Michael VanElzakker, interview with Llewelyn King - really worth watching

[Mary]

I stumbled across this interviews on the S4ME website - this guy is amazing. He is a neuroscientist affiliated with Massachusetts General Hospital and Harvard, incredibly articulate and makes complex concepts understandable, and is an ME/CFS advocate to boot. I'm sure some of you have heard of him before but it's the first time I've come across him.

Llewelyn King interview: https://www.youtube.com/watch?time_continue=1309&v=uO9j67WDYM4

Link to another interview (previously posted here: http://forums.phoenixrising.me/inde...-latent-infection-and-more.56521/#post-939913)

http://microbeminded.com/2017/12/07...-vagus-nerve-mecfs-latent-infection-and-more/

@Wayne and @Learner1 - He has hypothesized that ME/CFS may be caused by an infection of the vagus nerve.

He also has a crowd-funding campaign to fund ME/CFS research using brain scans, pre and post exercise: https://because.massgeneral.org/cam...onic-fatigue-syndrome-research-at-mgh/c153689

 

[Cort]

Looking forward to this. It's been a long time coming. I did a 2013 blog on his hypothesis which garnered over 170 comments. Such a fascinating idea.

http://simmaronresearch.com/2013/12...gus-nerve-infection-chronic-fatigue-syndrome/

I never dreamed it would take five years to get more data on hypothesis. I don't know if we have it yet. That's what poor funding will do for you - it lengthens the time it takes to do anything.

Here's another blog

http://simmaronresearch.com/2014/02...on-hypothesis-chronic-fatigue-syndrome-mecfs/

 

[Mary]

Good write-ups @Cort! But I'm wondering how the vagus nerve infection hypothesis would account for the delayed onset of PEM, often 24 hours or more? Any ideas?

 

[Cort]

Good write-ups @Cort! But I'm wondering how the vagus nerve infection hypothesis would account for the delayed onset of PEM, often 24 hours or more? Any ideas?

Hmm....I don't know that anybody but Nancy Klimas can really explain that but I think Nancy might be able to. She's intensively monitoring people with ME/CFS before during and after exercise - I think she's taking blood at 8 points and she's found that an inflammatory process starts which at some point whacks autonomic nervous system functioning.

Van Elzakker's hypothesis fits with that I think. There's a localized infection which messes with the vagus nerve which impacts parasympathetic nervous system functioning. I don't know about the time line.

It is interesting that in the normal when a healthy person over-exercises they feel really sore the next day or so - so there is a process going on even in healthy people which results in a kind of PEM when they overdo it. It just takes so much less in ME/CFS.

 

[Mary]

Thanks @Cort!

 

[CFS_for_19_years]

It is interesting that in the normal when a healthy person over-exercises they feel really sore the next day or so - so there is a process going on even in healthy people which results in a kind of PEM when they overdo it. It just takes so much less in ME/CFS.

The soreness that healthy people feel 24-48 hours after physical exertion is known as Delayed-Onset Muscle Soreness or DOMS for short. When an athletic person stresses their muscles with a challenging workout they cause micro-tears in the muscles. This is a normal part of working out, and rebuilding those fibers is key to the muscle-strengthening process. The micro-tears cause inflammation which leads to muscle soreness. So DOMS can be considered a symptom of the muscle breakdown process.

The only similarity I see between DOMS and PEM is the inflammatory cascade, but the inflammation in DOMS is only felt at the site of the stressed muscle, not all over the entire body as in PEM.

https://www.menshealth.com/fitness/a19542200/what-is-delayed-onset-muscle-soreness/

"The damage shows our body and our brain that our lifestyle demands more strength or endurance than our muscles can tolerate," Callaghan says. "Because the human body is extremely adaptive, this demand for increased strength cues it to build more muscle tissue and make us stronger."

DOMS generally shows up 24 to 48 hours after an intense workout, according to Jordan Metzl, M.D., a sports medicine physician at the Hospital for Special Surgery in New York City. And Callaghan explains that the delay happens as a result of a process called "the inflammatory cascade."

Basically, there's a ramp-up process involved in muscle repair, which means it takes awhile for the greatest amount of soreness to kick in.

