CFS is a metabolic condition!

[mellster]

Why bacterial? What I've seen suggests that intracellular infections of all kinds are common in ME/CFS.

IMO viral infections can be enablers/triggers or opportunistic bystanders adding to the damage, doesn't mean you shouldn't treat them if necessary. But the countless inconclusive serum studies suggest that a virus is unlikely as a chronic agent at this point. I don't have a problem if they eventually come around and announce a virus like EBV or coxsackie as the culprit, but I have the gut-feeling that this will not happen. Simply considering how much effort has been spent chasing viruses/parasites etc. and how little effort has been spent looking for misplaced opportunistic bacteria, it would make sense to do some research there. But again, this can only happen with tissue samples and biopsies which are notoriously hard to get due their invasive nature, cost, and legal reasons.

 

[SOC]

IMO viral infections can be enablers/triggers or opportunistic bystanders adding to the damage, doesn't mean you shouldn't treat them if necessary. But the countless inconclusive serum studies suggest that a virus is unlikely as a chronic agent at this point.

Have you taken into consideration that a number of the culprit viruses are mostly tissue-based in the chronic stages and therefore have very low serum levels? Many studies only used basic tests that wouldn't detect tissue-based infections and/or very low level serum levels.

I won't be surprised if the culprit is bacterial, viral, fungal, or simply a genetic immune abnormality. I don't think we have anywhere near enough evidence to rule out any of those possibilities.

 

[Gingergrrl]

@mellster, in my case although I had several triggers, everything really started when I had mono from EBV which is viral. I do not have the science/research background of many people on this site, but it seems like more people had a viral trigger vs. bacterial (except for Lyme.) But I could be wrong?

 

[Valentijn]

I agree with @Hip here. We may not recognize an event, but it may be there. My onset was slow...until I reached a "tipping point" that threw me into a very long term crash. But when I look back closely I can recognize "events" that were probably precipitous--a flu that lasted 3 months, numerous tick bites.

However the "crash" that dumped me into disability, came decades later.

Similar for me. I was bitten dozens of times by ticks when I was 13-14. I started having some inflammation issues around the same time, rashes, heat sensitivity, and some pain due to the inflammation.

By age 15-16, after leaving tick-country, I starting getting migraines with aura, lots of joint discomfort (to the point where I learned to crack my spine in several different ways), and more inflammation issues.

In my mid 20's I started getting "the flu" a lot, and was struggling with an aerobics class at university and later with Tae Kwon Do. For both I was simply sick almost all the time while trying to do them. I had to re-take the aerobics class, and dropped out of Tae Kwon Do eventually.

At 28 I had bronchitis and pneumonia, then a 3 week right-sided hemiplegic migraine a few months later. I was diagnosed with exercise-induced asthma, except the usual asthma meds didn't help at all, only Intal. This is also probably around the time where I started to have mild problems with sleeping on my right side. Pulse pressure was low at some doctor visits, and oral temperature was usually pretty low.

I had a couple bouts of probable pericarditis at around age 30-31. I also tried home exercises during this period (though not during the pericarditis!) and had serious blood pressure and heart rate problems, especially when going from lying to standing for different exercises.

Moderate and constant ME hit me suddenly in January, 2011, at age 32, following a nasty flu that kept me mostly out of classes for two weeks. Symptoms were milder at first, but I was mostly housebound within 6 months. It's been a slow and steady decline since then.

Everything is so much clearer in retrospect

 

[Hanna]

That's pretty interesting, thanks for the info. I'm curious about it because borrelia seems to be the only thing that fits my brain symptoms, yet I have severe PEM that I understand usually isn't there with Lyme or co-infections. Energy expenditure really is the reason my brain is so bad.

Professor Judith Miklossy from Switzerland (a neurologist) is researching this connection : Alzheimer-Lyme.
https://www.alzforum.org/member-directory/judith-miklossy

 

[heapsreal]

whatever the trigger or ongoing infection or whatever, the one thing in common is we all have a crapped out immune system.

If we can get it functioning properly then all these infections shouldnt be a problem or only need short courses of antivirals and or antibiotics?

I dont think they are going to find one cause, but i think they will need to group people into subsets, maybe using what infections they have or other dysfunction found. Also some may fit the hit and run theory too.

I think subsets because we know that certain people make good improvement with antivirals that fit the profile. We know people who make good improvement from antibiotics if they fit the right profile and get treated with the correct abx for the correct amount of time. Because 1 particular treatment doesnt help everyone doesnt mean its not helpful. Theres also that group that slowly improve or even fully recover without any aggressive type of treatment.

I also think 100% recoveries from av's or abx are probably rare because of something wrong with the immune system, if its damaged during the course of the illness or during the initial trigger or some other reason then its going to be hard to rid many of these infections for good and certain stresses may cause relapses as its an extra burden on the immune system.

At the end of the day i dont think we are going to find a cookie cutter theory or treatment to fit all, i think it has to be tailored to the individual( probably through trial and error) and this is what makes us so difficult for doctors to treat or research to study us.

 

[MeSci]

whatever the trigger or ongoing infection or whatever, the one thing in common is we all have a crapped out immune system.

