My thoughts on why I think ME/CFS is not, at its root, a putative neuroinflammatory disease

[heapsreal]

Have you thought or considered vasospasms as in prinzmetal (spelling) angina or something similar occurring in the brain. So as in PM angina which show ST elevation on an ecg, would normally be a sign of infarction in a chest pain episode. With pm angina , glycerol trinitrate gtn relaxes the vasospasm and the ST elevation goes away. But during a myocardial infarct gtn generally doesnt stop the ST elevation and myocardial perfusion. Although through colateral circulation improvements from gtn can help perfusion and reduce size of the infarct.

so i wonder if a similar vasospasm could be occurring in cfsme and like pm angina , can come on with increased activity. This being a possible cause of hypoperfusion seen in cfsme.

food for thought ? ?

@Bob
found it.

 

[leokitten]

I think you are courageous to discuss your illness and reveal your association with the NIH. Everything we do or say on the Magic Internet can and will be used against us in ways we can't even think of yet. We know these forums are monitored by Our Dear Leaders...

Yes I agree with @SOC I think we shouldn't be paranoid, but again I haven't experienced the kinds of prejudice and unfair treatment people on PR have gone through.

I guess I'm not afraid because I have given no one anything to worry about as of yet, I do an excellent job with my team at NIH, I've never asked for any special treatment, I never used any extra time off other than my own personal leave, and last but not least I really love my job and what I do and people at work see that and how much I do.

ME/CFS has made my life really bad, constantly managing the symptoms and fluctuations, PEM and crashes, doctors appts and treatment, and destroying my social life but for as long as I can possibly continue I will not let it affect my job and soldier on.

Hopefully one day public understanding will be such that we can tell people about this serious physical disease that we have without feeling people will think we are just lazy, or lying, or even worse crazy, because we all know none of those things are even remotely true and not at all what this disease is about. Heck ME/CFS isnt really about fatigue in the way most people think it is. Before I got ME/CFS like every healthy person I had been tired or fatigued from time to time because I had a lot to do, but this, what we all have now, this isn't just fatigue it's a constellation of symptoms that is so overwhelming and so serious that no matter what I do it just doesn't go away and the years being like this are ticking by.

 

[heapsreal]

Yes I agree with @SOC I think we shouldn't be paranoid, but again I haven't experienced the kinds of prejudice and unfair treatment people on PR have gone through.

I guess I'm not afraid because I have given no one anything to worry about as of yet, I do an excellent job with my team at NIH, I've never asked for any special treatment, I never used any extra time off other than my own personal leave, and last but not least I really love my job and what I do and people at work see that and how much I do.

ME/CFS has made my life really bad, constantly managing the symptoms and fluctuations, PEM and crashes, doctors appts and treatment, and destroying my social life but for as long as I can possibly continue I will not let it affect my job and soldier on.

Hopefully one day public understanding will be such that we can tell people about this serious physical disease that we have without feeling people will think we are just lazy, or lying, or even worse crazy, because we all know none of those things are even remotely true and not at all what this disease is about. Heck ME/CFS isnt really about fatigue in the way most people think it is. Before I got ME/CFS like every healthy person I had been tired or fatigued from time to time because I had a lot to do, but this, what we all have now, this isn't just fatigue it's a constellation of symptoms that is so overwhelming and so serious that no matter what I do it just doesn't go away and the years being like this are ticking by.

I totally understand as im in a similar boat. Isnt it strange that those of us who work in a health system are hiding this illness as we know that many dont understand and we would probably be victimized , even laughed at by our fellow health care workers .

 

[Jonathan Edwards]

Have you thought or considered vasospasms as in prinzmetal (spelling) angina or something similar occurring in the brain. So as in PM angina which show ST elevation on an ecg, would normally be a sign of infarction in a chest pain episode. With pm angina , glycerol trinitrate gtn relaxes the vasospasm and the ST elevation goes away. But during a myocardial infarct gtn generally doesnt stop the ST elevation and myocardial perfusion. Although through colateral circulation improvements from gtn can help perfusion and reduce size of the infarct.

so i wonder if a similar vasospasm could be occurring in cfsme and like pm angina , can come on with increased activity. This being a possible cause of hypoperfusion seen in cfsme.

food for thought ? ?

