This Is MS Multiple Sclerosis Knowledge & Support Community

Here are some specific links, 100---
Dr. Zamboni's Brave Dreams trial is currently the only blinded, placebo controlled trial. It is still underway. The BNAC PREMiSe trial was never published, because it did not meet the endpoint of >75% restoration of venous flow. It remains a poster. Obviously, we need more research.

679 people with MS and CCSVI will be enrolled in a randomized, blinded clinical trial (with a sham arm) to assess the safety and impact of percutaneous balloon angioplasty (PTA) on balance, motor, sensory, visual, and bladder function, and cognitive and emotional status. Post treatment assessment at 12 months will also include information on relapse rate and EDSS.
http://www.trialsjournal.com/content/pd ... 13-183.pdf

Here are other unblinded trials for venoplasty:

Examinations of 8 people with MS found all had internal jugular vein stensoses. After venoplasty treatment global arterial cerebral blood flow (GACBF) significantly improved. This supports the view that early symptomatic benefits after venoplasty may be the result of increased cerebral perfusion.
http://www.ncbi.nlm.nih.gov/pubmed/24321823

Balloon angioplasty intervention corrected blood pressure deviations in people with 50% or more narrowing in one or both internal jugular veins and three or more symptoms of autonomic system dysfunction.
http://phl.sagepub.com/content/early/20 ... 12824.full

Venography was performed in 1999 people with MS and CCSVI. At 30 days the major complication rate was 0.6% and the minor complication rate 2.5%, suggesting endovascular treatment for CCSVI is safe. The vast majority of complications occurred in the first 400 procedures.
http://www.ncbi.nlm.nih.gov/pubmed/23948669

Venous lesions requiring treatment were found in 94.7% (90) of 95 consecutive people with MS. Evaluation and management of CCSVI 30 days post treatment found it was safe.
http://www.ncbi.nlm.nih.gov/pubmed/23701076

Objective and subjective outcome measures utilized 12 months after percutaneous transluminal angioplasty (PTA) in 44 people with MS and CCSVI reflect different outcomes of PTA. For example, the objective measures noted disability worsening after PTA, but the Multiple Sclerosis-Quality of Life-54 Scale (MS-QoL-54) found improvements in physical and mental health.
http://www.ncbi.nlm.nih.gov/pubmed/23660636

Endovascular treatment of the azygous and internal jugular veins (IJV) of 72 people with MS and CCSVI found that the procedure was safe, signifcantly improved flow of the IJVs and reduced EDSS scores.
http://www.ncbi.nlm.nih.gov/pubmed/23563645

Angioplasty improved cerebrospinal fluid (CSF) flow and decreased CSF velocity in this study of 15 people with RRMS and CCSVI. The changes in CSF flow and velocity were linked to better clinical and MR outcomes and were indicative of improved venous drainage.
http://www.ncbi.nlm.nih.gov/pubmed/23523158

In a study of 823 people with MS and 60 controls, CCSVI was diagnosed in 90% of people with MS and 0% of controls. Of the 127 people examined after treatment for CCSVI, 69% (88) were negative for CCSVI. This was associated with symptom improvement.
http://www.minervamedica.it/en/journals ... 12N03A0141

This open label study of 94 people with MS and CCSVI who underwent catheter venography dilation found the number of venous narrowings was associated with more disabilty. A significant improvement in clinical disability was observed in people with RRMS who were treated.
http://www.ncbi.nlm.nih.gov/pubmed/23202144

After venous angioplasty treatment 259 people with MS were followed with the Multiple Sclerosis Impact Scale (MSIS-29) at 1 and 6 months. There were statistically significant improvements in clinical scores.
http://www.jvir.org/article/S1051-0443( ... 7/abstract

Here's the study Jeff was a part of. The change in his cerebral hemodynamics was documented and published, and his reversal of gray matter atrophy has been documented since treatment. So, you really can't call it "anecdotal."
Anomalies of the head and neck were found in 40 people with MS. Venous stents were placed in 38. Improvement in hemodynamics was associated with improved symptoms.
http://vmj.sagepub.com/content/17/3/131.long

The great thing about the CCSVI Alliance website, is that we track all the positive and negative studies.
I realize now you're looking after your husband. I wish you both well. Honestly, MS is the enemy. It's been hard to see my primary progressive friends (like Marc and Jason) not benefit from the CCSVI science. Perhaps PPMS is a completely different disease than RRMS----obviously, there's more to learn.

