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

Discussion in 'Other health news and research' started by JenB, Dec 9, 2019.

  1. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I missed that, but from the abstract it does not look as if this was a meaningful blinded controlled trial. 80% of people tend to say they are better if asked following an invasive procedure.
     
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  2. GloriaDG

    GloriaDG Established Member

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    Sorry, in that case I should have said that "they both have hemorrheologic properties" instead.
     
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  3. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Arteries have progressively reducing diameters until they feed in to arterioles where the calibre goes down to about 50microns before joining capillaries. 50 microns is less than the width of a hair. If Pentoxifylline has any useful effect on blood flow it is likely to be at the arteriolar level where red cell aggregates may matter. That is probably what people mean by use in arterial flow.

    In practice I am not sure that Pentoxifylline ever did anything very useful. I seem to remember it being around from about 1985 and there was initial enthusiasm but nobody really believed it did much.
     
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  4. Trish

    Trish Moderator Staff Member

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    I think the point is, whenever anything is posted on this forum which presents a new hypothesis, we will examine it in two ways. One, does the hypothesis make sense within current understanding of physiology? Two does the research evidence presented fulfil the requirements of research, for example, does a clinical trial have either double blinding or objective outcome measures.

    On the first of these, problems that strike me as not making sense physiologically include the hypothesis that stugeron has an effect on blood flow in a large vessel like the jugular, even if there is stenosis. I find @Jonathan Edwards explanation about the size of blood vessels helpful in understanding that this doesn't make biological sense.

    On the second, he points out that the trial mentioned of surgery on the jugular vein for Menieres disease appears to have been unblinded and to have subjective outcome measures, so scientifically unreliable, just like the PACE trial.

    We are a science based forum. It is not a matter of the eminence of researchers making claims, it is a matter of the quality of evidence placed before us, whether in an anecdote, or a secondhand report from a researcher, or peer reviewed publication.

    As the paper linked in the first post says the field of jugular vein stenosis and whether it leads to symptoms, and how it can be treated is not an established field. So it is hardly surprising if we want to challenge an unproven and seemingly implausible hypothesis based on a single anecdote.
     
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  5. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I think I am just saying that we should not be taking anybody's word for it.
     
  6. JenB

    JenB Senior Member (Voting Rights)

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    I have never heard of this. Is there anything published or is this described anywhere?
     
  7. JenB

    JenB Senior Member (Voting Rights)

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    So interesting. I didn’t realize Stugeron was cinnarizine.

    Cinnarizine is also an antihistamine and a calcium channel blocker. There’s a whole discussion on PR about its possible effects on symptoms in relation to this conversation: https://www.me-pedia.org/wiki/Neural_strain Specifically, biomechanical stress on nerves can cause calcium influx, and so some people wondered whether calcium channel blockers can help.

    Cinnarizine is used to help counteract the pathophysiology of early post-TBI, which looks a lot like the pathophysiology described on that MEpedia page. It may do this through multiple mechanisms, perhaps calcium, obviously by increasingly blood flow.

    I would not be surprised if this drug would be a part of doctors’ reperatoires in the US, if it were available here. It is not and I don’t think we have an equivalent.
     
  8. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I would assume that cinnarizine is used after traumatic brain injury for dizziness/nausea just as it is used for motion sickness - nothing to do with blood flow. I doubt the anti-vertigo effect has anything to do with calcium channel blocking. It is common to phenothiazine and antihistamine type drugs like prochlorperazine (stemetil) which is also used for nausea etc. and is available in the US I believe and is not as far as I know a calcium channel blocker.
     
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  9. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I think this started with the observation by Venables about 30 years ago that people with ME/CFS have higher levels of anti-phospholipid antibodies (APLA). APLA are associated with episodes of thrombosis but also with lupus-like illness.

    While the observation interesting I don't think it has been replicated. Also, there was no evidence of any thrombotic episodes in the cases of ME/CFS so there is no documented link to thrombosis in ME/CFS. Also note that this is not a haemorheological problem but a coagulation problem, although rheological problems of other sorts can precipitate coagulation.

    There has been some discussion in the past of individuals with ME having APLA and also genetic thrombotic tendencies like Factor V Leiden and Protein C deficiency. However, these are quite common genetic variations so it is unclear that there is anything significant in that.

