What if ME is simply brain damage after encephalitis?

[w john martin]

I think if that were the case, after 27 years, I wouldn't stlll be in a job. And there would be no patient-researchers.

In all seriousness, though, there's quite a variable range of blood perfusion within normal. You don't get brain damage from falling asleep, do you? Even though blood perfusion to most regions drops massively.

I have never heard of "sleeping" neurons. They're either active or they're not. If you have a stroke, they're dead, but you can't wake them up again, alas.

Dear Woolie,
Neurons and neurosensory cells initially become hyper-excitable in response to insufficient cellular energy (ICE). This can be followed by neuronal cell quiescence in which cells remain viable but without sufficient energy to perform more specialized cellular functions. Both conditions are potentially correctable with an additional input of cellular energy.

 

[alex3619]

I have to read the entire thread, I only just started, but let me say that I have been discussing this hypothesis, in a slightly different form, for a few months on these forums.

It is fairly clear that while there may be low grade diffuse inflammation of the brain, CFS or ME are not, in their entirety, encephalitis.

What is clear though is that there is a subset, tentatively labelled as Atypical (as opposed to Classical) ME/CFS. This subset consists of encephalitis survivors and a few exotic diseases. This is based on cytokine profiles, and is really really new data ... from earlier this year.

That point on recovery is important. We (and I had measles encephalitis 49 years ago) "recovered" from encephalitis.

Now, based on old and generalized data (its different now with better treatments for a few patient subsets with encephalitis) the death rate was about fifty percent. Twenty five percent had severe brain damage. The remaining twenty five percent were deemed recovered and not followed up.

Now we have a large survey, in the UK, of encephalitis survivors. It was based on membership of an encephalitis survivors group, so it has biases. However it showed the majority have a checklist of symptoms very much like ME.

My suspicion is there is some kind of neuroimmune problem after encephalitis, subtle enough that it manifests years later.

I very much doubt that encephalitis explains most ME or CFS cases. Its unlikely. I do think it is the primary causative trigger in a large minority of cases, pending further data.

 

[halcyon]

I'm sorry to hear that but I hope it's not true. Maybe future stem cell treatment or artificial brain cells can restore it. I don't have vestibulitis but I do have POTS, do you think that's in the same category?

I have POTS as well. I'm on the fence about that one. My experience is that the severity of it can slightly fluctuate along with other symptoms, which makes me think it's functional. But it also never goes away entirely which makes me think it's permanent damage.

 

[halcyon]

What is clear though is that there is a subset, tentatively labelled as Atypical (as opposed to Classical) ME/CFS. This subset consists of encephalitis survivors and a few exotic diseases. This is based on cytokine profiles, and is really really new data ... from earlier this year.

As I mentioned upthread, Peterson's classical ME patients had elevated interferon alpha in their CSF, which is consistent with viral meningoencephalitis.

 

[alex3619]

Do you think the brain changes imply a permanent damage or something that can go back to normal?

My tentative reasoning is this. If I have atypical ME, and its due to being an encephalitis survivor, then the fact that I have had many very short remissions, usually sudden and lasting about six hours, indicates the problem is dynamic. Something maintains it. That means that, in theory, its curable or at least treatable.

 

[Woolie]

Hmm what is the name of the state you would say they're in if they're not getting enough blood? At what point does not enough blood equal neuron death? And would that then show up on an MRI?

It pretty much needs complete and fairly sustained obstruction of the capilliaries serving that bit of tissue. Like an ischaemic stroke or heart attack. Or some other factor that cuts the blood supply off completely. Major blood loss could do it, like losing a limb and having it bleed out untreated.

People can have what's called vascular dementia, which is a series of small strokes. Each one can go unrecognised but their sum effect is to slowly reduce cognitive ability, so the outward effect is dementia-like. You can see it pretty easily on an MRI scan, though, as lots of little black spots. So not us, that one.

