• Phoenix Rising needs funds to operate: please consider donating to support PR

What is your personal theory or understanding of ME/CFS?

halcyon

Senior Member
Messages
2,383
Likes
5,634
I now believe that the key is hypothalamic dysregulation.

The hypothalamus becomes damaged by long-term chronic stress and trauma (explaining the tendency for PWMEs to be over-achievers, athletes, and people with histories of trauma and chronic stress).
Dysfunction of the hypothalamus is likely central to the disease, but I doubt it has anything to do with trauma or stress.

One of the Royal Free victims who later died of unrelated causes was autopsied and was found to have lesions and intense perivascular cuffing in the hypothalamus; a result not inconsistent with viral encephalitis, but sadly in situ hybridization and PCR technology wasn’t available in the 1950s to prove it. Thankfully it was available in the 1990s, when another ME case came to autopsy, and she was found to have enterovirus infecting her hypothalamus. This finding is consistent with John Richardson’s research showing patients with evidence of chronic enterovirus infection have provokable, measurable abnormalities in hypothalamic function.

Again, any hypothesis about ME must be compatible with recorded outbreaks. Chronic stress and trauma would fall under the hysteria umbrella in my opinion and this is incompatible with the outbreak evidence base which shows objective evidence of immune activation from a pathogen.
 

percyval577

Nucleus Caudatus
Messages
1,134
Likes
1,464
Location
Ik waak up
I think more generel now, it´s a breakdown of synaptical conjunctions of these structures which typically invovle dopamine (though not restricted to dopamine), i.e. basal ganglia and thalamus. I don´t know if this could be made visible say by PET.

Moreover I think this breakdown consists of a hypothetical silencing of some cells (say like in hibernating) or synaptical directions, and the back-foreward direction does not take place. If this inlolved a lesser amount of nerve actions, it could well made visible by PET, but if the same amount of actions took place, probably not.

I still think that this breakdown would say that the being would be in an wound healing process or something like this, and this would cause downstream actions.
Of difficulty should be, that such breakdown might cause some changes on the immunesystem which in turn would induce this breakdown, somehow a somersault for nothing.
Possible might be the breakdown only in humans, because a) the brain is bigger (than in our close relatives, and has not completly adapt to these new mightyness) - and here if I remember rightly, woman´s basal ganglia are bigger than those of men; b) humans are sweating with a concomittant loss of amino acids and with an altering of their homeostasis - and here women do sweat more.

Concrete, the cells would have switched into a silence, rejecting uptake of normal needed stuff (some vitamins), therefore this stuff would be needed to refeed more pronounced concomittantly to:
There are a lot of different metals in the brain which their tasks probably not are already known, however, they would needed to get reconfigurated, because actions should take pace where the metals are.

I also think that the structurers basal ganglia and thalamus allow for the relative wide range of symptoms, which ask for explanations.


CAUSES of a breakdown.

Here I think that an alteration of an initial pathway would have taken place. I prefer a double hit hypothesis, two impacts would have altered one first pathway with a following breakdown of that structres. Viruses, chemicals, maybe even by sudden calcium influx by whatever.

In my case the pathway is the inducible nitric oxide synthases: manganese + arginine = nitric oxide, with changes on all nerves, and especially pronounced in that structures (t-type-ca-channel, many NMDR´s).
I still would like to think that manganese is one good possibility for a dysregulation, because it´s comparable low but used for few tasks all of which seem to be able to be related to a wound healing or more generel to any defense of the body.
This would especially easily go along with the interpretation that our disease is an exaggerated sickness behaviour.


It´s needed to make plausible how a sickness behaviour is possible, and I think it would be easily possible to relate it, in high organsims, to basal ganglia and thalamus which have a lot of NMDR and t-type-ca-channels:
I think a sickness feeling can be made undestandable and deductionable by an initial learning mechanism. Such a mechanism could be compared to a movie where pictures come and go.
Now, when too much have come and wouldn´t go anymore, the being would feel exhausted (and enough is leaerned for today), thereafter a tiredness would take place, the pictures which are too much would go. Now, if the being is acute ill, being tired is a bad idea, instead it needs to be aware, but without wanting to concentrate in interesting things, being aware not to get eaten.
Additionally, too much "pictures" without building up any senseful movie could be interpreted as pain or at least as feeling bad. It also would allow to referre on first physical entities like waves, which can match up harmonically, but could also work against each other (pain). Furthermore, it is thinkable that such a chaos is "willingly" transmitted into an smaller amount of actions, saving some energy (say in higher organisms).
[Finally, the involvement of the learning mechanism would easily explain delayed PEM, because the brain needs to compare up all its experiences again and again, probably best in different time frames. Interestingly, delayed PEM would also imply that the proposed silencing and its concomittant distribution of metals and vitamins is virulent under "somersault for nothing" circumstances, which matches up with experiences that a sudden but usually not lasting good influence (say on the immunesystem) can give all relief. (And the question is how to downregulate the somersault for nothing effectively.)]

