Connective Tissue Disorders, Collagen and CCSVI

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.
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cheerleader
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Connective Tissue Disorders, Collagen and CCSVI

Post by cheerleader »

Below are my notes from Dr. Gabbiani's presentation in Bologna. It is still sticking in my head, and now that we have new people on board, I'd love some other thoughts...would love Dr. Sclafani's thoughts.
Dr. Guilio Gabbiani from the Centre Medical Universitaire in Geneve, Switzerland speaking on jugular wall changes in MS. His laboratory was interested in the fibrotic changes. He was interested in learning the importance of venous morphology, and is surprised so little is known.

Comparing arteries to veins: Arteries are thicker and there is more resistance.

Dr. Gabbiani took 5 specimens from IJV tissue removed by Dr. Zamboni from some of the patients he treated endovascularly. The tissue was from the area NOT damaged by angioplasty.
He compared it to healthy tissue from autopsy controls.
He looked at eosin, hematoxylin, Miller’s elastic stain and massons trichrome.
He found smooth muscle cells were numerous and increased in MS compared to controls. He then used isoelectric focusing to measure contractions in the smooth muscle cells via actin heterogeneity to ID the smooth muscle cells in the veins.
There is an increased expression of smooth muscle actin in MS, much more than controls.

By red staining for collagen and using unpolarized and polarized light, he saw that there is less collagen 1 type fibers in the MS jugular vein tissue, and more collagen III fibers in MS. This is the exact opposite of the controls.

Connective tissue in MS switches from collagen I to collagen III and this takes place in the IJVs. THis switch also happens in fibromatosis, colloids and hypertrophied scars, and this remodeling may play a role in CCSVI disturbances.


Dr. Lee makes a comment...
This collagen conversion from I to III happens in the arteries had no idea it could happen in the veins as well!

answer: Collagen III is stiffer, and fibrosis takes place for some reason. There was no inflammation on the tissue samples, but inflammation might have occurred before the the intervention and the fibrotic changes happened. All is still speculation, we do not know.

Dr. Zivadinov asks, so the testing was in the normal, non-stenosed part of the IJV?

Answer: Yes, we are trying to examine the normal part of the vein not affected by stenosis.

This collagen switch between type 1 and type 3 occurs in some genetic connective tissue disorders, and is present at birth. I keep wondering if there is a connection here (pun intended) between these other connective tissue disorders (which include RA, SLE, Raynaud's and others) and MS...and the area affected in MS is the veins. As Dr. Gabbiani noted, the venous system has not been studied as closely as the arteries. That is becoming more apparent everyday. We know Ehler-Danlos can affect arteries. And Dr. Dake's comment to Jeff sticks with me, "Your veins are sticky, the lining is like glue. Never seen anything like this." Or, it could just be the change occurs secondarily to inflammation. More research is needed, but it will be interesting to read the new genetic research coming out, and see if there are any shared loci between connective tissue disorders and MS.
link

cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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ikulo
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Post by ikulo »

This study would suggest that only the jugulars should have this Collagen I/III imbalance.
Bratisl Lek Listy. 2008;109(3):102-5.
Comparison of collagen subtype I and III presence in varicose and non-varicose vein walls.

Haviarova Z, Janega P, Durdik S, Kovac P, Mraz P, Stvrtinova V.

Institute of Anatomy, Faculty of Medicine, Comenius University, Bratislava, Slovakia. zora.haviarova@fmed.uniba.sk
Abstract