    None of this would be relevant to brains unless a clotting episode occurred. Venous sinus thrombosis usually produces very obvious and severe symptoms not likely to be confused with ME.
     
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  10. JenB

    JenB Senior Member (Voting Rights)

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    It could still very well be relevant. If you have transverse sinus stenosis for example (TSS), which is much better studied than jugular vein stenosis, at the margins, wouldn’t someone with a coagulation disorder be more likely to have intracranial hypertension as a result? In other words, the same level of stenosis that would be asymptomatic in some people might cause symptoms in others, due to the interaction of the two? In the case of TSS + IIH, it’s not actually full on thrombosis, just slow drainage that elevates ICP.
     
    Last edited by a moderator: Dec 15, 2019
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  11. JenB

    JenB Senior Member (Voting Rights)

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    It’s an old drug and not a front line treatment, but everything I see re: cinnarizine and TBI is that it’s used to increase cerebral blood flow.
     
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  12. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I would be interested to know where you see that.
    And I cannot quite see what increasing cerebral blood flow has to do with anything we have been discussing - which was the idea of outflow stenosis, not inflow. Increasing cerebral blood flow in the presence of raised pressure would be expected to make things worse if anything.

    We seem to be going round and round with unrelated snippets of physiology that add up to nothing relevant to this website!
     
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  13. JenB

    JenB Senior Member (Voting Rights)

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    Yes and no. There’s a whole line of inquiry around intracranial hypertension and ME/CFS, now being pursued by three different research groups in Europe, so in that sense this is all relevant. In addition to which, this story/thread was motivated by the experience of an ME/CFS patient.

    My understanding is that the vasodilation works on all blood vessels, whether they are veins or arteries, and that vasodilation could reduce pressure by generally improving blood flow. When you have poor venous drainage it can be associated with hypoperfusion, I assume due to feedback mechanisms (?). Cinnazarine might act to improve blood flow to the brain, within the brain, and from the brain.

    As to where I am seeing it, several different articles on Google Scholar. I am assuming this is how the idea ended up on Wikipedia. Do you want me to pull the articles for you? This isn’t really a central line of inquiry for me.

    If you just search for “cinnarizine cerebral blood” there are a lot of articles referencing its utility for increasing cerebral blood flow: https://scholar.google.com/scholar?hl=en&as_sdt=0,5&q=cinnarizine+cerebral+blood+&oq=

    As for TBI specifically:

    “Cinnarizine is an antihistaminergic and calcium channel blocking agent that has been used in Europe since 1955 for the treatment of motion sickness, vertigo, and to increase cerebral blood flow in post-traumatic brain injury.” https://zero.sci-hub.tw/2785/2bd2472f6cabbc79b13719eb7043b69c/disabella2014.pdf

    I came across some other references a few days ago but can’t find them at the moment.

    I think we are stuck in these weeds in part because you want to interrogate whether the information patients share here is anatomically possible. Given that everything is essentially contested, it brings us on many different tangents. I don’t mind this—I learn a lot in the process.
     
    Last edited: Dec 16, 2019
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  14. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    We have already had threads on this research and discussed the weaknesses in their approach. They are not relevant to the fact that we are going round in circles about confused physiology here.

    We have just discussed the fact that cinnarizine is thought to have a hemorheological effect, not a vasodilatory effect. And no, vasodilators work differentially on different vessels in general. I do not wish to go over it all again.

    There are always articles saying anything on Google Scholar. The question is whether or not anyone has any usable evidence. As far as I can see the great majority of stuff on this topic is speculative. It looks as if most of it is based on experimental systems in rats that probably have little relevance to real human clinical situations.

    It is all such a long long long long way from being of the slightest relevance to ME as far as I can see.
     
    Last edited by a moderator: Dec 16, 2019
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  15. Trish

    Trish Moderator Staff Member

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    The articles listed on the first 2 pages are mostly rather old research on rats, or not about cerebral blood flow. The only human one I found was not accessible. The sci-hub link you gave didn't work for me.

    Don't worry about trying to find more. As @Jonathan Edwards has said, this all seems far removed from anything relevant to ME.
     
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