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cheerleader wrote:

Cece wrote:'Since birth' is of greater importance in a disease when chronic longterm neurodegeneration is the key process. 'Since diagnosis' or since relapses and/or progression began would be of greater importance if the relapses themselves cause the neurodegeneration.

Exactly, Cece. Dr. Tremlett even stated that relapses were not connected to long term disability in the study. Dr. Tremlett stressed the need to really look at the results of this study, because soon we will no longer have a large group of treatment naive patients--and the natural history of MS disease progression will be lost.
cheer

I don't think any treatments have the power to prevent progression to "SPMS".

Even the ones that might also kill you or cause more problems (like mitoxantrone, which I think caused my heart attack) don't have that effect. Very premature to declare "MS" cured, by so-called DMDs, anyway. With the CCSVI procedure and related investigations, we are getting closer.

I do think it is vital, though, to have more information about the long term effects, and why they differ so much from "normal" aging.

It is tempting to apply every statistic to one's own case, and that is something I want to avoid. I don't think anybody will always be the norm.

cheerleader wrote:So, if EDSS is not an accurate measure of MS progression, white matter lesions are not good measures, nor is symptom relief---what can be used to chart progression in MS---for all clinical trials, be they interventional venoplasty, nutritional/lifestyle studies or drugs--?
Gray matter atrophy. It's the only parameter tied directly to debilitation and progression. It appears before white matter lesions, and continues after the white matter inflammation of MS is gone.

...in the last decade, substantial pathological, immunological and imaging evidence confirmed that tissue damage in the GM is a key component of the disease process in MS and that it occurs from the earliest clinical stages [2-5]. During the past few years, the number of studies investigating GM damage in MS has increased exponentially.
In the last 5 years, numerous cross-sectional and longitudinal studies established that GM damage is a better predictor of physical disability and cognitive impairment than WM damage [5]. Most studies examining this argument used novel imaging techniques that can indirectly assess the extent of GM damage, the most important being a measurement of GM atrophy [2,5]. Therefore, monitoring the evolution of GM damage by various imaging techniques is becoming an important marker in predicting the future disease course and response to therapy in MS patients. A number of current clinical trials examine the effects of immunomodulatory treatments on slowing down GM damage over time.

http://www.biomedcentral.com/1471-2377/12/9
This is what is being followed in my husband. His gray matter now looks normal, three years after venoplasty, atrophy is reversed. Yes, he's had symptom relief, improvement in EDSS...but this measurable parameter has changed, and will be monitored for the rest of his life. I suggest other pwMS ask to have their gray matter assessed. This is an accurate measure of neurodegeneration. (BTW, why wasn't this posted on the Tysabri or stem cell forums, only here??)
cheer

Hello Cheer,
Jeff's gray matter (GM) is great news for him. It would make a great longitudindal case study if you have MRI's showing Jeff's GM over many years. Do Jeff's early MRIs show GM? If you could show a decline in GM over his early disease then recovery in GM after the four fold therapy was introduced (CCSVI/Vit D/Vein health/Copax) that would be a strong message. In the UK not much attention is paid to GM in the general MS clinic just WM. Neuros are catching on to measuring GM but I am sure that will be slow as I think it requires a high resolution MRI machine. Let's not loose the GM idea as it will not be obvious to most IRs.
Kind regards,
MarkW

Cece wrote: http://koti.mbnet.fi/hiihoo/ccsvi/Arslan%20case3.jpg

CASE 3
34 y/o male who was fully functional 4 years ago
Primary progressive
14 y/o son and wife responsible for taking care of him and support family
Very weak, slurred speech (wife translates), wheelchair bound and legs-arms as well as neck with severe contractures, not able to move, legally blind with 20/200 vision
Significant muscle wasting and weight loss due to feeding difficulty – frequent choking – weight 90 lbs
Severe episodes of headache to the degree he would scream, pretty much every day

POST STENTING, FLOW SIGNIFICANTLY IMPROVED, COLLATERALS DIMINISHED
Gained 15 lbs in 2 months
Able to move arms and hands, vision to 20/30 from 20/200
Able to speak clearly with no evidence of slurred speech
No choking episodes since the procedure
Not a single episode of headache since the procedure (19 months)
Love placebo!

Here is an example of a patient's improvements after CCSVI venoplasty, as observed by Dr. Arslan.
I would think that if an example of this magnitude has occurred as a natural innate improvement, it should have been written up by whatever treating neurologist saw such a thing happen.

