For my understanding,all this is not the cause ,but the consequences.and I truly meanwhile believe because we are searching for a cure of the consequences and not looking at and treating the cause, we fail .and this applies to every chronic illness and western medicine.
In other words: We have to distinguish the etiology from the pathogenesis. The interesting point is where both cross over, e.g. when CFS/ME begins after a mononucleosis-type infection, which still seems to be the most commonly identified "trigger", even though mononucleosis isn't specific for an EBV infection and can happen with other viruses as well.
@nerd I think would say...
- Probably thinks highly of this: Chronic herpesvirus infection (EBV, CMV, HHV-6, etc) which dates back to the 1984 Lake Tahoe outbreak
- Ken Lassesen's "gut" model (Ken Lassesen) or that Microbiome one..
- He may actually be a fan of this one: Cortene's hypothesis (Lucinda Bateman, Cortene inc)
- Also prob anything viral in brain or systemic
To shortly address the pathogenesis, I think the vagus nerve explains a lot of it. The work of Dr. Michael VanElzakker was an eye-opener to me for how consistent the perceived symptoms are with the CNS dysregulation by vagus nerve stimulation and by immunological triggers such as microglia activation. This explains why many people have such consistent illness experiences but inconsistent perceived etiologies and biomarkers. Physical trauma and tumors, for instance, can trigger similar symptoms, so basically the same syndrome but with different therapeutic requirements.
It also explains why it is so easily dismissed as psychosomatic. The range of contributors to vagus nerve stimulation is huge. Biologically, women are more sensitive to this stimulation. The whole idea of attributing the perceived illness from women as psychosomatic stems from this misconception. They aren't hysteric at all. They are just more sensitive and men can be sensitive as well. This shows how nonsensical and biomedically inconsistent the whole idea of psychosomatic disease really is. It has never existed.
Of course, anxiety disorders can exist, but they do not explain the translation from psychological stimulus to physiological disease. On the contrary, the vagus nerve causes anxiety. That's why psychology shouldn't be mentioned in either context of etiology or pathogenesis.
Since I and
other patients (e.g.
@Martin aka paused||M.E. ) exhibit viral immune activation that is highly associated with EBV and possibly other gamma herpes infections, and since my first exercise intolerance symptoms began after ca. 6 months of mononucleosis, I think highly of gamma herpes viruses participating in the etiology. As far as I can tell, other viral etiologies such as SARS-CoV-2 might just reactivate EBV asymptomatically. This would also explain why many Post-Covid patients don't experience COVID-19 symptoms, don't build antibodies against it, but do experience infection symptoms.
One way in that a chronic herpes virus reactivation might transpire is a repeated reactivation and long infection time which leads to a growing number of latently infected cells. The sheer number of cells would reduce the threshold of how much stimulation (by oxidative stress and other viral infections) the virus needs to begin the signaling of the reactivation phase. The immune system would never recover because every tiny impulse would cause a reactivation (i.e. PEM). The pathogenesis and perceived illness would just be a physiological response to the repetitive reactivation, to protect the body from its potential damage, which, by the way, is also mediated by the vagus nerve.
Nevertheless, EBV alone can't explain why the immune system stops responding properly to stimuli (as seen in
Neuro-COVID). Something must contribute to a subclinical chronic infection first (at least in a significant amount of patients). Genetics, immune priming (
the original antigenic sin), sociocultural (e.g., depression, PTSD), and environmental factors (e.g., mold toxins, drug use, diet, physical trauma) must also contribute to it. Otherwise, the epidemic spread would be more clear. If it was supposed to be genetic only, it would be more clear within family trees. But it rather seems to be a mix.
I'm also fascinated by the idea of a dual infection, e.g. a herpes, zoster, or enterovirus triggering the pathogenesis that is mediated by another virus and overshadows its pathology. So it wouldn't matter if you already have a reservoir of HHVs, EBV, or CMV, they would just be opportunistic co-pathogens.
I'm not convinced by the microbiome theories. I think the microbiome is a correlative factor, just as basic blood, etc. It's interesting that a lack of butyrate-forming bacteria is associated with CFS/ME though. If they are able to identify distinct pathogenic bacteria, I'd change my view. Viral infection in the gut, however, is a completely different topic.
The
Cortene theory is similar to my
"GABA trap" hypothesis. It could explain microglia activation. What's still missing here is evidence for how this presumed dysregulation is maintained. Is it just a sustained dysregulation after a physiological and healthy response to a pathogen or is the pathogen still dormant and just waiting for another chance, e.g. by another infection that allows it to reactivate?
Another of my always-favorite theories I basically adopted from the field of MG is the chronic infection of the thymus or thymocyte progenitors from the bone marrow. It could explain why the immune system isn't able to recover from childhood infections and why the lymphocyte profiles are off. But the results on this subject aren't very consistent yet. Time will tell if they can reproduce the cytokine profiles and the double-positivity of CD8+CD4+ lymphocytes. If that's the case, the thymus would be the first place to look. These double-positives might be knocked out by EBV in the thymus when they are still thymocytes, so they can't mature properly into single-positives.
This and more, to sum it up in the following list:
- Double HSV-herpes infection as in Alzheimer's (incomplete but applicable as a general idea) [forum link]
- EBI2/EGR/NF-kB-mediated early EBV reactivation theory by Jonathan Kerr [forum link]
- Possible extension of this theory: Overgrown viral reservoir and immune exhaustion theory
- Many other theories that orient around EBV or HHV, e.g. the one of Dr. Prusty
- MG-like thymus infection theory
- Mast cell activation theory (Dr. Tina Peers)
- CNS infection and microglial activation theory (Dr. Michael VanElzakker)
- Original zoster infection sin
- Monocyte polarization theory as in Post-COVID (Dr. Bruce Patterson, Dr. Ram Yogendra et al.)
- Antibody cross-reactivity from viral antigens by genetically dysfunctional immune system and antigen presentation (basically autoimmunity)
- Various novel parasite findings that have never been followed up (e.g. Cryptostrongylus pulmoni)
- Viral infection of bacteria in the body (completely speculative, e.g. infection of borrelia or microbiota)