Understanding jugular venous outflow disturbance, 2018, Zhou et al.

[Mij]

@GloriaDG

It also pings for me as it is an example of a concept I keep encountering: that there are patients who have a congenital, anatomical abnormality that prior to an infection, is completely or largely asymptomatic, and that only becomes apparent after a major inflammatory event. That was the case for me with tethered cord syndrome and, apparently, in this patient with IJVS.

This sounds similar for the subgroup of patients who were in the hereditary hypercoagulation state group presented for ME years ago, that they needed a different treatment approach because the 'trigger' that caused thickening of blood resulted in some form of injury to the vascular system.

 

[Trish]

The symptoms you mentioned are also classical symptoms of Meniere's disease. Stugeron is also known to be prescribed for Meniere's disease. Here's an interesting study correlating Meniere's and CCSVI:
https://www.ncbi.nlm.nih.gov/m/pubmed/28034701/?i=2&from=/24594584/related
"CCSVI was diagnosed in 175 (87.5%) patients with MD. Venography was performed in 69 patients to confirm the diagnosis of CCSVI. In 80% of these patients, PTA of the IJV and/or AV was effective for treating signs and symptoms of MD. In the healthy cohort, CCSVI was observed in only 12% of subjects.

CONCLUSIONS: These results suggest a possible etiologic relationship between CCSVI and MD that warrants further investigation."

Just a coincidence you say?

I think perhaps we are talking at cross purposes here. I was focusing on the claim made in Jen's opening post about an individual finding their ME symptoms improved while taking Stugeron. I suggested that since stugeron has such a wide range of effects, it could be acting on something other than the jugular vein to have those effects.

The information in the research quoted about jugular vein stenosis and Meniere's disease is interesting. But the treatment there was surgical, not drugs. And the symptoms being relieved were of Meniere's disease, not ME.

As I understand it, the effect of stugeron on Meniere's disease is thought to be to do with the action elsewhere, not on the jugular vein:

Cinnarizine blocks the receptors in the vomiting centre, preventing it from receiving nerve messages from the vestibular apparatus. This helps to reduce symptoms such as nausea, vomiting dizziness and vertigo.

I am cofused also by the linking of stugeron and Pentoxifylline which seem to be two completely different drugs with different actions and used for different purposes.

 

[Jonathan Edwards]

I think that you're still reading lines in between paragraphs that are not there. Have I ever mentioned vasodilator properties?

The first post says Stugeron was suggested because it is a vasodilator.

So if a person with jugular stenosis takes stugeron or Pentoxifylline, the blood will pass through the narrowing much more easily,

No, that is highly unlikely. Rheological properties are unlikely to be of importance in the large venous vessels of the head. Rheology becomes important in very small tubes such as capillaries.

So in this case, the congenital defect that this patient had was likely triggered by the Dengue considering the way this virus affects blood and blood vessels.

I am not aware that there are any long term sequelae on blood vessels from Dengue of relevance here. The idea that Dengue was relevant appears to be a pure speculation on a single case.

Prof. Edwards, I'm not making this up, the effects of Stugeron/Pentoxifylline on the jugular venous system was explained to me by an Italian vascular surgeon that has been part of the CCSVI research and has been studying this for the past 10 years.

But that is precisely the problem. You are not making it up yourself but you are repeating pseudo physiology described to you by someone who does not understand real physiology. I have repeatedly come across people studying what they thinks physiology for decades who have failed to understand fundamentals. 95% of doctors misunderstand fluid physiology. Most think that oedema occurs in heart failure because of raised venular pressures and in nephrotic syndrome from low albumin levels and neither can be true. Bad physiology is the rule, not the exception. Fluid physiology was something I specialised in for a decade. Other people on the forum here are more knowledgeable than I about some other areas of physiology. I think you will find a general agreement that an awful lot of physiological studies are flawed.

 

[GloriaDG]

As I understand it, the effect of stugeron on Meniere's disease is thought to be to do with the action elsewhere, not on the jugular vein:

But how do we know that blocking these receptors is the reason why cinnarizine works in Meniere? My line of thoughts led to relating the way that Meniere was associated with CCSVI in that study, with the effects of PTA treatment and with the fact that Cinnarizine could work in Meniere in the same way this doctor suggested it worked in this Dengue ME patient, considering CCSVI as common denominator.

I am cofused also by the linking of stugeron and Pentoxifylline which seem to be two completely different drugs with different actions and used for different purposes.

Because both Stugeron and Pentoxifylline have the same hemorrheologic property.

 

[Jonathan Edwards]

The symptoms you mentioned are also classical symptoms of Meniere's disease. Stugeron is also known to be prescribed for Meniere's disease.

Stugeron is prescribed in Meniere's disease because of vertigo and nausea because it belongs to a group of antihistamines that help those symptoms in general. So the use in Meniere's has nothing to do with venous stenosis.