MarkW wrote: Hello Cheer,
Jeff's gray matter (GM) is great news for him. It would make a great longitudindal case study if you have MRI's showing Jeff's GM over many years. Do Jeff's early MRIs show GM? If you could show a decline in GM over his early disease then recovery in GM after the four fold therapy was introduced (CCSVI/Vit D/Vein health/Copax) that would be a strong message. In the UK not much attention is paid to GM in the general MS clinic just WM. Neuros are catching on to measuring GM but I am sure that will be slow as I think it requires a high resolution MRI machine. Let's not loose the GM idea as it will not be obvious to most IRs.
Kind regards,
MarkW

Thanks, Mark. Yes, Jeff's GM is being followed by Stanford, and is a proposed bio-marker in the upcoming multi-center study.
Standard MRIs show basic GM architecture, but most techs don't include it in reports. They focus on white matter lesions---but techs can also look for subcortical atrophy by studying the brain stem, thalamic atrophy and enlarged ventricles as signs of GM loss and comparing MRIs. This is what has been done for Jeff--and can be followed in anyone who has MRIs before and after venoplasty.
http://www.plosone.org/article/info%3Ad ... ne.0037049

What a PwMS cares about isn't necessarily disease progression but disability levels. I don't care if my brain is a mess if a treatment prevents increased disability, whether that disability is related to relapses or not. EDSS can be an important measure since mobility is such a critical function in living within our society. It may not cover all facets of deterioration, but it can certainly show physical decline consistent with MS progression.

I'm not sure if GM atrophy is going to be an accurate measure of disease progression either or as it relates to actual disability.

http://www.ncbi.nlm.nih.gov/pubmed/19100997

http://www.ncbi.nlm.nih.gov/pubmed/22764259

Age-related level of disability regardless of what age MS was diagnosed at is not a new concept but has been studied for many years. I know I read studies on it probably 10 or more years ago. Sometimes if you are recently new to the whole MS experience, you tend to feel that you are "discovering" new areas of research, when many of us who have been diagnosed for a very long time and following research for a very long time, have been familiar with these areas of research also for a very long time. I think sometimes it's important to keep a broad view and not fall victim of being unable to see the forest for the trees. For example, I read often the contention that MS has never been "proven" to be an autoimmune disease. While this may be technically true, there are countless studies, thousands, that support this theory and show some small facet of MS consistent with the autoimmune theory. They can't be dismissed just because it's never been "proven" and the EAE model of MS does not mimic MS pathogenesis in humans and is therefore not ideal. There is much support for the autoimmune theory in MS.

This particular research/thread was posted in the CCSVI forum because many people here have insisted their "improvements" to CCSVI treatment could only be due to treatment itself because they were SPMS and therefore, would not be expected to improve due to natural fluctuations in the disease itself since in SPMS, health progressively declines without the remitting characteristics of RRMS. I posted this research here for that reason, to demonstrate that improvements can and do occur in SPMS as well.

I recently posted about how the high ET-1 levels definitely seen in MS and not in controls are unrelated to disease course or "phenotype". Are they age-related? I would agree with statements that some improvements can be expected (although a pessimistic view on this is always easy to find) even in SPMS. I was not expecting the apparent connection between my symptoms (almost all of them) and my treatment for CCSVI. Though I should have been, shouldn't I?

This is to say, I have had a remission recently, and it was a good one. I was also treated with steroids for an apparent "attack" back when I had a neurologist. In fact an exclusion criterion of the study I was on at the time was that I could not be RRMS. More evidence in my mind that there is no such thing as SPMS.

I had a remission (and an attack) that I was not supposed to have. Maybe because disease course and ET-1 levels and who knows what all, are age-related, at least in my late-onset case?

In other words, you can't have it both ways. Either there is no such thing as SPMS, or there is. There is no reason some instances of remission in SPMS could not also be due to the procedure for CCSVI.

The current physical measures of MS do not correlate with MS disabiity, so more WM lesions does not mean more disability. The point about GM changes in MS is that GM alterations appear to correlate with MS disability. We do not know how and why brain repair happens in pwMS but it does sometimes. The point that Cheer made is that GM is the best physical measure we currently have. A key point is that this is a physical measure not an human assessed measure like EDSS.
Lets try to focus on this physical measure which correlates with MS disability/progression.
MarkW

eric593 wrote:What a PwMS cares about isn't necessarily disease progression but disability levels. I don't care if my brain is a mess if a treatment prevents increased disability, whether that disability is related to relapses or not.

I think this may be the first time you identified yourself as a pwMS? Sorry to hear it.
As a pwMS I care about disability, progression, AND whether or not my brain is a mess. The latter can affect the ability to work, to drive, to converse...these are not inconsequential.

For example, I read often the contention that MS has never been "proven" to be an autoimmune disease. While this may be technically true, there are countless studies, thousands, that support this theory and show some small facet of MS consistent with the autoimmune theory. They can't be dismissed just because it's never been "proven" and the EAE model of MS does not mimic MS pathogenesis in humans and is therefore not ideal. There is much support for the autoimmune theory in MS.

There is support for immune involvement in MS, not necessarily autoimmune involvement. There is an autoimmune response after stroke that is more pronounced than the autoimmune involvement in MS, but we don't consider stroke to be an autoimmune disease.