Everything you always wanted to know about non-cytolytic enterovirus but were too afraid to ask

Or the confidence with which a certain bald-headed member of S4ME makes his assertive comments?

 

I honestly admit @Graham I don't totally understand I just want to make sure that my post wasn't meant to critisize you, but to agree with you.

 

Sorry, @Inara , my strange sense of humour doesn't translate well! Even my friends have problems with it. I was agreeing with you completely: there are too many people in positions of influence and power who become utterly convinced that they are right, and become impossible to argue with. But I was also suggesting that I see that tendency in some of the things I say, so I need to keep prodding myself and reminding myself that a little humility is a good thing. As for criticizing me (and I know you were not), I never mind that anyway: I need to be reined in* at times.

I suppose I could make the effort to remove the humour, and be much clearer and factual as I write. But would that spoil the challenge?

*"reined in" refers to restricting a horse from galloping ahead (into disaster) by pulling on the reins.

 

I thought it might be a joke, @Graham, but since I don't know you good enough yet I didn't want to drop a brick. Thanks for your patience.

 

Sorry, I'm way behind on these threads and probably won't be able to catch up for another week or so, but one small thing. I'm a little confused your response to this @Jonathan Edwards as most of the information @chrisb presented is mentioned and incorporated in some way into these pages:

https://www.me-pedia.org/wiki/Epidemic_myalgic_encephalomyelitis
https://www.me-pedia.org/wiki/1934_Los_Angeles_atypical_polio_outbreak

And I know I brought this up before, on a previous thread where we discussed the epidemics. The pattern Wilson and Walker mention is seen over and over and over and over again in nearly all of these pre-1984 outbreaks. And yes, the "Los Angeles County Hospital outbreak" was actually happening all across California, involving people in LA who had no connection to the hospital with cases as far north as San Francisco. They recognized pretty early on that it wasn't polio but soon after that came to believe it was a related virus (i.e., a different enterovirus). That idea stuck for decades based on the close observation of physicians involved in these many dozen outbreaks and because of the pattern of transmission, incubation period, etc.

We'll never know for sure, but that's not the same as having no evidence or not being able to at least exclude certain possibilities. I think looking at the literature, we can say with some certainty that these outbreaks were caused either by an enterovirus or by some family of virus that has never been discovered (but shares the same epidemiology as enteroviruses). We can exclude nearly all other families of virus.

Thank you for the new citation @chrisb. I will make sure to include it. (Or perhaps you can, if you have access to the full text.)

And did Acheson really think that there was anterior horn cell damage? I find that bizarre given how many pre-Acheson case studies (that he would have read) specifically state there is no anterior horn cell damage. I haven't seen that anywhere, but I may have missed that in my reading.

I know your feeling was that these outbreaks are essentially irrelevant to what we call ME/CFS today. I think the only way to get a full sense of the range of observations and evidence is to go and read the primary literature. There is a lot of it, though, and I've only read about 20 or so papers. I ran out of steam, and my brain/neck issues have become pretty unbearable, but hope to finish the job at some point in the near future.

 

I think I have seen enough of the literature to be sure that this is a muddle, @JenB.
The 'pattern' is not consistent. Moreover, these are symptoms that a neurologist will encounter in any routine clinic in all sorts of combinations. What is being described is essentially a mixture of ME as we now understand it, which has nothing obvious in common with polio or other enterovirus infection, and a ragbag of vague neurological findings. The only specific pathology quoted is variable evidence of radiculopathy, but radiculopathy is not a characteristic feature of ME or of virus infections as a rule (zoster might be called a radiculopathy but there are overt clinical signs to go with that).

As I said before, and maybe you did not notice, there are lots of families of virus that produce local epidemics. Most of us have three or four a year. Nobody has yet said why we should pick on enteroviruses. Acheson seems to have done so for spurious reasons relating to thinking there was paralysis from nerve involvement. Acheson obviously did not think the problem was purely lower motor neuron (anterior horn cell). But if it was upper motor neuron there should have been spasticity and reflex changes. It is a muddle.

The key problem for me is that there is muddling between the possible neurological features of an acute viral illness and the chronic problem we now call ME. People with ME do not have specific neurological deficits of the sort associated with viral damage.

 

Not that one would wish ME/CFS on anybody, but in some respects we would probably learn a great deal if a new ME/CFS outbreak appeared today, as we now have a lot more tools that would enable us to quickly identify the virus involved.

It is something of a mystery why an ME/CFS outbreak has not occurred since the early 1990s, when prior to that outbreaks occurred somewhere in the world almost yearly (see this list of ME/CFS outbreaks). Assuming this is not just an issue involving failure to report an outbreak of symptoms (which seems unlikely), it suggests some factor in the environment may have changed since the early 1990s, which inhibits the occurrence of ME/CFS epidemics.

 

According to Statistics Canada, the ME rate increased by 37.6% in 2015 over the previous year, to about 560,000.

Fwiw, Canada also has the highest MS rates.

 

I think it also has one of the highest IBD rates.

 

Moderator note: This post and following posts have been moved from this thread:
Dr Byron Hyde surrenders his medical license


I'm just going to leave this here:

Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing post-exertional malaise following cardiopulmonary exercise testing

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212193

Patients meeting Canadian Consensus Criteria showed no evidence of virus infection or reactivation, before or after exertion that induced PEM in most of them.

The technique they used would allow them to identify any virus, even to date undiscovered ones.