There's such a thing as hypoxia, which is sometimes seen in suicide attempts involving the car exhaust method. The blood supply remains in place, but the blood is no longer delivering oxygen to the neural tissue. That tissue is lost for ever. Some areas of the brain are more vulnerable than others, so there is a very characteristic neuropsychological profile to it, which isn't at all like MECFS.

Of course, some neurons also die every day in everybody, but its unclear whether we lose any more than anyone else by this sort of attrition. If we lost a lot, it would be evident on scans as a major shrinking of our brain volume. That would be a thousand times more marked than the tiny and unreliable volume losses that have been reported in the literature. And then we would certainly no longer be in this limbo where no-one believes us.

I think PwMEs are pretty vulnerable to cardiovascular disease in general, and I worry about whether this could be a major life shortener for us. The incidence of death due to CV disease (e.g., heart attack, stroke), is undocumented in CFS. Lots of us have tachycardia.

 

[alex3619]

This can be followed by neuronal cell quiescence in which cells remain viable but without sufficient energy to perform more specialized cellular functions. Both conditions are potentially correctable with an additional input of cellular energy.

This is my current leading hypothesis. I would add the caveat though that this appears to be largely maintained by some factor or factors. In other words its dynamic. Whatever is causing that maintenance may be static, but the process itself is dynamic. I also suspect that the core maintaining problem/s may be different in different subgroups.

 

[alex3619]

The incidence of death due to CV disease (e.g., heart attack, stroke), is undocumented in CFS.

This is correct. However a local ME doctor, John Whiting, who I have talked to a few times, has observed that heart attacks are super rare in us, and every patient who he had seen who had a heart attack (at that time, more than a decade ago I think) was a smoker. He may have changed his views since, but I am not aware of this.

What appears to be likely from my reading of the literature is that this is correct. We get very few heart attacks. I see very little evidence of strokes either. What we get is heart valve failure, and most importantly we get diastolic heart failure. So we do get a lot of CVD, just not the typical population profile. Some percentage of us are also found to have viral heart infections, though this is usually on autopsy.

Jason has also identified, twice, that CVD is still a major cause of death in us, though with caveats because his surveys may have intrinsic biases. The leading three causes of death seem to be suicide, cancer (with increased lymphoma rates) and CVD, often diastolic heart failure (which is otherwise thought to be rare).

 

[silky]

Both conditions are potentially correctable with an additional input of cellular energy.

Paging Dr Davis! Paging Dr Naviaux!

This is based on cytokine profiles, and is really really new data ... from earlier this year.

Were there any cytokines that stood out?

That point on recovery is important. We (and I had measles encephalitis 49 years ago) "recovered" from encephalitis.

How long was the lag between your encephalitis recovery and ME onset?

I very much doubt that encephalitis explains most ME or CFS cases. Its unlikely. I do think it is the primary causative trigger in a large minority of cases, pending further data.

What do you make of the notion that there can be lower grade encephalacies that present as a severe flu?

But it also never goes away entirely which makes me think it's permanent damage.

Hmm, perhaps the right meds (better beta blockers) will be able to work around this issue

My tentative reasoning is this. If I have atypical ME, and its due to being an encephalitis survivor, then the fact that I have had many very short remissions, usually sudden and lasting about six hours, indicates the problem is dynamic. Something maintains it. That means that, in theory, its curable or at least treatable.

Wow how total are your remissions? It's amazing brain function would be restored so quickly

There's such a thing as hypoxia, which is sometimes seen in suicide attempts involving the car exhaust method. The blood supply remains in place, but the blood is no longer delivering oxygen to the neural tissue. That tissue is lost for ever.

But that would show up on an MRI right?

Whatever is causing that maintenance may be static, but the process itself is dynamic.

So in that case the static condition could be something like primed microglia, autoantibodies, or a dauer state rather than dead neurons?

 

[alex3619]

Were there any cytokines that stood out?

This was the Lipkin et. al. study. They had a specific cytokine profile for this subgroup. I do not recall the cytokines offhand.

