The 12th Invest in ME Conference, Part 1
OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.
Discuss the article on the Forums.

PEM/PENE delayed or immediate?

Discussion in 'General ME/CFS Discussion' started by anniekim, Oct 17, 2015.

  1. anniekim

    anniekim Senior Member

    Messages:
    768
    Likes:
    671
    U.K
    I see post exertional exacerbation of symptoms described often as delayed. I am bedridden 24/7 and I have immediate exacerbation of global symptoms if I go over my very strict activity limits. If I go over them considerably I will then not return to my baseline level of symptoms the next day but risk dipping below my baseline for days, weeks or longer. In the years when I was moderate I'd experience this combination of immediate and delayed too. Just interested if I am missing something in not relating to it being described as only delayed.
     
    Stuart, Ellie_Finesse, mango and 3 others like this.
  2. halcyon

    halcyon Senior Member

    Messages:
    2,305
    Likes:
    5,388
    From personal experience and reading the ICC criteria, it seems it can be both. Perhaps this helps, from the ME ICC, I've highlighted what I would call immediate effects:

     
  3. ScottTriGuy

    ScottTriGuy Stop the harm. Start the research and treatment.

    Messages:
    1,089
    Likes:
    4,398
    Toronto, Canada
    Yep, I call it present exertional malaise.
     
    halcyon and Effi like this.
  4. SOC

    SOC Senior Member

    Messages:
    7,841
    Likes:
    16,540
    I think it's possible that PEM is immediate, but I consider it equally possible that the immediate reaction is exercise intolerance (which many of us have as a result of OI) and the delayed response is the actual PEM.

    Neither my daughter, nor I, recover from PEM with 24, or even 48 hours. When I was severe, I did feel worse immediately after minimal activity, but it was different from the PEM that would hit 3-4 days later and last for weeks or months. The immediate symptoms (increase in fatigue and brain fog, headache, heavy limbs, etc) would generally clear within 24 hours, which isn't really a delayed recovery unrelieved by rest so I didn't consider it PEM. It is the flu-like symptoms (body-wide muscle aches, swollen lymph nodes, sore throat, complete exhaustion, severe cognitive dysfunction, etc) that took several days to start and months to recover from that I think of as PEM.

    That's just my personal feeling, though. Since we don't know what PEM is exactly, we have no way of knowing if it can occur immediately or not. For the time being we have to assume that if there are "prominent symptoms in the neuroimmune regions" and "Recovery period is prolonged, usually taking 24 h or longer" then it is PEM regardless of when it starts.

    The only reason I'd consider making a distinction between immediate exercise intolerance and immediate PEM is that there are treatments that might improve exercise intolerance, but not PEM. I think it's worth starting from the position that it's exercise intolerance and trying to treat it before accepting that the immediate response is PEM, which is currently untreatable.
     
    Last edited: Oct 19, 2015
  5. ScottTriGuy

    ScottTriGuy Stop the harm. Start the research and treatment.

    Messages:
    1,089
    Likes:
    4,398
    Toronto, Canada
    What are some of those treatments? When I googled, it returned studies looking at 'exercise therapy' for people with COPD and heart failure.
     
  6. SOC

    SOC Senior Member

    Messages:
    7,841
    Likes:
    16,540
    I'm mostly thinking of exercise intolerance as the result of some form of dysautonomia because I suspect that is the most likely cause of exercise intolerance in PWME, as opposed to COPD or heart failure.

    Fludrocortisone or desmopressin to increase blood volume is commonly prescribed by top ME/CFS specialists. Midrodrine to used improve vascular tone, I believe. Beta-blockers or calcium-channel blockers control tachycardia in some dyautonomia patients. There are other meds I'm sure I'm forgetting -- Strattera helps in some cases I believe. There are also some behavioral interventions that can help to some degree -- drinking more fluids, fluid loading, compression garments, elevating the head of the bed, etc.

    There's a lot of discussion about this here at PR. Try doing a Google site search at PR on "orthostatic intolerance" and/or "dysautonomia".
     
