This Is MS Multiple Sclerosis Community: Knowledge & Support

The abstract below demonstrates that persons with MS have a decreased capacity for immune suppression. I put this on to emphasize the point that MS is not simply a normal immune system invading the CNS due to CCSVI effects.
There is no doubt that CCSVI plays a major role in MS and needs to be treated as soon as possible. However, the data tell us that MS is best seen as being caused by CCSVI in concert with a faulty immune system (genetics plus environmental effects). A reduced capacity for immune suppression is one element of such immune dysregulation that helps to drive MS.

Transcriptional characteristics of CD4+ T cells in multiple sclerosis: Relative lack of suppressive populations in blood.
Edström M, Mellergård J, Mjösberg J, Jenmalm M, Vrethem M, Press R, Dahle C, Ernerudh J.
Mult Scler. 2010 Sep 16.

Abstract
Background: Multiple sclerosis (MS) is hypothetically caused by autoreactive Th1 and Th17 cells, whereas Th2 and regulatory T cells may confer protection. The development of Th subpopulations is dependant on the expression of lineage-specific transcription factors. Objective: The aim of this study was to assess the balance of CD4(+) T cell populations in relapsing-remitting MS. Methods: Blood mRNA expression of TBX21, GATA3, RORC, FOXP3 and EBI3 was assessed in 33 patients with relapsing-remitting MS and 20 healthy controls. In addition, flow cytometry was performed to assess T lymphocyte numbers. Results: In relapsing-remitting MS, diminished expression of FOXP3 (Treg) was found (p < 0.05), despite normal numbers of CD4(+)CD25(hi) Treg. Immunoregulatory EBI3 and Th2-associated GATA3 expression was also decreased in MS (p < 0.005 and p < 0.05, respectively). Expression of TBX21 (Th1) and RORC (Th17) did not differ between patients and controls. Similar changes were observed when analysing beta-interferon treated (n = 12) or untreated (n = 21) patients. Analysis of transcription factor ratios, comparing TBX21/GATA3 and RORC/FOXP3, revealed an increase in the RORC/FOXP3 ratio in patients with relapsing-remitting MS (p < 0.005). Conclusion: Our findings indicate systemic defects at the mRNA level, involving downregulation of beneficial CD4(+) phenotypes. This might play a role in disease development by permitting activation of harmful T cell populations.

Thanks !!! This isn't an autoimmune theory vs CCSVI battle at all. Dr Zamboni emphasized that in the CTV W5 documentary. I just hope that a CCSVI mouse model of MS is developed soon. I think that more than any other research that a mouse model will be the straw that breaks the camel's back and will lead to more immune system research for MS and a strong push for CCSVI research and treatment. If no one is able to build a mouse model then that may be the nail in the CCSVI coffin.

ozarkcanoer

sounds like a potential explanation for why Buffalo found CCSVI in a decent clip of non-MS. CCSVI + immune dysfunction in conjunction could contribute to what is known as MS.

While I hope an animal model is developed, my concern is that a mouse won't live long enough to develop MS symptoms....as I understand the CCSVI theory, it takes a long time for the damage to be done...

so if you close up a few veins in a mouse, it may die before the damage is detectable.....

maybe a 10 year study on dogs? monkeys?
Or to we go straight to human trials? (Oh wait.......)

I say that as my wife is on the Albany waiting lists....

to quote Dr. Zamboni ... '' I am not a mouse doctor "





Mr. Success

The P values reported here are p<.005 and p<.05. That means the odds of getting their results by chance is <0.5% and <5% respectively.
The P values reported by Zamboni in his paper were mostly p<.0001. That means only 1 chance in 10,000 of getting those results by chance. In my opinion that makes a far more compelling case for CCSVI than for auto-immune.
http://www.direct-ms.org/pdf/CCSVI/Zamb ... S%2009.pdf (See table 3.)

David, Dr Zamboni himself says that MS is an autoimmune disorder. We just don't know the trigger. CCSVI MAY be the trigger, and it may not. Nobody knows yet. CCSVI is worth pursuing because it is strongly correlated to MS. The question is why ?

ozarkcanoer

I now prefer to see MS as including an immune dysregulation rather than a specific autoimmunity. Possibly up to 20% of the population is born with venous malformations which result in CCSVI. Another smaller group of the population (1% ?) ends up with an immune dysregulation due to gentic susceptibity and environmental factors such as a virulent EBV infection during a time of low vitamin D and an overall poor immune education due to ultra-hygienic conditions.
Those with both CCSVI and acquired immune dysregulation (perhaps .2% of the population [1% of 20%]) get MS because CCSVI opens up the BBB and once the immune system gains access to the CNS, the immune dysregulation results in a poorly controlled immune/CNS interaction and ongoing damage. Other factors related to CCSVI can explain accompanying neurodegeneration.
Such a model explains all the known genetic, immunological, epidemiological observations as well as the postulated environmental factors of MS and also explains the presence of CCSVI in (almost) all cases. The bottom line is we need a disease model that factors in all we know about MS.

