Hypothesis: Nerve function causes CCSVI

H
You (Andy C) asked about the following paper.

EpubSternberg. Autonomic dysfunction: A unifying multiple sclerosis theory, linking chronic cerebrospinal venous insufficiency, vitamin D(3), and Epstein-Barr virus. Autoimmun Rev. 2012 Apr 28.MS is a disease with multiple aetiologies. The most recent theory of the vascular aetiology of MS, Chronic Cerebrospinal Venous Insufficiency (CCSVI), suggests that cerebral venous obstruction could lead to cerebral venous reflux, promoting local inflammatory processes. This review article offers strong evidence that the route of the observed narrowing of cerebral veins arises from autonomic nervous system dysfunction, particularly cardiovascular autonomic dysfunction.

The dysfunction of this system has two major effects: 1) the reduction of mean arterial blood pressure, which has the potential to reduce the cerebral perfusion pressure (the pressure following through the hole in the blood vessel) and the transmural pressure (the pressure going through the wall of the blood vessel), and 2) the failure of cerebral autoregulation (the blood vessel wall can change its thickness to make the hole in the vessel bigger or smaller) to maintain constant cerebral blood flow in the face of fluctuations in cerebral perfusion pressure. Alterations in cerebral autoregulation could in turn raise the critical closure pressure (if the pressure to keep the hole in the blood vessel falls below a threshold the vessel collapses and closes), indicated to be the cerebral perfusion pressure at which the transmural pressure will be sub-sufficient to overcome the active tension imparted by the smooth muscle layer of the vessel (Smooth muscle is only ffound around arteries and arterioles=small arteries and not veins or venules=small diameter veins). These two effects of autonomic nervous system dysfunction (reduction in arterial blood pressure and alterations in cerebral autoregulation), when combined with inflammation-induced high levels of nitric oxide in the brain, will lower transmural pressure sufficiently to the point where the threshold for critical closure pressure is reached, leading to venous closure. In addition, cerebral vessels fail to overcome the closure as a result of low central venous pressure, which is also regulated by autonomic nervous system function. Furthermore, through their neuroregulatory effects, infectious agents such as the Epstein-Barr virus and vitamin D(3) are able to alter the functions of the autonomic nervous system, influencing the rate of CCSVI occurrence. The absence of CCSVI specificity for MS, observed in recent clinical studies, may stem from a high prevalence of autonomic nervous system dysfunction in control groups which were recruited to these studies. Future studies should investigate CCSVI in relation to cardiovascular autonomic function.

Don’t understand..Check out Ali G on YouTube (First 30seconds 🙂

In brief the paper is trying to link CCSVI, virus and sunlight and immunity together, which one needs to do to make a compelling view of the disease in MS.

First you must accept that CCSVI is an entity and one must say that many people do not! If you think not then the whole story falls apart. However let’s not worry about that and we should look at what the person is infering assuming CCSVI occurs. My take is that this idea says that CCSVI is not the cause, but a consequence of MS.


They argue that CCSVI is not specific for MS, but is a problem in other conditions. Likewise treatment, is of limited value as it is not getting at the cause and that is why closure of the veins occurs quickly after venoplasty. They can link the problem to inflammation and its affects on the blood vessels. The author thinks that CCSVI does not occur in all MSers and this is better correlated to the proportion of people with defects in autonomic nerve problems.

The autonomic nervous system, which controls involuntary actions, like breathing, can innervate both the immune glands and also the blood vessels so it can control blood pressure. This can be through control by affecting muscles in arteries and on the heart etc. The nervous system can also affect how immune glands function and so this autonomic nervous system (see yesterdays video) is the linch pin that explains MS.

Because of damage to signalling within the autonomic nervous system due to MS, it is suggested that there can be relaxation of vessels (arteries) and that they collapse and restrict blood flow and this can lead to obstruction of the vein. This is not only influenced by the blood pressure but also the sponginess of the blood vessels (termed autoregulation). There can also be collapse of the veins because of autonomic nervous activity, so you have CCSVI. However if arteries collapse and block this would be the same as a stroke and MS is not stroke.

Inflammation leads to part of the autonomic defects and can affect the blood vessels directly. The author then says that the autonomic nerve system can affect the immune system and that virus can affect the autonomic nerve system and so this all hangs together….lovely However this link is abit strained and with abit of thought, you could link these outputs to a number of other causes and effects.

Therefore, this paper is not much for treating CCSVI, as the condition will come straight back. It affects arteries and reflux and back jets and values are not mentioned, which is not part of some CCSVIers world view.

This area is not my field so please accept my apologies if it is not quite spot-on or sufficiently described. There is information about how the arteries may collapse (relating to transmural pressure etc.) but I’m sure there will be CCSVIers saying it is all veins.

This is an just idea, but is it chicken or egg? The implication is that the autonomic nervous system effect is more chicken and the inflammatory response is more of an egg and the CCSVI would be a by-product of the chicken. Some of you may think that the problem is the vessel and egg.

But the problem is that this is just more armchair science and we will have to wait until the author or a follower actually does something to test the hypothesis. This means activity from the author is required. It is eay to build up ideas on facts that may be just half-truths, which I don’t have the knowledge to expose or the desire/time to learn and expose.

