Missing links?

[10yearsandstillkicken]

I have been chewing on this for a bit and I guess this must be the obvious direction of CCSVI in relation to MS. MS is generally associated with a myriad of symptoms, lesions on the brain and spinal cord, and brain shrinkage. This is the obvious part - The elusive cause, or trigger, or reason, of MS might be CCSVI? They have been looking for years in brain matter and have never found anything concrete. Various viruses have been thought to be the cause. But, there has never been anything found that was conclusive. That might be because the cause was never in the brain. I guess the obvious again - What if MS is triggered by CCSVI? CCSVI causes whatever damage, iron, blah blah, not sure what it does exactly. One of the link(s) from this forum had an MRI overlaid with a different MRI that showed the MS lesion and iron deposit in the same place. So one or the other is causing one or the other to be there. Maybe MS is the immune system going after the iron/damage/whatever is occurring and not just attacking the myelin because of an “auto immune” response. Maybe there is nothing wrong with the response per se or it is not proper but would be expected??? I guess something similar to what the immune system does when there is a spinal injury. Given there are several other “auto immune” diseases (Crohn’s and type 1 diabetes etc.), I wonder if there is similar issues with blood flow there as well?

One of the things that all MS drugs report is reduced lesions. But none ever mention brain shrinkage. That would be because none have ever had any impact on it. I wonder if the brain shrinkage is related to CCSVI? Could years/decades of reduced oxygen/blood flow damage the brain as a whole and cause the shrinkage.

I have yet to meet with my neuro since I stumbled, no pun intended, upon CCSVI. I generally grill him about what is happening in the research world. This will be topic number one along with the request to be tested for CCSVI.

This seems to logically fill in missing pieces of what causes MS.

[radeck]

It is an underlying thought in many posts in this forum that CCSVI is a necessary pre-condition of MS.

Within that thinking the immune system plays a secondary, yet dominating, role in causing damage early in the disease, and becomes its role diminishes as the disease progresses. It is not true that immune-modulators have no effect on brain shrinkage. It is also not generally true that immune-modulation has no effect on disability. If you google/read up carefully you will find plenty of information on this.

The point is whether MS is primarily auto-immune or not. It seems few neurologists have held the view that the immune-system starts attacking the body for no reason (i.e. MS is primarily auto-immune). However they were unsure as to the primary cause, as you write.

The thought about other auto-immune diseases being triggered by similar venous problems is a good one. In one of Zamboni's papers you can see diagrams, based on what he has seen in his patients, on blood flow being re-routed from an internal jugular veins through the thyroid vein. It is possible that this extra blood the thyroid vein has to take causes thyroid auto-immunity, which happens to be more common in MS patients than in the general population.

[10yearsandstillkicken]

I guess I meant to say that these drugs are not fda approved to say they reduce brain shrinkage. A quick peek at two sites.
Tysabri:
In a 2-year study, some people taking TYSABRI were considered to be free from MS disease activity, because they had no fewer flare-ups, no disease progression, and no new or newly active MRI lesions.
Rebif:
Is proven to work on all 3 key disease measures in MS: progression of disability, frequency of relapses, and activity and area of brain lesions on magnetic resonance imaging (MRI)*

I didn’t see any reference to a reduction in brain shrinkage.

It is also not generally true that immune-modulation has no effect on disability. If you google/read up carefully you will find plenty of information on this.

I didn’t intend to indicate that these drugs do not have an effect on disability. As you say, it is generally understood that they do. The snippet from the rebif site addresses that directly.

[radeck]

Chuck, CCSVI might be the reason for MS. But we shouldn't ignore the evidence for auto-immune involvement, so we can get as complete and unbiased a picture as possible, you know?

So, I personally have not seen convincing evidence for Interferons and Copaxone slowing disability progression. There's evidence of them reducing annualized brain shrinkage by 30% or so, but in my humble opinion this is on shaky grounds, because it is based on the assumption that the trials were truly placebo controlled. In reality the drugs in those trials had significant side effects and could be distinguished from the placebo by most participants, so that true placebo control is missing, and AFAIK placebo itself can easily yield 30% improvement.

I think it gets more interesting when you look at more intense immune suppressers like Alemtuzumab, which is currently in phase III trials for MS. In phase II trials it has shown *no* brain shrinkage and *no* disability progression in *early* MS patients (on average less than a year from diagnosis at trial entry) over two years. See this <shortened url>

Again one could be skeptical and say this could be placebo effect in action because Alemtuzumab has more side effects than the Rebif it was tested against, but I think a complete average stop of progression in 100 patients seems unlikely to be caused that way.

The reason I find this interesting is because I want to understand why in the beginning the immune-system causes most of the damage, while later it doesn't contribute much anymore.

(PS: Alemtuzumab makes your immune system destroy your T and B cells, and it's hard to imagine how that would improve the CCSVI itself.)

[10yearsandstillkicken]

I think we are on the same page. There have been many studies that indicate an auto immune response. Taking a step back, how might those results fit in with CCSVI or complement the discussion. It seems that those studies fit in well with this and that there is an immune response at play. I guess the question becomes, it the response appropriate or not. If we could find someone who does not have CCVSI and give it to them (theoretically speaking since actually doing that is abhorrent), would that person get MS. Given I have over 11 years in, I have this feeling that my time is running short. So I’d like to jump to the end of this book if you don’t mind.

[radeck]

If we could find someone who does not have CCVSI and give it to them (theoretically speaking since actually doing that is abhorrent), would that person get MS.

If CCSVI is plays an important role in MS I guess it would happen in the long run.

The reasoning would be this: if you acknowledge the 100% correlation Zamboni has found, that seems to be upheld by Dake and the Buffalo trial, AND you realize that at least a large percentage (I don't know what percentage, but it's appreciable) of the stenosies found are clearly MECHANICAL in nature (missing jugulars, twisted jugulars, jugulars pinched by arteries or by vertebrae extensions, or by muscles) it seems very likely that in at least these cases the MS came after the stenosis. Since these mechanical problems are very rare in the healthy population, it indeed seems likely that they are the necessary pre-condition of MS, i.e. that there's not just correlation. Something else like chronic infections of the endothelium of the veins up in the brain, may be contributing factor, and lead e.g. to relapses, but not the primary problem in these cases where the pathological vein feature is so clearly beyond the capabilities of a pathogen or the immune system.

[10yearsandstillkicken]

Wouldn’t it be ironic if MS isn’t a disease at all? Billions of dollars in R&D, drugs, doctors etc for something that might be prevented with a bit of surgery. Not sure if that makes me want to laugh or cry. I guess it is hurry up and get tested at this point.