If we can get it functioning properly then all these infections shouldnt be a problem or only need short courses of antivirals and or antibiotics?

I dont think they are going to find one cause, but i think they will need to group people into subsets, maybe using what infections they have or other dysfunction found. Also some may fit the hit and run theory too.

I think subsets because we know that certain people make good improvement with antivirals that fit the profile. We know people who make good improvement from antibiotics if they fit the right profile and get treated with the correct abx for the correct amount of time. Because 1 particular treatment doesnt help everyone doesnt mean its not helpful. Theres also that group that slowly improve or even fully recover without any aggressive type of treatment.

I also think 100% recoveries from av's or abx are probably rare because of something wrong with the immune system, if its damaged during the course of the illness or during the initial trigger or some other reason then its going to be hard to rid many of these infections for good and certain stresses may cause relapses as its an extra burden on the immune system.

At the end of the day i dont think we are going to find a cookie cutter theory or treatment to fit all, i think it has to be tailored to the individual( probably through trial and error) and this is what makes us so difficult for doctors to treat or research to study us.

I agree about a range of causes, and subgroups.

Another factor that adds to the confusion is that drugs can have more than one effect, e.g. an antiviral that also affects, say, the immune system, or an immune-modulating drug that also attacks viruses! So it becomes near-impossible to know whether success with a drug means that the illness was caused by the problem that the drug is designed to combat.

 

[MeSci]

Dr.Patient said: ↑
Thank you for this! I was in the middle of reading the three papers of Dr.Myhill when your msg came. It seems to make sense, but why is the ATP profile not offered routinely to patients in the US?

Hi Dr. There is no money in it for the drug companies .... That is why ....

I'm not clear on the relationship here. Do drug companies control what tests are ordered? AFAIK, at least in the UK, requests for tests are based on official guidelines plus doctors' opinions.

 

[xrunner]

I agree with @Hip here. We may not recognize an event, but it may be there.

I agree with @Hip and @Sushi, if we look carefully we may recognise an event or more likely more than one. For me it was a gut infection after which I felt I couldn't train 3-4 hours a day any longer (also had anxiety symptoms following), a few years later a lung infection (most likely Chlamydia Pn.) after which I needed an increased amount of rest to recover from a "normal" working week. However, the tipping point for me came about eight year later with another infection that felt like meningitis from which I nearly recovered but then had again gastroenteritis after which something seemed to have switched.

 

[Hip]

Of course, just because ME/CFS may have been primarily precipitated by an infection (likely in combination with other risk factors, such as significant mold or pesticide exposure), the condition of ME/CFS may still involve further downstream metabolic abnormalities, such as mitochondrial dysfunction, that appear as a later consequence of the infection. In other words, the infection may be an initial cause, but then additional downstream effects may arise as a result.

As an analogy, if you look at the enteroviral theory of type 1 diabetes, such a downstream causality is also proposed: the theory says that an enterovirus infection initially attacks insulin producing beta cells of the pancreas (both directly, and by the autoimmune attack on beta cells that enteroviruses can trigger), and then as a result, you get a dysfunction of insulin production, as a downstream effect of the initial infection (ref: here). We say that type 1 diabetes is due to lack of insulin production, but in fact this is a more downstream effect. The upstream initial cause of type 1 diabetes would appear to be an enterovirus infection, if this theory turns out to be correct.

 

[Dr.Patient]

Of course, just because ME/CFS may have been primarily precipitated by an infection (likely in combination with other risk factors, such as significant mold or pesticide exposure), the condition of ME/CFS may still involve further downstream metabolic abnormalities, such as mitochondrial dysfunction, that appear as a later consequence of the infection. In other words, the infection may be an initial cause, but then additional downstream effects may arise as a result

I agree, that is my opinion as well. A variety of insults happen, and they all ultimately hit the mitochondria. When all of these attackers fall on the mitochondria, the mitos are unable to get up.

 

[Sushi]

I agree, that is my opinion as well. A variety of insults happen, and they all ultimately hit the mitochondria. When all of these attackers fall on the mitochondria, the mitos are unable to get up.

Some other really important areas get "hit" downstream too.

For instance, the autonomic nervous system, methylation, changes in the gut (which may be related to neuroinflammation), neurotransmitters levels (perhaps due to changes in the gut?), blood volume and blood flow to the brain and heart, cardiac concerns such as diastolic dysfunction....A big mess that is very hard to unravel.

Sushi

 

[Dr.Patient]

Infectious- there are patients who have this without any infectious trigger, no conclusive organisms have been identified, no antiinfectious drugs have helped this, no person to person transmission, either directly or by bugs, etc occurs.

Will address the other causes shortly.

Muscular- nothing shows up on muscle biopsies, no particular muscle protein antibodies, no unusual EMG studies.

Neurologic- brain scans usually normal, some people have abnormalities, but nothing that would explain the levels of fatigue, no focal neurologic deficits on exam, normal nerve conduction studies. However, two things are interesting- abnormal functional MRIs, and some CSF ( not CFS) protein abnormalities.

On other causes, soon!

