Hello everyone and congratulations on a terrific website with great forums! It is my first day here and though this is not the standard way to introduce oneself I would like to do so by introducing what has been my single most pressing question for years and years: Getting at the heart of post-exertional malaise! Not very original, I know… Those crashes, those awful crashes which everyone inside the ME community know all-too well as the most salient and difficult feature of this illness, while everyone outside the community repeatedly misses that very point! Frustrating paradox. Ever since I fell ill I have tried to understand my crashes. Every time I have had the good fortune to see a good ME doctor or exchange with a fine researcher, I always asked what their views on the matter were (I will share some of them below). But I still don't have a definitive and cogent answer. For me this is not about ME "theory" and it certainly is not an intellectual musing. It is a visceral need to make sense of what is going on in my body. A diabetes patient can make some sense of his or her symptoms, so can an MS patient, but an ME patient who crashes isn't quite sure what is suddenly going on (other than: Damn, I went beyond my exertional limit once again…) As you all know crashes come in many colors, here are mine: I don't have delayed crashes that set in 24-48 hours after the exertion, my crashes don't vary in duration (e.g. sometimes 6-8 days, sometimes 2 weeks, 2 months) and I don't go on occasions for 2-3 months or longer without a single crash. Rather, my crashes or PEMs have a well-defined and constant aspect: they kick in 2 hours or less following my excess, they peak in intensity some 12 hours after, I wake up on the 2nd day still at the peak level, and by the 3rd day they fade out and I return to my poor baseline. I can then crash in the next hour all over again if I overdo it. And of course that never takes long before happening. I crash every week. At least once. That was the easy part - the temporal aspects of my PEMs. Describing what I experience is another story. It's hard to find the right words, but it starts with my brain being the first thing that gets hit. I get a cerebral "malaise", a feverish feeling, my head just feels... sick. I have other symptoms but this is the only one that truly matters to me. When your mind is wacked, what have you got left? I become unwell in an essential way, it is not just a part of myself, like muscle pain or a tense neck, but the core of my being. So, some 60-70 times a year I go through a miserable experience the nature of which still escapes me! Sometimes I am at peace with not knowing and I let it be, other times it drives me nuts. I would be so grateful to have any feedback from members here on crashes of the above nature (the "course" in the title refers to the one I myself need, I hope that is how it came across...) I will clumsily share my own three hypothesis, taking sitting at the computer as the typical trigger, since it actually is my most frequent trigger! Now that my physical activity level is near zero. I am horizontal most of the day, except for sitting at the computer and I typically crash after writing too long e-mails. On occasions I also sit briefly at the piano but seldom crash - thank god at least that.. - I guess because fewer cognitive efforts are involved. Itching as I am to know the "fabric" of a crash experience, what generates my malaise sensation, here, then, are my three layman speculations: 1- after 20 minutes of sitting and thinking at the computer I have been in anaerobic respiration mode beyond a critical duration after which my brain fills up rapidly with lactate which then takes three days to clear (apparently lactate builds up in the brain as well, not just in muscles..). My cerebral malaise might come from the lactate build-up? - and/or: 2- after 20 minutes on the computer my immune system fires off and takes three days to calm itself down... My malaise might come from all those cytokines flying in my brain and other immune events going on there? - and/or: 3- after 20 minutes on the computer my brain lacked blood beyond a critical duration after which… (I don't know how to finish that one. What would prolonged brain hypoperfusion suddenly trigger that would then take three days to clear?) Now to share with you some views of experts I was lucky enough to be in contact with. The first two are well-known ME researchers and I don't mean to be a tease by not saying their names and I apologize for not doing so but these were personal communications, I prefer not to go public with their identity, only with their ideas… The other two are ME clinicians, both having decades of experience, which I have seen in consultation. The former two are from the fields of genetics and epidemiology, the latter are specialists in infectious diseases and internal medicine. To each one I have submitted my same old question regarding my crashes. Researcher no 1 made a general comment on "the decreased ability to produce ATP which may not be a serious problem for patients at rest where they are not consuming a lot of ATP. But when they exert themselves they can consume much of their ATP reserves and many body systems start to shut down. If you were to continued to push your self you would die but instead you crash. The crash is the body protecting itself." (his exact words, it was an e-mail exchange) Researcher no 2, to whom I had described the aspect of sudden alteration in my states, i.e. when I crash I don't just feel "more" exhausted than 2 hours earlier but I feel "differently" as though some process had kicked in, - said straight away that a qualitative change like that suggests a "chemical imbalance" and involves microbiome bacteria flowing more and more into the blood stream at that point and reaching my brain. - Actually he said way more than that but too fast for me, that was a very packed five minute phone call! Clinician no 1 had a short and sweet answer: "Your brain senses the lack of blood and starts to shutdown to protect itself, there is your malaise" (I wondered if he was describing the first stages of a syncope more than my 3 day crashes but maybe they are a similar process?) Clinician no 2 said clinician no 1 was partly right… He also invoked constricted arterioles in the brain, to which I immediately asked "What do you think constricts them? " - "Perhaps antibodies", he said, and at one point in our session as I was struggling more and more with the effort to talk he said "You see it is probably happening right now, as you are trying to talk you are forcing blood into your brain but it doesn't make it". - I don't know if he was right but I was impressed to hear him comment upon the pathological process "in action" so to speak in the here-and-now of the session! Quite a present-minded clinician. I was wondering though whether he was describing a general ME issue instead of what specifically happens during a crash. That pretty much sums up what I wanted to say for now… Thank you for reading, even half way, and I promise to keep all future posts shorter!