Chronic Cerebrospinal Venous Insufficiency (CCSVI)-

[Jaded]

Soooo interesting guys and gals........in a way this explains why statins helps, surely???

J

[HUTTO]

all right cheer. i emailed my neuro to take a look at all the links you provided. i will let you know what he says. i emailed him before hand to let him know what it was about and he stated to email him..we will see.

[mrhodes40]

Just wondering what treatment Zamboni was discussing when you wrote the following.

Quote:
Also Zamboni mentioned that treatment had no effect whatsoever on the vascular pproblem, you have the problem whether you are on treatment or not.

He was talking about immunosuppressive therapies and saying, in the first Zamboni paper this thread is based on, that treatment with regular standard MS therapies makes no difference to these venous issues at all, it is immaterial to the severity of the venous irregularities.

[cheerleader]

An earlier Zamboni paper this one on 89 patients with matched controls.

http://www.ms-info.net/Intracranial_Ven ... erosis.pdf
This paper outlines how the backjets and anomalies related thereto are assoicated with MMP9 adhesion mlecules and other factors already known to be common in MS........answered my question above!

Therefore, venous reflux overloads microcirculation (Bergan et
al., 2006) and increases trans-mural pressure (Zamboni et al.,
2007); in MS, changes of microcirculatory MRI perfusional parameters,
have been shown to precede plaque formation in a longitudinal
study (Wuerfel et al., 2004). Furthermore venous reflux,
with consequent microcirculatory overload and increased transmural
pressure, facilitates erytrocyte diapedesis (Zamboni, 2006;
Bergan et al., 2006; Zamboni et al., 2007) resulting in increased
perivenous iron deposits demonstrated histologically also in MS
lesions (Adams, 1989; Adams 1988) and confirmed by advanced
MRI techniques (Haacke et al., 2005; Tjoa et al., 2005; Brass et al.,
2006). Moreover, the excess of stored iron in the brain triggers a
series of deleterious events that lead to neurodegeneration, possibly
involving mechanisms of iron-driven free radicals generation and
oxidative stress (Ke et al., 2003,

Thanks for posting the earlier Zamboni study, Marie. I think Dignan had this one on our iron thread, but so much has been posted recently, I may be mistaken.

Stored iron in the brain, iron which has been leaked out due to venous reflux and blockage. Iron which sets off mechanisms of neurodegeneration. The iron spots I saw on Jeff's legs. I believe this is our target.

The following is just my supposition: Endothelial dysfunction created by heavy metals, toxins, pathogens or an overwhelmed vascular system could explain MS in Faroe Islands, industrialized nations, in populations with EBV or Cpn infection and those born in northern latitudes with a lack of vitamin D. Any scenario where the endothelium and nitric oxide signaling is unbalanced and overwhelmed by oxidative stress and weakens the blood brain barrier- the cascade of iron deposit on brain and spine might begin. What makes it MS is venous blockage and reflux- creating unrelenting microcirculation. This may be due to a genetic predisposition. Zamboni's controls were probably exposed to all of the same external factors as the MS patients. But their bodies had not formed stenoses and reflux. They may have become sick, fatigued, or developed cancer, Alzheimers or heart disease. They did not have MS.

There are ways to clear stenoses and return normal blood flow with surgery, anticoagulants, stents and balloons. Chelation can remove iron from the brain and body. Perhaps a combination therapy would arrest MS. This would certainly explain the correlation of MS with antiphospholipid/Hughes syndrome and MS. But a baby aspirin wouldn't resolve all the stenoses shown in Zamboni's study. And a year of natural anticoagulants and my endothelial health program have helped Jeff immensely. But he could be better...
Anyone see a vascular doc yet?
AC

[dignan]

Here is another abstract along the same lines as Zamboni, and done from a circulatory system perspective, not from a neurologist/immunologist.


Hypothetical molecular mechanisms by which local iron overload facilitates the development of venous leg ulcers and multiple sclerosis lesions.

Med Hypotheses. 2008 Aug;71(2):293-7.
Simka M, Rybak Z.
Department of Angiology, Wodzislawska 78, 43-200 Pszczyna, Poland. mariansimka@poczta.onet.pl

This paper presents a hypothetical model of role for iron in the development of venous leg ulcers and multiple sclerosis. Elevated concentrations of iron were found in the skin affected by venous hypertension and also in the areas of brain with multiple sclerosis lesions.

