. For a disability claim, they may acknowledge that you have CFS, but refuse to accept that it is as severe as you say it is, or severe enough to prevent you from working. So in that situation, you need some way to objectively demonstrate how much your functional capacity is impaired by the disease, not just the fact that you have it. Being able to measure the severity of disease would also be useful for research. The really tricky bit would be developing a test that shows impairment of functional capacity without requiring the patient to do anything, or a test that "measures" a PEM without provoking a PEM. Unless it turns out that the most severe patients are in a more or less permanent state of PEM, which might be measurable.

  • Valentijn August 3, 2013, 12:17 am
    urbantravels

    It's important to define what information you are looking for and why. Since the two-day exercise test is cumbersome, expensive, stressful, and contraindicated for many people, I certainly don't want and don't expect it to become the standard diagnostic test to confirm the presence of ME/CFS…or at least the ONLY test available.

    A blood test for cytokines after a mild exercise challenge may become accepted as diagnostic. That would be quicker and cheaper and much more widely applicable.

    This is why it's especially important to have this test included in the research. By seeing which patients have the non-deconditioned abnormal response, they can look to see what non-exercise-induced markers are present in those patients. Then every patient can benefit by having the results of a blood test stand in as indicating vulnerability to exertion, versus having to do the two day exercise challenge themselves to prove that they're ill.

    They are NEVER going to take our word for it that exertion makes us sick. There has to be objective, unfakeable, physical testing clearly associated with the quick-and-painless testing methods that we want to be developed.

  • peggy-sue August 3, 2013, 2:45 am

    Personally, I'd rather risk a pretty massive crash before I'd have a lumbar puncture.
    (Actually, I'm not sure I'd not prefer to die than have a lumbar puncture, but that's just me.)

  • MeSci August 3, 2013, 3:02 am
    SOC

    Not exactly. :) Doctors do surgical biopsies and spinal taps when necessary for diagnosis. Both these procedures cause some degree of "harm". Some amount of trade-off is accepted.

    The relevant difference between the CPET test and GET is that the CPET is a one-time diagnostic(theoretically) from which one can recover, although it takes time. GET is presented as a continuing therapy, constantly stressing the system and not giving it time to recover.

    That said, I agree that 2-day CPET testing is not ready to be used as a universal diagnostic. First, it needs to be confirmed. Second, there's still a lot we don't know about it and its usefulness. My hope is that using 2-day CPET testing in research will provide enough information that someone will be able to develop a less "destructive" test for diagnosis.

    I have never done the 2-day test. I did the one-day maximal test while I was mild-moderate and had a moderate crash that was a week or two long. Not fun, but not catastrophic. I've had as bad, and worse, crashes from other activities and infections. It wasn't so bad that I wasn't willing to do it again about 5 years later. The second test was not maximal, though, only to VT and was easy — no crash afterwards.

    We've all had crashes. We get up, we move on. I'm willing to crash (as a one-time event), if necessary, to improve the knowledge base in this illness, especially if it's a planned crash so I can arrange my schedule, and maybe stick a few meals in the freezer. 😉

    Maybe we need to hear, all in one place, from some of the people who did the 2-day CPET — what their condition was before the test, if they crashed and for how long/badly, what their condition was after the crash. Anybody willing to chime in with their experience?

    I agree with much of what you say, but not all. Some people do not recover from crashes, but become permanently even more impaired. If people are managing part-time work or self-employment, a crash can have a serious impact on income for a person who may already be on the breadline. This happened to me in 2010 when over-exertion caused a crash that landed me in hospital. I ended up building up a large credit card debt which I have only just paid off thanks to maturation of small occupational pensions accrued before I became ill.

    No one has a right to make someone suffer such adversity just to prove that they are genuinely ill (and I do receive two disability-related 'benefits' – the disability element of Working Tax Credit, and a reduction in my council tax, and these have entitled me to a few further benefits such as free medications).

  • MeSci August 3, 2013, 3:05 am
    SOC

    Good point. I was a bit too flip there with the "we get up, we move on". Every crash I had in my viral-ish days left me little bit worse. Because my illness wasn't as well-managed in those days, I never lasted long enough between crashes to recover that little bit back. Every crash made me a tiny bit worse, and the accumulation was a slow but steady downhill slide.

    I guess I was thinking of participating in research — I would plan ahead for a crash and do everything I could to ensure I had the opportunity to go into mega-rest mode for up to a couple of weeks afterward. This is what I've done for other important things — my mother's funeral, for example. Not exactly "we get up, we move on" :whistle:. More like, we sometimes do what we have to do.

    No ME/CFS patient should be required to do a two day CPET. The potential consequences are too high to require that from anyone. I hope some people at all stages of ME/CFS will choose to do the test for the sake of forwarding our knowledge. I also hope those patients will be under the care of a good ME/CFS doc who will help deal with the symptoms involved in the crash — autonomic dysfunction, infections, cardiac problems, whatever they are. To plan research on severe patients without that kind of post-test support borders on unethical.