  7. anniekim

    anniekim Senior Member

    Messages:
    768
    Likes:
    671
    U.K
    Thank you for the replies. The ICC's explanation of pene with the various effects under that term seem to encompass the different responses we have with exertion, both immediate and long term.

    @SOC, thanks for your comments. Interestingly, if I do too much activity (being bedridden this involves no walking, activity for me is talking, a bit of reading, and being on line) I also will get immediate immune response symptoms such as sore throat, feeling of nasal congestion. I see the ICC criteria also list flu like symptoms as being able to be immediate.
     
    SOC and Debbie23 like this.
  8. Debbie23

    Debbie23 Senior Member

    Messages:
    137
    Likes:
    293
    Same. It could be exercise intolerance of course, but cognitive activity can trigger it, sometimes severely, and usually does because like you I'm so physically restricted. it contains the symptoms SOC lists under PEM rather than EI, like sore throat, a very specific type of pain right at the base of my skull, swollen glands, body wide pain (sometimes agonising) not necessarily in the parts of the body I have been using to trigger it, cognitive issues and a very particular type of body wide exhaustion where it can feel like my body is struggling to function, with things like breathing and even shutting my ability to perform some functions down with eating, talking etc. etc. These aren't everything it encompasses and I get a generalised worsening of other symptoms too.

    The recovery is still delayed, and it still usually peaks several days after the triggering factor, but when I can identify what the triggering factor is it's easier to notice this. In day to day terms it's very hard often to recognise where one one bout ends and another begins, it usually kind of spills over so as you can more easily recognise what I'd class as a 'flashpoint', where I suppose you could say it's a new bout starting, but this takes attention away from the prior one which was still ongoing. If that makes sense. So you pay more attention to the more immediate payback, rather than what is still going on from before, but it clearly is still ongoing. For me it's a bit like the difference between a fire alarm and the actual fire, the fire alarm can warn you of danger, but just because the fire alarm stops playing it doesn't mean the danger has gone or that the fire is out.

    But I would still class these flash points as PEM, it can come on very quick for me, but I definitely class it as PEM/ PENE as described in the CCC and ICC, combined with the muscle fatigue and delayed recovery described by Ramsey. When I first read those things I literally cried and cried because of how much they 'got' and validated what had happened to me for so long. I don't think I'd yet found PR or at least not been here long enough to read enough of other's experiences, so it felt like the first official validation I'd ever had. Whether delayed or immediate, they describe perfectly what happens to me. So immediate or delayed I would still class it as PEM/ PENE, personally.

    But, I think the speculation that severe patients are in a constant cycle of PEM is very possibly true. I have most of these symptoms pretty much all of the time at varying levels. They get worse after any type of exertion, which again is then much easy to identify as a trigger, and much worse if for me the exertion is big. But again, it can be very, very hard to work out where one bout ends and another starts when you are taking about day to day stuff. It's possible that it's PEM within PEM, although I would term it PEM within a crash, personally. For me I would describe a crash as a long term lowering of baseline, and PEM as the fluctuation of symptoms relative to that baseline in relation to activity. Not saying that's right, but that's how I have always thought about it.

    I can pinpoint when my baseline lowered, last year when I had surgery under GA, I can identify other bigger triggers that have happened since then and further lowered my baseline. But the triggers that make my day to day illness fluctuate in relation to that baseline, which I would label PEM/ PENE can be harder to identify because just day to day stuff can trigger it, and it seems ongoing. Far from resolving quickly I sometimes think it never seems to end, and these flashpoints are like someone throwing fuel on a fire, never letting it burn out. Bigger triggers, appointments, vaccinations, family visiting, emotional upset due to bereavement much much easier to identify. The day to day stuff that causes these 'flashpoints' much much harder to figure out because they occur At least a few times everyday as a rule. But again if the flashpoint seems to resolve and the fire alarm stops playing, does that mean the fire is out? I don't think so personally. I think it's just that when the fire alarm starts playing again it can be easy to think of it as a new fire rather than one that was caused by the Sparks of the one that came before.