 

[Hip]

I agree, that is my opinion as well. A variety of insults happen, and they all ultimately hit the mitochondria. When all of these attackers fall on the mitochondria, the mitos are unable to get up.

Have you seen VanElzakker's paper on the vagus nerve infection hypothesis of ME/CFS? VanElzakker explains that the inflammatory cytokines IL-1β, TNF-α and IL-6 released during infection serve to instigate sickness behavior. The vagus nerve possess sensors for these cytokines, and this nerve is designed to trigger sickness behavior in the brain when it detects these cytokines within the body. Sickness behavior symptoms are very similar to those of ME/CFS.

So here is an example of the driving cause being an infection, but the upstream effect of the infection is the activation of the vagus nerve, and in turn, the instigation of the sickness behavior state in the brain — a state which VanElzakker thinks creates the ME/CFS mental and cognitive symptoms.

 

[Dr.Patient]

Some other really important areas get "hit" downstream too.

For instance, the autonomic nervous system, methylation, changes in the gut (which may be related to neuroinflammation), neurotransmitters levels (perhaps due to changes in the gut?), blood volume and blood flow to the brain and heart, cardiac concerns such as diastolic dysfunction....A big mess that is very hard to unravel.

Sushi

Agree. Mitochondrial failure is the landslide that takes everything down with it.

 

[Hip]

Muscular- nothing shows up on muscle biopsies, no particular muscle protein antibodies, no unusual EMG studies.

But enteroviral RNA is often found in the muscles of ME/CFS patients. If you look at this list of early British ME/CFS studies, you see that a number of studies have found enteroviral RNA in the muscles.

 

[Sushi]

Have you seen VanElzakker's paper on the vagus nerve infection hypothesis of ME/CFS? VanElzakker explains that the inflammatory cytokines IL-1β, TNF-α and IL-6 released during infection serve to instigate sickness behavior. The vagus nerve possess sensors for these cytokines, and this nerve is designed to trigger sickness behavior in the brain when it detects these cytokines within the body. Sickness behavior symptoms are very similar to those of ME/CFS.

So here is an example of the driving cause being an infection, but the upstream effect of the infection is the activation of the vagus nerve, and in turn, the instigation of the sickness behavior state in the brain — a state which VanElzakker thinks creates the ME/CFS mental and cognitive symptoms.

Yes, the vagus nerve is often affected. In a TTT done by an autonomic specialist, my vagus nerve showed dysfunction. Some have even had vagus nerve pacemakers (?) (regulators, not sure what they are called) implanted which gave immediate relief from many symptoms.

Sushi

 

[Sushi]

...
Neurologic- brain scans usually normal, some people have abnormalities, but nothing that would explain the levels of fatigue, no focal neurologic deficits on exam, normal nerve conduction studies. However, two things are interesting- abnormal functional MRIs, and some CSF ( not CFS) protein abnormalities.
...

A lot of neuro-inflammation is showing up and many have reduced white matter and tiny white "spots."

Sushi

 

[lansbergen]

Muscular- nothing shows up on muscle biopsies, no particular muscle protein antibodies, no unusual EMG studies.

http://www.meassociation.org.uk/201...ope-for-me-sufferers-the-times-23-april-2013/

Professor Newton presented the findings at a meeting in London yesterday marking the launch of a collaboration aimed at generating more research into the disease.

In the study, scientists took muscle biopsies from ten patients and ten healthy but sedentary volunteers.

The muscle cells were grown into small pieces of muscle and then subjected to “exercise” in the form of electrical impulses.

The cells from ME patients produced on average 20 times as much acid when exercised, suggesting an underlying cause for the aching muscles that patients often experience as soon a they begin to exercise.

The cells also showed other abnormalities, such as reproducing more slowly.

 

[mellster]

Not disputing the viral and other triggers, but a virus usually either kills the host or gets entirely defeated by the body and in most cases completely expelled. There are exceptions such as HIV which mostly progresses slowly or some that stay latent and can flare up such as various members of the herpes family. However, even when they flare up, it is usually acute, with herpes you get sores or with VZV you may get shingles much later after having chickenpox, but they mostly stay dormant/latent and do not interfere much with the body. There are some exceptions to this, but the reactivations (which are still very much debated) could be of opportunistic nature and not the cause. Bacteria though have a much better profile to interfere with the body on a persistent basis, by forming colonies, films that prevent penetration of cell walls and developing resistencies to antibiotics, and causing structural damage to tissue (via H2S and H2O2 production) and blockages. And whenever a strong viral onslaught (such as EBV) or trauma (surgery etc.) brings the defenses down, it may be possible that those pathogens disseminate from their usual habitat (where they do not pose much of a threat) and then wreak havoc where they naturally shouldn't be (gut, lymphatic system, etc.). Also we all assume an infectious nature which is really pretty certain at this point, but it is also striking that the genetic abnormalities/predispositions are so hard to find. I think they exist but probably won't fully explain why some get really sick and others don't, simply because it could be a case of bad luck of a perfect storm onto the immune system, even for people that don't exhibit genetic abnormalities. And even if it is a virus or a host of viruses that somehow exhibit low serum levels, why all the serum studies and so little to none tissue samples?