MS Society eNews and CCSVI

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Postby mrhodes40 » Fri Nov 13, 2009 11:02 am

I think the idea is to do venograms on all patients but only add stents to some, the others stenosis would be measured documented and they they would be observed by a neurologist over time.

The benefit to this is to placebo control for the very strong effect surgery has on people in terms of placebo effect.

Surgeries are strong placebos, actually the strongest they've tested in allopathic medicine which is why someone in the audience in Bologna said it was not "fair" that this was a surgery. If you didn't know if you got a stent or not then they would control for this strong placebo and neuro's "could" accept the data as meaningful supposedly if treated people did a lot better afterwards. Potentially the patient and the neuro who follows up would not know which patient had the procedure so it could be double blind. Neurologists will only feel confident that they need to step aside for the vascular doctor after such has been done they seem to be saying. I do not agree with this idea of faking stent placement however.

I refer you to these facts that do not seem to bother any neurologists at all:

1. Stem cell transplants with chemo are not blinded. As far as I know it is not even true that a blinded neurologist even did the evaluations later, which would be weak blinding but at least an attempt at some objectivity. I have never heard of a neuro holding forth to a patient about how these trials were not blinded so steer clear of this "pseudo science". I suspect that if you were progressing rapidly and had run out of options, your doctor would entertain the idea--without disrespecting the fact your suggested it at all and likely without any lectures on the lack of evidence.

2. ASCT trials are not only done on really tiny numbers of patients (I have not personally seen a trial with a number over 30---and this matters because 30 is the minimum for any kind of validity at all) but they are uncontrolled as well.

Furthermore there is work that suggests these approaches which actually kill the pateint 5-8% of the time, do not work.

REFERENCE: ASCT Fails to stop demyelination and neurodegeneration in MS
Please note that while many studies look at how the pateints seem to be doing after the ASCT, in this case they looked directly at tissue and saw direct evidence of ongoing disease activity even after ASCT.

And from here ASCT REVIEW
Haematopoietic stem cell transplantation (HSCT) appears to represent yet a further escalation. Autologous HSCT encompasses mobilization and preservation of autologous haematopoietic stem cells (HSCs); subsequently, in most cases, myeloablative immunosuppression by a combination of chemotherapeutic drugs and often total body irradiation (TBI); and later the reinfusion of HSCs (Tyndall et al., 1999). Small treatment series with autologous HSCT during the last decade have shown remarkable suppression of inflammatory activity in most patients, but nevertheless—not rarely—at least some progression of disease.


and

Metz and colleagues (2007) now present interesting data and raise new questions that challenge the mechanistic concept as to how HSCT might work. Their histopathological findings from five MS patients who died after HSCT show that there remains at least some smouldering inflammatory activity, mainly consisting of CD8+ lymphocytes and activated macrophages and microglia, and that active demyelination and axonal damage continue after the profound immunosuppression and autologous HSCT (Metz et al., 2007). This information seems to discourage the further exploration of HSCT as a treatment for aggressive forms of MS.


apparently short of killing the person you can't stop all inflammation and even if you have seeming profound inflammation control (MRI proven) you still get degeneration anyway that you can't see. It is hard to see how you cold knock out the immune system any harder, yet the failure of this logical terminal end version of inflammation control is not apparently bothersome. If this doesn't work, why would weaker versions of suppression be effective?

There are other papers that suggest that ASCT works well for "long periods of time" like, gee, 1-2 years 8O in a stunning 3 people.

This procedure succeeded in halting the rapidly worsening course of disease. The effect was long lasting, as demonstrated by a sustained efficacy over a two-year period in two subjects and 12 months in the third case. In addition, a striking effect on inflammation-related MRI findings was obtained. These results support a role for intense immunosuppression


Huh. REALLY?. This is a good idea because ti worked so well in 3 people over 1-2 years?

Hicy suffers a similar fate in that it, too, has all been trial numbers under 30, as well as unblinded and uncontrolled work. Yet if someone wanted to discuss this with their neuro the chance is good they would be encouraged to go ahead if the regular regimens were not working.

I sincerely doubt eyes would be closed, head shaking "No, no no".

It is not about the quality of the science it is about the hypothesis they all believe is accurate: inflammation causes the lesions, the lesions cause the degeneration after the fact, and if the inflammation can only be controlled adequately then the disease can be managed. Never mind that there is ample evidence this is not accurate.

Because they believe this to be true, weak work, such as the 3 person study, that is based on that theory is treated as if it is automatically "good science" while good work coming from the new model is prejudiced as being bad even before it is read and fairly evaluated.

