If CCSVI is congenital...

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

Postby Shannon » Fri Feb 04, 2011 5:45 pm

I see what you all mean about the upright posture of humans. I hadn't really thought of that before. I was aware that mice were already being used, just not with figuring out how it comes to be. I am almost finished with a degree in biology, so these are the kinds of things that I think about. Even given that, I am not too sure how I feel about giving MS to our most recent common ancestors, the primates. I guess I would have to look at their average life spans. However, I doubt that they would ever be exposed to some (or some certain combination) of the environmental effects that have also likely contributed to MS, along with the CCSVI. I'm just curious about any specific maternal effects toward having the underdeveloped or malformed veins that we have. How will we ever know how this happens? The focus is where it should be, for now, which is what effect it has once it has happened. I'd love to see more evidence about the congeniality of it. Thanks for the links and information. :)

Edited to add: When I said "when the research ever gets going," I was referring to the particular obstacle before us, which is getting funding for it to proceed with any vigor.
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Postby ikulo » Sat Feb 05, 2011 8:49 pm

Wouldn't the animals also have to have similarly mutated immune system genes as PwMS? Or are we saying these mutations don't matter?
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Postby Cece » Sat Feb 05, 2011 11:41 pm

ikulo wrote:Wouldn't the animals also have to have similarly mutated immune system genes as PwMS? Or are we saying these mutations don't matter?

If they can create a mouse model that results in lesions like in MS, then no, genes wouldn't matter. The EAE mice don't have mutated genes, anyway.

It might be an imperfect model, but not as imperfect as EAE. :)
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Re: Animal MS Disease Model

Postby NHE » Sun Feb 06, 2011 4:56 am

Cece wrote:
ikulo wrote:Wouldn't the animals also have to have similarly mutated immune system genes as PwMS? Or are we saying these mutations don't matter?

If they can create a mouse model that results in lesions like in MS, then no, genes wouldn't matter. The EAE mice don't have mutated genes, anyway.

It might be an imperfect model, but not as imperfect as EAE. :)


Let's not forget that an EAE mouse is really screwed up to begin with. So much so that it is a poor model for MS. I'm fairly certain that among mice, the EAE mouse is a genetic anomaly.

NHE wrote:Not only do they have a high susceptibility to EAE, but they also develop prolific cancers as well as spontaneous myopathy making it a model for muscular dystrophy.


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Logic Please

Postby MarkW » Sun Feb 06, 2011 6:40 am

CCSVI syndrome is not a congenital disease and cannot be one by definition (please read Prof Zamboni's recent paper). A valve or vein malformation could be congenital in pwMS. The first step is to define the malformation which appears to be congenital and agree this amongst experts.
Step two is to show that pwMS have this malformation before the start of their MS. So people with CIS would need to be studied. Also families of pwMS would need to be screened for the malformation plus genes which predispose for MS plus using the Israeli blood test for MS. Many years of research.

A small animal model for MS (which many of us understand has genetic factors at its roots) is nearly impossible. Definitely impossible in a mouse model as the mouse would need to have all the potential human MS predesposition genes before the study could start. So the mouse would need not just the HLA complex but lots of other genes, which are being discovered as we speak.

So step one - what is the vein malformation proposed to be present before the start of MS ? Agreeing that would be 1-2 years work in my view.

Small steps not giant leaps please..........

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Mark Walker - Oxfordshire, England. Registered Pharmacist (UK). 11 years of study around MS.
Mark's CCSVI Report 7-Mar-11:
http://www.telegraph.co.uk/health/8359854/MS-experts-in-Britain-have-to-open-their-minds.html
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Postby Cece » Sun Feb 06, 2011 9:02 am

At least our steps are now in the right direction, after years of wrong-way and brick-wall.
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Postby ikulo » Sun Feb 06, 2011 11:06 am

Cece wrote:
ikulo wrote:Wouldn't the animals also have to have similarly mutated immune system genes as PwMS? Or are we saying these mutations don't matter?

If they can create a mouse model that results in lesions like in MS, then no, genes wouldn't matter. The EAE mice don't have mutated genes, anyway.

It might be an imperfect model, but not as imperfect as EAE. :)


PwMS are known to have a different genetic profile than healthy persons. Some of the genes control the immune system. If CCSVI indeed causes MS, it's not a stretch to think that maybe MS is actually CCSVI + bad immune genes. This would explain why healthy persons can have CCSVI and not MS.

We don't know just how imperfect a CCSVI animal model would be because we don't know enough to judge it. We need to be careful about an animal model at this stage of the research.
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Postby Cece » Sun Feb 06, 2011 2:52 pm

ikulo wrote:If CCSVI indeed causes MS, it's not a stretch to think that maybe MS is actually CCSVI + bad immune genes.

Exactly!! First there is the CCSVI that we are born with, then there is how the body responds to the situation caused by the CCSVI, from how big of collaterals developed to compensate to how the immune system reacted or over-reacted or, if we're lucky, under-reacted. I agree with you about the animal model too. Beginnings are tenuous times.
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Postby Shannon » Mon Feb 07, 2011 7:09 am

Actually, my point was just to suggest that if it is indeed congenital, then how does it happen? Is it something adverse that happens during pregnancy? Couldn't we test the effects of some of these things on animals?

I also made the point that while it seems cruel to animals, it shouldn't be as bad as what is seen in humans because primates may not even go on to get anything like MS from the CCSVI-like condition. They would then have to go on to live under certain environmental conditions, or a combination of conditions, as we did, for that to happen. Also, we could be sure to use only animals who did not have the premeditating gene mutation.