Vasculitis implies a structural change in the vessel wall. Vasospasm might occur with it short term but I would expect brain stem vasospasm to produce unconsciousness. Steady state hypoperfusion sounds like something different.

 

[xrunner]

Let me be clear I totally believe that there is some neuroinflammation in ME/CFS and it's been proven (Shungu et al, Nakatomi et al). I just think that it's a secondary effect to peripheral immune activation and this is also seen in a number of autoimmune diseases.

On Flagyl (but only late in my Lyme treatment as initially it made me feel worse) I used to feel brain power coming back on and as normal as I could remember. Physically it doubled my stamina (tested that). The effect went away after a couple of days off the drug.

 

[heapsreal]

Vasculitis implies a structural change in the vessel wall. Vasospasm might occur with it short term but I would expect brain stem vasospasm to produce unconsciousness. Steady state hypoperfusion sounds like something different.

I was thinking some sort of low grade vasospasm not necessarily Brain stem. Not uncommon cause of heaches. Something i fins is with brain fog is thatvit can turn into a headache and render me useless. Several episodes now where gtn has cleared this fog type headache feeling. Bp not high at 140/-,

 

[Scarecrow]

Several episodes now where gtn has cleared this fog type headache feeling.

Sorry if I've missed it in an earlier post but what is gtn?

 

[heapsreal]

Sorry if I've missed it in an earlier post but what is gtn?

Gtn is a shortened version of glycerol trinitrate amedication used in angina that stops blood vessels spasms and lowers bp. It also improves coronary blood flow by reducing cardiac workload through itsveffects on treating ans lowering the preload on the heart.

basically dilates blood vessels .

 

[heapsreal]

Unable to post a link as my computer has packed it in so doing all this on my phone which is a pain.

just want to add to the prenzmetal angina and vasospasm. There is research showing these vasospasms do have an element of inflammation . So with this in mind i think its possible that vasculitis is an issue in hypoperfusion and vasospasms could play a signicant role.

this may explain why dr jay goldstein had some success with nitrates as well as calcium channel blockers that help reduce blood vessel spasms that possibly improve fatigue and cognitive issue by helping relax these cerebral blood vessels.

this could also be why dr cheney has found low doses of klonopin helpful as its well known that benzos have muscle relaxing effects on blood vessels .

Viruses are a common cause of vasculitis that possibly cause these vasospasms that reduce cerebral perfusion ? ?

 

[Jonathan Edwards]

Unable to post a link as my computer has packed it in so doing all this on my phone which is a pain.

just want to add to the prenzmetal angina and vasospasm. There is research showing these vasospasms do have an element of inflammation . So with this in mind i think its possible that vasculitis is an issue in hypoperfusion and vasospasms could play a signicant role.

this may explain why dr jay goldstein had some success with nitrates as well as calcium channel blockers that help reduce blood vessel spasms that possibly improve fatigue and cognitive issue by helping relax these cerebral blood vessels.

this could also be why dr cheney has found low doses of klonopin helpful as its well known that benzos have muscle relaxing effects on blood vessels .

Viruses are a common cause of vasculitis that possibly cause these vasospasms that reduce cerebral perfusion ? ?

I think we need to distinguish inflammation from vasculitis. These are not the same. Inflammation is traditionally a process where a vessel allows white cells and fluid to enter a damaged tissue. Vasculitis is where the vessel itself is damaged by white cells. And vasospasm is by definition short lived so is not going to be reproducibly picked up on MRI done at a random time.

I agree that all these things have a degree of overlap, but it is important to keep in mind practical realities. Brain vessels normally leak even less fluid and cells than normal vessels in other tissues (the blood brain barrier) so even levels of fluid permeability tolerated by normal tissues tend to cause severe neurological problems. Vasculitis actually breaks the vessel wall. Basically a puff of wind overlaps with a tornado in theory but it does not get us far to think of puffs of wind as tornados.