 

[Trish]

Because both Stugeron and Pentoxifylline have the same hemorrheologic property.

Can you point me to information that says Stugeron has a hemorrheologic property? I can't find any.

 

[Jonathan Edwards]

But how do we know that blocking these receptors is the reason why cinnarizine works in Meniere? My line of thoughts led to relating the way that Meniere was associated with CCSVI in that study, with the effects of PTA treatment and with the fact that Cinnarizine could work in Meniere in the same way this doctor suggested it worked in this Dengue ME patient, considering CCSVI as common denominator.

But didn't we say that the PTA treatment didn't work? And why relate Stugeron to an obscure speculation about venous stenosis when the common value of this group of drugs in conditions with vertigo and nausea has been known since before I was a medical student fifty years ago?

 

[GloriaDG]

The first post says Stugeron was suggested because it is a vasodilator.

My bad, I didn't see that. Well, it's not about vasodilating properties anyway.

No, that is highly unlikely. Rheological properties are unlikely to be of importance in the large venous vessels of the head. Rheology becomes important in very small tubes such as capillaries.

Based on what evidence are you stating this?

But that is precisely the problem. You are not making it up yourself but you are repeating pseudo physiology described to you by someone who does not understand real physiology. I have repeatedly come across people studying what they thinks physiology for decades who have failed to understand fundamentals. 95% of doctors misunderstand fluid physiology. Most think that oedema occurs in heart failure because of raised venular pressures and in nephrotic syndrome from low albumin levels and neither can be true. Bad physiology is the rule, not the exception. Fluid physiology was something I specialised in for a decade. Other people on the forum here are more knowledgeable than I about some other areas of physiology. I think you will find a general agreement that an awful lot of physiological studies are flawed.

"Someone who does not understand real physiology" how do you know?
This doctor I'm referring to is a vascular surgeon whit decades of experience in his field and 10 years of experience in the CCSVI research field. Ultimately he is a medical professional just as much as you are, while other people in this forum are not. From my point of view, it's his word against yours.

 

[Trish]

@GloriaDG I appreciate you are doing your best to explain what the vascular surgeon has told you. Do you have a link to his published work on this subject?

 

[GloriaDG]

Stugeron is prescribed in Meniere's disease because of vertigo and nausea because it belongs to a group of antihistamines that help those symptoms in general. So the use in Meniere's has nothing to do with venous stenosis.

Can you point me to information that says Stugeron has a hemorrheologic property? I can't find any.

It's on Wikipedia:
https://en.m.wikipedia.org/wiki/Cinnarizine
"Cinnarizine inhibits the flow of calcium into red blood cells, which increases the elasticity of the cell wall, thereby increasing their flexibility and making the blood less viscous.[9] This allows the blood to travel more efficiently and effectively through narrowed vessels in order to bring oxygen to damaged tissue.[9]"

 

[Trish]

It's on Wikipedia:
https://en.m.wikipedia.org/wiki/Cinnarizine
"Cinnarizine inhibits the flow of calcium into red blood cells, which increases the elasticity of the cell wall, thereby increasing their flexibility and making the blood less viscous.[9] This allows the blood to travel more efficiently and effectively through narrowed vessels in order to bring oxygen to damaged tissue.[9]"

As I understand it that is talking about the flow of blood in capillaries carrying oxygenated blood the last stage into tissues. As Ron Davis's experiments have shown in trying to test deformability of RBC's in ME, they need to make extremely narrow tubes to see the effect. Capillaries are several orders of magnitude smaller than the Jugular vein. There is no suggestion here that the deformability of RBC's has any effect on the flow of blood in larger vessels.

I think haemorrhagic properties of blood are to do with platelets and clot formation, not RBC deformability. A completely different process.

 

[GloriaDG]

But didn't we say that the PTA treatment didn't work? And why relate Stugeron to an obscure speculation about venous stenosis when the common value of this group of drugs in conditions with vertigo and nausea has been known since before I was a medical student fifty years ago?

We said that PTA is not effective in treating or preventing progression in Multiple Sclerosis. That was a study of the efficacy of PTA in alleviating Meniere symptoms.
Are you sure that in these fifty years the understanding of pharmacodynamics of this class of drugs hasn't advanced or broadened?

 

[GloriaDG]

As I understand it that is talking about the flow of blood in capillaries carrying oxygenated blood the last stage into tissues. As Ron Davis's experiments have shown in trying to test deformability of RBC's in ME, they need to make extremely narrow tubes to see the effect. Capillaries are several orders of magnitude smaller than the Jugular vein. There is no suggestion here that the deformability of RBC's has any effect on the flow of blood in larger vessels.

I think haemorrhagic properties of blood are to do with platelets and clot formation, not RBC deformability. A completely different process.