"The first 24 hours include a slow increase in blood flow to the damaged muscles along with hormones and proteins to assist with healing," she says. "On day two, the whole team has arrived and your muscles are fully inundated with excess blood and cellular fluid. This inflammation creates extra pressure on structures in the area of affected muscles, which is what causes the pain."

More challenging workouts can create more of those tiny muscle tears, sparking greater inflammation, so it's more likely you'd see it after you do something like squats with heavy weight rather than a slow, easy jog.

The way to treat DOMS is with heat to the damaged muscle, stretching and low-impact exercise to loosen the muscles. These actions would have no effect on PEM.

When I was healthy I was a competitive swimmer and recreational cyclist who also regularly trained with weights (aka weight lifting). I've been through hundreds of DOMS cycles in 20 years of an active lifestyle.

With ME/CFS when I stressed my muscles the pain from DOMS was much more intense possibly because I also have fibromyalgia. I still had to follow through with heat, stretching and whatever movement I could manage. Even though the pain was intense I didn't feel like I had PEM. I had to learn to back off from stressing my muscles at all to prevent DOMS. (All of this is in the past tense since I don't have the energy to exercise at all any more.)

 

[CFS_for_19_years]

It is interesting that in the normal when a healthy person over-exercises they feel really sore the next day or so - so there is a process going on even in healthy people which results in a kind of PEM when they overdo it. It just takes so much less in ME/CFS.

Regarding muscle damage, or Delayed-Onset Muscle Soreness (DOMS): There is a localized immune response to the damaged muscle: See http://www.humankinetics.com/excerpts/excerpts/recent-research-provides-insight-into-muscle-soreness

Mononucleated cells in muscle are activated by the injury, providing the chemical signal to circulating inflammatory cells. Neutrophils (a type of white blood cell) invade the injury site and release cytokines (immunoregulatory substances), which then attract and activate additional inflammatory cells. Neutrophils possibly also release oxygen free radicals that can damage cell membranes.

The invasion of these inflammatory cells is also associated with the incidence of pain, thought to be caused by a release of substances from the inflammatory cells stimulating the pain-sensitive nerve endings. Macrophages (another type of cell of the immune system) then invade the damaged muscle fibers, removing debris through a process known as phagocytosis. Last, a second phase of macrophage invasion occurs, which is associated with muscle regeneration.

Viral infections produce a different kind of immune response: https://www.immunology.org/public-i...athogens-and-disease/immune-responses-viruses
A special cell of the immune system called a T cell circulates looking for infections. One type of T cell is called a cytotoxic T cell because it kills cells that are infected with viruses with toxic mediators. Natural killer cells also kill virally-infected cells. Virally-infected cells produce and release small proteins called interferons, which play a role in immune protection against viruses. Viruses can also be removed from the body by antibodies before they get the chance to infect a cell.

This article doesn't talk specifically about delayed-onset muscle soreness:
Exercise and the immune system
https://www.ncbi.nlm.nih.gov/pubmed/17826186

Exercise has a variable effect on the immune system. The underlying reasons for this variability are multifactorial and include infectious, neuroendocrine, and metabolic factors, with nutritional status of the athlete and the training load playing a role. Environmental factors such as living quarters, travel requirements, and the type of sport (team versus individual) also contribute to infectious risk.

Regarding the direct effect of exercise on the immune system, moderate exercise seems to exert a protective effect, whereas repeated bouts of strenuous exercise can result in immune dysfunction. Understanding the relationship between exercise and infectious disease has important potential implications for public health and for clinicians caring for athletes and athletic teams.

Full text: https://sci-hub.tw/10.1016/j.csm.2007.04.011

 

[Wayne]

He has hypothesized that ME/CFS may be caused by an infection of the vagus nerve.

I seem to remember reading a hypothesis once that ME/CFS can also be caused by an infection; through which the vagus nerve traverses. -- I believe my own ME/CFS started with a head injury and accompanying injury to my vagus nerve at age 15. Also, I would not be at all surprised that the vagus nerve can be sent into some sort of "shock" by various life traumas. I would put vaccinations at the top of my list for this category.​