 

[Woolie]

But that would show up on an MRI right?

It can be quite diffuse, you might need something more dynamic to show it really clearly. Like fMRI or SPECT.

But the profile, its things like severe amnesia, and visual agnosia. That's not really consistent with what we see in MECFS.

 

[heapsreal]

I have posted about this before but consider looking into mollarets meningitis, a chronic reoccurring infectious cause of meningitis which is most commonly associated with herpes 1 and 2 as well as varicella/shingles virus. Its quite possible to also have other infections involved such as ebv, cmv, entroviruses as well as other stealth pathogens as dr martin has suggested. Also i believe may be related to dr lerners work also.

There is significant overlap between mollarets meningitis and cfsme, although mollarets is diagnosed after a spinal tap and herpes 1, 2 or varicella are found. It can take several occassions and spinal taps before it is diagnosed.

Interesting watching Dr Chia on a utube video mention his theory of ME being from an enterovirus but also that has seen a smaller percentage of cases of ME that he believes were from varicella virus. I wonder if those cases he saw of varicella could also be diagnosed as mollarets meningitis too. I also recall dr chia in another video mentioning thats its not uncommon for drs to misdiagnose chickenpox or shingles rash with enteroviruses and vice versa.

Then Sophia Merza who's cause of death on an autopsy as ME was said to have had shingles 'type' lesions on her spinal cord. Possibly be varicella or enteroviruses or some other virus??

 

[alex3619]

How long was the lag between your encephalitis recovery and ME onset?

Its very hard to say. I had unidentified fatigue after about eight years. After about sixteen years I had fatigue bad enough to cause me to lose my job. At about nineteen years many other ME symptoms had kicked in. At about twenty one years I was diagnosed with CFS, using the Holmes criteria, though I was not sudden onset. At about this time I was again forced out of work. At about twenty five years I moved from mild to moderate symptoms, then kept moving toward severe, but this fluctuates enough that I consider myself at the severe end of moderate.

At about thirty years I started showing severe OI, in my case probably neurally mediated hypotension (complicated by baseline high bp), resulting in passing out and collapses, often on stairs. My version of OI can result in the heart stopping.

 

[kangaSue]

It pretty much needs complete and fairly sustained obstruction of the capilliaries serving that bit of tissue. Like an ischaemic stroke or heart attack. Or some other factor that cuts the blood supply off completely. Major blood loss could do it, like losing a limb and having it bleed out untreated.

Or something that causes systemic vasculitis.
http://www.meactionuk.org.uk/systemic-vasculitis-and-myalgic-encephalomyelitis.htm

 

[alex3619]

Wow how total are your remissions? It's amazing brain function would be restored so quickly

Not just brain function. Complete remission. I usually don't notice for an hour or two. I don't feel hyper, just fine, or normal. Then I notice. Then it goes away.

On one occasion I went from struggling with basic math to doing most of it in my head and being able to use a calculator without a struggle. (I was studying first year physical chemistry at the time, at uni.) On another occasion my reading speed went hyper, I was able to read book length material in minutes. (Let me add that I was a speed reader, but my regular speed with ME is super slow.) On another occasion I was suddenly able to walk, and run over a mile, without consequences. Basically whatever I am trying to do at the time becomes normal. They never lasted long enough for me to really test the full range of improvement.

These remissions ended about a decade ago. I have had improvements, but no longer get spontaneous remissions. However my severity became worse in about 2005. and I started declining again more than five years ago. In the last several weeks I have showed signs of improving again, though my old muscle pains have now all returned.

 

[alex3619]

Or something that causes systemic vasculitis.
http://www.meactionuk.org.uk/systemic-vasculitis-and-myalgic-encephalomyelitis.htm

Or something that interferes with vascular regulation, such as hormones, metabolic shifts, neuropathy or cytokines.

