Invest in ME Conference 12: First Class in Every Way
OverTheHills wraps up our series of articles on this year's 12th Invest in ME International Conference (IIMEC12) in London with some reflections on her experience as a patient attending the conference for the first time.
Discuss the article on the Forums.

What if ME is simply brain damage after encephalitis?

Discussion in 'General ME/CFS Discussion' started by silky, Jul 22, 2017.

  1. silky

    silky a gentle soul here to learn

    Messages:
    95
    Likes:
    185
    Orange County, California
    I've been reading a lot since I've been sick and this makes the most sense to me. I don't want it to be true since it's very scary, but it seems to be the simplest explanation (Occam's razor).

    I wouldn't make such a claim without well reasoned points so bare with me. And please show me why I'm wrong because I really don't want this to be true.

    By the way I'm talking about just post infectious cases not others that get lumped in because they have similar symptoms.
    1. It seems like there are several of the same viruses involved that attack the brain (herpes, enteroviruses) that cause ME and other more recognized encephalitis cases
    2. Rest is important to recovery early on because the brain needs rest to heal before the stem cells die. I think this is true in stroke and concussion
    3. Most adults don't fully recover after a couple years because adult brains don't heal after a certain amount of time. This is not seen in children and they seem to recover more often
    4. Damage to a specific part of the brain (middle and brain stem) would explain all the numerous symptoms and systems affected including the hormone, immune, and metabolic abnormalities
    5. Infections, inflammation, and autoimmunity can be involved and improving those issues can cause varying levels of symptom improvement. But they are almost never completely curative due to the permanent brain damage
    6. People can get permanently worse when they exert because they put more strain on already overtaxed braincells causing them to give out like in post polio. Or they get worse after a new virus because the virus goes to the brain and does more damage.
    7. The ME brain research from Stanford and Japan showing big brain problems
    If all this is true, then maybe the only possible future total cure stem cells or genetic modification.

    That's scary because maybe all these researches are not looking in the right place by looking at all the "down river" effects of brain damage or the viruses that cause the damage.

    Just my rambling thoughts. Hopefully the many people on here smarter than me can tell me why I'm wrong!

    - Sarah
     
    ErdemX, Sancar, Abha and 6 others like this.
  2. w john martin

    w john martin

    Messages:
    19
    Likes:
    50
    Dear Sarah,
    CFS fits within a broad spectrum of symptomatic illnesses caused by persisting virus infections. The infections persist because the viruses have lost or mutated the genes coding for the major virus components normally targeted by the cellular immune system. The body has an alternative cellular energy (ACE) pathway to suppress these "stealth adapted" viruses. Public Health acceptance of stealth adapted viruses has not been forthcoming, primarily because some of the viruses originated from monkey cytomegaloviruses as contaminants of polio vaccines. Overcoming this barrier will help facilitate clinical testing of methods for enhancing the ACE pathway. Public Health authorities are likely to be more supportive of these endeavors if the CFS communities discuss stealth adapted viruses.
     
    heapsreal likes this.
  3. aaron_c

    aaron_c Senior Member

    Messages:
    642
    Likes:
    1,000
    Hi Sarah

    Nice thought process! I know enough to ask questions of your theory but not necessarily to answer them. So here's my thoughts as to why vanilla "brain damage" probably (and hopefully) isn't the whole story:

    1. For most of us, our symptoms fluctuate even in the absence of exertion or PEM. Some days (or months) I can think better or walk farther, and some days things are worse. On a related note a not-insignificant portion of us experience gradual onset. If your theory covers these patients I think it would need to explain how an initial infection could cause brain damage with symptom severity that looks like a roller-coaster. Do you think this brain damage theory accounts for this? Personally (and inexpertly) I think that mechanisms linked to the immune system tend to explain this variation more convincingly.

    3. The Stanford MRI study mostly found problems with white matter--the myelinated axons, not the neuronal "bodies." Happily, I think this kind of "brain damage" is more reparable, and likely shows up as a byproduct of chronic inflammation.

    4. Rituximab seems pretty promising as a treatment that can cause significant improvements (back to school, work, et). We are of course waiting for the results of the current Norway trial, but assuming they cure a decent percentage of the patients, how does that fit into the brain damage thing? And at least in one case study (or more? sorry but my brain isn't up to looking things up right now, I'm going off of memory) Rituximab recovery persisted even after the b-cells had grown back. If the problem was just brain damage that caused the brain to problematically activate b-cells, wouldn't we expect their problems to return with the b-cells?

