People with ME/CFS can have hypervolemia and not low blood volume

[adreno]

Adreno, could you please name some examples of (selective) alpha-1 agonists and spare me the futile google search? I would appreciate it. Thanks.

Midodrine is one. I used mirtazapine, an alpha-2 antagonist (this has the same effect).

 

[Jonathan Edwards]

Why is this only imaginative? My understanding is that retrograde axonal transport of pathogens such as herpes, enterovirus, and rabies has been clearly demonstrated. Infection of the vagus and sciatic nerve by enterovirus has been demonstrated as well.

I guess because the for the other conditions the neuropathology has been known about for a century or more and it is hard to see why the vagus theory should leave no specific tell tale signs. There are just rather a lot of things that do not quite fit.. I don't rule it out. I think it's interesting. But it is an extrapolation without much to grasp hold of.

 

[lansbergen]

I guess because the for the other conditions the neuropathology has been known about for a century or more and it is hard to see why the vagus theory should leave no specific tell tale signs. There are just rather a lot of things that do not quite fit.. I don't rule it out. I think it's interesting. But it is an extrapolation without much to grasp hold of.

Why does a certain infectious agent move faster then the flow inside axons?

 

[halcyon]

it is hard to see why the vagus theory should leave no specific tell tale signs.

Signs like gastric motility issues, IBS, hypochloridia, cardiac issues without structural anomalies, tinnitus, etc? I think a lot of these are pretty familiar to people with ME.

 

[ahimsa]

Autoimmune basis for postural tachycardia syndrome

For those who want more information, the Dysautonomia International blog has an article discussing the research study that adreno referenced above -- http://www.dysautonomiainternational.org/blog/wordpress/new-evidence-of-autoimmunity-in-pots/

 

[NK17]

Please @Jonathan Edwards take a look at this fresh blog post:
http://www.virology.ws

It's from Vincent Racaniello's blog.

"Many well-known human viruses, including poliovirus, rabies virus, West Nile virus can infect cells of the nervous system, leading to the alterations of the function of that organ."

Vincent Racaniello is Prof. of Microbiology and Immunology in the College of Physicians and Surgeons of Columbia University.

 

[Gingergrrl]

I am surprised no one has mentioned chronic infection leading to disruption of the autonomic system leading to "shits" in blood volume.

@JBB This is exactly the point that I was trying to make and we are in agreement here!

I am not sure what a 'core theory' would be. I don't know of any serious researchers who have provided a theory on this - except perhaps the idea that viruses creep up the vagus nerve, which seems a bit imaginative. It seems from the Dubbo study that when persistent fatigue follows infection it does not matter much what the infection was. I certainly cannot think of a particular link between EBV itself and the autonomic system.

@Jonathan Edwards I have to respectfully disagree with you and want to explain why. When I said "core theory" I don't think theory was the right word. What I meant is that isn't autonomic dysfunction a core "symptom" or a core "part" of ME/CFS in most sufferers? Are you trying to say that it is either 1) Not a part of CFS or 2) a completely random coincidence that people like me who were in perfect health prior to mono now have autonomic dysfunction unrelated to the EBV or ME/CFS? I just want to make sure that I am understanding you correctly.

I bolded what you said re: it being imaginative and assume you are talking about the Vagus nerve theory by Dr. Michael Van Elzakkar? If so, what is wrong with new doctors and researchers being imaginative and trying to test out theories to help us find a cure? To me, being imaginative and creative here is what we need.

Lastly, I used the EBV virus in my example b/c it is the virus that made me so ill. But you could substitute any other virus or pathogen in it's place and I still stand by everything that I said re: a pathogen or infection leading to ME/CFS and the autonomic dysfunction that is a core part of the disease in most sufferers.

 

[Jonathan Edwards]

I am very grateful for all the due respect from everyone (you never know it might not be due) but I remain dubious - yet equally respectful of everyone.

