Chronic Cerebrospinal Venous Insufficiency (CCSVI)-

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Postby cheerleader » Tue Feb 24, 2009 3:44 pm

CureOrBust wrote:
http://bibamed.agcl.com/cx_2007/Tue%201145%20Zamboni.pdf
This looks like what he is presenting at the conference in Charing Cross next month.


Thanks for finding- that's from the 2007 presentation, but it's still cool to see how his research has been progressing. 2009's presentation is on the results of the endovascular surgery he's been performing on MS patients. REALLY looking forward to that. You doing anything re: jugular reflux, Cure?
AC
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby CureOrBust » Tue Feb 24, 2009 3:49 pm

I just read the presentation. He seems more focussed on the reflux in the IJVV(s) than the 2 or more failure cases. This bodes well for his work with my results, since I only had a single failure, and that was in my IJVV(s).

Now, I can not wait to get my detailed results back from the ultrasound, to check my delta in CSA (cross sectional area difference of the IJV between sitting and laying down).
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Postby cheerleader » Tue Feb 24, 2009 3:59 pm

Great, Cure. I'm really glad you're following up on your test results.
AC
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http://ccsviinms.blogspot.com
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Postby mrhodes40 » Tue Feb 24, 2009 4:09 pm

Cure I am glad you noticed that presentation hanging about somewhere else! That is a really nice overview of the whole idea.

One interesting thing to take note of is that slide 4 shows a list of things that are known to be present in MS lesions.
Every one of those things has also been the focus of autoimmune research, like this
OBJECTIVE: To 1) compare monthly serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-type 1 (TIMP-1) in patients with relapsing-remitting MS (RRMS) versus healthy controls and 2) determine the relationship among monthly serum levels of MMP-9 and TIMP-1 and MRI activity.

BACKGROUND: Activated T-cells and macrophages secrete MMPs that may facilitate their migration across vascular subendothelial basement membranes into the CNS. The serum concentration of MMP-9 is reported to be higher in patients with RRMS than healthy controls.

METHODS: Monthly evaluations including gadolinium-enhanced (Gd+) brain MRI and measures of serum MMP-9 and TIMP-1 were performed for up to 15 months in 24 patients with RRMS and for up to 4 months in 10 controls.

RESULTS: Serum MMP-9 but not TIMP-1 levels are elevated in RRMS patients compared to healthy controls (p = 0.025, p = 0.61). In a univariate analysis, high MMP-9 and low TIMP-1 levels precede appearance of new Gd+ lesions (respectively; odds ratio = 3.3, p = 0.008; odds ratio = 2.2, p = 0.086). In a multivariate analysis, in comparison to months when MMP-9 is low and TIMP-1 high, MRI scans obtained the month following high MMP-9 and low TIMP-1 serum concentrations are more likely to report new Gd+ lesions (p = 0.0006, odds ratio = 21.5).

CONCLUSION: An increase in the activity of matrix metalloproteinase-9 (MMP-9) relative to tissue inhibitor of MMP-type 1 (TIMP-1) may be related to formation of new MS lesions, suggesting that serum levels of MMP-9 and TIMP-1 may be surrogate markers of disease activity in relapsing-remitting MS


The implication is always that these things are abnormal; autoimmune attacks that are non sensical and causing the MS problem.

Such things are frequently followed by "Blocking the effects of MMp9 may represent a novel approach to prevent MS lesions" or some such

But venous lesions have the exact same profile..................Nobody is saying they are autoimmune...because they know the ulcer is related to the venous problem

The only reason they don't assume these same things are caused by a venous problem in MS is because nobody accepts that we have one....except Zamboni

But it is clear that the mere presence of these things does NOT indicate autoimmunity. If it did then venous lesions would be autoimmune.
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Postby mrhodes40 » Tue Feb 24, 2009 4:14 pm

Cure said
Now, I can not wait to get my detailed results back from the ultrasound, to check my delta in CSA (cross sectional area difference of the IJV between sitting and laying down).

