This Is MS Multiple Sclerosis Community: Knowledge & Support

[Rokkit]

Although getting excited about the 80% possibility is so tempting, it's just so hard to believe they wouldn't have mentioned that in the press release. Why on earth would they have included so many CIS? And why would they include CIS in the overall percentage? CIS is not MS. Just doesn't make sense.

[costumenastional]

Reading about the CIS issue in the Buffalo study i have to ask:

Isn't nowadays MS diagnosed right after the CIS following by immediate treatment? Aren't people concerned as patients after diagnosis? This was the last trend last time i checked. I know i feel like a patient and i have only had one obvious relapse so far. This doesnt change the fact i am getting worst so lets not stick in definitions rather than the real thing.
So, i think THEY DID THE RIGHT THINK to include CIS in the study because:
If CIS has a lower relation with the CCSVI and higher with the CDMS doesn't this mean that ms precedes ccsvi? Something very unlikely according to the logic i got left but then again who am i to tell? It is an angle that should be further investigated as it could give answers to the egg and chicken question.

Another interprentation could be that in the early stages of MS the ccsvi is not easily detectable by the methods they are currently using, but as the veins stenosis is getting worse for whatever reason so does the MS.
Another useful aspect if ever answered.

That would rule out the congenital factor of course and it is well known that they have already found patients missing veins,or veins pinched by bones, pathologies that cannot just happen but most certainly exist since birth. What if some of us are born with ccsvi and others develope it later in life?

What i worry about mostly is of critics that will now be even more agressive as the original high percentages are gone. Even if the last means that Buffalo widened up the road to research aspects that Zamboni didn't.
They WILL use just the numbers.
It s a good thing that Buffalo will keep investigating and we should continue to support them whatsoever.

I dont want to stick on numbers like them. I believe Zivadinov has seen things that will take the vascular issue much further. I believe there are very serious reasons for them to keep on looking into this. I believe that Zamboni made the discovery of the century using only 65 cdms patients and as the studies cohorts are widening it is only natural for the percentages to drop and make them seek were the differences are and why or what they may have missed. I believe all MS patients have vascular problems and if they dont, it is not MS what they have.

"Don't underestimate these findings," Zivadinov said. "There is more to this story."

Finally, i dont think of the 25% of controls having stenosis much worrying simply because not all people's immune system react the same way, thus having ccsvi should not make it a fact that one will develop MS. In addition, who knows what will happen to people with mangled veins in the future?
Nothing i hope but then again...who am i to tell?

[TFau]

Although getting excited about the 80% possibility is so tempting, it's just so hard to believe they wouldn't have mentioned that in the press release. Why on earth would they have included so many CIS? And why would they include CIS in the overall percentage? CIS is not MS. Just doesn't make sense.

I know Rokkit, I agree with you.

[TFau]

Another interprentation could be that in the early stages of MS the ccsvi is not easily detectable by the methods they are currently using, but as the veins stenosis is getting worse for whatever reason so does the MS.
Another useful aspect if ever answered.

That's a good point. I wonder if they chose people at the early stages to keep the study blinded. Perhaps it would be too obvious that a person has MS when they're in a more progressed stage.


The press release said that most people had RRMS - could that have included CIS? DId they mention the groups MS, CIS, OND, and healthy controls only for a post comparison, not necessarily for the final numbers (ie, they grouped these groups together whichever way for the calculation)?

[costumenastional]

Ummm, CIS is by definition not ANY type of MS. It is just that.
Clinical Isolated Syndrome.
And because MS may by it's nature be very slow to the point that no more symptoms will ever arise, they used to wait until they tag someone as an MS patient. Lets not forget diseases that mimic MS.
This doesn't mean that one should wait to start the CRABS or whatever.
It's foggy, like MS. They simply wait and see...

So, they DID include CIS cases most certainly in the patient cohort to finally concude that they are less probable to have ccsvi as it is defined until today.
What does this mean? It could mean a million things.

Lets wait to hear what THEY think.

[costumenastional]

Also, let's assume that in exception of people that are born with CCSVI of some type, others begin to develope vascular problems later in life. It s only natural to start experiencing symptoms which finally lead to the CIS and some kind of demyelination disease diag. When these persons are tested for ccsvi it could be very difficult to see the problem according to Zamboni's criteria. He used CDMS patients where vein problems may be more profound as time has gone by and they got worst. All i am trying to say is that indeed, an early stage ccsvi may consists with an early stage ms.
Lets not forget Zivadinov saying that a relationship between the progression of the two diseases has been found, something that Zamboni didn't have the chance to see by testing only cdms cases.
Hmmm, take 55 add 10 that are unsure then add CIS that might be able to get diagnosed with CCSVI when better equipment is available. Where does this lead us to? Higher and higher!
Zivadinov will use more advanced equipment in the following trial and this may be due to exactly that. To find out more ccsvi cases, in a more early stage etc etc.
CIS usually tend to lead to a full blown MS after some time and attributing this to worsening stenosis has a huge potential. It could be of a great help for misdiagnosed people in the future.

Do i even make sense hahaha

[ClaireParry]

Costumenational,

I had the same thought....

May be there are people with CCSVI who will never go on to develop MS, because their bodies cope with it. As you say, everybodys immune system will not react in the same way.

All the results are not in yet, add the 10% to the 55 and the result creeeps up, and quite honestly, I'll take most of my lead from people reporting of their progress. The proofs in the pudding, right??

Claire

[costumenastional]

Right on!

I believe in this theory. It just makes sense.