The viruses that we know attack central nervous structures all have very individual characteristic pathologies. It seems that ME can occur after EBV, enterovirus, any other virus, no virus, organophosphate and maybe thirty seven other things and it tends to look much the same every time - or at least nobody has found any clearly defined clinical subgroups. It seems stretching the imagination to put all these down to creeping up the vagus nerve. As I have said several times before, a theory needs to be right on the details, not just the broad brush.

And the list halcyon gives does not actually look like vagus nerve failure to me. Autonomic, mostly yes, but not specifically vagus failure. (Tinnitus is as far as I know cochlear nerve, not autonomic.)

I agree Gingergrrl, that these autonomic features are characteristic of ME but my scepticism is directed at a theory that says they are caused directly by virus in a particular place. Of course there are theories that they are caused by the aftermath of an immune response with maybe 'cytokine storm' and 'central sensitisation' but I think it would be wrong to see that as analogous to rabies or varicella, which parasitise the CNS in very specific ways.

But it is useful to argue about all this because it does bring the questions in to sharp focus.

 

[lansbergen]

Cochlear nerve is part of a cranial nerve. I always thought most if no all cranial nerves are affected Looking at how improvement goes lately I am pretty sure in my case all cranial nerves are involved.

 

[Jonathan Edwards]

Cochlear nerve is part of a cranial nerve. I always thought most if no all cranial nerves are affected Looking at how improvement goes lately I am pretty sure in my case all cranial nerves are involved.

Yes, but it is not autonomic - that was the issue.

 

[Marco]

Yes, but it is not autonomic - that was the issue.

Bearing in mind that tinnitus is another non-specific symptom with potentially many causes, some on line summaries do list tinnitus as a symptom of autonomic/peripheral neuropathy although I'd like to see the source material.

One paper though hypothesises long term T1 diabetes affecting the function of auditory brain stem mechanisms :

http://www.tinnitusjournal.com/detalhe_artigo.asp?id=155

 

[Jonathan Edwards]

Bearing in mind that tinnitus is another non-specific symptom with potentially many causes, some on line summaries do list tinnitus as a symptom of autonomic/peripheral neuropathy although I'd like to see the source material.

One paper though hypothesises long term T1 diabetes affecting the function of auditory brain stem mechanisms :

http://www.tinnitusjournal.com/detalhe_artigo.asp?id=155

It would be a cranial neuropathy, by definition, rather than peripheral. The trouble is that people tend to get that idea that 'diabetic neuropathy' is a process in its own right rather than the neuropathy caused by diabetes. I am sure diabetes could damage the cochlear nerve just as it damages almost everything else!

 

[Marco]

It would be a cranial neuropathy, by definition, rather than peripheral. The trouble is that people tend to get that idea that 'diabetic neuropathy' is a process in its own right rather than the neuropathy caused by diabetes. I am sure diabetes could damage the cochlear nerve just as it damages almost everything else!

A little sloppy to list tinnitus as a symptoms of 'diabetic neuropathy' but the linked paper does suggest, as you suggest, that whatever is causing peripheral and autonomic neuropathy in diabetes (oxidative stress is often blamed) may also damage sensory nerves which makes perfect sense with a systemic illness.

Tinnitus interests me, because I've had it constantly since ME/CFS onset and while not a significant symptom in itself I can't help thinking that it may point to some specific disease pathway. I'm not sure if it's mentioned (can't access the full paper) but in the following intervention using CoQ10 for Gulf War Illness (where symptoms have a high degree of overlap with ME/CFS) I was told prior to publication that one one of the symptoms that improved markedly was tinnitus :

http://www.mitpressjournals.org/doi/abs/10.1162/NECO_a_00659#.VGYmnvmG9O0

I'm also surprised that abnormalities in event related potentials as used in the diabetes/tiinnitus paper haven't been studied more in ME/CFS. If there is an issue of disturbed sensory processing, given that nerve conduction speed can be estimated, you could potentially 'map' the dysfunction to the brain stem of later/higher brain structures.

Anyway, back to hypervolemia.

