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I am asking what pressure gradient we would expect in a healthy vein

I guess maybe the hangup is gradient, I do not believe there is a gradient in normal veins and gradient refers to the difference between two areas in comparison. There may be gradients between something like pulmonary veins and, say, the vena cava but I am not aware of it being something we check or monitor in people

Dear Marie, thank you, yes, that answers it pretty much. The way I understand it now is that during the procedure the pressure above the stenosis decreases by 3-5 cm H2O and the one below increases somewhat, so that in the end the pressure equilibrates above and below, i.e. there's no remaining gradient. I'm curious to ask Dr. Dake why he thinks the numbers don't matter. I can imagine that the absolute pressure numbers are not very meaningful, but it seems that the relative numbers, i.e. the gradient values, are meaningful. This is supported by the fact that the gradients appear to drop measurably.

It makes sense that there's no measurable gradient in a healthy vein, unless that would be measured over a large length span.

Thanks also Rose for sharing your experiences re pain.

Marie wrote:

The main point is there is enough pressure behind the stenosis to reflux and create collateral circulation and after the stent these are gone. Dr Dake told me the readings and numbers themselves are not actually meaningful, what matters is that the collaterals disappeared--they wouldn't be there if the pressure was not significant to the body and they wouldn't go if you didn't relieve it with the stent.

DITTO Dake told me ( and I am sure others) the same thing. Important thing is the collaterals became smaller or disappeared almost immediately.

cheerleader wrote: I think we need to rename this thread "Ask Marie" or "Dear Marie"
It's a terrific idea...so glad we have our med cred girl in the house!
cheer

I was just actually wondering, why does Marie spend so much time explaining things but doesn't make a salary like my neuro?

Lew, I'm on the other side of the spectrum as far as getting to the "O" is concerned, but this seems to be quite widespread among men and so probably isn't due to the CCSVI...Only wish we could trade some of our drawbacks and both be happier! Ok, sorry if this is TMI for the ladies...

Hello -- here is a question for Marie -- I saw the info about people with MS having differences in collagen in their veins compared to people without MS. It makes me wonder if this might turn out to be a connective tissue disorder, perhaps something along the lines of Ehlers-Danlos in which the there is one form where the blood vessels can have abnormalities (but the degree of abnormality is expressed differently in each individual who has it). I have known other people on MS boards who have EDS in their families.

So maybe we should get rheumatologists interested, not just neurologists?

LOL, thats all we need - so now we have neuros, inter radiologists, vascular surgeons, phlebotomists, immunologists, GP's, natural health docs (chelation of iron), nerve pain docs (name?) and we will add the rheumatologists!
Soon, we will have every specialist there is involved!!!
Just kidding, but it's amazing how many area's we are hitting.

Hi Marie and everyone else, too. This is a terrific thread! I'm learning lots of imortant information.

This is a lot of questions, I know, but even just a few answers would help immensely.

I have had a difficult time explaining how ccsvi causes damage. Am I terribly incorrect in saying (and believing) the following:

Types of Damage due to Reflux
1. Formation of collateral veins through delicate brain tissue causes damage to that brain tissue thereby causing new MS symptoms,
2. Stretching/straining of vein wall due to increased pressure ahead/before/in front of (is there a standard way of saying this?) the stenosis causes damage to the vein wall,
3. Iron deposition in a vein causes known (and unknown?) damage to the nervous system, such as ???
4. Inflammation, in and of itself, causes damage to delicate brain tissue.

Where/how/when do the following fit the ccsvi paradigm?
Inflammation - From 1 - 4 above?
Demyelination
Axonal loss
Lesion
Atrophy
Relapses - From 1 thru 4 above?
Remissions - From the immune system cleaning up iron deposits? From collateral veins finally linking up with main vein? From rewiring and/or remyelination? From all of the above?

Misc Questions
Why does/doesn't stroke happen with veins?
How do the collateral veins actually form?
What causes the BBB to be breached, what passes through it, and what are the effects?
Hypoxia causes what type of damage exactly?

Lately, right or wrong, I just tell people ccsvi is like having varicose veins in one's brain instead of one's leg... this is the closest analogy I have found, and it seems to please people -- I don't tell them venous insufficiency is the cause in both nor do I try to explain it anymore.

Thank you all very, very much.

~HP

HappyPoet, just a quick note. I think one has to distinguish between AREA OF BLOCKAGE, which is usually away from the central nervous system, i.e. in the jugular vein or azygous vein, and AREA OF NEURONAL DAMAGE, which is, obviously, upstream from the area of blockage. In that sense your point 1. of damage is a little confusing: the collaterals at the site of the stenosis do not affect the brain tissue, they're just an attempt to re-route the blood. This attempt is not completely successful, which is why there are measurable pressure differences above and below the stenosis.