Individuals with hemochromatosis gene (HFE) mutations: C282Y and H63D, which result in a less efficient transport of iron by macrophages, are characterized by an increased risk for venous leg ulcer and multiple sclerosis. Multiple sclerosis is a T cell-mediated disease, and T cells probably participate in the development of venous ulcers. This deleterious role of ferric ions could be related to the regulation of T cell proliferation and apoptosis. Under normal conditions excessive accumulation of T cells cannot take place, because nitric oxide and interferon-gamma drive these cells toward apoptosis. However, in tissues with a high concentration of iron, T lymphocytes proliferate instead of undergoing apoptosis. This is possible due to the internalization of the INF-gammaR2 chain of the interferon-gamma receptor, the downregulation of inducible nitric oxide synthase expression in macrophages and the inactivation of the active site of caspases.

Yet, it should be emphasized that this hypothesis does not claim for the increased concentration of iron as a direct causal factor for the development of venous ulcerations or multiple sclerosis, but rather, iron is a factor that modulates and exaggerates the autoimmune process. Iron chelators, administered systemically or locally, should potentially exhibit therapeutic and prophylactic activity against venous leg ulcers and multiple sclerosis.

Pubmed link


There is also a newer, related article from Simka, but with no Pubmed abstract available:

"Evidence against the role for dural arteriovenous fistulas in the pathogenesis of multiple sclerosis."
Med Hypotheses. 2008 Oct;71(4):619.
Comment on: Med Hypotheses. 2008;70(6):1112-7.
Simka M.

[mrhodes40]

Hi Cheer,

Thanks for posting the earlier Zamboni study, Marie. I think Dignan had this one on our iron thread, but so much has been posted recently, I may be mistaken

Zamboni did a study on iron in MS in 2006 which Dignan the Wonder finder posted. I too have many times read TIMS and looked at the incredible work Dignan did on those pipeline lists and have been very glad of his great effort. Dignan you are the man! This is really looking positive thanks to all these papers you post!

The one I referenced is from 2007 and is directly related to hemodynamics in MS. It is important because in addition to the hemodynamic issues, he outlines other things like MMP9 and adhesion molecules that play a role.

This adds weight to the idea in that it accounts for some inconsistencies in attributing MS solely to venous back jets. I'm the one who brought up the question of how UTI could worsen MS if it is backjets, and this alludes to the answer to that question, so I wanted it in this thread specifically. Here it is again;

abstract from
Intracranial Venous Haemodynamics in Multiple Sclerosis
Paolo Zamboni1,*, Erica Menegatti1, Ilaria Bartolomei2, Roberto Galeotti1, Anna Maria Malagoni1, Giovanna
Tacconi1 and Fabrizio Salvi2
1Vascular Diseases Center, University of Ferrara, Italy

Abstract: In multiple sclerosis (MS) plaques are known to be venocentric; in addition, MS lesions and peripheral venous disorders share
a number of key features. To date, however, despite the anatomical relationship between MS lesions and the venous system, no information
on the intracranial venous haemodynamics of MS is available. Eighty-nine consecutive MS patients (58 relapsing-remitting, 31 secondary
progressive) matched with 60 controls underwent transcranial color-coded duplex sonography (TCCS). We assessed, in supine as
well as in sitting positions, the direction of flow at the activation of the thoracic pump in the deep middle cerebral veins (dMCVs), and in
the transverse sinus (TS). In the dMCVs, we also measured peak systolic velocity (PSV), peak diastolic velocity (PDV), as well as the resistance
index (RI). Reflux/bidirectional flow rate was significantly higher in the MS population determining also significant differences
in PDV, characterized by negative values (16.2±1 cm/sec in controls vs. –1.3 ±2.6 cm/sec in MS, respectively, p<0.0001). Consequently,
RI was dramatically increased in the MS group, affecting impedance of cerebral venous drainage (0.48±0.04 in controls vs. 1.1 ±0.08 in
MS, respectively p<0.0001). Therefore, the detection of reflux directed toward the subcortical grey matter was significantly associated to
highest disability scores (p < 0.0001). Our study of MS patients demonstrated significant haemodynamic alterations detected in veins
anatomically related to plaque disposition. Our findings should contribute towards understanding the role of altered venous flow and tissue
drainage in the MS inflammatory chain, as well as in the neurodegenerative process.
Key Words: Multiple sclerosis, transcranial color-coded duplex sonography, cerebral veins, venous haemodynamics