    Even my the highest hopes for Rituximab only imagine it curing maybe 2/3 of us--which still leaves at least 1/3 of us with some other problem.

    5. Spontaneous Recovery, or Just Temporary Improvement: It happens. Recovery might be rare once the person has been sick for more than a few months, but temporary improvement is not uncommon. Granted, it might just be that there is a subgroup where the cause is some sort of current environmental exposure (mold has been getting a lot of attention in this light) or maybe even psychological, and that this subgroup is the one responsible for these improvements.
     
    Abha, AndyPR, Mel9 and 1 other person like this.
  4. svetoslav80

    svetoslav80 svetoslav80 at gmail.com

    Messages:
    694
    Likes:
    821
    Bulgaria
    Unlike CFS onset, I think there's always fever present with encephalitis.
     
  5. silky

    silky a gentle soul here to learn

    Messages:
    95
    Likes:
    185
    Orange County, California
    Hi @aaron_c! Some great points!

    Let's see if I can take a crack at these :)

    Hmm. My guess would be that there's a continuum between levels of brain damage and the maladaptive immune response that varies with each person. So those with less permanent damage and more immune activity would tend to see wider ranges of fluctuation. The variations in immune activity could have any number of causes.

    My thought is that gradual onset without an infectious trigger is a different disease and perhaps more immune or hormone modulated. Of course there could be a blurring of the two when onset is staggered. Maybe there's a sort of pre-ME stage that is purely metabolic or hormonal that sets the stage for the infectious triggered brain damage and symptoms like POTS.

    That's great! I didn't realize that :)

    I do worry about other studies that have shown grey matter changes, but I can't recall them right now to add sources

    Yes the Rituximab responses encourage me, but (and it seems like there's always a but) the stories I've read here and other places of people who tried Rituximab in America are always disappointing. In fact I don't think I I've seen one positive one where the person didn't have another autoimmune condition. You hear more positive stories about LDN or b12. Makes me wonder if something is unique about Norway or the patients in the studies there.

    Yes remission could be misdiagnosis or subsets or... neural sprouting. The neurons eventually form new connections, and recovery takes place, but like in post polio wear and tear eventually exhausts the overburdened neurons and the person relapses worse than before. Or... recovery cases are just more immune modulated

    Or I'm totally wrong, and the brain damage is minimal :) and it's just variations in individual immune responses that dictate recovery and treatment success
     
    ErdemX, MeSci and aaron_c like this.
  6. silky

    silky a gentle soul here to learn

    Messages:
    95
    Likes:
    185
    Orange County, California
    Hmm perhaps a form of lower grade encephalitis takes place in ME that does not always cause fever
     
    Webdog likes this.
  7. silky

    silky a gentle soul here to learn

    Messages:
    95
    Likes:
    185
    Orange County, California
    @w john martin I havent heard of ACE, do you have a link to more info?
     
  8. silky

    silky a gentle soul here to learn

    Messages:
    95
    Likes:
    185
    Orange County, California
    Another thought I had is that all the differences in people's symptoms are because different parts of their brains have been affected than in others
     
    aaron_c likes this.
  9. aaron_c

    aaron_c Senior Member

    Messages:
    642
    Likes:
    1,000
    I think it's much more rare for people to try Rituximab in the USA, both due to costs and concerns with taking an unproven drug outside of clinical trials. But I agree, it's very possible that we'll see a higher response rate in the Norway studies than we will in other places.

    I didn't (and still don't!) know much about the course of post-polio. That's interesting. What's the timeline that this generally happens over and what is the evidence that "exhausted neurons" is really what's going on in these cases? I ask because it sounds like the kind of thing they might have decided back in the day, when diagnostic tech wasn't as good as it is now--and even now observing live brains is more involved than observing other tissues.

    If you haven't looked at both Elzakker's Vagus Nerve Hypothesis and Eriksen's Ectopic Lymphoid Tissue Theory you might enjoy reading up on them. They both use that very idea, and I also think it's one of the better explanations for the wide variety of symptoms we see.
     
    Last edited: Jul 22, 2017
    silky likes this.
  10. w john martin

    w john martin

    Messages:
    19
    Likes:
    50
    Dear Sarah,
    You can Google Stealth Adapted Viruses and look for publications. You are welcomed to directly e-mail me for more info.
     
  11. Woolie

    Woolie Senior Member

    Messages:
    1,930
    Likes:
    14,556
    I've seen my fair share of encephalitis cases, and its one of the few things worse than CFS. It is horrible. Nowadays, its pretty easy to detect damage caused by encephaliitis on an MRI scan. I know we with CFS get short shrift, but I can assure you, if we had encephaliitis, that situation would change dramatically.