EDIT: There's a paper by Barnett&Prineas that argued for hypoxia being the original cause of inflammation and iron deposition. This is from before CCSVI was known. I don't know if these authors had a theory up their sleeve what was the reason for the hypoxia. Marie knows i think, and maybe can reference that paper again...

Sharon wrote:Marie wrote:
DITTO Dake told me ( and I am sure others) the same thing. Important thing is the collaterals became smaller or disappeared almost immediately.

I wish I could understand this point of view. It seems to me that the pressure differences are meaningful as proven by the fact that they measurably change with the intervention. Seems to me this is quantitative proof, while the collaterals are qualitative proof.

I saw the info about people with MS having differences in collagen in their veins compared to people without MS.

I am excited to see what the research brings along these lines, there will be a lot to investigate it seems. I believe that most of the collagen diseases currently described are considered AI in some way, mixed connective etc are things treated with steroids. Ehlers Danlos is something an unrelated family member has, I actually know a little about that, it is genetic. What is so cool about this new avenue of research is it gives a new place for the researchers to look, perhaps even new gene areas to investigate.

In regards to this comment

I was just actually wondering, why does Marie know more than my neuro but doesn't earn $380 for each 15 minutes she spends explaining things on this board?

Thank you very much for the compliment but I absolutely do not know more than a doctor no way.

But I am not a doctor. When I am here it is as a fellow patient trying to navigate this crummy disease. Doctors could not spend their time answering our questions very well, it costs too much to put a roof over their secretaries, medical assistant's and patient's heads

I like doctors, they work hard and most sincerely care about quality patient care. Many have little time at home because of the demands of the work. Many times I have called a doctor at 2 am to get new orders for someone who was doing unwell and they have to wake up and think at that time of day..... Frequently they spend their lunch hour doing rounds at the hospital, and then after the work day of seeing demanding (hey, they're sick!) patients back to back, rounds at the nursing home. They are required to meet documentation regulations and thus a lot of the day is spent making sure t's are crossed and i's are dotted. On top of this, thousands of new research papers come out every week and they simply do not have time to read them. They rely on their respective guiding bodies for the answer as to what new research is important to understand.

Then they go in to the office and have to hear their patient say that they have now found the answer for MS... on the Internet. If they can reject it quickly, then they can get on with their day and get through what they need to get through. It is really understandable, given the real life demands of a doctor's schedule, that the majority are not interested in seeing this new work as important yet and do not want to make time to judge it for themselves, it is easier, and in many ways safer, to simply wait and see if it catches on with the medical boards; they'll find out soon enough if it is real. If you are the doctor, waiting 5 years to find out is fine, you can rationalize that being certain is worth the wait, and, like all medical professionals, you have learned that some patients will not be saved and you have learned to accept that as just a fact of life. If you did not learn to live with that you'd go mad.

Then there's me...Because my quality of life is already severely impacted by MS, and standard therapies have failed, I am really interested in this new model. It is not OK in my personal situation to wait 5 years; I do not have 5 years, and I am not willing to accept my own loss as an acceptable "cost" to waiting to see if blocked veins are related to MS causation or not. For me what makes sense is to treat the issue and see what happens. My personal doctor agreed with this. I am hugely biased by the urgency of my situation and I was willing to accept risk to get there.

But please understand that all the literature research in the world and anything I can say or explain about it is not equal to actual research proof. When 1000 people have been treated and 3 years have gone by with no new iron deposits, no new lesions and recovering EDSS, then we will know for sure.

Do I think this is the key to MS? Yes I do, but that is just OPINION based on preliminary materials available now. Real research will prove it. Luckily I think that is going to happen relatively soon.

i'll answer other questions in a minute
edit: I guess I should explain why I went OT on my OT physiology thread; I get really uncomfortable with being compared to a doctor, I do not want anyone to think I am a substitute for good medical advice because I am not

I wish I could understand this point of view. It seems to me that the pressure differences are meaningful as proven by the fact that they measurably change with the intervention. Seems to me this is quantitative proof, while the collaterals are qualitative proof

Rad, you like numbers. But in medicine numbers are not hard and fast often because people vary a lot. They are taking these number measurements for another data point, but apparently the proof is the body's response to the stents-disappearance of the collaterals. I am just repeating what he said as which is more important.

your point 1. of damage is a little confusing: the collaterals at the site of the stenosis do not affect the brain tissue, they're just an attempt to re-route the blood. This attempt is not completely successful, which is why there are measurable pressure differences above and below the stenosis.

