This Is MS Multiple Sclerosis Community: Knowledge & Support

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

J

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.

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.

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

_________________
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
dual stents placed 5/09
CCSVI in MS

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.

Hi Cheer,


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

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

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.

_________________
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,

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!!

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

_________________
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
dual stents placed 5/09
CCSVI in MS

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

Happy Christmas Everyone!!!!

_________________
3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,

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

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.

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

_________________
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
dual stents placed 5/09
CCSVI in MS

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

Any ideas on how it explains the Faroe Islands?

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.