    I replied to your earlier message before seeing this one, SOC. Let me know if you want me to edit it, as I agree with you now! :)

  • MeSci August 3, 2013, 3:23 am
    urbantravels

    I had the test for disability documentation. I can't speak to how they did it for clinical trials, but the disability test includes a symptom questionnaire that asks you about symptoms for a week after the test. I did have PEM symptoms for more than a week, but I think a week's cut-off is practical for the purpose of documenting disability…meaning that being sick for a week after exertion is enough to interfere with your ability to work full-time consistently week to week, and after that going on to be sick for more days isn't relevant for that purpose. Also, self-report of symptoms, as we all know, isn't measurable and objective, so it has only a little usefulness in the context of the whole test. It's more in the nature of supporting evidence.

    I had no permanent or long-term setback from the test. I think I was fully back to baseline within 5 or 6 weeks and the really bad symptoms only lasted about 4 days. I am fortunate in having no particular responsibilities beyond basic self-care, so with preparation (lots of food laid in and everything otherwise arranged so I didn't have to go out or do anything but rest) the recovery period was long, but not agonizing or stressful. I was hitting my pain pills far more than usual due to muscle pain – that is, flu-like muscle pain, not muscle strain from unaccustomed exercise, although of course I had that too. Easy to tell which muscles got overworked from a bike test. But the muscle strain went away real fast compared to the PEM muscle pain.

    The worst crash symptoms actually did not fully set in until four days after the test. I actually felt OK on the second day in terms of general malaise symptoms – better than I expected. In fact, I got home OK (short flight Sacramento –> Los Angeles, accompanied by my dad) and was all settled in for my recovery period before I started feeling really sick.

    But – and this is important – I still had a *huge* plummet in my performance (workload at ventilatory threshold went down 60%) from Day 1 to Day 2 even though I certainly didn't *feel* 60% worse at that point. From this, I think it's possible that PEM symptoms do not track exactly with the decrease in your energy production capability – the decrease in ability to seems to happen quickly, but all the inflammatory-type symptoms may take longer to fully build up.

    I don't know how this fits with the Lights' findings that pro-inflammatory cytokines go up within hours of an exercise challenge. It may be that the cytokines don't have their full effect for a while after they start being produced. Or, it could be that the cytokines continue to rise after the Lights' relatively short follow-up time…meaning that what the Lights are measuring actually isn't yet enough to provoke major symptoms, but it indicates the disease process is kicking off. Or that the body can clear the cytokines for a while at first but is eventually overwhelmed by them. I don't think this is a fault in their research. They are not looking at the entire life cycle of a PEM episode, but for a biomarker that distinguishes people with the disease from people without it.

    I have been trying to work out the sequence of events from my own exertion, but don't have time to go through all my notes and do a proper analysis, as I am still having to work self-employed to keep the wolf from the door. It's very frustrating.

    But so far I have observed:

    1. Initial muscle pain that lasts up to about 48 hours, often much less
    2. No obvious worsening on 2nd day
    3. Mild head and neckache, arm muscle tightness, calf muscle twitching, apparent solute diuresis (evidenced by polyuria that does not respond to desmopressin) Mild upper abdominal pain? Looser bowel movements? Swollen cervical lymph nodes and submandibular glands with very pale skin over them? Twingeing maxillary lymph nodes? Itchy and blocked ears?
    4. Poorer sleep, mild-moderate toothache.

    There are other symptoms that I haven't included and I am not 100% sure of the chronological order.

    Possible explanations for some observations:

    • Excess lactic acid production overloads the liver, hence upper-abdominal pain
    • Hyperlactaemia acidifies gut, hence loose bowel movements, possibly including loss of some nutrients that way
    • Solute diuresis involving excretion of excess lactic acid as sodium lactate and other salts
    • Consequent mineral deficiency leading to toothache and poor sleep

    After my first severe episode of hyponatraemia I started suffering dental damage and also had my only-ever fracture, from a minor fall, supporting my theory of mineral loss, hence the fact that I now take a bone mineral supplement. I don't get these severe effects any more.

  • MeSci August 3, 2013, 3:32 am
    peggy-sue

    Personally, I'd rather risk a pretty massive crash before I'd have a lumbar puncture.
    (Actually, I'm not sure I'd not prefer to die than have a lumbar puncture, but that's just me.)

    I wouldn't go that far, but I would only agree to a lumbar puncture to diagnose a possible life-threatening illness that needed urgent treatment. It's a dangerous procedure, the after-effects can be very nasty, and if they go wrong (which some do) it can be catastrophic.