But then aren't we kind of back to wondering why drugs that suppress the immune system aren't very effective in treating MS?

This disease is as complex as quantum mechanics...

http://www.ncbi.nlm.nih.gov/pubmed/20802204

The University of California San Francisco has a substantial MS research program, with particular strengths in genetics and imaging. Scientists from both of these disciplines recently collaborated on a project to learn more about the role of inherited gene variants in MS. In addition to influencing who gets MS and who doesn't, genes may also affect the course or severity of disease, but this aspect of MS has not yet been as extensively explored.

This project focused on the role of glutamate. Glutamate plays an important role in nerve signal transmission in the central nervous system, but it can be harmful to cells if concentrations are too high. Normally oligodendrocytes help to regulate glutamate concentrations by taking in excess glutamate, but this process is impaired in MS, and past research has documented elevated levels of glutamate in MS brains.

The imaging researchers scanned the brains of 382 MS subjects using spectroscopy, which measures the level of different molecules in tissue. The geneticists performed a genome-wide genetics screen on the same subjects. The team then analyzed the genetic results with respect to the glutamate levels determined by spectroscopy. They found several variants in genes associated with glutamate biology that were more common in subjects having the highest concentrations of glutamate. Further analysis showed similar genetic associations in subjects with higher brain atrophy (shrinkage) and lower concentrations of a molecule found in axons (N-acetylaspartate).

These results suggest that inherent genetic differences in nervous system biology among people with MS may influence concentrations of glutamate within the central nervous system, which may then affect survival or death of axons. It is encouraging to see scientists from different disciplines coming together in MS research, because looking at a question from more than one angle can lead to a much better understanding of the disease.

I thought the Buffalo results were skewed on account of Zivadinov's using people related to the CCSVI patients, in his group of 'healthy individuals'. This made me skeptical of anyone using the 20% number for much. Indeed, before his full publication, which may include a recalculation, we cannot speculate on what the prevalence of CCSVI in 'MS' or 'healthy' people is.

I am not convinced of anything, especially auto-immunity, less so genetic influences, etc. Today someone posted a link to a paper which speculated that whatever is driving MS is intermittent (i.e. posture-dependant reflux?). That might explain the differing lengths of time in different people, for it to affect their abilities, etc.

I think we must distinguish between first-order influences, such as genetics, and second- or third-order, such as sunshine levels which may or may not influence Vitamin D levels which may or may not influence immunity or auto-immunity.

I think of good circulation as a first-order influence on your health.

_________________
"Try - Just A Little Bit Harder" - Janis Joplin
CCSVI procedure Albany Aug 2010
'_MS' is over - if you want it
Patients sans/without patience

Monozygotic twins have a risk of 30% that both get MS. So if the second twin develops MS too, 30% of this risk comes from his genes and 70% from the environment, other conditions or are mere chance. (so if you change the environment/conditions e.g. by ballooning veins, Vitamin-D.... you may modify the disease or you may never get it).

Assuming the genetic part comes from two independent factors, a son or daughter from MS-parents should have roughly a risk to get MS of 30%/4 = 7.5%

This only is true, if both factors are very rare. If one factor is more common (CCSVI 20%) the value must be enhanced approximately to 7.5%*1.2 = 9%.

This large study

http://www.neurology.org/cgi/content/ab ... 40851.d6v1

with 3088 MS-families with 8401 children shows, that the risk that a MS-father or MS-mother transfers the disease to his/her son or daughter is 9,41%(father) and 9,76%(mother). 798 of the 8401 children had MS.

This simplified probability calculation shows that there are arguments, that the genetic part of MS comes mainly from two factors. One of these may not be rare.

R.

I could be wrong but my understanding of auto immunity diseases is that the problem arises directly due to immune malfunction. The reason could be gene defects etc.

And there are other disease of immunity which are classified as auto-immunity as the issue can be traced to immune activity but the reason for such an activity is not unknown.

On the other hand, per CCSVI, immune system is not malfunctioning at all.

_________________
A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it
- Max Planck

With the Buffalo-data CCSVI should not be the only genetic part. From the monozygotic twins risk value one would expect, that 7% of the population has MS (or the selectivity of the CCSVI-diagnosis must be increased).

If you use CCSVI with 25% in the population and another more rare genetic component (<1%) you will get exactly the risk profiles of the monozygotic twins and the MS-parents-children of the study above.

My speculation(!):

- genetic CCSVI (20-30% in population)
- more rare genetic part: liver/immune dysfunction (<1% in population)
- Very important: environment - including infections...

If you alter or repair one of these components, you may modify or stop the disease.


Why liver ?
Years ago after a liver transplant the MS of a patient disappeared.
But that's pure speculation.

R.

My speculation is that the Buffalo study assessed not only Doppler findings but operator's skills also.

For me, only catheter based studies will show the true prevalence.

But that's just my wild guess.