Is your Hypothalamus up the creek?

[andyguitar]

Here's an idea to ponder....... ME/CFS is caused by dysfunction of the Hypothalamus. Nothing else.

 

[Pyrrhus]

Dysfunction of the hypothalamus has been implicated by a number of studies. But that is only one part of the subcortical brain that has been similarly implicated by a number of studies.

John Richardson was the researcher who first championed the idea of a dysfunction in the hypothalamus:
https://me-pedia.org/wiki/John_Richardson

For the other parts of the subcortical brain that have been implicated by studies, see:
https://forums.phoenixrising.me/thr...e-subcortical-brain.80923/page-2#post-2291789

ETA:

Here's a 2013 review of research into the Hypothalamic-Pituitary-Adrenal Axis in ME/cfs by Cara Tomas, Julia Newton, and Stuart Watson:
A Review of Hypothalamic-Pituitary-Adrenal Axis Function in Chronic Fatigue Syndrome (Tomas, Newton, & Watson, 2013)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045534/

A paper on Warren Tate's theory on the paraventricular nucleus of the hypothalamus:
A compromised paraventricular nucleus within a dysfunctional hypothalamus: A novel neuroinflammatory paradigm for ME/CFS (Mackay and Tate, 2018)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291860/
Discussion:
https://forums.phoenixrising.me/thr...-and-limbic-system-theory.62675/#post-1021106


More discussions might be found in our "Hormones: Hypothalamus/Pituitary/Adrenal (HPA) Axis, etc." forum:
https://forums.phoenixrising.me/forums/hormones.96/

 

[andyguitar]

Yeah thanks for the tip @Pyrrhus it's been a while scince I had a look at the Hypothalamus. I'm thinking along the lines that, although other areas of the brain have shown abnormalities, they are secondary. Hypothalamus being the the primary site. Also the "Neuroinflammation" that has been suggested by some studies, ie Jared Younger, is not inflammation at all. Just temperature abnormalities, thats all. And that those abnormalities are caused by Hypothalamus dysfunction. Not a pathogen or metabolic disorder.

 

[Rufous McKinney]

is not inflammation at all. Just temperature abnormalities, thats all.

since molecules that are warmer, vibrate more...they take up more space, therefore we'd call that inflammed. And so the tissue is a bit swollen if its one degree hotter- its seems to me.

so I don't understand how one can say- the tissue is not inflamed when its temperature is higher.

 

[Pyrrhus]

Also the "Neuroinflammation" that has been suggested by some studies, ie Jared Younger, is not inflammation at all. Just temperature abnormalities, thats all.

Quite true. Unfortunately some researchers use the term "neuroinflammation" as if it were a synonym for "neurological inflammation", which is not at all what the 2004 definition intended.

If you're interested in hearing about real neuroinflammation, see this post:
https://forums.phoenixrising.me/thr...n-in-me-subcortical-brain.80923/#post-2289868

Hope this helps.

 

[Pyrrhus]

since molecules that are warmer, vibrate more...they take up more space, therefore we'd call that inflammed. And so the tissue is a bit swollen if its one degree hotter- its seems to me.

so I don't understand how one can say- the tissue is not inflamed when its temperature is higher.

You're talking about classical (Greco-Roman) inflammation, not neuroinflammation. Don't worry, you're not the only one confused! Even some scientists are similarly confused.

In classical inflammation, an inflamed tissue swells up because of an influx of blood-borne immune cells and the fluid that transports them. The inflamed tissue feels hotter to the touch because of this flow of blood from the interior of the body to the inflamed tissue. The tissue also feels hotter because of the increased metabolism of inflammation. (increased metabolism generates heat)

Hope this helps.

 

[andyguitar]

so I don't understand how one can say- the tissue is not inflamed when its temperature is higher.

Yep take your point. But if you were out in the sun and your skin warmed up a bit that would'nt mean it had got inflammed. If you got sunburn it would. So a rise in tissue temperature does not equal inflammation. Depends how high the rise is. Two other points I should drop in. If it was inflammation in the brain how come anti-inflammatories are of little or no help? And if there was a state of chronic inflammation that lasted years (and in some cases decades) how could anyone recover and not sustain lasting brain damage?

 

[Pyrrhus]

The tissue also feels hotter because of the increased metabolism of inflammation.