  • MeSci August 3, 2013, 3:47 am
    urbantravels

    I always tell healthies that I'm actually capable of rapid movement in an emergency, though I couldn't sustain it for long and would pay consequences later. I kept saying "I could run from a bear if I had to" so often that my friend asked me if bear attacks were a big problem in my neighborhood. 😮

    I can sometimes react quickly, and sometimes not. If I could always react quickly I would not have broken my wrist in 2008. I could have stopped myself from falling. I would not have sprained my ankle badly on a step more recently. Again, I could have stopped myself from falling. When I am dizzy, or disorientated, or weak, or ataxic, I cannot react on the way I need to, and the same would be likely to apply in a life-threatening situation. Yes – when not already suffering adverse effects from over-exertion, I can – to a degree. But the distance I would be able to run, or, for example, my ability to climb over a fence or up a tree, would be limited by my ability to keep producing ATP fast enough, which would vary according to my state of health but would probably always be less than what it would be without ME.

    I also cannot rescue all the wild animals caught by my cats as I used to, which is upsetting. I even accidentally killed a mouse I was trying to rescue, due to weakness, slow reaction times and poor coordination.

    I had to turn down my brother's invitation to go on his motorbike to see the solar eclipse a few years ago, as I know there was a danger I would not be able to hold on for long enough, so could end up falling into the road.

    This inability to protect myself and others due to my illness is frightening.

  • MeSci August 3, 2013, 3:54 am
    urbantravels

    It's important to define what information you are looking for and why. Since the two-day exercise test is cumbersome, expensive, stressful, and contraindicated for many people, I certainly don't want and don't expect it to become the standard diagnostic test to confirm the presence of ME/CFS…or at least the ONLY test available.

    A blood test for cytokines after a mild exercise challenge may become accepted as diagnostic. That would be quicker and cheaper and much more widely applicable. (Actually I've no idea how cheap it is to measure what the Lights are measuring, which is, as I understand it, activation of the genes that produce certain cytokines, not the cytokines themselves.)

    Here's one problem though, drawn from my personal experience, that goes beyond the need to diagnose. For a disability claim, they may acknowledge that you have CFS, but refuse to accept that it is as severe as you say it is, or severe enough to prevent you from working. So in that situation, you need some way to objectively demonstrate how much your functional capacity is impaired by the disease, not just the fact that you have it. Being able to measure the severity of disease would also be useful for research. The really tricky bit would be developing a test that shows impairment of functional capacity without requiring the patient to do anything, or a test that "measures" a PEM without provoking a PEM. Unless it turns out that the most severe patients are in a more or less permanent state of PEM, which might be measurable.

    I wonder whether blood could be used for a test similar or roughly analogous to that which was conducted on muscle biopsies – subjecting them to the equivalent of exertion in vitro.

  • alex3619 August 3, 2013, 9:09 am
    MeSci

    I wonder whether blood could be used for a test similar or roughly analogous to that which was conducted on muscle biopsies – subjecting them to the equivalent of exertion in vitro.

    I have been making similar comments. We need more research in this area. This appears to be the case with fibromyalgia, its probably the case for ME as well. We need this investigated.

  • Firestormm August 3, 2013, 9:10 am
    alex3619

    I have been making similar comments. We need more research in this area.

    Me three :) Think we have a couple of threads capturing our thoughts on this kind of testing.

  • SOC August 3, 2013, 10:22 am
    MeSci

    I replied to your earlier message before seeing this one, SOC. Let me know if you want me to edit it, as I agree with you now! :)

    No problem. :) I wasn't clear the first time around, so it's reasonable people would call me on it to clarify.

  • SOC August 3, 2013, 10:46 am
    MeSci

    But so far I have observed:

    1. Initial muscle pain that lasts up to about 48 hours, often much less
    2. No obvious worsening on 2nd day
    3. Mild head and neckache, arm muscle tightness, calf muscle twitching, apparent solute diuresis (evidenced by polyuria that does not respond to desmopressin) Mild upper abdominal pain? Looser bowel movements? Swollen cervical lymph nodes and submandibular glands with very pale skin over them? Twingeing maxillary lymph nodes? Itchy and blocked ears?
    4. Poorer sleep, mild-moderate toothache.

    During crashes I don't have the initial muscle pain, but I do get joint and muscle aches different from overuse muscle pain. They don't usually hit the first day, either.

    Before I cleared my chronic infections, crashes used to give me swollen cervical lymph nodes and salivary glands. In the worst crashes, I'd look like a chipmunk, the side of my face were so swollen. The good news is that now I don't get swollen node and glands with crashes, so I'm assuming that they were related to the infections. The toothache thing also disappeared. Doc and dentist think, and I agree, that the toothache was from swelling in the jaw area, not directly dental.

    I still get the itchy and blocked ears. I'm wondering if it's a histamine thing…

    MeSci

    I can sometimes react quickly, and sometimes not.

    For me, there's definitely an element of muscle stiffness (probably from lack of exercise) and clumsiness (which could be related to muscle stiffness or neurological problems) that prevent me from being agile and athletic. I've fallen down stairs 4 or 5 times in as many years. 😮

    Still, if I had only 15 minutes to get out of a burning airplane, for example, I could do it as well as 50% of the other passengers. There'd just be hell to pay later.