There might be some truth in the enterovirus theory in that enteroviruses might be particularly good at inducing ME in people and that would explain the epidemics of the past. But the part of the theory that says there is continued infection or even reactivation seems to be totally wrong.

 

But would that not only include any pathogens they find in the blood? I presume the possible reasons they give for the absence of differential gene expression between ME/CFS patients and controls would be same re viruses. In the paper it says:

“Reasons for the absence of differential gene expression between ME/CFS patients and controls include (1) the lack of objective diagnostic testing for ME/CFS and reliance on subjective definitions, resulting in heterogeneity in the ME/CFS study cohort, (2) the lack of an immunological signature in ME/CFS that is detectable by transcriptomics, (3) localization of ME/CFS pathogenicity to a specific tissue (e.g. skeletal muscle or brain tissue) rather than blood“.

 

That is a good point. I overlooked reason 3. A study that can specifically find enterovirus in the brain would be useful.

 

It could be that an enterovirus infection can permanently alter the microbiome, and it's the changes in the microbiome's constituents that are promoting ME long after the virus is gone.

The paper below describes a daily longitudinal study of the microbiomes of two people over the course of a year. The first subject's microbiome was altered when he relocated to Asia and began eating the local food, but it returned to its previous distribution of components upon his return. The second subject's microbiome was altered permanently following an enteric infection. This infection was bacterial as opposed to viral, but, apparently, viruses can do the same thing.

https://genomebiology.biomedcentral.com/articles/10.1186/gb-2014-15-7-r89

National Geographic article on the paper above:

The Quantified Microbiome Self
https://www.nationalgeographic.com/science/phenomena/2014/08/06/the-quantified-microbiome-self/

Disruption of the Human Gut Microbiota following Norovirus Infection
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0048224

 

I believe my ME started with food poisoning - definitely was a gut reaction at any rate. Then EBV of several months duration shortly thereafter. Don't know about whether the entero virus theory is correct. I understand early on, several decades ago, that was thought to be the cause.

 

There are 3 such studies that show exactly this, and to date zero studies that refute it. There is no available way to find the virus in a living brain, so the cost of each study is one human life.

And no, testing of CSF for virus is not an acceptable proxy. Enterovirus infection only produces a detectable viremia of spinal fluid when there is acute infection of the meninges.

 

If classically described ME is indeed caused by enterovirus infection of the brain, as the evidence supports, this would make ME and poliomyelitis cousin diseases. Numerous experts (Bruno, Dowsett, Behan) have stated that clinically, ME and post-polio syndrome are difficult or impossible to tell apart. If AFM is indeed caused by enterovirus, as the evidence is starting to support, this would also make AFM and ME cousin diseases, and it’s probable that in the coming decades these AFM victims might suffer from an ME-like clinical syndrome just as post-polio patients do. None of this has anything to do with Byron Hyde.

And actually, health authorities did have difficulty finding the enterovirus(es) linked to AFM in the victims, because again, largely their spinal fluid was clear of virus by the time the neurological syndrome had been in full swing. This is not unusual as in poliomyelitis also it’s very rare to isolate virus from the spinal fluid. The CDC had to enact a special protocol and fast track a bespoke PCR test in an attempt to catch the (EV D68) virus in body fluid samples before it disappeared from secretions.

I don’t have the stamina to reply to every message in the same vein, so I will just say once that I encourage everyone to avoid engaging in the ‘genetic’ logical fallacy. Just because Bryon Hyde is abysmal at medical charting doesn’t mean that enterovirus isn’t the cause of ME or that SPECT scans don’t provide evidence of a pathology in ME. There should be a separation between the evidence for a hypothesis and the people who champion it.

If you do require a “hero” to have championed this hypothesis before you believe in it, rest assured that many others (Ramsay, Dowsett, Richardson, Spurr, Hooper, Mowbray, Bruno, Leon-Sotomayor, Chia, etc.) have believed this hypothesis has merit. I would recommend instead actually reading and understanding the several dozen studies available on the subject yourself and coming to your own conclusions however.

 

Sounds like these researchers are more interested in playing with the latest molecular method viral detection toys, rather than taking the viral infection theory seriously.

If they went the extra mile to take tissue samples rather than blood samples, they'd likely find ample evidence of viral infection. Prof Lipkin told me that using molecular methods on blood samples will not detect enterovirus infections which are located in the tissues; and we know from numerous previous enterovirus studies that the tissues is where they are located.

Every ME/CFS doctor knows that when you perform PCR tests on ME/CFS blood samples, they usually come out negative. So the blood is not the place to look for infections in ME/CFS (unless you use antibody blood tests, which give indirect evidence of infection).

This study is another complete waste of taxpayers' money.

Dr Chia does not think SPECT scans are useful, as SPECT scans are not conclusive and low blood flow can mean many different things including depression. Chia does not think enough studies have been done connecting SPECT scans to CFS/ME. Ref: 1

 

The terrible tale of Amy Brown
https://www.healthrising.org/blog/2017/05/23/doctors-hyde-amy-browns-m-e-enterovirus-story/

 

The purpose was to test the hypothesis of viral reactivation during PEM. There are patients who say this happens to them. Also patients who say they are infected with some virus. I think it's good that researchers are listening to patients and testing these ideas.

 

I appreciate that, but if you want to observe viruses reactivating, it's best to look at the areas where the viruses are located.

Likewise, if you want to observe penguins giving birth, you'll see that in Antartica, but not on the French Riviera.

Getting blood samples from ME/CFS blood banks is quite easy, it requires minimal effort. Getting tissue samples from patients requires more effort. This is I think why they did not bother.