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Venous Insufficiency in Multiple Sclerosis

There is an interesting controversy raging in the Multiple Sclerosis (MS) world that reflects many of the issues we discuss at science-based medicine. Dr. Paolo Zamboni, and Italian vascular surgeon, has now published a series of studies claiming that patients with clinically defined MS have various patterns of chronic cerebrospinal venous insufficiency (CCSVI). Further Dr. Zamboni believes CCSVI is a major cause of MS, not just a clinical side-consequence, and is exploring treatment with venous angioplasty or stenting.

The claims have captured the attention of MS patients, many of whom have a progressive course that is only partially treated by currently available medications. There are centers popping up, many abroad (such as India), providing the “liberation procedure” and anecdotes of miraculous cures and spreading over the internet. There is even a Facebook page dedicated to CCSVI, and you can read the anecdotes for yourself. Many profess dramatic improvement immediately following the procedure, which seems unlikely even if Zamboni’s hypothesis is correct.

Zamboni is also getting attention from neurologists and MS specialists, who remain skeptical because Zamboni’s claims run contrary to years of research and thousands of studies pointing to the current model of MS as an autoimmune disease.

There are at least two stories to follow here. The first is the scientific story – the questions being proposed are answerable with scientific research, and they will be answered. MS remains a serious illness that is inadequately treated (not to downplay the important advances we have made, but we certainly are far from an adequate cure for MS). The potential of a new treatment deserves serious research attention, and CCSVI is getting it. It will probably take another ten years for the research to play itself out adequately for there to be a confident consensus on CCSVI, but eventually we will have a scientific answer.

The other story is the the reaction of the public and the MS community. This has been mixed, but already there are conspiracy theories that the neurology community, the MS society, and Big Pharma (of course) are fighting against CCSVI as part of a misguided turf war. (See the comments to my previous posts on this topic at NeuroLogica for some examples.) Anecdotes are being used to argue against published scientific evidence, and negative studies are being dismissed. If CCSVI is eventually found to be a scientific dead end, I have to wonder if it will survive as just another fringe “alternative” treatment, like Laetrile, psychomotor patterning, and other discarded ideas in medicine.

The Scientific Story

So far there is not much of a scientific story to tell. A PubMed search on CCSVI yields a total of 19 publications (a pittance), indicating how new this concept is. I suspect this number will grow into the hundreds at least before this story plays itself out. If CCSVI is proven to be legitimate then this number will grow into the thousands over the next few decades. If it is disproved, publications will trickle off.

Most of the current research is published by Zamboni’s team. He is building an impressive list of studies, exploring various aspects of CCSVI and MS, but evidence that derives entirely from a single research team is always suspect. The role of bias in research is well documented, and further most new ideas in medicine turn out ultimately to be wrong. Therefore skepticism is the proper approach to bold new claims being supported by a lone research team. Replication will be necessary for the broader scientific community to take CCSVI seriously.

The core claim made by Zamboni is that most patients with MS display 2 or more out of 5 criteria on studies of venous anatomy (using ultrasound or venography) of venous insufficiency. While control patients (healthy subjects or those with other neurological disorders) display 1 or no criteria, and never 2 or more. All other claims (benefit from angioplasty, matching patterns of venous insufficiency with types of MS) derive from this core claim.

I found four independent replications in the literature, three very recently published. The first is by Al-Omari MH, Rousan LA, who found:

“According to the described criteria, 92% of the MS patients showed abnormal findings and 84% of them showed evidence of CCSVI, however; only 24% of controls showed abnormal findings, but none of them showed evidence of CCSVI (OR=7.25, 95% CI 2.92-18.01, P<0.0001).”

These are similar numbers to Zamboni, although the 84% is a little less. This study used only ultrasound, which is a non-invasive technique and therefore good for screening, but the results are very operator dependent. There is no indication in the study that the patients were assessed in a blinded fashion.

The next study by Florian Doepp et al used the following methods:

We performed an extended extra- and transcranial color-coded sonography study including analysis of extracranial venous blood volume flow (BVF), cross-sectional areas, IJV flow analysis during valsalva manoever (VM) as well as ‘CCSVI’ criteria. 56 MS patients and 20 controls were studied.

They found no subjects met the Zamboni critieria for CCSVI – a completely negative replication.

The second was performed by Krogias at al, who found:

The authors conclude that the „chronic cerebrospinal venous insufficiency (CCSVI)“ cannot represent the exclusive pathogenetic factor in the pathogenesis of MS. In our cohort, only 20% of the patients fulfilled the required neurosonological features of CCSVI. So far, the pathogenetic relevance of these findings remains speculative. Thus, based on the current scientific position we cannot justify invasive „therapeutic“ approaches, especially if they are performed outside of clinical trials.

