This Is MS Multiple Sclerosis Community: Knowledge & Support

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.

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]

healthy veins contain significantly more of collagen subtype I and varicose veins contain significantly more of collagen subtype III in their walls.

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

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.

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