    I would actually measure how 'well' I am tbh by how long it is before I get payback. When very ill like now payback can hit hard and quickly, and it definitely includes the PEM symptoms of feeling like you have a head cold, sore throat, body aching like you have the flu etc etc. That's not at all a minimisation of PEM for others which hits later or their levels of illness, it's simply how I've observed onset in relation to my own specific experience with illness. In my case the times when I've been doing comparatively better have been the times when PEM has been more obviously identifiably delayed in onset, even though I've still been ill overall. Usually for me, or at times of being very ill like now, my threshold seems much lower and onset seems much quicker. Again recovery is still delayed, but when pretty much most things you do can trigger PEM, it's hard to differentiate 'recovery' because what's more always obvious IME is a new 'flashpoint' , a new onset point attached to any activity, which steals focus of what came prior.

    I have no idea if any of that ramble makes sense! But yeah I would definitely say I get PEM that is comparatively immediate in onset. Resting soon after what triggered the 'flashpoint' can minimise the flashpoint itself sometimes, emphasis on sometimes, but it doesn't eradicate the symptoms itself. So the fire alarm gets switched off but when it goes on again, it's not clear if it's a new fire or sparks from the one that came before.
     
  9. Hip

    Hip Senior Member

    Messages:
    9,455
    Likes:
    14,946
    According to Wikipedia, exercise intolerance is a primary symptom of chronic diastolic heart failure.

    So I presume you would have to have diastolic heart failure in order to suffer from exercise intolerance (or some other condition known to cause exercise intolerance). It apparently requires an echocardiogram to diagnose diastolic heart failure (an echocardiogram is an ultrasound scan in which a computer converts the ultrasound echoes into moving real-time images).

    I know Dr Cheney thinks diastolic heart failure / diastolic heart dysfunction plays a central role in ME/CFS, though I have not seen much other research in this area.

    Though I did just find this study on cardiac function in ME/CFS (but I am not sure if this is detecting actual diastolic heart failure):

    Impaired cardiac function in chronic fatigue syndrome measured using magnetic resonance cardiac tagging
     
    Last edited: Oct 19, 2015
  10. Hip

    Hip Senior Member

    Messages:
    9,455
    Likes:
    14,946
    I just came across this intriguing paper:

    Alpha1A-adrenergic receptor-directed autoimmunity induces left ventricular damage and diastolic dysfunction in rats

    So alpha 1A adrenergic receptor autoantibodies can cause diastolic dysfunction.

    And as has been discussed on these forums, this 2014 study found that alpha 1 adrenergic receptors were present in POTS, which some ME/CFS patients have.

    So I am thinking that the diastolic heart failure / diastolic heart dysfunction which Dr Cheney says is present in ME/CFS may also be driven by autoimmune processes, and might be connected to POTS alpha adrenergic autoantibodies.

    Thus any exercise intolerance in ME/CFS could be cause by autoimmunity.
     
    Last edited: Oct 19, 2015
  11. alex3619

    alex3619 Senior Member

    Messages:
    12,521
    Likes:
    35,220
    Logan, Queensland, Australia
    Alan Light mentioned some work about to be published showing that for about half the patients with both CFS and FM the drug Lyrica improves the biochemical response that is associated with PEM. The other half of the patients get worse though. This should be published soon, I hope. He mentioned this during a recent webinar. Gabapentin might be an alternative.


    It has to be kept in mind though that this is preliminary research, and only done on patients with FM, or CFS+FM (plus I think some controls). It was also a small study. However it looks like the effect size is largish from the graphs ... but this is the case for responders and anti-responders (its worse than a non-response). However it is clear the anti-reponders have a different exercise challenge biochemical profile to start with , so its likely that a blood panel can show who will respond and who will not, and so in time we might know who to give it to and who should not have the drug.

    It is also too soon to say if this results in any great improvement in symptoms.
     

See more popular forum discussions.

Share This Page