    Behaviourally, encephalitis can have dramatic effects. Severe amnesia, changes in "frontal" functions (which can include things like becoming more disinhibited), difficulties retrieving knowledge or speaking. A large proportion of sufferers also have seizures. In the worst case, patients become institutionalised.

    Its an acute onset disease, and once you have it, there's no such thing as spontaneous remission. The damage is permanent.

    Herpes simplex is often involved in encephaliits, along with some others like measles virus.

    Could CFS somehow be encephalitis that's so mild you don't see it on a scan? I don't think so, if it were that mild, then why do we have so many other symptoms - ones that are not characteristic of encephalitis at all? Why are we so disabled? It just doesn't add up.

    I also disagree with 7. There is no evidence for "big brain problems". There are tiny pockets of unreliable evidence that show some tiny functional or structural differences. Most have not been replicated even a single time. I do not trust them (this is my field of expertise).

    Everything in CFS points to the immune system.
     
    Last edited: Jul 22, 2017
    ErdemX, echobravo, GreyOwl and 7 others like this.
  12. silky

    silky a gentle soul here to learn

    Messages:
    95
    Likes:
    185
    Orange County, California
    I believe it is over several decades. I'm not sure of the physical evidence or if the concept has been revised. I do know that the poliovirus is related to enteroviruses

    Thanks! I'll take a look

    Yes mild enough that it doesn't show up on an MRI or CT but does show up on a PET or SPECT

    Perhaps classical herpes / measles encephalitis affects different parts of the brain more profoundly, whereas ME viruses affect the midbrain and brainstem more subtlety in perhaps a diffuse way. The subtle effects are enough for significant impairment and widespread symptoms but not concentrated or physically prominent enough for an MRI or CT.

    I saw an interview with Anthony Karamoff where he said something to this effect. He also mentioned physicians are so used to classical encephalitis that they miss the milder ME presentation.

    We should also remember Melvin Ramsay's choice of the name encephalomyelitis though perhaps the spine is not inflamed

    That is good to hear! What is your background? Forgive me I'm new here and not familiar with everyone yet :)

    And what is your take on the studies mentioned in these links:

    https://cfsremission.com/2015/09/06/brain-injury-and-the-chronic-fatigue-syndrome-brain/

    http://www.cfstreatmentguide.com/blog/the-elephant-in-the-room-brain-studies-politics-and-mecfs
     
  13. wastwater

    wastwater Senior Member

    Messages:
    942
    Likes:
    640
    uk
    Some researchers have wondered if it's a hit and run type condition but it's not really like encephalitis that would usually have you in hospital,I think it's an ongoing condition more like MS but not MS
    I think the varying symptoms come from the side effects of cytokines
    I wonder if it is a very soft encephalitis maybe encephalopathy
     
    Last edited: Jul 22, 2017
    silky likes this.
  14. silky

    silky a gentle soul here to learn

    Messages:
    95
    Likes:
    185
    Orange County, California
    I'm very interested in this. Tell me more about cytokines if you're willing :)
     
  15. wastwater

    wastwater Senior Member

    Messages:
    942
    Likes:
    640
    uk
    I always refer back to IL-2 mentioned in oslers web was sky high if you look at the side effects of IL-2 I think you can find most of the effects of ME but this may not be accurate as further studies don't really mention IL-2
     
    silky likes this.
  16. Woolie

    Woolie Senior Member

    Messages:
    1,930
    Likes:
    14,556
    I'm a neuropsychologist/cognitive neuroscientist.

    The brain is really fashionable at the mo, and lots of people are looking to neuroscience for sexy answers to their questions - for everything from psychopathy to depression to the cognitive enhancing effects of exercise or the benefits of mindfulness. The brain is also appealing because the way we currently do imaging studies, there are hundreds of thousands of opportunities to observe differences between your group of interest and a control group. There's always something for the ambitious researcher to report.

    It is important when you view brain data not to assume it has some sort of privileged status in the causal chain. Psychopaths show abnormal activation of certain brain regions when they view images of human suffering (e.g. the amygdala, involved in emotion). Does this mean psychopaths have a brain disorder? Of course not, their brains are merely reflecting their behaviours - they don't feel particularly moved by the pain of others. So why would we expect a lot of activity in emotion structures?