For this in first order (in my case):
1) looking at the first pathway if existing, I know that lower manganese diet helps.
2) reconfigurating (some) metals
3) intake of some vitamines, which must not contradict 1), of course

4) patience and trying to do espcially 2) and 3) adroitly, being careful with 1)
finally) not overdoing, because - after this approach - the involved learning mechanism would lead to more chaos again, and the metals might get wrongly placed once again.

I hope it will hold the water (at least in my case).
 
Last edited:

ljimbo423

Senior Member
Messages
2,749
Likes
6,687
Location
United States, New Hampshire
Has anyone changed their mind about causation scince posting on this thread?
Before Jarred Youngers' presentation at the OMF symposium last September. I thought the primary cause of symptoms was mitochondrial dysfunction in the body.

Then, after seeing Jarred's presentation, I thought it was probably the brain inflammation he talked about that was causing symptoms.

Now I think it's probably a combination of both mitochondrial dysfunction in the body and low grade brain inflammation that's causing most or all of the symptoms in ME/CFS.

So, yes, my personal understanding of ME/CFS has changed and will continue to as more research comes in or something just makes more sense.
 
Last edited:

ljimbo423

Senior Member
Messages
2,749
Likes
6,687
Location
United States, New Hampshire
What, people changing strongly-held beliefs without incontrovertible evidence for a different theory? :wide-eyed:

I've just cherry-picked new evidence that fits my theory. :D
I agree. I think that most of us will hold onto our basic understanding of ME/CFS and maybe just find new evidence to support that. That's certainly what I have done too. :) I love picking cherries!:lol:
 

debored13

Senior Member
Messages
2,650
Likes
3,556
Location
Vermont, school in Western MA
My personal belief is that, like @jeff_w states in mechanicalbasis.org , that a number of pwME have some form of cervical spine or brainstem compression. But in my opinion, there may be something upstream of this, at least in a number of cases. And I believe that what @Hip calls the “dual-factor” theory of an infection combined with an environmental factor that suppressed immunity , is consistent with this mechanical theory. The reason I think this is because many people w/ cci diagnoses do not have a genetic connective tissue disorder OR head trauma to explain the damage to their collagen.

So I believe that some environmental variable yet to be discovered is wreaking havoc on connective tissue and also suppressing immunity, to the extent that whatever initial infection people have as a trigger does more damage.
So (infection plus x) > collagen damage > brainstem compression > all ME/CFS symptoms.
 
Messages
3,990
Likes
9,770
I agree. I think that most of us will hold onto our basic understanding of ME/CFS and maybe just find new evidence to support that. That's certainly what I have done too. :) I love picking cherries!:lol:
Re-evaluating my n= 1 personal theory here, with some of the newer info and contemplating collagen......

So this one paper simply confirms that collagen is involved in: the permeability of the gut..

https://www.ncbi.nlm.nih.gov/pubmed/28174772

1) Sick here since: 1 year old. (food allergies severe)

2) likely: my gut was not properly set up in the original first place. And some genetic predispositions. Chances are my mom was potentially laced with anti-biotics and I know she had IBS symptoms her whole life.

3) I had IBS symptoms in elementary school, sick with everything, add vaccinations.

4) Eppstein Barr arrives at 10. Exposure to pesticides living in orchards.

5) gut repairs and dietary adjustments that improve gut function seem to generate the biggest direct benefit to feeling better here....

6) why is my head now falling off my spine? 50 years later?
 

ljimbo423

Senior Member
Messages
2,749
Likes
6,687
Location
United States, New Hampshire
Re-evaluating my n= 1 personal theory here, with some of the newer info and contemplating collagen......

So this one paper simply confirms that collagen is involved in: the permeability of the gut..

https://www.ncbi.nlm.nih.gov/pubmed/28174772
I had seen the connection with collagen and gut permeability before but had completely forgotten about it. Very interesting considering how many of us have weak tendons and joints that often slip out of place. Maybe that has to do with weak collagen?


2) likely: my gut was not properly set up in the original first place. And some genetic predispositions. Chances are my mom was potentially laced with anti-biotics and I know she had IBS symptoms her whole life.
I think my mother might also have had many antibiotics before I was born and she also had IBS. Some people have not yet heard that we get inoculated with mothers microbiome when we pass through the birth canal.

If that microbiome is in a state of dysbiosis from antibiotics. We start life off with an unhealthy gut flora- dysbiosis.
 

Wishful

Senior Member
Messages
2,294
Likes
3,951
Now I think it's probably a combination of both mitochondrial dysfunction in the body and low grade brain inflammation that's causing most or all of the symptoms in ME/CFS.
I think you can ignore the mitochondrial dysfunction in the body. I don't seem to have any reduction in muscle function or endurance, so my body's mitochondria are probably functioning more or less normally. Others have said the same thing, so problems with the body's mitochondria aren't essential for ME. It's more likely a common secondary symptom.

It should be possible for the brain's mitochondria (specifically the microglial ones) to have genetic problems that don't affect the body's mitochondria. I think it's quite likely that my microglial mitochondria are malfunctioning. That may cause neuroinflammation or be caused by it; I don't know which is more likely.
 