STUDY OBJECTIVES: The connective tissue alterations in varicose vein wall are supposed to be one of the main causes of primary varicose vein (main sign of human lower limbs chronic venous insufficency). METHODS: 5 varicose vein samples from 5 patients undergoing stripping surgery of long saphenous vein were compared with 5 control samples of healthy (non-dilated) long saphenous veins from necroptic material (with no history of varicosis). They were fixed in a Baker solution, processed by use of light microscopic method, cut to ultra-thin sections (4-5 microm) and stained with PicroSirius Red for collagen. Sections were scanned with light microscope (Leica, Germany) and camera Canon S50 (Germany) and analysed by morphometric programme Image J v.1.38g (National Institute of Health, USA). RESULTS: In the group of healthy (non-dilated) veins the mean collagen I/III ratio value was 31.40 and in the group of varicose veins the mean collagen I/III ratio was 12.35; the difference is statistically significant: healthy veins contain significantly more of collagen subtype I and varicose veins contain significantly more of collagen subtype III in their walls. CONCLUSION: The statistically significant difference in the collagen I/III ratio between the groups of healthy (non-dilated) and varicose (dilated) vein walls is worthy of further following (Tab. 2, Fig. 7, Ref. 12). Full Text (Free, PDF) www.bmj.sk.

PMID: 18517131 [PubMed - indexed for MEDLINE]
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cheerleader
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Post by cheerleader »

Thanks so much for that study, ikulo...
actually, it looks like the same switch from type 1 to type 3 happens in varicose veins....which would be further evidence of Dr. Zamboni's likening chronic venous insufficiency in the legs to what is happening in the CNS veins....
healthy veins contain significantly more of collagen subtype I and varicose veins contain significantly more of collagen subtype III in their walls.
Dr. Gabbiani reported the same switch from type 1 to type 3 in the jugulars. Interesting!

cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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sou
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Post by sou »

A friend of mine has been diagnosed with MS 4 years after being diagnosed with scleroderma, a disease of the collagen. I have been thinking that her scleroderma led to vein malformations which, in turn, damaged her nervous system. If that is so, her MS is not a disease but a major symptom/complication of scleroderma.

sou
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cheerleader
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Post by cheerleader »

sou wrote:A friend of mine has been diagnosed with MS 4 years after being diagnosed with scleroderma, a disease of the collagen. I have been thinking that her scleroderma led to vein malformations which, in turn, damaged her nervous system. If that is so, her MS is not a disease but a major symptom/complication of scleroderma.

sou
Look at this research, sou...scleraderma as "localized" venous insufficiency-
wow.

http://www3.interscience.wiley.com/jour ... 6/abstract
Localized scleroderma is a cutaneous disease that is characterized by an initial inflammatory response, followed by sclerosis of the skin. The cause of localized scleroderma has not yet been determined. Seifarth et al. reported two cases of localized scleroderma at sites of chronic venous insufficiency. We document here three more patients in whom localized scleroderma was located at insufficient veins. Treatment of underlying chronic venous insufficiency (CVI) leads to a substantial clinical improvement of scleroderma at the site of insufficient veins, but not elsewhere. Experimental data support the concept of chronic venous insufficiency creating a microenvironment, which may lead to localized scleroderma. Local hypoxaemia, which is present in CVI, induces the release of endothelium-derived cytokines, such as IL-1. Subsequently, expression of endothelial adhesion molecules and consequently leucocyte extravasation are induced. Infiltrating leucocytes secrete a number of inflammatory mediators, including transforming growth factor β, which is a potent stimulus for collagen synthesis. Therefore, it may well be that CVI is a potential trigger factor for localized scleroderma. In addition, localized scleroderma may only develop if a certain amount of trigger factors are present – and resolves if one or more of the contributing factors (i.e. CVI) can be treated.
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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bluesky63
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Post by bluesky63 »

Cheerleader, I really appreciate your efforts -- everyone's efforts! -- in bringing out this research. I have a son diagnosed with Ehlers-Danlos, as well as many, many family members with varying issues that all make sense when viewed through this lens.

It is so exciting to think that we are getting closer and closer to understanding how everything fits together -- and most important -- how to get healthy and keep the kids healthy.

I would do anything to keep my children from going through what I have experienced.
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cheerleader
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Post by cheerleader »

Now we have three diseases that are potentially linked by venous insufficiency, collagen changes from I to III and sclerotic plaques as a result....
1. Chronic Venous Insufficiency of the legs and venous ulcers
2. Localized Scleroderma
3. CCSVI in multiple sclerosis

I believe this pattern makes even more sense.