The third study is a Swedish study by SundstrÃm et al (“Venous and cerebrospinal fluid flow in multiple sclerosis – a case-control study.” Peter SundstrÃm, Anders WÃ¥hlin, Khalid Ambarki, Richard Birgander, Anders Eklund and Jan Malm. Annals of Neurology) – not yet available online. This study used MRI scanning to assess blood flow in the internal jugular vein in 21 MS patients and 20 controls, and found no difference.

Conclusion

One of four replications found results similar to Zamboni. A second found only 20% of MS patients met Zamboni’s criteria, while two others found that no patients with MS did. Four studies is not a lot – and is not even close to ending this controversy from a scientific point of view. But these early results are not promising and will tend to deepen skepticism within the neurological community.

Clearly there is a need for more research so that both patients and professionals can feel comfortable that CCSVI has been given a thorough investigation and we can say with confidence what role, if any, it plays in MS. The results, also, do not have to be black and white. While it seems unlikely that Zamboni has discovered the sole and ultimate cause of MS in most or all patients, it is possible he has found a significant consequence of MS. Chronic inflammation may result in venous insufficiency in some patients. This venous insufficiency may further play a role in worsening the clinical course in a subset of those patients, who may benefit from treatment. So CCSVI may ultimately play a minor but important role in the management of MS.

Or it may all turn out to be a figment of Zamboni’s imagination, spawned by the sincere hope of finding a cure for MS. Time and research will tell.

My open plea to the MS community, especially those who are going down the rabbit hole of conspiracy theories, is to keep this discussion about the scientific evidence. This is not the place for cheap conspiracy theories. I fear my plea will fall on deaf ears, but it never hurts to ask.

Posted in: Neuroscience/Mental Health

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60 thoughts on “Venous Insufficiency in Multiple Sclerosis

  1. phren0logy says:

    Thanks for another thoughtful and informative post. As a clinician, I often wonder about the current state of medicine with the combination of the internet, a push for more patient autonomy, and our existing tort system.

    It would seem that patients have access to more information, and are more likely to request or demand treatments that are outside of a science-based scope.

    The move toward a “customer is always right” approach is, in my opinion, significantly at odds with the role of the physician in collaborating with the patient about the nuances and shortcomings of well-validated treatment options, and the medicolegal system’s stance that the buck stops with the doctor.

  2. Epinephrine says:

    Thanks, I was hoping for some good coverage of this. I will admit to skepticism about this treatment (and especially about the supposed etiology suggested by Dr. Zamboni), as my graduate studies were in neuroscience, and this is contrary to everything we learned about MS. Of course, as you point out, it could be that it is a consequence of disease, possibly being involved in worsening the symptoms for some patients.

    (Here, in Canada,) The Saskatchewan government has pledged to fund trials of the surgery in that province. Perhaps, if these trials are performed well, they will shed some light on the matter. I hope that blinded screening is first tested, to test whether the MS group really exhibits this anomaly with greater frequency than the control group. Only then should a clinical trial be approved for the surgery, with a proper sham surgery used as a control, and with blinding.

  3. gorebug says:

    There is a further article about this in Canada’s Postmedia.

    Apparently MS sufferers in MB are excited to get the chance to cross the border and pay, out of pocket, for this untested procedure.

    Furthermore they are criticizing the provincial government for not funding the procedure.

    http://www.calgaryherald.com/health/clinic+expects+flood+Manitoban+patients/3384758/story.html

    ~bug

  4. Robin says:

    The move toward a “customer is always right” approach is, in my opinion, significantly at odds with the role of the physician in collaborating with the patient about the nuances and shortcomings of well-validated treatment options…

    Well, consider that the average patient has no science education or understanding about how medical science works. Physicians have very little time to explain such things. Mine has 15 minutes for an office visit. Many physicians I have met, especially the older ones, were not given much training about patient communication, either.

    So, if you have a patient with a horrible disease like MS where the quality of life has been diminishing, many looking at a future of progression and eventually dependence and incapacitation, if they’re not at that already. Coping, psychologically, with a health issue of that magnitude has got to be absolutely horrible.

    Taken all together it’s a tough situation and presents a greater burden on the physician who’s on the front line with patient desperation/hope. On top of everything they have to do — diagnostics, keep up with their CME, deal with health insurance, run their businesses — they have to be treatment “counselors” for patients. Helping a patient understand why they should wait for the science on a new treatment when the patient may not have much time left to wait, or steering away a patient from a quack cure when patient has such hope, it’s tough.