The full paper can be found and read here;
http://www.ms-info.net/Intracranial_Ven ... erosis.pdf

This information is in several threads so it can get complicated, BUT the addition of this paper I just referenced a second time to the one you started this thread with we now have 2 papers looking directly at venous back jets in MS by Zamboni with large numbers.

To summarize;
Zamboni 2008; 65 MS patients 235 controls, some with OND
ALL MS patients have CCVI NONE of the controls did including people with OND

Zamboni 2007; 89 MS patients 60 matched controls
ALL MS patients had CCVI NONE of the controls did.

Zamboni 2006; paper on how iron deposits might cause problems in MS and leg ulcers related to T-cells

Taken together, this is a lot of patients! There have already been more patients evaluated for this anomaly than some stage II trials have, and since all patients have it, this is big news.

My assumption is all of us actually have it. The question is can it be stopped with procedures currently available and "standard of practice" so that the physician doing it is comfortable that he is doing a safe, approved procedure. (Please God, I hope so--I can't wait until some people talk to vascular specialists and we start to get feedback there)

The horrible alternative is that it would require an unusual new procedure that would need to be evaluated for a decade while they "see" if it helps.

Another question is will the BBB in the affected area return to normal if the venous back pressure is alleviated so the area can heal to whatever degree it can. Brains heal somewhat and definitely stabilize after hemmorhagic stroke, they do not chronically get worse, so it seems likely we MSers could if the pressure could be relieved.

and finally can things like chelation as you mention, antibiotics (assuming some CPn or other things snuck in while the BBB was open), antivirals (assuming maybe some B cells got in with the EBV in there) antioxidants to clean things up where the leak was and other strategies like stem cells repair the area and return some function as well. I bet so.

Overall this seems super positive to me. Cheer, like your hubby I had venous issues when I got sick in 91 also. I complained that my legs were "greyish" and seemed to have circulation problems. I had to go through some leg venous doppler stuff to check it out. Too bad they didn't do my head!

Everything was normal... how I hated hearing that back then! I knew I had big problems and it was really hard to get anyone to listen. I have RA too, so it was thought I was having a psych reaction to that and "was afraid to bend my legs for fear of pain". It was assumed this also hampered circulation. Can you imagine?
marie

[gibbledygook]

Thanks for answering my question, Marie. I was frightened Zamboni's failed treatments was stent insertion. I'm going to badger the quacks until I get to know how easy/difficult this procedure might be.

[mrhodes40]

Gibbles,
I'm sorry that I wrote so unclearly. I'm nursing a broken arm and am not up to speed sometimes...

I am beside myself with anticipation for what people hear, I think about this night and day. I can't drive myself anywhere with the arm so I am stuck for a while at least, so you others who do see a vascular specialist will be my vicarious thrill for a bit anyway.

I've had MS for 18 years. In that time I can guarantee you that EVERY immune suppressive thing that came out engendered huge excitement. Doctors confidently stated that MS was going to be a manageable disease and preened about the fantastic times we are in, how lucky I have MS now! We can control the abherrent immune system!

And every time the excitement of the medical community has not been justified. The excitement of people at my local MS support group has given way to gradual acceptance of more disability as they realize the treatment did not actually help them. We have become justifiably jaded and cynical, and I personally have directed the mistrust at the autoimmune as causitive model (like I think autoimmunity could be a cofactor, ie your body is trying to clean up this mess and there is some epitope spreading and you end up with some cells that are autoreactive as a side issue. Lucky thing there is that autoimmunity is actually usually self limiting. think of rheumatic fever. EAE is too.)

This model here in this thread seems right to me, it's novel, it is based on an indisputable fact that is ignored by regular medicine, and it accounts for a lot of what is going on in MS. I hope it means a real cure!