  • MeSci August 3, 2013, 11:34 am
    Firestormm

    Me three :) Think we have a couple of threads capturing our thoughts on this kind of testing.

    Can you point me to any? Not sure if I have seen them or not. Don't worry if you can't find them easily.

  • MeSci August 3, 2013, 11:40 am
    SOC

    I still get the itchy and blocked ears. I'm wondering if it's a histamine thing…

    I think there's some evidence that it's lymph-related. I may have saved the info somewhere, and I think it's been discussed on here as well.

    SOC

    For me, there's definitely an element of muscle stiffness (probably from lack of exercise) and clumsiness (which could be related to muscle stiffness or neurological problems) that prevent me from being agile and athletic. I've fallen down stairs 4 or 5 times in as many years. 😮

    Still, if I had only 15 minutes to get out of a burning airplane, for example, I could do it as well as 50% of the other passengers. There'd just be hell to pay later.

    I wish I could be as confident. I thought I could react quickly in emergencies but experience has suggested to me that it won't always be the case.

    I have very nearly fallen down the stairs a couple of times due to no longer knowing instinctively where my feet and legs are in relation to the ground. One occasion was pretty scary – I grabbed the handrail and involuntarily swung round about 90 degrees, holding on for dear life. That would have potentially been a bad fall, and it shook me up, with visions of breaking my neck as I might well have gone down headfirst and hit the wall at the bottom. It was a close thing. I have been very careful since then.

  • Simon August 3, 2013, 11:58 am
    MeSci

    I wonder whether blood could be used for a test similar or roughly analogous to that which was conducted on muscle biopsies – subjecting them to the equivalent of exertion in vitro.

    That would be great.

    Perhaps more likely is something like the Lights work on gene expression after moderate exercise, which also has the advantage, compared with maximal tests, that it represents real-life situations where patients actually experience PEM. They now have a substantial NIH grant to try to replicate the findings of very different results in ME/CFS patients so perhaps when that study reports there will be an altogether more moderate test with objective findings of abnormal response to exercise.

  • Mij August 3, 2013, 1:05 pm
    Bob
    SOC


    That said, I agree that 2-day CPET testing is not ready to be used as a universal diagnostic. First, it needs to be confirmed. Second, there's still a lot we don't know about it and its usefulness. My hope is that using 2-day CPET testing in research will provide enough information that someone will be able to develop a less "destructive" test for diagnosis.

    I have never done the 2-day test. I did the one-day maximal test while I was mild-moderate and had a moderate crash that was a week or two long. Not fun, but not catastrophic. I've had as bad, and worse, crashes from other activities and infections. It wasn't so bad that I wasn't willing to do it again about 5 years later. The second test was not maximal, though, only to VT and was easy — no crash afterwards.

    We've all had crashes. We get up, we move on. I'm willing to crash (as a one-time event), if necessary, to improve the knowledge base in this illness, especially if it's a planned crash so I can arrange my schedule, and maybe stick a few meals in the freezer. 😉

    Maybe we need to hear, all in one place, from some of the people who did the 2-day CPET — what their condition was before the test, if they crashed and for how long/badly, what their condition was after the crash. Anybody willing to chime in with their experience?

    I agree that this is very important research, and that CPET testing should be carried out with willing volunteers, who know that they will not suffer from long-term consequences from an exercise test.

    But I don't agree that "we get up, we move on" after crashes. Obviously, it's different for everyone, but my ME is very reactive and my crashes tend to be severe, deeply distressing and long-lasting, and I spend my whole life trying to avoid them. I would never agree to any exercise testing unless I was in a very stable period of remission and I was absolutely confident that the exercise was within my safe limits. (Safe enough to avoid a crash.)

    It is very interesting how we are all different. From my experience having ME for 22yrs would make me a good candidate for this test. I always stay within my boundaries because PENE is something I try to avoid at all costs, it's just too distressing.
    I have gone through periods when I felt up to 80% improved fir a couple of years but if I do the SAME amount of exercise as when I'm feeling 40% the PENE is always the same. How I'm "feeling" makes no difference in exercise capacity, so the test result will show abnormalities no matter how well I am feeling at the time of exercise, there will be a unique physiological change upon doing just a small amount. If I'm going through a viral episode the PENE will come on within 2-3hrs, so like someone else wrote earlier is that we need immune testing added to the mix.

  • urbantravels August 3, 2013, 1:06 pm

    I think there's a distinction between the ability to produce a short burst of *energy* versus coordination and reflexes. I'm definitely klutzy since I've been sick – I've broken a lot of dishes and water glasses, walked into tables and chairs, etc. etc. But on a bike for the exercise test I managed to put in maximal effort without falling off or anything. No need for coordination or reflexes there – just hang onto the bike handles for dear life and pedal straight ahead.