  5. Jayne Crocker says:

    “As a clinician, I often wonder about the current state of medicine with the combination of the internet, a push for more patient autonomy, and our existing tort system.

    It would seem that patients have access to more information, and are more likely to request or demand treatments that are outside of a science-based scope.

    The move toward a “customer is always right” approach is, in my opinion, significantly at odds with the role of the physician in collaborating with the patient about the nuances and shortcomings of well-validated treatment options, and the medicolegal system’s stance that the buck stops with the doctor.”

    Goodness me!

    Thank goodness we do have the intelligence to research debilitating diseases that we get diagnosed with. We are the ones living with these diseases and I believe any qualified medical professional should listen to their patients. You can’t ignore patient evidence, especially with MS when it is already out that none of the current drugs for MS works http://license.icopyright.net/user/viewFreeUse.act?fuid=OTA3NDM0MQ%3D%3D

    Patients do have a voice and surely those in the medical field can’t ignore such astounding evidence?

  6. dr.cosa says:

    great to see this topic being explored at the larger site, i wont reiterate my previous comments from Dr. Novella’s prior excellent post on Neurologica, but i believe some additional points are in order.

    with respect to findings of blockages via ultrasound that constitute the CCSVI theory, i find it quite interesting that we current send scores of patients with herniated discs for surgeries that have shown over the course of several decades to be at best average to below average in providing long term relief. in addition we now have the power of MRI studies that have shown a number of disc herniations and other spinal abnormalities in patients with no back pain.

    if blockages exist in people with MS and their symptoms are relived over a long time frame as a result of this surgery, they should be considered a success much the same way orthopedic surgeons consider arthroscopic knee surgery and discography procedures to have worked if the patient “feels better”.

    i would submit that our current approach to surgery for a host of conditions are at best weakly supported in face of a growing body of evidence that many of them fail to elicit a successful response or are the result of placebo effects. (numerous studies of sham arthroscope and/or physio vs. surgery, worker’s compensation stuides from Australia highlighting the higher failure rate of compensation related surgery vs. regular patients) all of these types of issues will no doubt enter the fray in the CCSVI debate but appear to be holding back a treatment that in any other instance is considered a side bar issue.

    treatment for MS is sorely lacking (at least in canada) for those suffering severely, simply because the medications place undue stress on the patients and our system is barely able to provide the kind of round the clock care for those in advanced stages.

    what i find most strikingly absent from the discussion is the other side of Dr. Zamboni’s thesis- hemachromatosis of the brain and spinal cord tissues. i haven’t fully explored this idea i only have a casual understanding of what he believes is causing the problem, but i wonder if this issue has been considered in greater depth?

    iron overload is a problem in far too many who have no idea, i would be curious if the issue is less to do with a blockage and more to do with iron saturation in specific areas which may make them susceptible to a host of immune responses that other areas of the body arent.

    for the record i am not a doctor, only an interested bystander suffering from grandiosity!! ha!!

  7. Kenneth says:

    Last month in publishing a radical new hypothesis about gravity, Erik Verlinde, PhD, said this in an interview: “If I am proven wrong, something has been learned anyway.”

    I think this quote applies to your conclusion, Dr Novella. Even if this shows to be a figment of Dr Zamboni’s imagination, something is likely to be learned from it, and the MS community will be better off, even if just a little, because of it.

  8. aaronupnorth says:

    “Or it may all turn out to be a figment of Zamboni’s imagination, spawned by the sincere hope of finding a cure for MS.”

    Or it may just be a figment of his data set. He may be doing totally honest and rigorous research and have had the bad luck to stumble into a strikingly unusual data set that is actually simply a result of chance (or he may have stumbled into something real, that is still to be proven).

    The first null here is that there are differences in cerebral venous blood flow between patients with and without MS. That question should be answered in a trial with a data set that is properly powered to give a specific answer to that question. Ideally that would be a trial of a gold standard test (actual venography, perhaps MR-venography if that is too invasive) in both groups with test readers blinded to the patients condition.

    I know the MS community is excited about this, and hopefully they will demand that the research be rigorous.

  9. aaronupnorth says:

    Oops…..should read ‘that there are not differences’.

  10. daedalus2u says:

    I would also like to see if there are changes in blood flow following the stenting of the veins. I understand you can’t do before and after with MRI if you put a metal stent in.

    It is my understanding that stenting of veins is somewhat unusual. Usual treatment for varicose veins is compressing the surface leg veins with elastic garments. That seems to me to be the opposite of stenting.