I write about the science behind the vascular connection to MS--and there are lifestyle, nutrition and exercise modalities that have peer-reviewed science behind them, showing less MS progression, less brain atrophy and fewer relapses--like vit. D, exercise, smoking cessation, sleep, phytonutrients. There is much that can be done, while we wait for the rest of the research to come in. http://ccsviinms.blogspot.com
we're all on the same team,
cheer/Joan

cheerleader wrote:I write about the science behind the vascular connection to MS--and there are lifestyle, nutrition and exercise modalities that have peer-reviewed science behind them, showing less MS progression, less brain atrophy and fewer relapses--like vit. D, exercise, smoking cessation, sleep, phytonutrients. There is much that can be done, while we wait for the rest of the research to come in. http://ccsviinms.blogspot.com
we're all on the same team,
cheer/Joan

ok; fair enough. thank you for the reply.

You are misinterpreting the results of the study which refer to long term disability. As I said before, there is class 1a evidence that the FDA approved multiple sclerosis drugs decrease the rate of accumulation of MRI lesions and decrease the rate of multiple sclerosis relapses in relapsing multiple sclerosis. Some of the drugs have evidence for decreasing the rate of "EDSS progression" a measure of short term disability. Ebers is stating that these factors are not as important as and not strongly correlated with long term disability. I agree with him.

What I am saying is the CRAB drugs have been terribly overrated for years and that is no secret! The companies who make these drugs have hung their trial hats on the reduced numbers of brain lesions but we know lesion have little or no correlation with MS symptoms. We know long term use do these drugs makes no difference from those who do not take them. So does it matter whatsoever if the companies gives us stats that say that EDSS progression is slightly reduced. The huge cost to patients and the side effects of these drugs doesn't make sense.

It does not mean that they do not work at all

I didn't say that...I said they were very overrated. Some MS patients control the disease with diet, some with healthy living habits and some get some benefit from the drugs.

As an example, click the link and peruse figure two (From the Affirm trial, natalizumab vs. placebo EDSS progression)

Not talking about Tysabri here...that's a different ball game and a much more powerful drug that shakes the daylights out of many who use it...and that topic is better left for another day.

Of course, being less disabled on average in the short run is not as meaningful as being significantly less disabled in the long run, but your hubris in dismissing the drugs as worthless and ineffective is absurd

Geez I dislike it when people put words into my mouth like you just did!! I didn't say that the drugs were worthless. I said their effectiveness was highly overrated and in the long run did little for MS patients. I have never told any MS patient not to take a MS drug but to ensure that he/she makes a well informed decision.

Anecdotes are not as meaningful as high quality trials

Of course they aren't...but they are the only option in the absence of scientific studies.

I don't think that this is entirely fair. Medical equipment companies have motivation to promote the research. A significant amount of privately funded research has been done, and the results are heretofore unimpressive. Again, the underlying therory isn't even solid.

Hmmm...That comment leads me to believe that you have little understanding of how the research is done in the world of medicine.

...but evidence shuts everyone up.

Again, you really don,t understand how the drug companies operate.

Show me the evidence that CCSVI is related to multiple sclerosis and that liberation improves outcome in MS. If you demand this evidence from drugs, you should demand this evidence from any purported treatment of MS.

Cheer has answered that question.

Harry

centenarian100 wrote:liberation on the other hand is founded on a shaky theoretical concept that hasn't even been consistently correlated with MS in different studies. There are a bunch of meaningless anecdotes and low quality unblinded studies and one negative small high quality study whose methodology has also been questioned.