The thing that is making me crazy is the consistent characterization of Dr Zamboni's work as far less well done that it is, for example not mentioning the fact that it is blinded and rigorously controlled, or mentioning only the one study instead of all 3, or not making a point about the absolutely HUGE study sizes compared to other more typical early work, ignoring the concordance in the face of blinding or pretending that this is a single tiny insignificant study that is very VERY preliminary. There is very little excitement or real interest expressed in this work at all, yet in reality it should be incredibly exciting. Where is a single positive statement about how thrilling it is to have a new avenue of understanding showing such concordance.?

And in the end I keep wondering--

Exactly how much and what evidence does it take an entire field of medicine to convince themselves that, in fact, the seminal event of this disease is not IN their field at all and an entirely new group of doctors is going to be the main physician?

The fact is the neurologists want to only accept CCSVI on neurological terms, they want to define it, find its limits and determine mechanics of the lesion all through the neurological lens as if the vascular lens does not matter and is completely irrelevant.

The oft repeated comment that "I don't see how lesions occur this way" is direct evidence of that.

Yet if this is a vascular disease the only lens that matters is vascular in the same way the only thing that matters in a stroke is the clot or bloodflow, only once that is restored can the neurological clean up begin

Seen through that light the stenosis is important on its own merit, the sluggish blood flow matters because it is there, reflux is a significant sign and the neurological event, even though it exists and is the main way a patient experiences CCSVI, is a side event.

Naturally this is just my opinion and this is op-ed. :roll:
I'm not offering medical advice, I am just a patient too! Talk to your doctor about what is best for you...
http://www.thisisms.com/ftopic-7318-0.html This is my regimen thread
http://www.ccsvibook.com Read my book published by McFarland Health topics
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Postby ozarkcanoer » Fri Nov 13, 2009 11:10 am

mrhodes, good idea for proof of concept for ballooning or stenting for CCSVI, i.e. stenting some stenosis or malformations but not others in a random fashion !!!!

However, once Zamboni and Buffalo make their next announcements who will want to volunteer with the possibility of NOT having any stenting ??? Maybe there are some MSers out there who would do this. I wish I had the courage to be one of them. But I suffer every day from MS and all I want IS SOME HELP !!!!!
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Postby patientx » Fri Nov 13, 2009 12:00 pm

radeck wrote:patientx, I really don't understand where you're trying to go with this!?

Opening veins is a known treatment to closed veins! What about this is difficult to understand?

The fact that it may help with MS (and is being discussed here because it makes a lot of sense that it would help and has actually helped nearly every person receiving the therapy) is not an argument against doing the procedure, but for doing the procedure.

You seem to be falling in the same trap so many do, that MS patients fall into a special category of human beings that are at the hands of neurologists&big pharma, because they have MS. As such they're not allowed to have their congenitally or otherwise malfunctioning veins fixed, but must wait until the effect on MS is proven in placebo controlled trials (for the googleth time, placebo controlling is NOT necessary to establish scientific rigor)? They're not allowed to receive well-established or novel angioplasty in order to advance CCSVI treatment, despite lack of evidence that ballooning or stenting those veins causes harm?

If I break my friggin bone, will you allow me to receive a friggin cast?

I'm calling BS, BIG TIME!


Please don't tell me that I am falling into some trap. Despite the conspiracy beliefs expressed here, I am not at the hands of a neurologist or drug company. And I never wrote that placebo-controlled studies are necessary to establish scientific rigor. I simply pointed out the sham surgeries have been performed in the past as part of clinical trials. I didn't say that I agree with them.

Lack of evidence that ballooning are stenting causes harm? How about lack of evidence that it won't? Stenting of jugular veins has not been done before and is not well-established (there's not even agreement among the current CCSVI experts that it's a good idea). And even in the cause of venous leg ulcers, to which this CCSVI is often compared, surgery is not the first treatment option. But by your reasoning, if the surgery may not kill you, then why not do it? So, in the case of your broken bone, why start with a cast - why not go right in and put screws or pins in the bone?

Regardless, I have MS, and that's what I am interested in treating. As for CCSVI, I guess I will keep a look-out for the symptoms, and then consider diagnosis and treatment options. What are those symptoms again?
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Postby radeck » Fri Nov 13, 2009 12:29 pm

patientx, concerning your point of testing the safety of stents, I agree that's an important point.