This is not Research it is Armchair science,

CCSVI Research Posts at the End of the Month

About the author

MouseDoctor

4 comments

  • Hi Mouse Dr,

    Thanks for the acknowledgement that I am a real person, it's much appreciated.
    If you're the Guy with the ponytail and a penchant for real ale, we did in fact meet at MS Life in Manchester. You might remember me as being the Father of the 12yr old who had her leaflets confiscation, who at this action took it upon herself to ask you a few questions. It certainly wasn't a us and us situation that weekend and definitely still feels like us and them situation, but I do appreciate you giving me/us your time on this paper.
    As you say, "enough of this cack".

    It's a bit early in the morning, but I'm glad you agree with the possibility that given the funding and if thoroughly tested this set of theories can enlighten us all.

    Having first hand experience and understanding the very nature of veins / valves with their unpredictability and possible failure shouldn't mean they should not be dealt with if a problem can be seen.Surely the challenge should be to overcome with better and newer techniques.
    The argument re the Chicken and Egg is one to muddy the waters at this stage and when considering symptom relief is one that shouldn't be entertained, especially given DMD's are not addressing the cause.
    Most pwms would give their right arm for some symptom relief regardless of if the disease is not fully understood yet, as I'm sure you appreciate.

    I thank you and will go away and digest with interest your comments and track down the Author.
    a
    By the way, one piece of news whether reported in 100 or 1000 different media still only makes it ONE piece of news. The irony of posting it ten times amounts to you spamming your own blog, I do hope the moderator will have a word with yourself, as this doesn't fit well with the new 'Entente Cordiale' Relationship'.

    Regards Andy Clarke
    (still many more questions than answers,"I'll be back")

  • Dear Arnie 🙂 (I'll be back) sorry Andy

    Re Grey Ponytail and perchant for Real Ale….

    Must have been someone else as I don't drink or like real ale.

    Re Symptom Relief… Lets hope the trials show it.

    Re: The multiple posts and spamming. Nice one:-). I didn't do them the moderator will have to have words with the boss

  • Well said Andy. Surely the bottom line is that it is time for MS to move out of the one size fits all explanation, there is need for a concerted effort at looking outside the auto-immune box for the cause or causes of MS. One thing is known: inflammation is secondary to oligodendrocitic unprogrammed death, therefore auto-immune theory needs to be put aside even if only temporarily. One question that comes back to me over and over is why are these multiple scars we call a disease not evident sooner in a person's life? Something is happening which takes time to develop and it develops faster in some people than others, multiple scars are symptoms of something else and maybe CCSVI is also a symptom of something else, but in the meantime as CCSVI treatment relieves some of the symptoms resulting from an unknown cause then is it not worth doing, after all DMDs are aiming at reducing symptoms and the proof that they are working is pretty scant. We need to redraw the lines and we need to do that now.

  • I forgot to turn commennts off as is usually for CCSVI posts but I have done so now.

    I have removed my Cack from the beginning of the post. As thought it was well abit naff.

    Whilst Andys first papragraph may not appear easy to understand now, it was when it was posted.

    However with regard to comment by Michelle

    "There is need for a concerted effort at looking outside the auto-immune box for the cause or causes of MS".

    Maybe read the posts of Prof G and the Charcot Project, he is not convinced by the autoimmune hypothesis.

    However should one think that autonomic nerves and blocked veins are the box, I am not so sure as there is not sufficient evidence.

    "One thing is known: inflammation is secondary to oligodendrocitic unprogrammed death, therefore auto-immune theory needs to be put aside even if only temporarily".

    At present it is known that inflammation is present when oligodendrocyte death is occuring.
    Microglial responses are part of the inflammatory response, do not just think lymphocytes are inflammation.

    "One question that comes back to me over and over is why are these multiple scars we call a disease not evident sooner in a person's life?"

    How do we know when the scars really start? You only get to see them after death with is years down the line. This is no doubt occuring before diagnosis so I think you are right

    "Something is happening which takes time to develop and it develops faster in some people than others",

    Sounds good

    "multiple scars are symptoms of something else"

    I think that the scars are part of a repair process, just as a scar on the skin is part of a repair process, but in this case it is not repair back to normal. So perhaps a failed repair process.
    They are a "sign" of past disease activity.

    "and maybe CCSVI is also a symptom of something else",

    Some might say imagination :-), but others such as the present post believes their is a cause for CCSVI. I think that they would have been better to focus their article on this.

    "but in the meantime as CCSVI treatment relieves some of the symptoms resulting from an unknown cause then is it not worth doing",

    We will see if CCSVI is relieving symptoms then the results of the trials are in, then we can dismiss a placebo effect, natural history of disease course". If it works then we can look into the reasons for it working. That we do not know how things work is not a reason for not doing things.

    "after all DMDs are aiming at reducing symptoms and the proof that they are working is pretty scant".

    No aim of of DMD is not aiming at symptom control e.g inhibiting spasticity, pain, etc. but at the
    disease process that result in symptoms occurring. There is clear proof that DMD so something useful for RRMSers. You are diluding yourself if you think otherwise.

    The problem I have with this argument is that even if autoimmunity has nothing to do with MS, this is irrelevant to whether CCSVI is a valid approach.

    TWO WRONGS DO NOT MAKE A RIGHT

    When CCSVI is shown to be an entity and angioplasty is shown to work to a standard that we ask of any drug then great. If fact if angioplasy works, does it matter if it has anything to do with CCSVI. Answer is no. But all we ask for is the same burden of proof as we would for any other drug.

    We have been through all these arguements before and that it why it is best not to take comments not because we want to stiffle free speech, but the arguments are circular and move us nowhere

By MouseDoctor

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