    The first link you gave seems to be a collection of quotes from different studies, and too many to comment on individually. Some I have read, others I haven't. The findings are all over the place, with very little overlap between any two studies. Red flag, anyone? Many studies seem to claim comparability of results for CFS with those for people with depression. Unless these patients have encephalitis too, something is not right here.

    None of these results should be taken seriously until their findings have been replicated.

    Also, the link doesn't seem to offer any explanation or interpretation of any of the studies. There is no description of method. You can't review science through a series of quotes, you first have to have an idea of what makes for a good or a bad study.

    In the second link you gave, I recognised most of the studies. The blurb is from 2014, but these studies remain unreplicated to this day (one has been replicated, but using the same scans for the same CFS group of 20 odd patients used in the first study so not much of a replication).

    Also, the interpretations of the findings in these studies are often very loose and stray widely from the data. The final study, that found reduced white matter volume in the occipital lobes, tried to say that visual disturbances are a huge feature of CFS. We know that's not true. More generally, they also suffer from the "reverse inference" problem. Just knowing a brain region is implicated in some phenomenon does NOT mean we know what's going on from a mental/cogntive viewpoint. Many regions do multiple things, some we don't even know about yet.

    The Goldstein limbic account is well, not that far from a psychosomatic account - but dressed up in neuro language (expect to see a lot more of this from our psychosocial researchers).

    I have no doubt that CFS will change your brain. But then going for a jog or having a good nap will also change your brain. Most studies, if they're measuring real effects at all, are measuring effects, not causes.
     
    Last edited: Jul 22, 2017
    MeSci, daisybell, Abha and 8 others like this.
  17. wastwater

    wastwater Senior Member

    Messages:
    942
    Likes:
    640
    uk
    I now think my condition maybe linked to Th-17
     
    Last edited: Jul 22, 2017
  18. Woolie

    Woolie Senior Member

    Messages:
    1,930
    Likes:
    14,556
    Yea, but then you have your causal explanation, right there in the (very clever) immune system. Why would we need to involve the brain?

    Simple is good. Complex usually means there's something in the explanation that isn't doing much explanatory work, something we need to let go of.

    If you're having to do backflips to explain just what the brain has to do with it, you're probably looking in the wrong place.
     
    Valentijn likes this.
  19. lnester7

    lnester7 Seven

    Messages:
    2,397
    Likes:
    3,454
    USA
    I don't think the damage is permanent or at least not too bad, the ones like me that get remissions on viruses or get some random remissions get full control back. At first I was afraid the damage was permanent but now I am convinced it is not (in most cases) not sure on severe even though I have heard of some being ok after lot of ME years.
     
  20. halcyon

    halcyon Senior Member

    Messages:
    2,297
    Likes:
    5,375
    The short answer is that I don't believe it's simply this, only part of it.

    The name ME wasn't chosen arbitrarily. The people seen in outbreaks clearly had their brains and spinal nerves affected, based on signs and symptoms. Anatomically the disturbance may not have been inside the spinal cord, but those nerve functions were clearly affected somewhere. This makes the 'myel' part of the name questionable, though some definitions of myel include the brainstem, which many believe is affected in ME as well based on some evidence.

    I believe that ME is a low grade, non-lytic chronic enteroviral encephalitis + systemic infection. Obviously it is not a frank, destructive viral encephalitis otherwise it would have been recognized as such long ago and we wouldn't be here having this conversation.

    The evidence is there to support this though. Enteroviruses are notoriously difficult to isolate from bodily fluids, including CSF, but it can and has been done, first by S. B. G. Innes in the 1970s on several ME patients. To date, three different groups, across two countries, all utilizing several district techniques have shown the presence of enterovirus in the brain tissue of dead ME patients. The recent CSF study by Peterson showed that in the classic acute ME patients, there was elevated interferon alpha in the CSF, which is an expected finding in viral CNS infection. I'm not going to spout off all the evidence as there are several dozen studies. One of the more interesting findings though is that the enteroviruses isolated from some ME patients are genetically distinct from normal wildtype virus. We don't know if they were caught this way or if the patient mutated the virus, but to me this seems very compatible with an infection that doesn't behave as expected, i.e. causes a low grade, non-lytic infection that doesn't destroy tissue massively but modifies function and provokes constant immune response.

    So, to answer the original question, I think parts of the disease are a result of initial CNS damage, but the main parts that we really notice (PEM, fatigue, neuroendocrine dysfunction, metabolic dysfunction, etc.) are a functional consequence of ongoing immune activation resulting from a chronic infection of brain and body.
     
    Dechi, Sancar, dangermouse and 6 others like this.

See more popular forum discussions.

Share This Page