Of course, true neuroinflammation also increases metabolism, so a slightly increased temperature is perfectly compatible with true neuroinflammation as well.

 

[Pyrrhus]

So a rise in tissue temperature does not equal inflammation.

Quite true.

If it was inflammation in the brain how come anti-inflammatories are of little or no help? And if there was a state of chronic inflammation that lasted years (and in some cases decades) how could anyone recover and not sustain lasting brain damage?

Most anti-inflammatories are designed for classical inflammation, not for neuroinflammation. And some patients do indeed report some help from anti-inflammatories:
https://forums.phoenixrising.me/thr...hort-term-but-may-not-in-the-long-term.80492/

Note that neuroinflammation can last for years without permanent brain damage. This is because evolution has provided protections against such brain damage, such as:

• The nerve cells in the brain can not easily be phagocytosed by macrophages, as easily happens in other tissues.
• Nerve cells are intrinsically resistant to apoptosis.
• The tissue-resident macrophages in the brain work primarily by secreting cytokines that stimulate the interferon pathway inside nerve cells, which is a message to the nerve cell saying "You've got a problem, nerve cell, time to activate your internal intracellular defenses."

If you think about it, there's a very good reason why evolution discourages inflammatory tissue damage in the brain, but allows it in other tissues. You simply can not regenerate nerve cells like you can regenerate other types of cells. If evolution allowed nerve cells to be destroyed and regenerated so easily, you would continuously be losing the memories stored in those nerve cell connections.

Hope this helps.

 

[ljimbo423]

And if there was a state of chronic inflammation that lasted years (and in some cases decades) how could anyone recover and not sustain lasting brain damage?

I think @Pyrrhus is right about the brain not getting damaged from low grade neuro-inflammation. This might not be a good example but it's the only one I have at present.

I have non-allergic rhinitis and have for years. The inside of my nose is almost constantly inflamed and use to bleed very easily from me wiping my nose. But there isn't any scar tissue that I can see.

Maybe it depends on the degree of inflammation as to weather or not there is permanent damage in the brain. It's seems like at some point though, if the inflammation was high enough long enough, there would be brain damage.

But that's not the kind of brain inflammation that's found in ME/CFS, I don't think.

 

[JES]

Quite true. Unfortunately some researchers use the term "neuroinflammation" as if it were a synonym for "neurological inflammation", which is not at all what the 2004 definition intended.

If you're interested in hearing about real neuroinflammation, see this post:
https://forums.phoenixrising.me/thr...n-in-me-subcortical-brain.80923/#post-2289868

Hope this helps.

That's a good explanation, I tend to just use microglial activation, even though both the terms inflammation and microglia can confuse people. And yeah, these processes can go on for years or decades until you'll start to notice the damage. Diseases like e.g. Alzheimer's or Parkinson's have been associated with neuroinflammation, but I have seen evidence that suggests the processes that resulted in e.g. Alzheimer's started many years before the actual disease was clinically observable.

The million dollar question is if this neuroinflammation is somehow self-fueling or if it's a protective mechanism of the brain against a greater threat, like a pathogen. I'm not convinced either way, as I found very little benefit with anti-inflammatory medications and supplements and even the ones that initially yielded results stopped working at some point in time. To me that may point towards the suspicion that treating neuroinflammation itself might unfortunately not lead us very far.

 

[Gingergrrl]

@Pyrrhus and all the other wise people in this thread...

I have a question, where does “hypophysitis” (inflammation of the pituitary) fit in with this topic? Is it considered temporary neuroinflammation that does not cause permanent damage to the brain or to the endocrine system (meaning to the hormones that are regulated by the pituitary like ACTH, TSH, etc). Thanks!

 

[andyguitar]

And some patients do indeed report some help from anti-inflammatories:

But the benefits dont seem to last. Which suggests to me that the benefit is from the placebo response.

To me that may point towards the suspicion that treating neuroinflammation itself might unfortunately not lead us very far.

Particularly if there is no neuroinflammation to treat. Just temperature abnormalities. Which is not to say that those abnormalities cant cause symptoms. It's more a case of how they cause symptoms and what to do about it.

 

[Pyrrhus]

The million dollar question is if this neuroinflammation is somehow self-fueling or if it's a protective mechanism of the brain against a greater threat, like a pathogen.

You're absolutely right. The million dollar question is:
"What is the cause of the neuroinflammation?"

Causes could include:

• Autoimmunity
• Metabolic problems, as seen in ischemia
• Pathogens
• Something else entirely

To me that may point towards the suspicion that treating neuroinflammation itself might unfortunately not lead us very far.

That may well be.

 

[Pyrrhus]

I have a question, where does “hypophysitis” (inflammation of the pituitary) fit in with this topic? Is it considered temporary neuroinflammation that does not cause permanent damage to the brain or to the endocrine system (meaning to the hormones that are regulated by the pituitary like ACTH, TSH, etc). Thanks!

The pituitary gland, also known as the hypophysis, is a neuroendocrine gland. This means it is directly connected to the brain, but it is not part of the brain. So it is not protected by the blood-brain barrier, and is probably subject to inflammatory damage, but may be able to regenerate itself somewhat.

However, anyone who has been diagnosed with an "empty sella" on a brain MRI, indicating a shrunken pituitary gland, knows that it doesn't regenerate itself that fast...

Hope this helps.

 

[Gingergrrl]

The pituitary gland, also known as the hypophysis, is a neuroendocrine gland. This means it is directly connected to the brain, but it is not part of the brain. So it is not protected by the blood-brain barrier, and is probably subject to inflammatory damage, but may be able to regenerate itself somewhat.

Wow, I did not know that the pituitary gland was also called the hypophysis! That makes so much more sense now!

So the pituitary is not actually part of the brain? I knew it was an endocrine gland but I thought it was considered part of the brain?! Does this mean that pituitary inflammation would be like inflammation anywhere else in the body versus neuroinflammation?

However, anyone who has been diagnosed with an "empty sella" on a brain MRI, indicating a shrunken pituitary gland, knows that it doesn't regenerate itself that fast...

Would hypophysitis (pituitary inflammation) be like the opposite of “empty sella”?

Hope this helps

Yes, definitely! Thank you so much.

 

[Wolfcub]

Yes I think my Hypothalamus is up the creek. I just don't know what it has taken with it on its journey over the river Styx

I'm only up to the Anterior Hypothalamus at the moment. It's a fascinating piece of engineering with so many cogs and wheels:
https://www.sciencedirect.com/topics/medicine-and-dentistry/anterior-hypothalamus

Then there's the posterior.....

More or less everything on the anterior Hypothalamus list is up the creek with me

 

[Rufous McKinney]

Particularly if there is no neuroinflammation to treat. Just temperature abnormalities. Which is not to say that those abnormalities cant cause symptoms. It's more a case of how they cause symptoms and what to do about it.

Interesting discussion... and I think I am simply arguing that if tissue has a higher temperature...that tissue will expand- due the direct effect of heat on molecules.

Basic: this-

"What does heat do to a molecule?
When heat is added to a substance, the molecules and atoms vibrate faster. As atoms vibrate faster, the space between atoms increases. The motion and spacing of the particles determines the state of matter of the substance. The end result of increased molecular motion is that the object expands and takes up more space."

I"m arguing there is an expansion and I"m calling that inflammation. But maybe there is no expansion. It just seems like there would be. Neuroinflammation- maybe thats something else I"m not referring to.

I get angiodema-type symptoms in all the tissue thats near by central brain. But maybe "edema"...an increase in fluid- which is that type of swelling- cannot happen in the brain tissue. But in me, it feels like that is whats happening.

 

[Gingergrrl]

I get angiodema-type symptoms in all the tissue thats near by central brain.

Do you mean that you had an MRI of your brain that showed inflammation in the central part of your brain? I apologize if you explained this elsewhere and I missed it! (I might be having an MRI of my pituitary in the future and am in the process of putting some information together).

 

[Marylib]

@Pyrrhus Thanks for your explanations of what are, to me, very complicated things. Thinking about classic inflammation (heat, swollen tissues) is this why the structural issues, such as cranio cervical instability and lax ligaments might make sense in some cases? I keep thinking that an obstruction to the normal pathways to clear the byproducts of inflammation might keep that whole process going if the infection does its thing in the brain. But I am thinking of a very simple structure, such as when you blow up a balloon and then try to let the air out via a collapsed "neck" of the end of the balloon. There's a glymphatic system, from what I read.