    Of course any given emergency or survival situation is probably going to require a combination of energy, strength, and coordination, so I'm not sure I could make good on my bear-eluding promises, unless it was on a straight even track. And it was a really short sprint. Hmm, this analogy may not be so good after all. Maybe I should go with "escaping from a burning building." Or "getting out in case of an earthquake." Not like those would require balance and coordination or anything..well, I now have no analogies, except "I could do an exercise test on a stationary bike if I had to."

    Mind you nobody *requires* you to take the two-day exercise test to prove disability. It's just pretty much the only tool you can use that gives an objective measurement of functional capacity, impossible to fake or exaggerate. And I'd also add that no disability insurer is *required* to take any note of this test or consider it proof of anything, since it is not an "officially" accepted test of disability from CFS. The Social Security Administration, in its guidance on CFS claims, says an "exercise test" may be submitted as supporting evidence but is careful to point out that no test is considered *proof* of CFS or its severity. They could, at their complete discretion, ignore a Stevens test completely, or decide it is invalid or irrelevant. Hypothetically.

    Without going any further into matters of which I should not speak…although I have seen a number of reports from people who prevailed in disability claims by taking the test, I feel obliged to point out that it is not a dead lock or a guarantee.

  • rosie26 August 3, 2013, 2:55 pm

    I think in ME we are in PEM all the time aren't we. (sorry I am struggling cognitively today). As our threshold for exercise is so low. We are feeling unwell everyday, always something wrong.

    As for what day extra PEM sets in after exercise, for me it can happen anytime. There is no predictability. I can head out to an appointment and find myself doing a quick run to catch a bus and that short burst of a run can set me back in an hours time, my inflammation starts intensifying, I feel extremely sick. And there is also the accumulation upon accumulation PEM as well. That can result in a major relapse.

    Cheers to the ME sufferers who put themselves up for the exercise testing. x

  • Firestormm August 3, 2013, 3:16 pm

    rosie26 I think I tend to equate 'exercise' with physical exercise. And therefore it's more likely to be worrisome and in need of more careful consideration. I'd probably plan some time out to better account for any PEM even if my exercise now equates to a brisk walk.

    But a period of 'mental exercise' also can lead to consequences. So unless I have to – see below – I try and break it all up with distractions. Takes me longer but I am the tortoise now to the hare and usually get there in the end.

    It is hard to judge what activity or intensity is going to be more likely to lead to a 'flare' and subsequent need for rest. I think through experience we tend to learn our own limitations at any given time and can make judgements accordingly.

    Establishing routines if we can that fit to our own abilities is key but retaining some flexibility is also necessary. And that kind of makes it harder to commit to regular things – though I am ever full of praise for those who can.

    I was just saying to Simon that I anticipated after my night's stay in hospital, the travel and disruption; and then a 3 hour intense meeting on Wednesday; that I would be in need of at least a few days of cleared decks. It still though comes as a surprise and I find it very annoying when the 'flare' hits.

    Not always predictable the degree to which it can affect us – is it? And it's never just about the physical exertion; it's also the mental and emotional that we need to consider.

  • MeSci August 3, 2013, 3:22 pm
    rosie26

    I think in ME we are in PEM all the time aren't we. (sorry I am struggling cognitively today). As our threshold for exercise is so low. We are feeling unwell everyday, always something wrong.

    I think that people who are relatively badly-affected may always feel unwell, but I don't, and suspect that many others don't, as long as we adopt measures to prevent it, e.g. suitable diet and supplements and careful pacing. When I feel 'well' I have negligible bodily discomfort and my brain and body are able to do what I ask of them, which has to be not too much so as to avoid PEM later. So I am not recovered, but feel what I regard as 'fine', a lot of the time. I wonder how often sufferers and health workers mix up the two conditions – well and recovered. Is 'well' the right word for feeling OK?

  • SOC August 3, 2013, 5:13 pm
    MeSci

    I think that people who are relatively badly-affected may always feel unwell, but I don't, and suspect that many others don't, as long as we adopt measures to prevent it, e.g. suitable diet and supplements and careful pacing. When I feel 'well' I have negligible bodily discomfort and my brain and body are able to do what I ask of them, which has to be not too much so as to avoid PEM later. So I am not recovered, but feel what I regard as 'fine', a lot of the time. I wonder how often sufferers and health workers mix up the two conditions – well and recovered. Is 'well' the right word for feeling OK?

    I'm in the same place since I cleared my known chronic infections and, equally importantly, learned to use my HR to pace my activities. Without HR-based pacing, I was always overdoing (while doing very, very little) and constantly had symptoms.