Concerning your question about symptoms of CCSVI and effect of therapy, the upcoming Zamboni paper should describe this. Also, you may find the tracking thread informative if you believe the accounts of people there.
Last edited by radeck on Sat Jan 16, 2010 8:29 pm, edited 1 time in total.
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Postby patientx » Fri Nov 13, 2009 12:45 pm

radeck wrote:Concerning your question about symptoms of CCSVI and their alleviation by therapy, you can look here: http://www.thisisms.com/ftopict-8346.html

Concerning your comment on the broken bone, you are correct that while some fractures require only a cast, others require screws or pins to be fixed long-term, but what was your point?


No offense, but is there something from a doctor or medical professional listing the symptoms and complications of CCSVI?

My point is that, if I have a broken bone and it will heal fine without surgery, then I will let it heal without surgery. Likewise, even if I have narrowed jugular veins, if they are not causing any problems, why go through having stent surgery?
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Postby radeck » Fri Nov 13, 2009 1:18 pm

My point is that, if I have a broken bone and it will heal fine without surgery, then I will let it heal without surgery. Likewise, even if I have narrowed jugular veins, if they are not causing any problems, why go through having stent surgery?


Note that Zamboni has shown on a large number of patients that the vein problems leading to CCSVI can be fixed without stent surgery, using balloon angioplasty. He describes the risks of this procedure as acceptable (to me, anyway) in his papers. Now once you have a diagnosis of a problem in your vein it is a matter of how much you believe that it could cause you problems whether you want this balloon angioplasty to be applied.
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Postby radeck » Sun Nov 15, 2009 8:31 am

Quoting this from the "meet and greet at Sheraton" thread, since it fits in here:

Lyon wrote:Now, you've got to admit that I've been pretty good (quiet) lately and haven't come out of my hole in the rocks to comment on infractions, even ones like this example which are as full of doodoo as the Christmas goose
GiCi wrote:I wish to join cheerleader: congratulations and please focus on the fact that MS is not a disease but a consequence of a congenital malformation of our neck veins: it can be fixed.
GiCi


Hi Bob, I think you may have misunderstood GiCi's comment. As I understand it he was simply combining

1) the theory that obviously many in this forum have that CCSVI is the cause of MS, which they think makes a lot of sense based on what we know

with the fact that

2) MS is not a disease in the classical sense in that it's the result of a differential diagnosis, i.e. after having ruled out diseases whose pathogenesis is known. As that, "MS" is a label given to a bunch of symptoms/findings that include neurological symptoms that are not unique to MS, brain lesions that are not unique to MS, and CSF findings that are not unique to MS, if all diagnosis with diseases of known origin have failed.

The jury is out on that origin, and GiCi (like I and some others) think that CCSVI is the best theory as of yet.

Hope that makes sense to you.
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Postby Lyon » Sun Nov 15, 2009 8:58 am

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Postby ozarkcanoer » Sun Nov 15, 2009 11:34 am

radeck.... KUDOS.... You defined MS better than anyone. When I was diagnosed two years ago I read the "MS for Dummies" book and came away feeling more confused than before. The book (and all the MS literature) is full of such nonsense like "MS is thought to be...." etc. etc. What I want to know is, who are the people doing the "thinking". Right now I believe what you said. MS is a syndrome. A doctor friend told me that "MS is the great imitator".
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Postby radeck » Sun Nov 15, 2009 11:51 am

Bob, I understand your skepticism with respect to Zamboni's finding that each one of the 65 CDMS patients Zamboni looked at seemed to have the same underlying pathogenesis. However I would not focus on it too much simply because the fact that MS is nothing but a differential diagnosis, and therefore a syndrome and not a disease, does not entail that that differential diagnosis can not be done with good precision. In other words, IF MS really has an underlying pathogenesis (I think it is CCSVI, you think it is X), it just depends on how well you rule out alternative diseases like Lyme's, etc.

Unless you provide data showing exactly how unreliable the revised MacDonald criteria for clinically definite MS, which Zamboni used, are, your skepticism therefore does not have much leverage.

Your point is good in principle, but may not be so relevant in practice. Does that make sense?

Rest assured that the data from the Buffalo trial will help clear things up a bit. I've heard that they had one control patient with CCSVI, which they had to give an MS diagnosis based on MacDonald after looking at the brain/spine MRI. Perhaps they'll also have CDMS patients without (detectable) stenosis or reflux? We'll see...
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Postby ScutFarkus » Sun Nov 15, 2009 12:13 pm

radeck wrote:And as a side, the Interferon and Copaxone trials weren't placebo controlled in the true sense either. Patients were given either a drug with major side effects, making them fully aware that they were on the real drug, or an injection with no side effects.


