A New Hypothesis for Viral ME Symptoms
- Thread starter Wishful
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@Wishful do we have any evidence that there is immune activation in ME? Cytokine studies show nothing, autoantibody studies nothing, plasmapheresis is disappointing, clonal T cell expansion studies are inconclusive at best, acute phase reactants are lower than the mean, and NK cells are usually low. I went down the immune rabbit-hole and came out empty handed. No real evidence except that corticosteroids and cyclophosphamide are helpful, but they do many things, for example corticoids flatline CRH, which is a pro-nociceptive substance.
At this point I believe that ME is a central neural processing defect, maybe similar to a hypothetical subchronic epilepsy, with excessive NMDA-depentent glutamatergic tone. Nnociceptive and danger signals are amplified, and they lead to feeling sick/poisoned, with neuropathic and centrally mediated (aka fibromyalgic) pain.
At this point I believe that ME is a central neural processing defect, maybe similar to a hypothetical subchronic epilepsy, with excessive NMDA-depentent glutamatergic tone. Nnociceptive and danger signals are amplified, and they lead to feeling sick/poisoned, with neuropathic and centrally mediated (aka fibromyalgic) pain.
I find this view interesting. Could you expand a little on it? Do you think ME is basically a brain disorder of some kind? Where do you think the "danger signals" are coming from or what causes them? Thanks!
No evidence that the main body's immune systems are chronically activated in ME. My observations indicate that t-cell activation significantly worsens my ME symptoms, so I assume that the cytokines from that trigger (or worsen) glial activation, which in turn causes the ME symptoms. There is evidence of chronic neuroimmune activation: thermal scans, PET scans with markers for microglial activation, and I forget whether fMRI also showed glial activation. I think some glial communication is quite short-ranged, and thus hard to sample, aside from the problem of sampling fluids from live brains.
I'm strongly convinced that glial cells are a critical part of ME. Some slight shift in response to signals, or in the ability to return to normal state, or something else of that nature.
I'm strongly convinced that glial cells are a critical part of ME. Some slight shift in response to signals, or in the ability to return to normal state, or something else of that nature.
Sure. I think ME is a gating problem in the brain/CNS, driven by excessive Long Term Potentiation and NMDA signaling, resulting in many signals given inappropriate salience/relevance/importance.
Now, the body has many danger signals, for example, extracelular potassium is a signal for hypoxia, extracelular ATP, the kinins etc... are also compounds produced by stressed cells. I dont think that they are overproduced in the body, rather the ME body overreacts to physiological amounts of these signals, resulting in the familiar, yet nonspecific symptoms of feeling inflamed, infected, toxic, as well as the ANS not working correctly.
This also explains why study after study finds no obvious biochemical difference between controls and PwME. With this theory it also makes sense why gabapntin, clonazepam, phentoiyn, lamotrigine, topiramate, low dose abilify, cabergoline (and other D2 agonists) etc... can result in striking symptomatic improvement for some people. They all modulate aberrant nmda signaling.
There is one thing that im still integrating, and thats the lymph node swelling and pain.
Now, the body has many danger signals, for example, extracelular potassium is a signal for hypoxia, extracelular ATP, the kinins etc... are also compounds produced by stressed cells. I dont think that they are overproduced in the body, rather the ME body overreacts to physiological amounts of these signals, resulting in the familiar, yet nonspecific symptoms of feeling inflamed, infected, toxic, as well as the ANS not working correctly.
This also explains why study after study finds no obvious biochemical difference between controls and PwME. With this theory it also makes sense why gabapntin, clonazepam, phentoiyn, lamotrigine, topiramate, low dose abilify, cabergoline (and other D2 agonists) etc... can result in striking symptomatic improvement for some people. They all modulate aberrant nmda signaling.
There is one thing that im still integrating, and thats the lymph node swelling and pain.
Have you looked at glial serine racemase, and glial D-serine (over)production? D-serine is a potent nmda co-agonist at the glycine site. I also believe a stable maladaptive neuron-glial crosstalk is probably causative. Whats missing is the mechanistic link between glial cells and the symptoms of ME. In my opinion, that link is neuronal nmda overactivation.