  • alex3619 August 3, 2013, 7:30 pm

    In terms of general markers that might apply to ME patients, I discussed this a while ago on a thread on NADPH.

    http://forums.phoenixrising.me/inde…surement-at-riordan-clinic.15641/#post-252023

  • Little Bluestem August 3, 2013, 10:26 pm
    MeSci

    After my first severe episode of hyponatraemia I started suffering dental damage and also had my only-ever fracture, from a minor fall, supporting my theory of mineral loss, hence the fact that I now take a bone mineral supplement. I don't get these severe effects any more.

    This is interesting. I have never had severe hyponatraemia. I don't know if I have had mild hyponatraemia.

    I have had two filling replaced this spring. X-rays show that another is deteriorating. I was diagnosed with osteoporosis.

  • Valentijn August 3, 2013, 10:55 pm
    SOC

    I'm in the same place since I cleared my known chronic infections and, equally importantly, learned to use my HR to pace my activities. Without HR-based pacing, I was always overdoing (while doing very, very little) and constantly had symptoms.

    Heart rate has been a huge help to me too. I use a pulse oximeter since it's small and easy to take with me (it even came with a carrying pouch to go around my neck).

  • MeSci August 4, 2013, 3:41 am
    Little Bluestem

    This is interesting. I have never had severe hyponatraemia. I don't know if I have had mild hyponatraemia.

    I have had two filling replaced this spring. X-rays show that another is deteriorating. I was diagnosed with osteoporosis.

    Standard general-health blood tests in the UK include blood sodium, and I would guess that this would be the case elsewhere. Can you see if you have more results for this? If not, you could ask for a test. In the UK I would expect patients to be told if their blood sodium was worryingly, or consistently, low.

    But maybe different people are prone to deficiency in different minerals. Lactic acid can also be excreted as a salt of potassium, for example.

  • SOC August 4, 2013, 10:29 am
    Valentijn

    Heart rate has been a huge help to me too. I use a pulse oximeter since it's small and easy to take with me (it even came with a carrying pouch to go around my neck).

    I use a pulse oximeter now, too. When I was going over my AT walking across the room, I wore a chest belt HR monitor because I needed to watch every little activity to avoid going over my AT. Now I only need to check occasionally during the day.

  • pamb August 4, 2013, 1:47 pm
    peggy-sue

    Having been ill for nearly 11years, it can now take up to a week before PEM hits me. It laso lasts for a lot longer (for the same amount of overdoing) than it did earlier on.
    I'm not sure testing just one day after (on myself) would actually show anything (apart from reaching the lactic acid thing far too soon and not being able to get into aerobic metabolism at all, which is what shows on the first testing anyway.)

    I would be really interested in seeing exercise testing done even later – and then some more to see how long it lasts for.
    And to have that related to the length of time the subject has beeen ill.

    I don't think I'm the only person who has found this peculiarity.

    Thank-you, Simon for reporting this great bit of research.
    It really is incredibly hopeful to, finally, see the right things being looked for and tested.

    Hi Peggy Sue,
    Thanks for sharing this interesting bit of information, that the longer your illness goes, the longer the delay before PEM hits. My husband has been ill for 13 years now and we've seen so many symptom changes over the years I've lost track. But, I had never considered PEM delayed longer than 2 days. We'll start watching and see if we are able to note a similar pattern. I can see it may be tricky as there as so many opportunities in a week to over due it.

    Pam and John

  • urbantravels August 4, 2013, 3:04 pm
    MeSci

    Standard general-health blood tests in the UK include blood sodium, and I would guess that this would be the case elsewhere. Can you see if you have more results for this? If not, you could ask for a test. In the UK I would expect patients to be told if their blood sodium was worryingly, or consistently, low.

    Sodium is part of the standard electrolyte panel. Everybody gets this as part of a routine physical. I'm usually at the low end of the normal range on sodium, occasionally a point or two below the normal range, but nothing worrying. A truly low value is definitely something that would be treated, in anyone.

  • Ember August 4, 2013, 4:48 pm
    SOC

    I'm also wondering if some people have some kind of autonomic crash after overexertion that could be alleviated with, I dunno, IV saline or meds…?

    According to Jennie Spotila, Dr. Dan Peterson offers IV saline to help patients recover from exercise testing:

    Disability evaluation and exercise testing will now be performed in two locations: the XCEL Physical Therapy Clinic in Ripon, California and Sierra Internal Medicine in Incline Village, Nevada (Dr. Dan Peterson’s clinic). Stevens says that the relocation actually enhances the quality of care that Workwell can provide patients. Working in Dr. Peterson’s office will not only offer patients access to his expertise in ME/CFS, but patients can receive IV saline to help them recover from the CPET.

    Perhaps this CPET support will become standard procedure.

  • MeSci August 5, 2013, 1:09 am
    urbantravels

    Sodium is part of the standard electrolyte panel. Everybody gets this as part of a routine physical. I'm usually at the low end of the normal range on sodium, occasionally a point or two below the normal range, but nothing worrying. A truly low value is definitely something that would be treated, in anyone.