Bluesky...the reason I'm still sticking around is because of my teenage son and the fact that Jeff's jugular veins are much better, but not perfect by any means. I really hope there will be more answers coming...
cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Asher
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Post by Asher »

cheerleader, thank you! My heart is pounding. The unraveling of this mysterious and intricate disease is really exciting!
Last edited by Asher on Wed Apr 21, 2010 12:01 pm, edited 1 time in total.
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lumpc1
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Post by lumpc1 »

cheer, check this out. from what I gather it is safe even at high doses. Although I can not find a dose MG. any info would be fine.
http://jba.sagepub.com/cgi/content/abstract/23/2/101
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Post by babiezuique »

the last time i felt intelectually stimulated like i'm now is when i dis my master in philosophy 13 years ago... Since 5 months i'm really for the firt time in decades.... reading about lins that you bring that explain how complicate is ms....

I read for 10 years about this sickness i had... but everything seem so clueles... and now, with this vascular way... everything seem to be clearer...

I have cognitive problems... but i can assure you... you are stimulating my brain and it is part of my recovery ( before my liberation in poland this year...)

Thank you!

As always... Cheeleader acuteness...( my french is better i assure you;) and lucidity in this adventure is very inspiring!
Barbara
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cheerleader
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Post by cheerleader »

I really want to encourage research and thinking, rather than arguments and petty, personal attacks on this site. That's how we started this CCSVI journey, and that's really how I hope we'll move ahead.

It's been incredible seeing the variety of doctors involved in trying to understand MS. Dr. Zamboni's Bologna conference brought together geneticists, vascular doctors, MS specialists, and imaging researchers. As patients and advocates, we can help facilitate greater knowledge by bringing doctors together and taking them the published research.

lumpc1---I had looked into chitosan for Jeff, but didn't include it in his program. Maybe it's time for more research...thanks for that.
babiezuique--Votre anglais est bien meilleur que mon français! I'm glad you're enjoying this challenge...me too.

keep reading, keep learning...I really believe we're getting closer-
cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Post by Loobie »

Thanks a lot Joan :evil: . Here I thought I was all done having to think anymore :D
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Post by ozarkcanoer »

Wouldn't it be wonderful if all the academics and doctors who research MS would openly trade ideas with each other much like we MSers and Dr Sclafani do on this board ? Last fall I was asked to be a patient advocate for a neurological research organization and when I asked them if I could attend their symposia I was told no. My feeling is that many researchers are protecting their turf. That seems to be a sad state of affairs for patients who are looking for help.

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cheerleader
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Post by cheerleader »

ozarkcanoer wrote:Wouldn't it be wonderful if all the academics and doctors who research MS would openly trade ideas with each other much like we MSers and Dr Sclafani do on this board ? Last fall I was asked to be a patient advocate for a neurological research organization and when I asked them if I could attend their symposia I was told no. My feeling is that many researchers are protecting their turf. That seems to be a sad state of affairs for patients who are looking for help.

ozarkcanoer
Agree, OC. That's why Dr. Zamboni is so special...he is open and thrilled to work with other doctors and patients. He's literally pleading with them to investigate his findings. His turf is open! His convocation in Bologna last September felt like the beginning of a new model for medicine--specialists gathering to share their very specific research with each other and patients/caregivers in an open environment.

Check out this seminar in Toronto on Sunday...it's the new model-
http://www.facebook.com/event.php?eid=1 ... 256&ref=mf

Lew, you don't have to think...you're a studly track star/jock again :)
cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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hwebb
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I think times are a-changin'

Post by hwebb »

I think times are changing. A friend of mine works as a research scientist.

She was recently telling me that there's a push to use "online lab books" which are shared with other scientists before the science hits the journals, rather than the old paper version which is for personal use only.

Predictably, a large group of researchers are stubbornly refusing to move to the new system for fear someone will steal their ideas. However, it's been demonstrated that peer exchange if ideas at this early stage of research minimizes early mistakes as well as redundant research (if it's been done before), and generally helps science move forward more quickly.

Helen
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