  11. WilliamLawrenceUtridge says:

    @ Kenneth

    “Last month in publishing a radical new hypothesis about gravity, Erik Verlinde, PhD, said this in an interview: ‘If I am proven wrong, something has been learned anyway.’

    “I think this quote applies to your conclusion, Dr Novella. Even if this shows to be a figment of Dr Zamboni’s imagination, something is likely to be learned from it, and the MS community will be better off, even if just a little, because of it.”

    But the wasted money, lost time, frenzied raising, then dashing of hopes will all produce more net suffering than if the “hypothesis” had been tested and replicated better, before being publicized widely. I don’t know enough about the circumstances to see if Zamboni took the Pons/Fleishman approach of press release before publication, or if it simply got picked up by the media and propagated well in advance of meaningful findings. But no matter what, we’re always better off with the slow and steady progress of science than we are with the mad dashes of false hope. Since this is a blog of science based medicine, all editors and probably most readers would agree that plausibility is an important consideration in all research – and this implausible frenzy of poor-quality testing isn’t helping anyone. There are much, much better ways of learning new things about MS.

    That reads as quite the dick comment, my apologies Kenneth – I couldn’t think of a better phrasing. There’s certainly merit to any and all research, even if it produces a negative result.

  12. pmoran says:

    Also, why not similar symptoms/pathology with frank, severe, venous engorgements, from vena cava obstructions etc?

  13. windriven says:

    @Jayne Crocker

    “Patients do have a voice and surely those in the medical field can’t ignore such astounding evidence?”

    Had you read Dr. Novella’s post you would clearly know that the medical field is not ignoring “such astounding evidence.” In the first place the evidence, such as it is, is equivocal. Remember that anecdotes and evidence are different things. Were they not we would all believe in ghosts, UFOs and speaking in tongues.

    In the second place an immense scientific effort has been mounted by ‘those in the medical field’ to get a grip on multiple sclerosis. Substantial advances have been made in treating MS in the last few decades and the etiology of the disease is increasingly well understood.

    We pay physicians to give us the benefit of specialized knowledge and skills acquired and honed over tens of years. Should they abandon their training and experience because a newspaper reporter thinks a therapy looks promising? If so and if the new treatment doesn’t work for the patient and that patient’s condition deteriorates, what are the ethical and legal consequences?

  14. tmac57 says:

    “There are centers popping up, many abroad (such as India), providing the “liberation procedure” and anecdotes of miraculous cures and spreading over the internet. ”
    This caught my eye,as I had just finished reading a BBC news item entitled “New ‘superbug’ found in UK hospitals”
    http://www.bbc.co.uk/news/health-10925411
    They report:”A new superbug that is resistant to even the most powerful antibiotics has entered UK hospitals, experts warn.

    They say bacteria that make an enzyme called NDM-1 have travelled back with NHS patients who went abroad to countries like India and Pakistan for treatments such as cosmetic ”
    Maybe Dr. Crislip can look into this angle.

  15. JMB says:

    I would like to see a study giving a measure of the number of initial positive reports appearing in the literature 15 years ago, that have actually withstood the test of time. I’ll make a guess that it would be 1 in 20 or less. Skepticism of such claims comes from disappointing experience. A 1 in 20 chance justifies further study. It does not justify patients having a potentially dangerous surgery.

    I can think of two known chronic diseases/syndromes that have documented occurrence of venous insufficiency of drainage of cerebral veins, superior vena cava syndrome and tuberculous meningitis. I don’t think in either case have there been any lesions that mimic MS plaques.

  16. Edward Murray says:

    I used to consider myself a medical skeptic and ranted and raved about alt med.

    But as someone whose wife has MS, I now see that what passes for Science Based Medicine is mostly junk science used to justify the sale of questionable drugs or defend the status quo.

    Anyone who thinks MS drugs work hasn’t been reading the scientific literature or looking at their patients get progressively more disabled.

    Of course if you redefine “work” to be something that isn’t clinically relevant and juggle the data, you can get some regulatory authority to approve your drug. A comment on a NY Times article on CCSVI said it all: the “science” of clinical trials is about incomes, not outcomes.

    If you don’t want me to believe in conspiracies, then don’t conspire.

    How is it that these new anti-CCSVI studies got IRB approval and rushed into print in what is undoubtedly record time while those attempting to actually scientifically investigate CCSVI can’t get approval to do a study let alone publish anything?

    And these studies. Doepp et al and SundstrÃm et al do studies with very small “n’s” which purport to address Zamboni’s research although they clearly took a different approach, scientifically rendering their conclusions irrelevant to the question of whether Zamboni is on to something and what happens to this junk science?