Have you read Marie's book yet?
http://www.ccsvibook.com/

centenarian100 wrote:While the MS drugs may not be that great and have side effects, at least they do have clearly proven benefits on relapses and short term disability in multiple class I studies (in other words, there is class Ia evidence that these drugs work). Relapse rate, short term disability ("disability progression") and possibly time to SPMS may not mean that much in the very long run, but I assure you it means something to a 20 year old with RRMS with 4 myelopathic attacks in the last year trying to get through college.

Ifn-B didn't help me much when I was in grad school. In fact, the side effects likely impeded my success.

I agree. That's why drugs don't get approved based on success in EAE studies. They get approved based on results in high quality studies in humans with multiple sclerosis

Yep..like the initial Copaxone trials which didn't reach the minimum required end points for FDA approval. So the makers revisited the data,massaged it very carefully and voila, they just managed to get approval on the slimmest of margins.

And the Cochrane Group did an independent investigation on Copaxone to determine its efficacy a couple of years later and reported it was all but useless in the treatment of MS!!

Yes,approval from a high quality study!!

Harry

HarryZ wrote: What I am saying is the CRAB drugs have been terribly overrated for years and that is no secret!

I agree for copaxone and beta interferons, but I don't know if I would include rituxan in that category.

The huge cost to patients and the side effects of these drugs doesn't make sense.

From a cost perspective, you may be right

HarryZ wrote:Not talking about Tysabri here...that's a different ball game and a much more powerful drug that shakes the daylights out of many who use it...and that topic is better left for another day.

Ok fair enough...and it remains unproven that tysabri has significant long term benefits.

HarryZ wrote:Geez I dislike it when people put words into my mouth like you just did!! I didn't say that the drugs were worthless.

I was referring to the overall tone of the thread and what multiple people are saying, not necessarily your posts

I said their effectiveness was highly overrated and in the long run did little for MS patients.

Again, for copaxone/avonex/extavia/betaseron/rebif, I agree with you

HarryZ wrote:Of course they aren't...but they are the only option in the absence of scientific studies.

But you should apply the same skepticism and analysis to all forms of treatment

Hmmm...That comment leads me to believe that you have little understanding of how the research is done in the world of medicine.

I'm not sure what you mean by this.

Again, you really don,t understand how the drug companies operate.

I think that it's fairly clear from the results of the trials that first line injectible agents for multiple sclerosis (copaxone and beta interferon) suggest modest benefit for preventing relapses and improving MRI outcomes in relapsing MS. In some trials, beta interferons but not copaxone have shown modest benefit in short term disability ("disability progression").

Drug company marketing tries to exaggerate these claims, apply these claims to non-relapsing forms of MS, and to imply significant long term benefits in MS. I agree that this is bullshit.

However, I think that the actual data in the original published papers is probably fairly accurate. If the drug companies had control over the data, I assure you they would make it look much more impressive. For instance, take a look at figure one in the CONFIRM trial for tecfidera:

http://www.nejm.org/doi/full/10.1056/NEJMoa1206328

Did the drug company execs make up that disability progression data?

NHE wrote:Have you read Marie's book yet?
http://www.ccsvibook.com/

I read the excerpts. Nothing really out of the ordinary. It's basically just the stuff that's on the CCSVI alliance website.

Again, an association between CCSVI and MS has not been consistently demonstrated, and there are no successful blinded randomized controlled trials for liberation.

Am I being unreasonable for asking for this level of evidence?

Would you take a drug based on non-reproducible correlations and no positive high quality trials?

I was referring to the overall tone of the thread and what multiple people are saying, not necessarily your posts

Fair enough. Those who have followed the efficacy of the CRAB drugs for several years have a tendency to realize that their efficacy isn't very good and that they have been overrated.

HarryZ wrote:Of course they aren't...but they are the only option in the absence of scientific studies.

But you should apply the same skepticism and analysis to all forms of treatment

Trying to compare anecdotal information results to that of double-blind trial results is all but impossible. Until they complete the CCSVI trials only then can some comparison be done. But even then, you are going to compare a surgical procedure to that of using a drug. My skepticism for the CRAB drugs has been nurtured after years of looking at the results and horrific cost of them. The jury is still out on CCSVI and not until a lot more research has been completed will anyone be able to see how effective the procedure will be in the long run. So my comments on CCSVI have been a wait and see, pretty much relying on anecdotal evidence in the interim since that's all that there is. What irked me about the drug companies and some of the docs was their immediate attempt to discredit CCSVI in order to protect their sacred cash cow.