Goodness Cure you've really got this whole thing figured out. I have been hoping I could just turn the whole thing over to my vascular guy and let him tell me what's what, but it sounds like you are schooling yours.

Once you have some more clear understanding of what your tests "said" make a post and quantify it all please?
marie
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Postby Loobie » Tue Feb 24, 2009 4:38 pm

I am sure glad you guys are all over this. Who knows where it will go, but you have at least one person here who is thankful for all you guys' efforts.
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Postby cheerleader » Tue Feb 24, 2009 5:11 pm

But venous lesions have the exact same profile..................Nobody is saying they are autoimmune...because they know the ulcer is related to the venous problem

Ha! Maybe we should notify big pharma, Marie...they can try to sell their immune-modulating MS meds to folks with venous ulcers! It's a whole new market :!:

If only we could see what is going on inside the cerebral venous system as clearly as we can see tortuous veins and ulcers in chronic venous insufficiency of the LEGS...wait a minute, now we can....

Lew...you've been such a terrific support the last couple of years...from pep talks to olive oil mayo. The feeling's mutual.
AC
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby CureOrBust » Tue Feb 24, 2009 5:28 pm

mrhodes40 wrote:I have been hoping I could just turn the whole thing over to my vascular guy and let him tell me what's what, but it sounds like you are schooling yours.
Well, now that I saw this presentation, back from 2007 :oops: (I got a little over excited...), there is a graph for the ΔCSA, it will be interesting to plot myself on it. My neuro that did the investigation, would of performed the calculation, as it is a basis of the 5th test. However, I was obviously not negative, but maybe, I am close to the curve? at roughly 3.5EDSS, by Zamboni's graph, you can still have a positive ΔCSA
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Postby mrhodes40 » Tue Feb 24, 2009 5:40 pm

Ha! Maybe we should notify big pharma, Marie...they can try to sell their immune-modulating MS meds to folks with venous ulcers! It's a whole new market


:lol: Funny you should mention that, I spent one afternoon looking to see if anyone recommends the use of steroids for venous ulcers and if it made them "seem" better in any way. Nothing except that some patients will come in having used steroid creams, this results in extra germ loads for the ulcer, which already is a breeding ground.

But, I'll say in this thread what I mentioned in another: That entire list on page 4 of Zambonis list of inflammatory markers in venous lesions and MS lesions is ALL...........ALL..............under the control of the immune system so if you knock it out that stuff is not going to get into the lesion.

That would be, if Zamboni is correct, why immune suppressive things seems to work.

It would also be why they eventually fail..........
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Postby mrhodes40 » Tue Feb 24, 2009 5:42 pm

CUre you are a numbers person, you get around graphs like nothing I've seen. Man! Thanks
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Postby cheerleader » Tue Feb 24, 2009 10:11 pm

Perivascular iron deposition and other vascular damage in multiple sclerosis
C W M ADAMS From the Division of Histopathology, United Medical and Dental Schools of Guy's and St Thomas's Hospitals, University of London, UK

SUMMARY Evidence of damage to cerebral vein walls was sought in 70 cases of multiple sclerosis.
Seventy control cases were also examined. The multiple sclerosis cases showed venous intramural fibrinoid deposition (7 %), recent haemorrhages (17%), old haemorrhages revealed by haemosiderin deposition (30%), thrombosis (6%) and thickened veins (19%). In all, 41% of all multiple sclerosis cases showed some evidence of vein damage. It is concluded that the cerebral vein wall in multiple sclerosis is subject to chronic inflammatory damage, which promotes haemorrhage and increased permeability, and constitutes a form of vasculitis.