One thing is certain in my mind, if they do not recognize and address this it never will be a complete cure....even if it looks good in the near term.
Like I said, I've had MS for 18years... All of us will get to that point someday. I'm not too impressed by 5 year results.

I can't wait to hear if ordinary stents are going to be a reasonable approach!

Can't wait to hear of people's dopplers

Cant wait!!

[cheerleader]

Thanks so much for breaking down all of Zamboni's studies, Marie. It seems he has established alot of evidence on venous backjets in MS. And yes, Dignan is my Nobel nominee this year. Or maybe I'll just rename by dog Dignan, or needlework his name on a pillow....

Well, put a bow on my computer and call it Merry Christmas. Dr. Schelling forwarded my e-mail to Dr. Zamboni. I got the sweetest reply this morning. Dr. Zamboni's "diagnostic protocol and treatment" for MS patients is being brought over to the US- to Buffalo (he did not say hospital or university) through the non-profit Hilarescere Foundation. He states that his Italian MS patients have benefitted from this diagnosis/treatment, and he looks forward to sharing it around the world. He states that it is important to "treat patients from US reaching more rapidly the requested scientific evidence."

In the new year I'll follow up and ask him what/where/how/when his studies in upperstate NY will be held.
AC

[mrhodes40]

How on earth can I possibly express the incredulous joy I feel reading that? its beyond expression on the internet..maybe ....
Right here in the States? Already an outlined protocol? Man! Wow! Yahoooooo!

but that seems totally inadequate.

I'm beyond beside myself..........

I hope there is so much interest and success that we end up with a special forum for it.....
Marie

[gibbledygook]

Happy Christmas Everyone!!!!

[CureOrBust]

I simply tried a search on "Hilarescere Foundation" within Google, and stumbled across the following PDF, which if you haven't read it yet, may be of interest to those on this thread (and the iron thread).

I am trying to get these test done so was pretty interested in the article, as they "propose a list of reproducible clinical parameters".

Doppler Haemodynamics of Cerebral Venous Return

...The authors have summarized the current knowledge of the Doppler haemodynamics of the cerebrovenous system and propose a list of reproducible clinical parameters for its sonographic evaluation. In future, the development of this diagnostic technique could be of singular interest in iron-related inflammatory and neurodegenerative disorders like
multiple sclerosis.

[mrhodes40]

Cur-o
That paper is perfect for taking to the vascular person involved. Thanks for sharing it!
I'm assembling a packet to send a vascular doc in Seattle, that's going in too.

[cheerleader]

Dr. Paolo Zamboni will be presenting his "Rationale and preliminary results of endovascular treatment for multiple sclerosis at Charing Cross (CX) vascular symposium in April of '09 (cxsymposium.com)

Endovascular vein treatment utilizes a catheter and is usually an outpatient procedure, with a low risk of complications.
AC

[CureOrBust]

I'm beyond beside myself..........

Could this possibly be an emot-icon on the way there?
>

This model here in this thread seems right to me, it's novel, it is based on an indisputable fact that is ignored by regular medicine, and it accounts for a lot of what is going on in MS.

Any ideas on how it explains the Faroe Islands?

Dr. Paolo Zamboni will be presenting his "Rationale and preliminary results of endovascular treatment for multiple sclerosis at Charing Cross (CX) vascular symposium in April of '09

This is the one item that would be missing from both mrhodes and my pack for our ultrasounds.

I would LOVE to hear what results they had achieved. When I searched the net, I could find nothing about it. However, I did find this previous, older study; again, the full article / details of results are hidden from me...

Surgical treatment of vertebral artery insufficiency in patients with diagnosis of multiple sclerosis.
This was performed in 1977! I can only guess that the results achieved were not that great.

Surgical treatment of vertebral artery insufficiency in patients with diagnosis of multiple sclerosis.

Hurvitz SA.

Nine patients with signs and symptoms of vertebral-basilar artery insufficiency and with the diagnosis of multiple sclerosis experienced partial restoration of lost neurologic function with the revascularization of ischemic tissue of the hindbrain by an operation to correct partial extraluminal obstruction of the proximal segment of the first part of the vertebral artery. The selection of patients is dependent on preoperative angiography of the aortic arch with visualization of the vessels of the neck, the vertebral and the carotid arteries. There was no mortality and no significant morbidity among these patients.