Messages
3,990
Likes
9,770
So I believe that some environmental variable yet to be discovered is wreaking havoc on connective tissue and also suppressing immunity, to the extent that whatever initial infection people have as a trigger does more damage.
So (infection plus x) > collagen damage > brainstem compression > all ME/CFS symptoms.

Collagen Theories Here Continue: the Chinese TM acupuncture and meridian system:

in China, and elsewhere, they continue to examine this topic and develop theories for further evaluation and study....

Regarding Acupuncture Merideans: There is continued interest in pinning down the merideans, channels, Qi flow and looking for this anatomically. The paper below: raises a theoretical connection between the fascia, Primo Vascular System, and COLLAGEN.

"Fascia is an uninterrupted viscoelastic tissue which forms a functional 3-dimensional collagen matrix"..connecting all organs and muscles groups....

"Fascia is also capable of transmitting electrical signals throughout the body [9]. Collagen, which is one of the main components of fascia, has been shown to have semiconductive, piezoelectric, and photoconductive properties in vitro. Electronic currents could flow over greater distances. These electronic currents within fascia can be altered by external influences and cause a physiologic response in neighboring structures."

Chinese scientists have also identifed a Primo Vascular system (not blood, not lymph). This MAY be also involved in the acupuncture merideans. See article below. This vascular system is made up a collagen bundles.

https://www.sciencedirect.com/science/article/pii/S2005290113002082

So I am continuing to: talk to and empower Collagen to: beef up.
 

ljimbo423

Senior Member
Messages
2,749
Likes
6,687
Location
United States, New Hampshire
I think you can ignore the mitochondrial dysfunction in the body. I don't seem to have any reduction in muscle function or endurance, so my body's mitochondria are probably functioning more or less normally. Others have said the same thing, so problems with the body's mitochondria aren't essential for ME.
I think you are most likely right about that. Although I do feel like the mito. in the body play some role in some people, I just don't no how big or small a role that might be.

I think it's quite likely that my microglial mitochondria are malfunctioning.
I agree. I think some of the supplements that I take that have helped so much with my symptoms, are improving mitochondrial function in my brain. Lowering inflammation and therefore symptoms.
 

kday

Senior Member
Messages
366
Likes
334
My theory is based on evidence, genomics, toxigenomics, and my own personal research. Some old evidence is forgotten about, but it doesn't mean the evidence was wrong or bad.

I believe that ME/CFS is mainly caused by exposure to Organochlorine pesticides, mainly gamma-hexachlorocyclohexane (Lindane) and Hexachlorobenzene (HCB), but potentially other organochlorines. There may be subtypes (such as Gulf War Illness) that are exposed to high amounts of other organophosphates and organophoshphorous compounds, but I think these may be more rare. It's known that Lindane causes Multiple Chemical Sensitivity. Chlorpyrifos can do the same.

It's in scientific literature that organochlorine pesticides are twice as high in patients than controls, but the last study I know of is from 1996. This needs to be followed up on. The scientific CFS literature also showed that there are treatments that both reduce organochlorine loads as well as symptoms.

I believe the exposure to the substances causes a permanent CYP1B1 upregulation (negative feedback loop) that causes one to become sensitive to anything else that upregulates CYP1B1 (molds, pollution, perfumes, smoke, etc) and other CYP450 enzymes in a similar manner.

I believe the genetic predispositions for ME/CFS come from European or more specifically of Northwestern-european heritage.

I think the most common genetic predisposition for the immune breakdown may relate Caspase-8 function, but there may be others. In my own citizen scientist research, ME/CFS patients have a specific CASP8 variant that's prevalent in over 50% of patients while the global minor allele frequency is only around 9%. SNPs that impair calcium ion homeostasis can also make the immune dysfunction (especially Natural Killer cell function) worse.

The same chemical toxicants that upregulate CYP1B1 also upregulate CASP8. I think the CASP8 emzyme may be both upregulated and breaking somehow in regards to immune dysfunction, but I haven't been able to put these pieces together yet.

There are other risk factors and other enzymes involved that I haven't mentioned. MTHFR for example is a major risk factor. In my ME/CFS genomes sample pool, the minor allele frequency for MTHFR is almost 2.5x higher than controls. This doesn't mean it's causative, but definitely a risk factor.

But in summary, I think the cause of ME/CFS has already been discovered in the 90's and is very simple: Nerve agents such as organochlorines and potentially other similar compounds. I think ME/CFS is a specific type of toxic encephalopathy that causes general hypopituitarism. They actually thought of Chlorpyrifos as a causative agent all the way back in 1985. I think the couple times that we "discovered" retrovirus involvement in ME/CFS really got us chasing our tail.

Treatments for organochlorine poisoning include supplemental phosphatidylcholine, vitamin c, and binders like cholestyramine to prevent enterohepatic circulation and l. Olestra and Lipase inhibitors such as Orlistat might be an option to prevent enterohepatic recirculation of these lipid-soluble toxicants.

Immune breakdown, high titers, infections, etc exist. But I believe all of things things are secondary. But since we can measure the abnormalities of titers and the immune system, it's hard to shift our focus away from the viruses and infections.
 
Last edited: