What if ME is simply brain damage after encephalitis?

[silky]

To summarize so far, the general consensus seems to be

1. Some neurological impairment exists but that it is more likely to be mediated by ongoing activity of the immune system, chronic pathogens, and/or systemic hypometabolism and thus is different than classic post encephalitis.
2. Given remissions and recoveries, much of the damage, if there is in fact any, can be theoretically be reversed in many individuals
3. We are likely not talking about dead tissue. Instead it is likely impaired blood flow from inflammation
4. The numerous studies showing brain issues do not agree, do not show grievous injury, and have not been reproduced
5. There are some subsets whose onset followed classic encephalitis with more profound neurological symptoms, but even then remission and recovery are possible

This is comforting to be certain, and I thank everyone for participating in this discussion with so much enthusiasm, intelligence, and formidible knowledge

Can anyone answer some of the original points in the context of what's been summarized so far? Namely...

1. Why rest is so essential early on (as is true in brain injury)
2. Why children recover more frequently (also true in brain injury)
3. Why after a certain amount of years recovery is less likely (true again in brain injury)

Thanks!!!

 

[Mij]

Given remissions and recoveries, much of the damage can be theoretically be reversed in many individuals

Or, there wasn't any damage to begin with.

 

[silky]

Or, there wasn't any damage to begin with.

Yes I certainly hope so!

 

[alex3619]

Let me give an alternative view.

If the Norwegian research, and Ron Davis, are right about blood factors, the entire problem might be due to some kind of signal in the blood. We know the metabolic issues are to some extent determined by such a factor. The brain is very susceptible to low energy states, look at genetic mitochondrial disorders and heart failure. So its less to do with hypoperfusion than metabolic shutdown, though this hypothesis has yet to be proven. However any low metabolic demand might induce hypoperfusion as a response.

This signal has a large micron range, indicating its a protein. It might not be though ... other large molecules might be created by our body or by pathogens.

Our cells normalize in healthy blood serum. Healthy cells fail in ours. Again, this needs further verification.

The source of the signal is unknown. Brain immune responses might be responsible, as might responses from other essential organs like the heart. Or it could be an unidentified pathogen, such as a slow growing fungal infection. Or the pathogen could actually be in the gut, or it could be from dysbiosis ... the list of candidates is way too long.

My best guess is that with the right treatment we might start to recover in just hours. Full cure will take much longer, and include rehab.

We just don't know enough yet, but the research we are seeing now is very promising.

 

[jimells]

I am really interested in how you treated your POTS. Is it completely gone now?

And how did you draw the links between extracellular ATP, mast cells, and POTS?

I have wondered about mast cells but I do not have allergic reactions

I no longer have POTS crashes that send me to the Emergency Room, but I would not say that it is gone. Rather, it is now well-controlled. Just yesterday I had a mild episode a few hours after I ate a few peanuts. I don't want to believe that I can no longer eat them, so I had to try again - and confirmed that I do indeed react badly to them.

So after an hour of tachycardia on standing, elevated blood pressure, sweaty hands, etc. I took a small dose of trazodone (an effective adrenergic alpha blocker among other effects) and a small dose of atenolol to resolve the symptoms. I also resolved not to eat any more peanuts!

Three decades ago, long before ME became apparent, I suffered terribly from allergic rhinitis and asthma triggered by grass pollen, especially timothy. But that stopped by the mid 1990s. I've been sick with ME for 14 years, but it is only within the past year that I started developing itching, dry eyes & mouth, and trouble swallowing. So until recently I would not have said that I have allergic reactions.

It was the steadily-worsening itching that prompted me to try an anti-histamine, about the same time I stumbled over a letter in some journal that mentioned a possible role for mast cells in POTS and IBS.

The "missing link" in autoimmunity and autism: extracellular mitochondrial components secreted from activated live mast cells

We specifically showed that human mast cell degranulation and preformed TNF secretion in response to both allergic (IgE/anti-IgE) and non-allergic [substance P (SP)] triggers require mitochondrial fission and translocation to the cell surface.

We further showed that human mast cell degranulation is accompanied by secretion of mitochondrial DNA and ATP extracellularly without cell death. These mitochondrial components then stimulated human mast cells, keratinocytes, and primary human microvascular endothelial cells (HMVEC) to release inflammatory cytokines

The Afrin 2016 paper in my previous post includes a very long list of symptoms and the prevalence of those symptoms. Many of those symptoms would not generally be described as allergic reactions. Only about half of mast cell patients have hives, about a third experience flushing, which is a real problem, because without those hallmark symptoms it is nearly impossible to get a mast cell diagnosis or a referral to a mast cell specialist.