I am extremely fascinated by the mechanisms which are involved in venous development. I want to know what is required for proper development and what would cause the conditions that we are seeing in CCSVI.
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Postby Lyon » Mon Feb 07, 2011 7:23 am

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Last edited by Lyon on Sun Jun 26, 2011 6:47 am, edited 1 time in total.
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Postby Rokkit » Mon Feb 07, 2011 8:31 am

Lyon wrote:MS was just terribly rare in our Grandparent's time and incidence has drastically increased since then and it's said that genetics in humans isn't capable of changing that quickly so if it really is congenital, it makes you wonder how it came to happen.

Yes but suppose it takes congenital malformations plus something else like immune system malfunction to make MS. In that scenario the congenital malformations could have existed subclinically for a very long time. And then due to environmental changes, hygiene theory or whatever else, the second factor comes along.
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Re: If CCSVI is congenital...

Postby NHE » Mon Feb 07, 2011 4:47 pm

Lyon wrote:MS was just terribly rare in our Grandparent's time and incidence has drastically increased since then and it's said that genetics in humans isn't capable of changing that quickly so if it really is congenital, it makes you wonder how it came to happen.


First, a diseased condition must be recognized in order for it to be diagnosed. People throughout the centuries have likely developed neurological problems such as MS. The earliest recognized case of MS is from the late 1300's.

MS-Gateway wrote:MS Through History
St. Lidwina of Schiedam (1380-1433)

St. Lidwina of Schiedam Possibly the earliest known descriptions of a case of multiple sclerosis referred to the woman depicted in this woodcut, St. Lidwina of Schiedam. Lidwina lived in 14th century Holland and historical texts reveal that she was afflicted with a debilitating disease, sharing many characteristics with MS.


Moreover, once a disease is recognized, the ease at which a disease is diagnosed can influence an apparent increase in its prevalence. The wide-spread adoption of MRI scanning alone likely increased the number of people diagnosed with MS.

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Re: If CCSVI is congenital...

Postby Lyon » Mon Feb 07, 2011 5:03 pm

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Last edited by Lyon on Sun Jun 26, 2011 6:46 am, edited 1 time in total.
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Postby CCSVIhusband » Mon Feb 07, 2011 8:36 pm

Lyon wrote:MS was just terribly rare in our Grandparent's time and incidence has drastically increased since then and it's said that genetics in humans isn't capable of changing that quickly so if it really is congenital, it makes you wonder how it came to happen.


Generations of living in conditions where sunlight (and exposure to the sun) is less prevalent - and less people work outdoors regularly to get vitamin d. Vitamin D lacking then could be a cause of CCSVI (don't know yet, not that far into the research, but it's not hard to draw the link for sure) ... Vitamin d may be critical in forming proper veins in the uterus - passed from mother to child in the womb.

The sun drives life on earth ... makes things healthy, feeds them on a cellular level ... it's not a far reach to assume the sun is important in development and health. And with the known Vitamin D relation to MS - the sun obviously plays a role ... so again, it's not a far leap to connect vitamin D to (potentially) vein development and CCSVI ...

hence the 38th parallel or whatever it is
hence the high incidence of "MS" in babies born in late spring/early summer when most of the pregnancy would have been spent indoors from the cold
hence when people began getting indoor jobs, the industrial revolution, MS rate increased dramatically - in a few generations as you point out
hence when Iranian women were forced to cover head to toe, MS incident rate increased dramatically in GENERATIONS
Huh, what if CCSVI is caused by lack of vitamin d in the mother passed to the womb ... what a new neat idea that should certainly be explored.

Pittsburgh/Western PA is the 2nd cloudiest place in the US ... high incidence of MS.
Same through western NY and the great lakes regions ... very cloudy, very cold ...
Same for Canada (very cold much of the year)
Same for the pacific northwest - lots of gray days.
Same for England/Scotland - very cloudy. Little sun.
Same goes for Iranian women increasing in prevalence (when women became forced to cover up from head to toe and get VERY limited exposure to sun)

Little MS in Mexico (or other third world areas, as you point out - though I'm not sure why people can't make the connection I did above) ... lot of out door work - or whatever people in sub-saharan africa do during the day, still because, plenty of sun. Same goes for down through central america ... same goes for islanders ... little rate of incidence among african americans ... (generations haven't been not getting sun long enough though ... whereas caucasians have for many many generations)
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Postby cheerleader » Mon Feb 07, 2011 9:17 pm

Lyon wrote:MS was just terribly rare in our Grandparent's time and incidence has drastically increased since then and it's said that genetics in humans isn't capable of changing that quickly so if it really is congenital, it makes you wonder how it came to happen.


Actually, epigenetics accounts for genetic changes within one generation, Bob. Things can shift very quickly. And if environmental issues influence MS incidence and severity, epigenetics matter. Here's a great feature Time Magazine did on epigenetics.

At its most basic, epigenetics is the study of changes in gene activity that do not involve alterations to the genetic code but still get passed down to at least one successive generation. These patterns of gene expression are governed by the cellular material — the epigenome — that sits on top of the genome, just outside it (hence the prefix epi-, which means above). It is these epigenetic "marks" that tell your genes to switch on or off, to speak loudly or whisper. It is through epigenetic marks that environmental factors like diet, stress and prenatal nutrition can make an imprint on genes that is passed from one generation to the next.


http://www.time.com/time/health/article ... 68,00.html

I know Bob's environmental issues would include loss of parasites and the hygiene hypothesis. Mine would include endothelial/nitric oxide disrupters like high fat and processed food diets, lack of vitamin D, toxins, smoking, etc.

Modern living could have messed us up pretty badly, and pretty quickly.
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dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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