The results reported here reinforce the view that damage to the vein wall is an important aspect of the pathology of the multiple sclerosis plaque. The vasculitis caused is different from and of a more modest nature than that, for example, in systemic lupus or polyarteritis nodosa but is, nevertheless, enough to cause haemorrhage, and structural and permeability changes in the vessel wall. The term proposed by Lendrum22 for a wide range of vasculitic disorders is plasmatic vasculosis, and the damage to the vein wall in multiple sclerosis could be regarded as causing a minor degree of such plasmatic vasculosis. Inflammatory and reparative changes in the vein wall might be exacerbated by pulsations or surges in intracranial venous pressure23 24 and may result in increase permeability of the multiple sclerosis plaque, as shown at necropsy,25 by immunohistochemistry9 26 and by brain scan.27

link to pdf
A study from 1988. Gee, only 20 years....
AC
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby AndrewKFletcher » Wed Feb 25, 2009 12:17 am

http://bibamed.agcl.com/cx_2007/Tue%201 ... amboni.pdf

Read the relationship between posture and pressure changes inside the venous return. Although Zamboni addresses the change in pressure from horizontal rest to standing and identifies a corresponding reduction in the cross section of the internal jugular vein, the same pressure changes must apply to sleeping on an inclined bed compared to a flat bed.

You appear to have missed the link to my own research on vascular insufficiency and venous pressure changes due to sleeping at an angle.

This is a very important link.

What we need now is for someone with varicose veins to provide pictures before during and after 4 months of IBT and see if there is a correlation with varicose veins deflating and ms recovery.

I suspect there is.

Andrew


CureOrBust wrote:Andrew, I am surprised, you did not post Zamboni's presentation here (like you posted in the other thread). :? I mean, this thread could be subtitled "The Zamboni Thread"

http://bibamed.agcl.com/cx_2007/Tue%201145%20Zamboni.pdf
This looks like what he is presenting at the conference in Charing Cross next month.
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Postby CureOrBust » Wed Feb 25, 2009 4:25 am

mrhodes wrote: I spent one afternoon looking to see if anyone recommends the use of steroids for venous ulcers and if it made them "seem" better in any way
I do not think we can expect an exact mimicry between the two diseases. The tissue in the brain is very different from that found around leg ulcers. Specifically with my limited knowledge, nerves themselves; brain mylinated by oligodendrocytes, peripheral by schwann.
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Postby cheerleader » Wed Feb 25, 2009 7:46 am

CureOrBust wrote:
mrhodes wrote: I spent one afternoon looking to see if anyone recommends the use of steroids for venous ulcers and if it made them "seem" better in any way
I do not think we can expect an exact mimicry between the two diseases. The tissue in the brain is very different from that found around leg ulcers. Specifically with my limited knowledge, nerves themselves; brain mylinated by oligodendrocytes, peripheral by schwann.

You're right, Cure...the tissue is different. But, the activation is the same. Circulation is slowed, blood leaks, iron is deposited, fibrin cuffs form, and the white cells and the immune system go in to "clean up". On the legs it makes hideous ulcers (google image venous leg ulcers, eek) On the brain? I think demyelinating lesions.
AC
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby mrhodes40 » Wed Feb 25, 2009 8:10 am

Cure said
The tissue in the brain is very different from that found around leg ulcers. Specifically with my limited knowledge, nerves themselves; brain mylinated by oligodendrocytes, peripheral by schwann.
I agree! I just wondered if it had been tried at all.........apparently not!

I'd like to expand on an idea in one of my posts above by adding info from another thread I wrote so it is here regarding how/why immue suppression might seem to work if Zamboni is right. My mind has been turning this over a lot because obviously it looks like it helps to knock it out. Why might that be?

here's that list again on slide 4 of the Zamboni presentation Cure linked. It is a list of inflammatory factors known to be present in MS lesions and also in venouos ulcers:


Table 1 Common findings of the inflammatory chain in CVD and MS
Finding CVD References Multiple sclerosis References
Altered venous haemodynamics
Perivenous inflammation
erythrocyte extra-vasation
Haemosiderin deposits
Adhesion molecules and white cells activation
Macrophage migration-infiltration
T cell migration-infiltration
Iron laden-macrophage
MMPs hyper-activation
TIMPs hypo-expression
Local iron overload
Urine haemosiderin test
HFE mutation
Fibrin cuff (on going reparative process)


Note about the chart: : you see that everything that is listed is known to be true of venous ulcers AND MS lesions, in the real chart, which I was unable to paste in, there are references for each and every one of those things; it's not like Zamboni is making this theory from now where, it comes from known research. The only thing not known is the first; the altered haemodynamics. THAT's what his research on those 750 people set out to show. IMHO, he showed it well.