Here is one of the few papers that discuss ME and mast cells:
Chronic Fatigue Syndrome, Mast Cells, and Tricyclic Antidepressants

We hypothesize that corticotropin-releasing hormone (CRH) and other related peptides secreted by acute stress, activate diencephalic mast cells, either directly or through neurotensin (NT), leading to the release of proinflammatory cytokines that contribute to CFS pathogenesis.

Mast cells and their mediators have been implicated in diseases that are comorbid with CFS; in fact, there may be altered mast cell function in some tissues of CFS patients.

Mast cells can be activated by stress hormones, such as CRH, and neuropeptides, such as NT.

Mast cells are located perivascularly in close proximity to neurons in the thalamus and hypothalamus, especially diencephalon and the median eminence; there 50% of histamine derives from mast cells, whereas the rest is of neuronal origin.

 

[alex3619]

• Why rest is so essential early on (as is true in brain injury)

• Why children recover more frequently (also true in brain injury)

• Why after a certain amount of years recovery is less likely (true again in brain injury)

All three of these are associated with brain plasticity and its loss. If the brain has become substantially hypometabolic then this could be expected.

The low recovery rate after some years is tentatively hypothesized as due to the cytokine shift in classical ME patients at about three years. This is not the encephalitis survivor (ES) group. The ES group has stable cytokines.

The ES group has very slow onset, but it appears to be more relentless. Preliminary interpretations suggest its permanently ongoing, but so little is known this could very well be wrong. Its also not clear why a good percentage of ES are symptom free ... due to the nature of the survey in the UK it might be that they represent the longer term patients. Or not.

ES research appears to be where classical ME research was half a century ago. The good news is that there has been half a century's research into better medical technology since then. Its also likely that MS or even classical ME research may eventually lead to a clue for the ES group.

Again we can only speculate. The science is not advanced enough. However I think things are advancing fast enough we will likely start to see answers in the range of years, rather than decades as before.

 

[Mij]

My best guess is that with the right treatment we might start to recover in just hours.

I believe this could very well happen based on my experiences with this illness for the last 26 years.

 

[silky]

I believe this could very well happen based on my experiences with this illness for the last 26 years.

Interesting Mij! Do tell more

 

[Mij]

@silky it's such a long story to tell. The first 5-6 years of illness I had was is describe as PVFS, I was considered 'atypical' M.E by an M.E specialist. I slowly started to improve but still felt 'something' wasn't right. I feel that if I didn't push myself with aerobic exercise during that period of feeling 'better' which brought on PEM symptoms and take immune modulators (which caused a severe relapse) I may have gone into remission. That's the very short version. Who knows, maybe there is a 'switch' that's turned off at this point.

 

[silky]

Fascinating stuff Alex

If the Norwegian research, and Ron Davis, are right about blood factors, the entire problem might be due to some kind of signal in the blood.

This is my favorite theory and I love Ron Davis, Fluge, and Mella dearly.

I wonder though, is that blood factor the same for everyone? (For classic ME and ES?)

Or is there even a blood factor for everyone?

And do other conditions like traumatic brain injury and classical post encephalitis have a similar pathogenic blood factor?

I worry that there is an element of wishful thinking here (including my own).

All three of these are associated with brain plasticity and its loss. If the brain has become substantially hypometabolic then this could be expected.

Yes, so how do we contextualize that with Ron Davis' blood factor and a treatment that might work in hours?

The low recovery rate after some years is tentatively hypothesized as due to the cytokine shift in classical ME patients at about three years.

How might diminished cytokines thwart recovery?

The immune system gives up trying to self correct?

Or it's a knock on effect of deepening hypometabolism?

I suppose this could also be a red herring given that Hornig's cytokine study hasn't been replicated (to my limited knowledge)

 

[silky]

@Mij very interesting thank you for sharing, initially at what point did you slowly start to improve and did you have POTS / cognitive symptoms or was it more fatigue and immune symptoms?

 

[Mij]

@silky I would say I started to improve near the 5 year mark, up then back to baseline, then up a little more and more. Never had cognitive issues until I started aerobic exercise.

No POTS, but developed OI issues after the immune modulator relapse. Yes, I would say immune symptoms were and are what affect me the most.