A slightly occluded vein, a slight reflux, everything related can lead to CNS damage. We are talking for sensitive material here...

[eve]

I read this commment on Fb:

not all CIS patients will covert to CDMS (22%, Cohen & Ruddick 2007), I think that the true CDMS CCSVI results are skewed significantly by lumping the 2 groups.

Looking for this research (which I have not found) I stumbled upon this:

However, the question remains how to predict that a patient with CIS will develop CDMS? Several prospective studies addressed this issue using MRI as a surrogate marker in patients with CIS who already showed evidence of occult disease dissemination by the presence of asymptomatic white-matter lesions.[37-42] The majority of these patients will go on to develop CDMS.

In the Optic Neuritis Treatment Trial (ONTT) the number of brain lesions present in patients with monosymptomatic optic neuritis was a strong predictor of the likelihood for developing CDMS (Class I evidence).[43]

A recently published 14-year prospective study on the use of MRI to predict the risk of developing MS in patients with CIS revealed that almost 90% of patients with abnormal baseline MRI developed CDMS during the follow-up period.[4]

Interestingly, the conversion rates to definite MS did not depend on the number of lesions present on brain MRI at baseline.

Thus, multiple demyelinating lesions as seen on MRI at the time of CIS support the contention that the clinical presentation does not reflect the first pathological manifestation. Prospective MRI studies have shown[44]:


•Lesional dissemination on brain MRI in a patient with CIS strongly predicts future conversion to CDMS (Class I).[4,34,35]

•Gadolinium-enhanced lesions at baseline strongly predicts future conversion to CDMS (Class I).[45]

•The application of the new McDonald criteria more than doubles the rate of the diagnosis of MS within a year of presentation with a CIS (Class I).[41]

•In patients with a classical syndrome of inflammatory demyelination and an abnormal baseline MRI, the possibility of an alternative diagnosis is negligible (Class I).[4,34,35

http://www.medscape.com/viewarticle/459967_3

Now I am no medic so not sure how to interpret. As I understand it people with CIS and certain lesions as seen on MRI have a 90% chance to develop MS. So what percentage of the CIS patients in this study have those lesions?

[costumenastional]

As I understand it people with CIS and certain lesions as seen on MRI have a 90% chance to develop MS. So what percentage of the CIS patients in this study have those lesions?

Sorry that i am the one to tell you but they MOST LIKELY already have develepod MS, they just havent been told yet because there is a very slight change that they might have an ever worse disease

[Direct-MS]

Here is another way of looking at this. As stated in an early post, most people with CIS convert to MS. So let's be conservative and say only 70% of those with CIS in the Buffalo study will actually end up with MS.

If CCSVI was the primary cause of MS then we would expect close to 70% of the CIS patients to exhibit CCSVI. However if we go objectively with the Buffalo data and that only 60% of persons with MS have CCSVI then we would expect a result of 70 X .6 = 42% of those with CIS to exhibit CCSVI and that is approximately what was found.

To me the Buffalo results say CCSVI is a very major risk factor for MS but something else is the primary cause (i.e. all persons with MS are affected by it). As a major risk factor which can be related to the disease pathogenesis, one would predict resoution of CCSVI would be of significant benefit.

[Cece]

As a major risk factor which can be related to the disease pathogenesis, one would predict resoution of CCSVI would be of significant benefit.

Yes! There are many risk factors for MS that we can do nothing about. Can't relocate my childhood to somewhere sunny or ensure that I had vitamin D growing up or didn't catch Epstein Barr. So the research into those areas are informative but not actionable, for those already with m.s. But here suddenly comes along a risk factor that, for many, can be surgically treated. This is big.

[Cece]

If CCSVI was the primary cause of MS then we would expect close to 70% of the CIS patients to exhibit CCSVI. However if we go objectively with the Buffalo data and that only 60% of persons with MS have CCSVI then we would expect a result of 70 X .6 = 42% of those with CIS to exhibit CCSVI and that is approximately what was found.

Interesting. I didn't understand your numbers until I reread this. So the numbers fit with CCSVI being congenital and don't have to assume that the people with CIS who do not have CCSVI will develop it concurrently with developing MS.

[TFau]

We also don't know what the level of detection for CCSVI yet. It is possible that there is undetectable subtle reflux that can lead to an MS-like event. If CCSVI progresses for some reason, such as hardening of veins as one ages, and then becomes detectable, this could show a lower preponderance of CCSVI in the early stages of progression.

Or, perhaps there is subtle reflux which causes a continuous accumulation of iron, which increases disability without the reflux becoming detectable.

Or, some people never have CCSVI and progress anyway...

[Direct-MS]

Here is one way of looking at the stat that 80% of more advanced PwMS have CCSVI as found in the Buffalo study. One would intuitively think that MS with CCSVI would progress more rapidly and farther than MS without CCSVI. Accepting this premise, you would expect to find a higher % of PwMS with CCSVI in each subsequenct EDSS category. Thus EDSS of 1 might have a 60/40 ratio of those with CCSVI versus those without. An EDSS category of say 4 might have a ratio of 75/25 and an EDSS category of 6 might have 85/15. This would explain the Buffalo finding.
Of course such data might be interpreted to mean CCSVI develops as MS progresses but if one accepts the consensus opinion of the vascular researchers that the vascular malformations that constitute CCSVI are congenital, then the hypothesis that CCSVI makes MS worse (as opposed to the hypothesis that MS makes CCSVI worse) would be the best one.
This is one more solid reason that one would want CCSVI resolved asap.