 

[silky]

It can be quite diffuse, you might need something more dynamic to show it really clearly. Like fMRI or SPECT.

But the profile, its things like severe amnesia, and visual agnosia. That's not really consistent with what we see in MECFS.

Might the symptoms more closely resemble ME if it just affected the midbrain?

 

[silky]

I'd also like to introduce the concept of primed microglia into this discussion. How does this fit in alongside potential hypoxia, immune cuffing, autoantibodies in the brain, CNS cytokines, or virally induced cellular damage.

Would really love to hear @Jonathan Edwards thoughts on this as well

 

[Hip]

What were your ME symptoms like?

Pretty classic ME/CFS symptoms that satisfy the Canadian consensus criteria. I have brain fog (and all that entails), fatigue, unrefreshing sleep, sleep cycle inversion (awake at night, asleep in the day), the need to sleep 10 hours each day otherwise I can't function mentally, POTS, sound sensitivity, emotional flattening, emotional sensitivity to social discord or stressful situations, irritability, chronic sore throat, recurrent occasional headaches swollen lymph nodes, occasional chest pains, anxiety, depression, crimson crescents, dry mouth, blurred vision, irritable bowel, cold hands and feet.

Although what's unusual is that I don't seem to suffer from physical exercise induced PEM, although I do get a lot of mental exertion PEM, especially from the excitement and energy used up when socializing with people. I also developed some very nasty mental symptoms from my virus, which in many ways are worse than the ME/CFS.

How has your cognition and personality changed?

It's was a strange thing, but my brain infection seemed to instantly sever the link between my intellectual, reasoning brain and my emotional brain. Usually human beings respond both intellectually and emotionally to situations, and there is constant interplay and give-and-take between the emotional and reasoning mind. But the brain infection seemed to cut connection between the two; I literally felt this happen as the virus infected my brain. I am guessing the virus must have infected a part of the brain tasked with emotional processing.

In a strange way, it initially felt liberating, as my reasoning mind suddenly became free of the constraints and pressures placed on it by the emotional mind. I was not aware of these constraints and pressures until they were suddenly severed away! But of course it is not good to have a mind that is unconnected from its emotions.

In addition, I lost faculties in the areas of facial recognition, recognition of facial emotions in others, and in my empathetic skills. I regained the facial recognition and the recognition of facial emotions after some time, but sadly the empathetic skills remain permanently diminished.

On the cognitive side, the brain infection caused severe ADHD/ADD symptoms, such that for years I was barely able to read anything. Even a short 5 sentence email was very difficult for me to read. My whole brain was just scrambled. This is separate issue to brain fog. That ADHD/ADD slowly improved though, in the 12 years since my brain infection.

And do you think if you got the right antiviral or immunemodulator your neurological symptoms might improve?

I read that chronic brain inflammation impedes brain repair after any brain injury (such as traumatic brain injury), which is unfortunate because usually brain injury triggers neuroinflammation. So it is possible that because I descended into ME/CFS after my brain infection, the chronic neuroinflammation of ME/CFS may have hampered my brain's attempts to heal itself.

A while ago I came across an account of very high dose fish oils (18 grams of DHA and EPA a day) helping to repair non-healing traumatic brain injuries, as these high doses have potent anti-inflammatory effects in the brain, as well as of course providing the essential fatty acid substrates needed by the brain.

So a few years ago I decided to try this myself (though at a slightly lower dose), but I noticed no benefits. However, more recently I read about pure EPA fish oil with little or no DHA (such as VegEPA), and tried this out at doses of around 4500 mg of EPA daily. After a few months, I noticed some improvements in my ADHD, which might be an indication of some brain healing; or it might just be because VegEPA has been shown to improve ADHD in clinical trials.

 

[A.B.]

If the Rituximab results are confirmed then about 50%, possibly more, have a B cell dependent autoimmune disease. The patients were recruited from neurologists and met the CCC criteria (I hope I remember this right). This autoimmune disease seems to mess up energy metabolism.