Hmmm...That comment leads me to believe that you have little understanding of how the research is done in the world of medicine.

I'm not sure what you mean by this.

You mentioned that medical surgical equipment companies would have a big interest in something like CCSVI and perhaps invest research money. Compared to drug research money and interest that has been done in MS medications, this would be TOTAL non-player and certainly nothing to be gained by surgical equipment companies.

I think that it's fairly clear from the results of the trials that first line injectible agents for multiple sclerosis (copaxone and beta interferon) suggest modest benefit for preventing relapses and improving MRI outcomes in relapsing MS. In some trials, beta interferons but not copaxone have shown modest benefit in short term disability ("disability progression").

I guess it depends on what side of the fence one may be on this. When Tysabri first started to be used, many MS docs stated publicly that they were glad to have the opportunity to quit using the CRABs on their patients because they were very ineffective over the long term. But they had to eat their words when Tysabri was pulled for several months and the patients had to go back to these same CRAB drugs.

However, I think that the actual data in the original published papers is probably fairly accurate. If the drug companies had control over the data, I assure you they would make it look much more impressive. For instance, take a look at figure one in the CONFIRM trial for tecfidera:

They do and have control over the data. Copaxone failed to reach statistical significance in its first trials and was rejected by the FDA. TEVA took the data, massaged it and tweaked it and just barely reached FDA approval numbers.

I also attended a Betaseron promo presentation years ago and watched the neuro display his charts at how the drug reduced the number of lesions for the MS patients who were on placebo. During the question period I dared asked him the question if any of the patients actually felt better during the trial and he paused and sadly mumbled "no". You could have heard a pin drop in the room and the glare I got from him was unmistaken. And since then we now know that white matter lesion count has no correlation to MS symptoms.

So even though the numbers are there for all to see, how they are interpreted and marketed by the companies is a work of art! Just watch how Biogen sells their MS drugs.

centenarian100 wrote:

NHE wrote:

centenarian100 wrote:liberation on the other hand is founded on a shaky theoretical concept that hasn't even been consistently correlated with MS in different studies. There are a bunch of meaningless anecdotes and low quality unblinded studies and one negative small high quality study whose methodology has also been questioned.

Have you read Marie's book yet?
http://www.ccsvibook.com/

I read the excerpts. Nothing really out of the ordinary. It's basically just the stuff that's on the CCSVI alliance website.

Again, an association between CCSVI and MS has not been consistently demonstrated, and there are no successful blinded randomized controlled trials for liberation.

Am I being unreasonable for asking for this level of evidence?

Would you take a drug based on non-reproducible correlations and no positive high quality trials?

Marie's book is not Dr. Seuss and should not be so readily dismissed. It cites about 280 references nearly all of them are from peer reviewed journal articles. Your statement above seemed to imply that the CCSVI hypothesis was based on anecdotal evidence. It is not. Marie's book would be good start on reviewing the supporting literature.

centenarian100 wrote: 1) The placebo effect driven by patient expectation for a beneficial effect
2) The regression to the mean phenomenon, particularly in relapsing multiple sclerosis. For instance, the placebo arm in all drug trials reveals a decrease in relapse rate compared to the preenrollment period
3) Reporting bias; people are more likely to report dramatic changes than null results. Take a look at the wheelchair kamikaze blog for example. He essentially stopped posting about CCSVI after his unsuccessful treatment
4) The availability heuristic-the tendency to remember dramatic or emotionally impactful events or stories

...or maybe we should stick to the scientific method.

You already know my opinion.

I have to agree with Centenarian100 on this subject... if you are trying to bring capital gain into the discussion look at the 200,000 people that have traveled abroad to get CCVSI treatments done at a hefty cost. The vast majority seem to receive temporary benefit and reduction of symptoms which return months or weeks later.