The definition of hemorrheology:
hemorrheology
[he″mo-re-ol´o-je]
the scientific study of the deformation and flow properties of cellular and plasmatic components of blood in macroscopic, microscopic, and submicroscopic dimensions and the rheologic properties of vessel structure with which the blood comes in direct contact."

Also, Pentoxifylline is used to improve blood flow through arteries too, so it's not just about capillaries:
https://www.rxlist.com/consumer_pen...m#what_is_pentoxifylline_and_how_does_it_work
Pentoxifylline belongs to a class of drugs known as hemorrheologic agents. It works by helping blood flow more easily through narrowed arteries. This increases the amount of oxygen that can be delivered by the blood when the muscles need more (such as during exercise) thereby increasing walking distance and duration.

 

[Jonathan Edwards]

"Someone who does not understand real physiology" how do you know?

Because I am a physiologist, amongst other things. When I see theories that misuse physiology the mistakes are apparent to me. I have pointed out some of the problems. There is a list as long as my arm of others but I am not sure it is worth wading through.

This doctor I'm referring to is a vascular surgeon whit decades of experience in his field and 10 years of experience in the CCSVI research field. Ultimately he is a medical professional just as much as you are, while other people in this forum are not. From my point of view, it's his word against yours.

I absolutely agree, but the story about venous stenosis we have been presented with so far looks to be full of holes and so far we have not seen any evidence to validate it. It is just a theory. If this chap had some evidence then it would be interesting to discuss but I have not seen any yet. 'His word' is as far as I can see baseless speculation. 'My word' is pointing that the theory does not add up and there is no evidence. Judging by the post quoted by Mij lots of other people are sceptical too. The real problem is that if his idea was true all sorts of other things would occur that nobody has observed. What matters most in science is the things that theories predict and don't happen.

Based on what evidence are you stating this?

Newton's law of viscosity.

 

[Jonathan Edwards]

Pentoxifylline belongs to a class of drugs known as hemorrheologic agents. It works by helping blood flow more easily through narrowed arteries.

Is there actually any evidence for this and a known mechanism? There may be but I have had difficulty tracking it down. The most obvious thing would be altering red cell rigidity, but that would only be relevant in capillaries and venules.

 

[Jonathan Edwards]

I found some studies suggesting that Pentoxifylline works by reducing red cell aggregation. That would make sense. I would expect that to become relevant for vessels of calibre less than 1mm - so narrow arteries and certainly arterioles might be included. I don't see it being likely to be relevant to venous sinuses.

 

[Jonathan Edwards]

t's on Wikipedia:
https://en.m.wikipedia.org/wiki/Cinnarizine
"Cinnarizine inhibits the flow of calcium into red blood cells, which increases the elasticity of the cell wall, thereby increasing their flexibility and making the blood less viscous.[9] This allows the blood to travel more efficiently and effectively through narrowed vessels in order to bring oxygen to damaged tissue.[9]"

So that would be likely to be relevant to very small vessels only - down at the 10-20 micron calibre.

 

[GloriaDG]

Ok, so you're saying that we shouldn't be believing everything that neurosurgeons and other surgeons or psychiatrists theorise and recommend as treatment within their own field of specialty, but we should take your word for it, on an online forum, without you providing any citation of evidence that backs up what you're saying, just because physiology is your field of specialty?

 

[GloriaDG]

Newton's law of viscosity.

But Pentoxifylline is used to improve arterial blood flow too, and arteries seem to be big blood vessels to me. https://www.rxlist.com/consumer_pen...m#what_is_pentoxifylline_and_how_does_it_work

 

[Trish]

The definition of hemorrheology:
hemorrheology
[he″mo-re-ol´o-je]
the scientific study of the deformation and flow properties of cellular and plasmatic components of blood in macroscopic, microscopic, and submicroscopic dimensions and the rheologic properties of vessel structure with which the blood comes in direct contact."

Also, Pentoxifylline is used to improve blood flow through arteries too, so it's not just about capillaries:
https://www.rxlist.com/consumer_pen...m#what_is_pentoxifylline_and_how_does_it_work
Pentoxifylline belongs to a class of drugs known as hemorrheologic agents. It works by helping blood flow more easily through narrowed arteries. This increases the amount of oxygen that can be delivered by the blood when the muscles need more (such as during exercise) thereby increasing walking distance and duration.

OK fair point, on that basis if Wikipedia is right, then the effect on RBC deformability would be classed as a hemorrheologic property. But to clarify the point I was trying to make, you said:

Because both Stugeron and Pentoxifylline have the same hemorrheologic property.

And I was trying to point out that it appears from what I have read that they may have different hemorrheologic properties, that may affect blood flow in different ways, including in size of blood vessels, so the possible relevance of one to flow in larger blood vessels doesn't automatically imply the other is relevant too.