I agree, you have to remember that the jugulars and azygos are in the neck/chest area not the brain

Barnett and Prineas

P&B Paper Pathology of a newly forming lesion

This paper primarily argues--actually shows-- that the brand new MS lesion occurs WITHOUT the t cells or any immune response. The oligodendrocytes had died before any immune cells arrived. The most recent announcement by Prineas as ECTRIMS was that new work is going to be really hugely groundbreaking and will show that there is something in the serum that causes the cell death in MS not the t cells etc (see ECTRIMS thread by Dignan, general section) The paper is a bit of a slog because it is so technical, but you can get it if you try

stretching the vein

My HP, what a lot of questions I will do my best

See the Simka monaco presentation and note the part about "tight junctions" (Research thread)

Also in venous insufficiency, ASSUMING this is the same and we do not have proof of that, the veins do become kind of stretched out and leaky allowing iron to cross into the tissue instead of it being contained in the vascular space. Iron is very necessary for many things including some brain stuff, but it is always tightly handled and controlled. When it leaks in to where it does not belong, the immune system responds to phagocytose the iron which changes its form to hemsiderin. In this form it is useless to the body and must go out through the kidneys. People with MS and people with venous insufficiency show hemosiderin in the urine (reference the big idea, research thread).

I am not sure if iron is damaging before the immune reaction to it, or if it is only a problem because the immune system is cleaning it up. I do know that the level of disability correlates well to the amount of iron deposition in the brain, but again is it the iron or the immune damage? I am not positive. It is known that immune activity is part of damage in venous insufficiency. Because of the decades of research on MS immune activity it is obvious that immune activity is key in CCSVI too.
Your other issues offered we have speculated on in these threads before but it is speculation...a guess based on the CCSVI model and what MIGHT be causing for example the relapse.

There will be a lot of new research into all of these aspects. Right now a lot is not known for certain though some guesses will be made so a direction for research can be planned (ie if someone thinks relapses are because of an intermittent worsening because of endothelial breakdown after stress, they will design a study to see if that is right)

The big thread has a lot of these things guessed and speculated about, the research thread actually has some resources. Please do read those. I will say that the big thread at 55 pages or so would be a TINY book--plus you can skip all the nonsense chatter posts...

Marie, I understand what you mean re pressure gradients. Probably comparable gradients are present in healthy veins so that they're not a good criterion for pathology.

mrhodes40 wrote:

I saw the info about people with MS having differences in collagen in their veins compared to people without MS.

I am excited to see what the research brings along these lines, there will be a lot to investigate it seems. I believe that most of the collagen diseases currently described are considered AI in some way, mixed connective etc are things treated with steroids. Ehlers Danlos is something an unrelated family member has, I actually know a little about that, it is genetic. What is so cool about this new avenue of research is it gives a new place for the researchers to look, perhaps even new gene areas to investigate.

Hold on, you guys are moving too fast for me...who showed that the collagen in MS patients veins is different than the one in others? If that's the case, the most crucial question (which the person claiming there's a difference should be able to answer) is: is the collagen different everywhere or only at the site of the narrowing/stenosis?

I would be VERY puzzled if somebody e.g. where the carotid artery or a vertebrae pinches the jugular vein has a different vein wall structure anywhere outside the site of narrowing, since these defects (carotid artery growth and vertebrae-malformation) SHOULD have nothing to do with veins. Can you two please clarify what findings you're referring to? Thank you in advance.

I had to go back to remember where I saw it in the first place! The info was in a post by cheerleader near the beginning of this thread in which she talked about Dr. Gabbiani's research:

"He also saw that there was less collagen I type fibers in the MS jugular vein tissue than controls, and more collagen III fibers in MS. This was the exact opposite of the controls. Collagen III is stiffer and fibrosis takes place. This was the main point of his presentation- "

By the way, it's been a looooong time since anyone thought I did anything fast. Made my day.

Thanks bluesky63. The crucial extra bit of information is that the tissue samples underlying these findings were taken from places AWAY from the stenosis, i.e. in apparently healthy looking parts of the veins. In other words we're looking at a new venous disease. If Gabbiani's findings prove true it would mean that there are two fundamentally distinct forms of CCSVI:

1) where stenosis is formed by an unknown venous disease, a BIOLOGICAL problem

and

2) where blockage is caused by MECHANICAL problems, like twisted jugulars, jugulars pinched by carotid arteries, vertebrae extensions, etc. We have heard of several such cases here on TIMS.

Gabbiani obviously only looked at patients with true stenosis (category 1), i.e. not those with external objects pinching on the veins.

Scarry news...

If you search for collagen and multiple sclerosis in Pub Med, you see some interesting info.