    OK. Hopefully in the US they have a better idea of how to treat it than here in the UK, where they have no clue about how to assess a person's hydration status and are therefore prepared to restrict fluids in an already-dehydrated patient!

  • MeSci August 5, 2013, 1:13 am
    Ember

    According to Jennie Spotila, Dr. Dan Peterson offers IV saline to help patients recover from exercise testing:

    Perhaps this CPET support will become standard procedure.

    That's interesting, Ember. Presumably he checks people's sodium and fluid levels first? This may seem a silly question, but in the UK doctors often do very silly things!

  • peggy-sue August 5, 2013, 2:52 am

    Reporting on my current status, after my very busy holiday catching up with family and friends (24th-29th of July).
    Today being 5th August, I noticed yesterday that somebody has turned the gravity up. I think payback is starting. I have wet washing in the machine, but have ignored it for 2 days – I am clearly "catastrophising" 😉 – or in other words, my guts are telling me that hanging it up will be a really big job of overdoings.
    That's a delay of 6 days since I got home.

  • Ember August 5, 2013, 5:08 pm
    Sasha

    That was done by the Drs Light, wasn't it? And showed huge effects in PWME vs healthy & MS controls.

    Gene expression isn't available as a clinical test at this point, but you may find Dr. Bateman's discussion of the Light AR, Bateman L, Jo D, et al. (2012) study interesting (5:00 – 18:00). Dr. Bateman discusses individual patient responses, attributing the low-level results of one of her patients in her 60s to her being a master of pacing and good health practices.

    The initial study by the Drs. Light highlights the comparison with MS controls:

    Although both CFS and MS patients reported greater physical and mental fatigue than controls, the CFS group reported more fatigue and pain at pre-exercise than the MS group, and their postexertional symptoms increased more and were still increased after 48 hrs while the MS group recovered by 24 hrs. Gene expression of metabolite-detecting receptors increased following exercise only in the CFS group, and only in this group was there a correlation between P2X4 increases and severity of post-exercise fatigue and pain. Thus, the pathology of CFS may include a susceptibility to disproportionate fatigue in response to exercise stress that is uniquely expressed in this patient group. The pattern of gene expression may have potential for use as a biomarker for diagnosis and treatment responses.

    Dr. Bateman suggests test combining and says that serial CPET testing “is hopefully going to be a signature of this illness as well.”

  • Snowdrop October 20, 2013, 7:58 pm
    pamb

    Hi Peggy Sue,
    Thanks for sharing this interesting bit of information, that the longer your illness goes, the longer the delay before PEM hits. My husband has been ill for 13 years now and we've seen so many symptom changes over the years I've lost track. But, I had never considered PEM delayed longer than 2 days. We'll start watching and see if we are able to note a similar pattern. I can see it may be tricky as there as so many opportunities in a week to over due it.

    Pam and John

    This is my situation also. This is the first I've heard mention of the longer than 2 days PEM delay but I've come to realise that for me it's more like 4-5 days. Again, I'm not as alone as I thought.
    SD

  • SOC October 20, 2013, 8:14 pm
    Snowdrop

    This is my situation also. This is the first I've heard mention of the longer than 2 days PEM delay but I've come to realise that for me it's more like 4-5 days. Again, I'm not as alone as I thought.
    SD

    By the time I started paying attention to PEM — about 4 years after the initial flu-like illness — I was having about a 4-5 day delay before PEM. I'm starting to think the 3-5 day delay is more common that is currently believed.

  • MeSci October 21, 2013, 2:25 am
    SOC

    By the time I started paying attention to PEM — about 4 years after the initial flu-like illness — I was having about a 4-5 day delay before PEM. I'm starting to think the 3-5 day delay is more common that is currently believed.

    That's perhaps the opposite to what I have found. I said earlier in this thread that after I made appropriate changes to diet and supplements my PEM became more delayed (and almost imperceptible). It was hard to be sure as it had become so mild, but the delay seemed to have increased to about a week, from an initial two days.

  • peggy-sue October 21, 2013, 4:29 am

    I first read an article by the Dr. David Smith who has his own pet theory about ME?CFS quite early on in my internet trawlings to find out more about what the heck was wrong with me.

    He's the chap who reckons it can be cured by mixing SSRIs and Tricyclics (officially contraindicated because of the risk of heart failure).

    But his website had an article on pacing and how to calculate payback.
    I wasn't neccessarily going to believe it.
    I had read and dismissed a lot of garbage on the net (LP, Mickel, Reverse etc.)

    But it did give me something to watch and observe, see if that was what did happen.

    His "calculation" was that;

    For every year you have been ill, PEM will delay by another day.

    For every year you have been ill, the PEM will last that number of days
    times the lenght of time you spent overdoing yourself.

    so, for example,

    a 2 week bout of 'flu after 6 years of being ill will give rise to payback of

    14 x 6 days, (3 months) delayed by 6 days from the end of the 'flu.

    I am not sure if it carries on getting delayed much after a week…. I have not observed that at all.