I will not dismiss CCVSI, I would never dismiss anything that has an interesting hypothesis and potential but so far studies are not looking favorable for it being the smoking gun causing MS (much like all other theories) , which is what seemed to be what was promoted by Zamboni. As MS has been described as the "perfect storm" of conditions to bring on the diagnosis perhaps blood flow contributes to the issue. But i have trouble seeing how opening 1 or 2 veins at a single point can affect drainage from the brain. You would think MS patients on blood thinners for other conditions would get the same relief of symptoms?

There is a study ongoing at several universities in Canada which will start to show results in mid 2015. Some preliminary studies they did leading up to the major one were not promising though...

http://news.ubc.ca/2013/10/08/definitiv ... sclerosis/
“Our results confirm that venous narrowing is a frequent finding in the general population, and is not a unique anatomical feature associated with multiple sclerosis,”

http://med.ubc.ca/research/ccsvi-research/
These studies aim to provide evidence that can concretely move forward the discussion on CCSVI and MS, as well as potential treatment.

NHE wrote:Marie's book is not Dr. Seuss and should not be so readily dismissed. It cites about 280 references nearly all of them are from peer reviewed journal articles. Your statement above seemed to imply that the CCSVI hypothesis was based on anecdotal evidence. It is not. Marie's book would be good start on reviewing the supporting literature.

Currently, the efficacy of liberation in multiple sclerosis IS based on anecdotal evidence and low quality observational studies. There are exactly ZERO high quality randomized controlled studies where liberation performed better than placebo in disability, relapse, or MRI outcomes.

If you disagree with this statement, please provide the source.

I am not going to read the book right now, but would you help me out by providing the links to peer reviewed journal articles which you believe provide strong evidence for the efficacy of liberation? I will review them and give you my opinion. You certainly can't expect me to be convinced just based on the fact that there is a book supporting CCSVI that mentions journal articles, and you certainly can't expect me to read every book you ask me to read.

I am not necessarily dismissing the book as I have not read it.

Kronk wrote:I have to agree with Centenarian100 on this subject...

Thank you.

Allow me to remind you that this post is titled "The Drug/MRI Fallacy". I believe Science will eventually confirm the CCSVI factor in MS, but for now it appears to have debunked the validity of current drug therapy. This discussion reminds me of the Tobacco companies who resisted responsibilty by stating that there was no scientific proof that cigarettes caused lung cancer or heart disease. Well, the scientific proof did come in eventually. It's too bad the big Pharma/Neurology lobby with the help of the FDA is placing obstacles before American Interventional Radiologist research. That may mean that foreign researchers will advance more quickly, and MSers in other countries will profit by the advance. Check out the development of Stents and Interventional Radiology, a relatively new specialty. I don't think the FDA limited development of the specialty. Randomized Double Blind studies were done, but by the time they were completed, the treatment was often obsolete, knowledge had evolved.
Centenarian, it's a question of CHOICE. If someone chooses to take any drug they want, fine. But I should have the choice of venoplasty by a competent experienced Interventional Radiologist paid for by my insurance company (which was possible before the FDA declared the procedure "experimental" May 2012). Right now the FDA is fast tracking new drugs. I call this Luddite médicine.

vesta wrote: it's a question of CHOICE. If someone chooses to take any drug they want, fine. But I should have the choice of venoplasty by a competent experienced Interventional Radiologist .

Excellent point, I dont see how a person can do plastic surgery, lipo-suction, rhinoplasty where they need to be put under sedation and there is a very real risk of death is considered as less risk as a CCSVI procedure. Maybe it could be re-classified as "internal cosmetic surgery. You see 'doc the width of my veins are just unfashoinably narrow..."

Unfortunately we live in such a "babysitter state" in the world freedom of choice is severly restricted. We need the Government to tell us how fast we can drive, how much we can drink , when we are old enough to be an adult, etc. etc. Its now suggested that they will remove or regulate the sales of vitamins and supplements. If we didnt have the Government and federal agencys to protect us from ourselves we might regress back to monkeys hurling poop at each other...