Actually, patients on placebos typically have many of the same side-effects as people on the actual drugs, which is a big part of the point for having placebo controls. For example, if you consult the Copaxone prescribing information, they provide a handy table comparing side-effects reported for Copaxone versus the placebo controls. As one example, 15% of Copaxone patients reported "nausea", compared to 11% for placebo. Placebos also reported numerous other side-effects, including the usual ones such as injection site pain. That's far from "no side effects". Given the wide range of reactions reported here even among people who are all receiving Copaxone, it defies credibility to believe that everyone (or even the majority) of people in the studies knew exactly which group they were in.

radeck wrote:Butting it bluntly, the patients on the real drug were on the placebo,


To roughly quote one of my favorite movies, The Princess Bride, "this word you keep using, I don't think it means what you think it means".

You apparently believe Copaxone doesn't work, but even if that were the case, it wouldn't make it the placebo. "Placebo" is not a Greek word meaning "doesn't work." That word is "homeopathy". :)

radeck wrote:hence it is not surprise that they did about 30% better on various measures, exactly as somebody on placebo would do better (you can read up on how powerful the effect is really). So trying to "live up" to the standards set by these trials would really be a disgrace, IMHO.


Placebo controls do not have a specific fixed benefit you can expect. If they did, there would be no need for placebo controls, because you'd just subtract 30% from your uncontrolled results. I encourage you to read up on placebos.

A common misconception is that placebos exist to capture the "imaginary" or "fake" effects of a sham treatment. But that's not correct. Placebos are used to capture the "other" treatment factors that are outside the specific factors you're trying to measure. Most treatments include a lot of steps, including extra doctor attention, maybe applications of other drugs such as anesthesia, physical steps such as touch, injections, surgery, etc. Any number of these factors might have real effects on the outcomes being measured. The placebo attempts to replicate all of these other factors, such that any remaining difference in outcomes is due to as few factors as possible, preferably just the drug or intervention being studied.

An important corollary is that the "placebo" arm of a study can include real treatment effects. For example, there was a recent placebo-controlled acupuncture study that used sham acupuncture (toothpicks that didn't puncture the skin) for the placebo group. While much of the media reported on the real pain reduction reported by the people getting acupuncture, the more interesting result was that the placebo group did just as well. This basically tells us there is something real going on, but that real thing is not about getting poked with needles.

/Scut
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Postby Lyon » Sun Nov 15, 2009 12:22 pm

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Postby radeck » Sun Nov 15, 2009 12:30 pm

Scut, thanks for your thoughts. The side effects I had in mind are those that are peculiar to Interferons and Copaxone, and that at least a large number of the trial participants must have been aware of since the drugs had been in use for a while when the biggest trials were done. I seem to recall that those peculiar side effects were elevated in the treatment arms, no?

I don't believe Copaxone doesn't work. 30 years of research into Copaxone/Glatiramer Acetate(GA)/Copolymer-1 have shown that it has some general anti-inflammatory properties, which are non-specific to myelin (this is a big deal, since folks assumed for a long time that there was a myelin-specific protective reaction taking place), i.e. they should help also in other conditions accompanied by inflammation, just like other, less high-tech than Copaxone, anti-inflammatories should help in MS.

Sad thing is that unlike in rodents with EAE, the effect of Copaxone/GA on inflammation in humans with MS seems to have no measurable effect on disability.
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Postby Rokkit » Sun Nov 15, 2009 1:02 pm

SkutFarkus, welcome to TIMS. I REALLY hope you stay around and post. You are a welcome addition to the large group of bright and informed people around here. I am not part of that group, but I know one when I see one. :-)
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Postby radeck » Sun Nov 15, 2009 1:03 pm

Lyon wrote:
radeck wrote:Rest assured that the data from the Buffalo trial will help clear things up a bit.
I hope it doesn't sound negative but I do look forward to it, but obviously I (and everyone else) can only believe it when I see it.


Well Bob, I'm not sure you'll believe it when/if you see it, since there are always possible ways to be skeptic of any study. Even if these studies have been peer-reviewed like Zamboni's, you seem to posit that skepticism never has to be measured or argued for. Science doesn't function that way, you know? There's never complete knowledge that is robust to any skepticism. Science (and human everyday life) functions by using good theories of reality and improving upon them. Among scientists, indeed even skepticism has to be plausible skepticism. So if I question the meaningfulness of your skepticism (without ever having doubted it, btw), the burden of the argument becomes yours indeed!
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