    I've been sick 11years, my last big bout was still only delayed by 6 days.

    I'm still getting over it – it was a very big and lengthy overdoing, in unbearable heat.

    (but it was such a good time I had;
    full of fun and laughs and confidences… and most important of all, love.:love: )

  • MeSci October 21, 2013, 5:32 am
    peggy-sue

    I first read an article by the Dr. David Smith who has his own pet theory about ME?CFS quite early on in my internet trawlings to find out more about what the heck was wrong with me.

    He's the chap who reckons it can be cured by mixing SSRIs and Tricyclics (officially contraindicated because of the risk of heart failure).

    But his website had an article on pacing and how to calculate payback.
    I wasn't neccessarily going to believe it.
    I had read and dismissed a lot of garbage on the net (LP, Mickel, Reverse etc.)

    But it did give me something to watch and observe, see if that was what did happen.

    His "calculation" was that;

    For every year you have been ill, PEM will delay by another day.

    For every year you have been ill, the PEM will last that number of days
    times the lenght of time you spent overdoing yourself.

    so, for example,

    a 2 week bout of 'flu after 6 years of being ill will give rise to payback of

    14 x 6 days, (3 months) delayed by 6 days from the end of the 'flu.

    I am not sure if it carries on getting delayed much after a week…. I have not observed that at all.

    I've been sick 11years, my last big bout was still only delayed by 6 days.

    I'm still getting over it – it was a very big and lengthy overdoing, in unbearable heat.

    (but it was such a good time I had;
    full of fun and laughs and confidences… and most important of all, love.:love: )

    I'm glad you had some fun, peggy-sue

    But that David Smith stuff sounds like BS to me. (Bad Science :lol:)

    I took an SSRI and a tricyclic at the start of my ME and they turned me into an insomniac zombie unable to speak or swallow properly and with numbness in my hands which made it hard to use them. When I stopped them both I seemed to come alive again, once more aware of the beauty of nature, which I had become oblivious to and which had always been a source of pleasure for me, and one of the few things that I could still enjoy after becoming ill. All pleasure had been numbed by these drugs.

    A lot of us don't get colds or flu. I still did in the early stages, and actually felt relatively well when I had them. I appear to have been immune to them for many years now.

    It can be confusing when a website or other source has some good info/advice and also some BS. If you know one or more things to be correct, you may tend to assume that the rest is too. But it ain't necessarily so…(Cue music).

  • peggy-sue October 21, 2013, 7:47 am

    "It can be confusing when a website or other source has some good info/advice and also some BS. If you know one or more things to be correct, you may tend to assume that the rest is too. But it ain't necessarily so…(Cue music)."

    Exactly, MeSci.

    But his website was the first thing I found on the internet which had any pacing advice at all.

    I could see the rest was BS, same as I read up about LP and Mickel and Reverse, and dismissed them as BPS –
    (Bad Pseudo Science:p)

    This was before I found any ME forums.

    Pacing made sense, so I started applying pacing principles. They helped. A lot.

    I don't get colds or 'flu often either. I felt what he said about that was daft.
    apologies for using 'flu as an example of an overdoing!:redface:

  • alex3619 October 21, 2013, 8:21 am

    (Bad Pseudo Science:p)

    😆

  • SOC October 21, 2013, 1:26 pm
    MeSci

    That's perhaps the opposite to what I have found. I said earlier in this thread that after I made appropriate changes to diet and supplements my PEM became more delayed (and almost imperceptible). It was hard to be sure as it had become so mild, but the delay seemed to have increased to about a week, from an initial two days.

    I wonder if it might be related to OI issues compared to energy production issues. Both could cause PEM, but on different time scales.

    In my case, PEM occurred about 4 days after exertion in the time before I had any OI symptoms. As OI developed, the PEM delay got shorter and shorter. Since I've been treating OI, my PEM delay has lengthened again, although that may not be as certain since management has helped me to mostly avoid significant PEM over the past few years. It's hard to know for sure what's going on with such a small amount of data.

    It might be interesting if researchers doing 2 day CPET also recorded when post-test PEM hit their "victims". 😉

  • alex3619 October 21, 2013, 2:11 pm

    The problem with PEM and current science is that it is still a syndrome. We don't understand it. I suspect its a composite symptom cluster with multiple issues, each of which has their own time scale. Some aspects of it are being unravelled though, from mitochondrial and delayed energy production issues, to more immediate muscle lactate responses.

    Given that this involves metabolism, nerve signals, hormonal signals and immunological signals, each with its own time frame, the way to think of PEM might be one to many overlapping curves, each with its own maximum intensity spike\s, and what we experience is the combination of these effects. In terms of waves, this means intensification or nullification based on how the waves superimpose on each other. Three big waves coincide and whammo, you have big symptoms.

    Which leads me to a question I have not thought about much, are there stages to PEM, with different symptoms in those stages?