 

[Jonathan Edwards]

Tinnitus interests me, because I've had it constantly since ME/CFS onset and while not a significant symptom in itself I can't help thinking that it may point to some specific disease pathway. I'm not sure if it's mentioned (can't access the full paper) but in the following intervention using CoQ10 for Gulf War Illness (where symptoms have a high degree of overlap with ME/CFS) I was told prior to publication that one one of the symptoms that improved markedly was tinnitus :

Tinnitus is extraordinarily 'gate' sensitive. I have had it for forty years and it can either be a real pest or completely unnoticeable - and I don't think anything is changing in the cochlear nerve during this. To me a link with ME would reinforce the idea that there is a gating failure in the brainstem.

 

[Marco]

Tinnitus is extraordinarily 'gate' sensitive. I have had it for forty years and it can either be a real pest or completely unnoticeable - and I don't think anything is changing in the cochlear nerve during this. To me a link with ME would reinforce the idea that there is a gating failure in the brainstem.

As I said there's a dearth of 'gating' studies in ME/CFS. I'm aware of only three over many years. One found no abnormailites, one (student dissertaion) did after controlling for other variables and one large study of childhood 'CFS' using a visual stimulus found no early (50ms post stimulus which might equate to the brain stem) abnormalities but significant differences in amplitude and latency at 300ms which is assumed to reflect attentional processes.

None of these used a somatosensory stimulus which might be particularly interesting.

 

[Jonathan Edwards]

As I said there's a dearth of 'gating' studies in ME/CFS. I'm aware of only three over many years. One found no abnormailites, one (student dissertaion) did after controlling for other variables and one large study of childhood 'CFS' using a visual stimulus found no early (50ms post stimulus which might equate to the brain stem) abnormalities but significant differences in amplitude and latency at 300ms which is assumed to reflect attentional processes.

None of these used a somatosensory stimulus which might be particularly interesting.

I think the trouble with lab based studies is that the sort of gating we are interested in may not operate. If I was to be a subject for a tinnitus study I would hear it all the time in the lab but might not when I went for a cup of tea. In ME the theory might be that the gate cannot by closed even in the tea room. One might need quite a clever distraction study. This might be where James Baraniuk's fMRI of pathway use might come in?

 

[Marco]

I think the trouble with lab based studies is that the sort of gating we are interested in may not operate. If I was to be a subject for a tinnitus study I would hear it all the time in the lab but might not when I went for a cup of tea. In ME the theory might be that the gate cannot by closed even in the tea room. One might need quite a clever distraction study. This might be where James Baraniuk's fMRI of pathway use might come in?

I'm pretty sure that a gating deficit operates at a pre-attentive level and yes I'm also sure that when distracted my tinnitus goes unnoticed but that doesn't mean it isn't there.

But these are fundamental measures of the general reactivity of the nervous system and unlikely to context dependent. While you and I may both not notice our tinnitus while having a cup of tea in the cafeteria I'm pretty sure that the general ambience of the cafeteria is bombarding all of my senses much more than yours. Many of us struggle with environments such as a supermarket because of the overstimultion.

I doubt that the lab environment would underestimate the gating deficit if it's there.

 

[Jonathan Edwards]

You are probably right, Marco. It has to be something more subtle. That always seems to be the trouble!

 

[Gingergrrl]

I have never had tinnitus and not sure how the topic shifted! but I was trying to understand if Dr. Edwards believed that blood volume issues are autonomic as part of ME/CFS. I used the Vagas nerve theory as one explanation (and think it holds promise) but regardless if it is Vagas nerve or another cause, I was just confused when he seemed to imply that autonomic issues in the brain were not affecting things like the regulation of blood volume, BP, heart rate, breathing, temperature, and maybe even hunger and thirst in ME/CFS? That is what I was trying to clarify.

 

[Marco]

You are probably right, Marco. It has to be something more subtle. That always seems to be the trouble!

Not sure that's what I was saying Jonathan. There are many causes of tinnitus. You may have tinnitus as an isolated sensory hypersensitivity/gating deficit (for want of a better description) due to?. I'd suggest any gating deficit is generalised in ME/CFS and 'should' show up in these sort of lab based tests.