nice article!
Before getting the viral-type of CFS, I had many bouts of postexertional malaise, and 4 or 5 serious crashes that put me in bed for 2-5 weeks each time, almost completely unable to function on any level.
The regular PEM (I'll abbreviate it), all came after physical exertion. Last winter, before I had the more viral-type feeling of CFS, I got so stir crazy that I decided to try some walking. I walked to the end of my street (about 500 yards) and back every day for about 3 or 4 days. I didn't feel too bad from that, so I decided to extend it about double. Big mistake! I could probably walk about that distance at least throughout the day, but all at once and at a faster than normal pace it was too much and I crashed for a couple of days with increased fatigue and just completely BLAH. But with pacing myself, I could go most of the day doing things without crashing or too much PEM. It's only when going over the edge that I would have problems.
The major PEM crashes all came as the result of emotional meltdown, mostly from toxic family interactions. Maybe those aren't even rightly described as postexertional malaise, but just functional adrenal failure or something like that. It's definitely neuroendocrine in origin, but what exactly is involved in maintaining the complete wipe out I don't really know. "Low cortisol" is the usual answer, but that is way too simplistic imo. If it were just that one could just take cortisol and bounce back immediately, but it's not like that at all. You just have to wait until the system comes back "online" itself.
Now with the viral-type of CFS, I don't really know what to expect. My activity is severely limited relative to what it was before, the fatigue is constant and worse, and I seem to get extremely wiped out with PEM in a different way than before, and with much less activity. But it doesn't seem to be adrenal/HPAA mediated like the original fatigue (which is still there "underneath" this new fatigue, or alongside it).
So I think there are actually several different mechanisms of PEM, one adrenal and neurohormonal, one cellular/mitochondrial, and one immunological. I also crash from thyroid hormone, and the answer most often given for that is also "low cortisol." But I noticed that was different from the cortisol crashes, too. That seemed to affect my muscles and heart, but didn't give the adrenal crash brain fog.
What I think it has to do with is cellular carnitine levels or functioning, because hyperthyroid patients are carnitine deficient, and one of the parameters of the Myhill ATP profile test measures the fractionated amino acid functioning, including l-carnitine. And carnitine depletion would be expected to impact exactly what gets affected from adding thyroid: namely, skeletal and cardiac muscle, but not brain, which would be more acetyl-l carnitine.
Those are my observations, at least. I wish I knew what caused this viral-type fatigue and PEM, I just know that it's different and apparently separate from the mitochondrial/cellular/neurohormonal fatigue. There's something else doing it, maybe involving those things to some degree, and neurobiology, but I don't have a sense of what it is yet. Nothing so far seems to impact it in a positive way, only negative by doing too much and getting the PEM.