They have, of course, now had roughly 750 people go through the clinic in 3 blinded controlled research studies and it turned out that all the people with MS had reflux and abnormal doppler readings in 2 or more findings where the other people, whether they had other neurological disease or other vascular or disease or were older normal people, had no more than one abnormal reading

This is to me the most exciting new research along the MS lines to come along in a long time: it's novel and a completely new direction for research.

People who've been in the autoimmune camp find the whole notion hard to get their minds around, the biggest question being 'Yeah, but why does revimmune/campath/tysabri etc work? He can't be right.'
Look at that chart /list, those things will be impacted by knocking out the immune system because they are all inflammatory markers dependant on immune activation to happen, that's likely why it seems to help to knock out the immune system. Some of the damage is caused by these inflammatory markers.

That should not be new ideas to anyone, that's what they've been telling us for years; the inflammation itself is causing the damage. What they have not recognized is that this inflammation may be SECONDARY to a mechanical damage in the first place, according to Z, caused by reflux.

For example; by what measure do they go around telling us that "revimmune worked"?

PRIMARILY because the main criteria they use for "did it work" is whether or not new inflammation and GD enhancement shows up, well, when the immune system has been hamstrung it can't do that even if it wants to/needs to when degeneration is happening in that area.

To offer the idea that something like ASCT which severely suppresses immune function does NOT "stop MS damage" as is often said, I will add a chunk from another paper on autologous stem cell transplants that shows that after such treatments when the patient's immune system has been completely wiped out, people STILL show degeneration of brain tissue even though the inflammation is gone. This comment is from a pathologist who austopsied brain tissue after people died post ASCT:
Autopsy samples from these patients revealed that in
all cases there was an almost complete absence of inflammatory
markers in the brain, notably of T cells. On
the other hand, there was significant staining for amyloid
precursor protein (APP) inclusions, a marker of
acute axonal damage (Fig. 5). This suggested that even
though inflammation had been abolished, neurodegeneration
was still proceeding in the brains of these patients,
and thus that neurodegeneration was not a direct
consequence, at least in the short-term,of inflammatory
damage to the nervous system.

from Wolfgang Bruck "Inflammatory Demyelination is not central to the pathogenesis of multiple sclerosis" (I own a copy)

Could the reason for the ongoing degenerative damage in brain be that the mechanical damage of reflux has been ignored? Are these immune treatments kicking all those immune factors out of the lesion, until the next time there is a big dose of reflux to cause new damage and new invitation to the immune system to come in and clean up?

Is that why some people do better for a while after immune suppression then reactivate: mechanical damage sets the stage for a whole new round of immune activation?

I don't know the answer but these speculations might be an explanation for how Zamboni can be right even though it "seems" like severe immune suppression helps MS.

One thing is true, there is a fair body of research like the Bruck bit I added a paragraph from that makes a reasoned and supported case for the idea that MS is primarily degenerative not autoimmune, but that having been said it may be possible that the eventual "best" treatment includes some form of immune suppression AS WELL AS vascular repair.

What will make the difference is whether or not there is some compartmentalization (locking into the brain behind the BBB) of some of these inflammatory factors and possibly a need to control them somehow after the fact.

OTOH stroke survivors do not need lifetime immune suppression so maybe not.

More work will need to be done before the eventual best management of this issue is known, but one thing is sure, addressing the reflux, assuming it turns out to be pathognomic for MS, will be critical irf we want to stop progression.
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