 

[heapsreal]

@Jonathan Edwards
i originally mentioned vasospasms or maybe some type of low grade spasm after u mention blood vessel inflammation is unlikely . This is what reminded me of prenzmetal as its a vasospasm or coronary spasm which can last for minutes to hours. I'm also thinking in reverse how vasodilation can cause headaches and is sometimes mentioned as a cause of migraines . My thoughts were that this could happen in reverse.

just a thought about cerebral hypoperfusion . Other than systemic changes in blood pressure which happens in pots/oi, Im wondering what else could lead to this. Adrenaline , nor adrenaline receptors in blood vessels ? ?

the answer to this hypoperfusion i think will help alot with brain fog and cognitive impairment in cfsme.

 

[Eeyore]

Another point regarding hypoperfusion - Dr. Jay Goldstein noted in his patients that every effective treatment he used in ME (in terms of patients reporting symptomatic improvement) showed REDUCTION of cerebral perfusion. Why this is the case is unclear - but suggests that hypoperfusion may not cause the symptoms.

 

[Dr.Patient]

I think the core problem is acute or chronic mitochondrial dysfunction, citric acid cycle, etc hence the inability to produce energy.

The neurological part exists in all patients, if not cognitively, definitely in the autonomic nervous system, as seen by orthostatic intolerance. I don't think it is a primary central or peripheral nervous system problem.

When I have a good day, my gut is fine. On bad days, the gut starts acting up, with constipation. I still have no strength to digest chicken. The gut problems I attribute to low energy and autonomic dysfunction. I haven't messed around with gut microbes, etc, because I believe that microbes here are not the problem.

The immune part comes in in that a lot of these are caused by flu viruses that hit and run, something deranged with the immune system. The damage is already done. There is nothing great that immune modulators can do, as seen by the lack of consistent response to rituxan, for eg.

It is also not a persistent bacterial or Lyme either, hence the failure of antibiotics. Antiviral drugs help, by suppressing herpes and other viruses, since infection and relapses of viruses themselves can cause fatigue even in those without cfs.

There is no primary inflammation problem. Hence, the lack of response to anti inflammatory drugs.

For some reason, aggressive resting is the only thing that works (except in the really "gone" cases) somewhat, to some extent.

Until we crack this exertion-PEM link, there is no real treatment for this condition.

I'd like to call it Mitochondrial Neuro Immune Disease to reflect the components that are affected.

I have understood this illness as a physician, and feel it and live it everyday as a patient.

That's why I stuck to just rest and antiviral, other than other drugs for symptoms. I feel a little better than I did three years ago when this started, although I'm still homebound.

Now, the factor of Time comes in. Some people have gotten better after a decade, so that's what I'm hoping for.

If I weren't a physician, I would have probably tried all the treatments that people do.

I cannot imagine how I would have dealt with this illness if I hadn't had the medical knowledge and understanding and judgement.

 

[Dr.Patient]

Hence the term "myalgic encephalomyelitis" is clinically inaccurate and inadequate.

 

[xrunner]

If I weren't a physician, I would have probably tried all the treatments that people do.

There's only one way out of this illness and that is by trial and error.
There are a few small imperfect studies that may help people choose treatments a bit more rationally but in the end it is a trial and error journey. Best wishes.

 

[Marky90]

There is nothing great that immune modulators can do, as seen by the lack of consistent response to rituxan, for eg.

It wont be consistent if we are dealing with subgroups, but it can still be consistent for one subgroup. And thats what the 2/3 response rate is indicating. Some people also get their life back from IVIG

So saying that there is nothing great immune modulators can do, is simply a false statement

 

[docdan401]

It's very easy to obtain this from a reputable Japanese online pharmacy. I have tried it. It did next to nothing.

How long did u try it for and at what dose?

 

[Sidereal]

How long did u try it for and at what dose?

I can't remember unfortunately.

 

[docdan401]

How long ago was the experience? Can you elaborate any further? Was it from the mamaki-family-Japan site?

 

[leokitten]

How long did u try it for and at what dose?

Ibudilast in healthy volunteers: safety, tolerability and pharmacokinetics with single and multiple doses
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2675769/