 

[alex3619]

I wonder though, is that blood factor the same for everyone? (For classic ME and ES?)

Or is there even a blood factor for everyone?

And do other conditions like traumatic brain injury and classical post encephalitis have a similar pathogenic blood factor?

Ask me again in five years.

 

[charles shepherd]

What do you think contributes to the animals' recovery?



I really respect and admire Dr Naviaux and think his metabolic work is groundbreaking. But I don't see what solid evidence he has that a cell danger response exists other than the metabolic links he's drawn to c elegans. To me his theory seems to be one of many that could explain the symptoms. We know brain injury is real and can have systemic effects, we don't yet know if the cell danger response exists (at least that is my understanding). I would prefer that Dr Naviaux is right though, and that a drug like suramin could flip the switch and bring back everything including the brain.

I am really interested in how you treated your POTS. Is it completely gone now?

And how did you draw the links between extracellular ATP, mast cells, and POTS?

I have wondered about mast cells but I do not have allergic reactions



Point taken choice of language can certainly affect the qualitative course of discussion

Dr Shepherd, my understanding is that you yourself recovered from ME. Were your cognitive symptoms severe?

I have made a significant degree of improvement in relation to both physical capacity and cognitive capacity over many years

But I do still have ME - which was originally diagnosed by Dr Melvin Ramsay at the Royal Free Hospital

My overall condition still fluctuates and I have relapses from time to time, mostly related to acute infections

CS

 

[Woolie]

Just a couple of modifications.

To summarize so far, the general consensus seems to be

1. Some neurological impairment exists but that it is mediated by ongoing activity of the immune system, chronic pathogens, and/or systemic hypometabolism and thus is different than classic post encephalitis.

No, all we can say is that some cognitive impairment exists. That's not the same thing.

1. Given remissions and recoveries, much of the damage can be theoretically be reversed in many individuals

Then its not brain damage. Its something else. Much of the cognitive dysfunction can be reversed.

Can anyone answer some of the original points in the context of what's been summarized so far? Namely...

1. Why rest is so essential early on (as is true in brain injury)

Its no truer of brain injury than any other major illness. In fact, after a stroke, you want to get the person up and about ASAP.

1. Why children recover more frequently (also true in brain injury)

more, faster improvement in kids also true for just about anything.

1. Why after a certain amount of years recovery is less likely (true again in brain injury)

No, there's no real "recovery" from brain injury. There's some functional improvement as you learn to compensate for the cognitive loss, and possibly some neural reorganisation, particularly in younger folks. But no recovery. You're impaired for life.

 

[Woolie]

I suppose a good definition of cognitive would be useful. I can still reason, and retain much of the vast information I have read since being sick. I can also hold coherent conversations, plan, and visualize. And I can still do mental math

However I am very easily overwhelmed by emotion, or external stimuli. My memory is not as sharp or precise as it once was. And my mental stamina is greatly reduced. Multitasking also feels tortuous, and the speed at which I can think is much slower. Everything generally seems harder

What you describe sounds to me like the classic ME neuropsyc profile. Its awful. Many of people here say that their cognitive symptoms are the thing they find most debiltating.

"cognitive" = thinking, remembering, identifying, perceiving, making decisions, solving problems, calculating, orienting, attending, navigating in the world. Its bigger than thinking, as it also covers all that stuff that goes on without our awareness (identifying what a visual object is, orienting towards a stimulus that might be important).

 

[silky]

@Woolie yes it's quite unpleasant. I am grateful that it's not worse as I can still identify objects, navigate, and even drive for up to an hour on better days

Not to beat a dead horse but the neurological symptoms I described would not imply brain damage right?

As you can see another symptom of mine is anxiety and worry

 

[Woolie]

Not to beat a dead horse but the neurological symptoms I described would not imply brain damage right?

No. They will probably diminish when your condition improves.

And it will. We don't know when, how much or for how long. But variability is at the core of ME. I'm pretty sure every one of us has had periods where our symptoms have seemed to lessen, and our cognitive problems eased. For some, this might be a good day here or there, for others, it may ve a decade or even more.

 

[Woolie]

As you can see another symptom of mine is anxiety and worry

PS you would be weird if you weren't worried. I was totally freaking out in the first year.

 

[silky]

Thanks @Woolie I appreciate the kind words and encouragement!!

If there is an issue with brain hypoxia do you think there's any benefit in using an oxygen concentrator for 30 minutes twice a day?

I read that some have maintained recovery using this method