No. I tend to look at things that are indicted by observation. If some dietary change affected my cognitive function, and the change correlated with serine intake, I'd definitely follow up on that. Without that sort of link, it's hard to get motivated to research everything. 
One link is kynurenines. My ME symptoms correlate with cerebral TRP levels and IFN-g, and there are other possible correlations involving kynurenines and my symptoms. I'd really like to find a paper answering the question of "Precisely what causes our feelings of flu symptoms?" I think neurotoxic kynurenines are responsible for some of them. Picolinic acid leads to fever.
As for other ME symptoms, glial cells are critical for neural function. They assist neurons and maintain a proper environment for them If glial cells malfunction, likely so do the neurons, and in ways that vary with the individual.
One link is kynurenines. My ME symptoms correlate with cerebral TRP levels and IFN-g, and there are other possible correlations involving kynurenines and my symptoms. I'd really like to find a paper answering the question of "Precisely what causes our feelings of flu symptoms?" I think neurotoxic kynurenines are responsible for some of them. Picolinic acid leads to fever.
As for other ME symptoms, glial cells are critical for neural function. They assist neurons and maintain a proper environment for them If glial cells malfunction, likely so do the neurons, and in ways that vary with the individual.
Update: the extra symptoms from protein foods continued. Then on my next trip to town, I bought some elderberry gummies (elderberry, VitC and Zinc citrate). After 3 days of taking those (took 4 on the 3rd day), the zinc taste became too unpleasant, so I stopped. I ate some sausage that day, and was really brainfogged the next morning. Two days later I tried sausage again, and didn't get the brainfog. I've also gone back to having coffee and hot chocolate with milk without problems. Yesterday I tried peanut butter again, and this time it didn't cause the brainfog. So, while this is hardly strong evidence (maybe the problem would have gone away without the elderberry), it sure looks like the elderberry fixed whatever was wrong. Maybe it allowed my immune system to fully clear out a virus, or maybe it jolted my immune system into returning to normal function (like whacking a device or jiggling a handle).
It looks like it was worth the $20.
... but if there's a next time, I'll look for an elderberry product without zinc.
It looks like it was worth the $20.
... but if there's a next time, I'll look for an elderberry product without zinc.
my experience of the illness very much feels like some kind of sub seizure, the coma sleep, the myclonic jerks, the word loss, I’ve even had episodes similar to absence seizures, I often feel like I have all over body migraines and for a couple of days after the crash I often feel very depressed which I think happens in epilepsy too, interestingly Tourette’s comes with rage episodes which I also experience, it doesn’t Explain the muscle aches or flu like feeling I get in PEM but the actual crash is certainly like some kind of seizure.
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This is consistent with the central fatigue hypothesis
Central nervous system fatigue - Wikipedia
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Central nervous system fatigue - Wikipedia
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Yeah, my crashes feel similar. I didn't know the term myoclonic - that's exactly what happens to my muscles when I have a bad crash. For days I get these sudden, brief jerks of muscles. Thanks for the descriptive term.
I also get the coma sleep, word loss, migraine, deep exhaustion, rage, etc. This can be triggered by doing too much physically or mentally, by allergies (mold, animals, etc), and who knows what else.
I also get the coma sleep, word loss, migraine, deep exhaustion, rage, etc. This can be triggered by doing too much physically or mentally, by allergies (mold, animals, etc), and who knows what else.
I drove to town a couple of days ago. When I got back, I ate some BBQ chicken, and less than an hour later, I started feeling very lousy. Was this cerebrally-induced PEM from driving, or was it a continuation of my sensitivity to protein? I still felt lousy the next day, ate the same amount of chicken, and felt abruptly much worse 2 hrs later, but the abrupt increase was at 4:40 PM both days. This morning, I felt back to my pre-drive symptoms, and had a nice long hike. I guess it was cerebrally-induced PEM, and it enhanced my usual 'feel worse in the afternoon' cycle. That's really good, since I enjoy eating meat, and want to do that a lot more often than I want to drive to town.