    The Wall Street Journal covers it. The LA Times covers it? Even Science-Based-Medicine covers it.

    That smells much more like a conspiratorial hatchet job than science to me.

    I have seen nothing that convinces me that MS is an auto-immune disease other than the constant repetition that it is.

    @ windrivenon
    Had you read Dr. Novella’s post you would clearly know that the medical field is not ignoring “such astounding evidence.”

    Right. It is hellbent on finding ways to keep the drugs flowing to patients. Don’t tell me with $10 billion on the table, no one is working on blocking Zamboni. That would be illogical.

    @ windrivenon
    In the first place the evidence, such as it is, is equivocal.

    How so? Two underpowered studies that did not replicate the research prove absolutely NOTHING scientifically about what Zamboni found.

    But the fact that they were rushed into print in what I believe was record time AND were widely touted as undermining Zamboni in publications such as the Wall Street Journal and LA Times tells me this is not science, it is a hatchet job.

    @ windrivenon
    In the second place an immense scientific effort has been mounted by ‘those in the medical field’ to get a grip on multiple sclerosis. Substantial advances have been made in treating MS in the last few decades and the etiology of the disease is increasingly well understood.

    Really? We have an animal model of the disease that has been completely discredited. We have a bunch of useless drugs with horrible side effects which do not stop progression of the disease and were based on the notion that the disease was viral, not auto-immune. If that’s Science Based Medicine, I’ll take voodoo.

  17. phren0logy says:

    @Jayne Crocker:

    I’m afraid my post didn’t make the “collaboration” part strong enough. Of course patients should have a voice, that is not in question. Access to information means that patients can be more informed about their illness.

    My concern is that they can also be more misinformed. Everyone is vulnerable to some degree of bias, and a person with an illness such as MS (or their loved ones) are even more vulnerable to sketchy and unproven hypotheses.

    My point was not that patients should not be informed, or not have a voice in their treatment. Of course they should. My concern is that vulnerable patients can fall victim to the marketing hype of unproven therapies. My point is that ideally physicians can be more neutral, and more informed, and therefore collaborate with these patients.

    Increasingly, I hear colleagues saying that patients see them as a speed bump to the prescription or procedure they are already sure they need. That’s not collaboration. That’s a loss for everyone, and it’s not good health care.

  18. windriven says:

    @ Edward Murray

    First and foremost, I am sorry to learn of your wife’s affliction.

    I must take exception though to some of what you’ve said.

    “Anyone who thinks MS drugs work hasn’t been reading the scientific literature or looking at their patients get progressively more disabled.”

    I am not aware of any MS drugs that claim to deliver a cure. The best on offer right now are drugs that can slow the progression and ameliorate some of the symptoms of the disease. Compared to a cure this may be cold comfort. But compared to the disease untreated?

    “How is it that these new anti-CCSVI studies got IRB approval and rushed into print…”

    Is that how you think it works? One goes to the IRB and says, “Look, we want to debunk this procedure that is a threat to Big Pharma so get on with the approval.” I don’t know any of the researchers involved but I have absolute faith that they went into the study skeptical but curious and very likely hopeful that they would learn something new about MS. Yes, the n’s have been small. Pilot studies often precede large studies.

    “Right. It is hellbent on finding ways to keep the drugs flowing to patients. Don’t tell me with $10 billion on the table, no one is working on blocking Zamboni.”

    One of the beauties of science is that the truth always comes out. NIH alone spent $169 million dollars on MS research in 2008. And there are a number of other organizations including the National MS Society that fund research. If Zamboni’s therapy works, it will be proven and adopted. Period.

    “Two underpowered studies that did not replicate the research prove absolutely NOTHING scientifically about what Zamboni found.”

    I don’t believe that anyone suggested the book would be closed after “two underpowered studies.” Look, scientists are by nature both curious and skeptical. The investigations will continue and a body of evidence will accrue that either supports or discredits the Zamboni intervention.

    “We have an animal model of the disease that has been completely discredited.”

    Problems described don’t get touched with the magic wand of science and immediately become problems solved. It sometimes takes many years of careful work to unravel a single thread of what may be a very large rope of a problem.

    Perhaps Zamboni has discovered an incredible breakthrough. If so his work will be replicated and will redefine our understanding of the disease and its treatment. On the other hand all efforts at replicating his success may fail and it will become obvious that there was no breakthrough at all.

    This is the way of science. It isn’t fast but it is sure. I hope you will read Dr. Novella’s post again, or at least the last 6 or so paragraphs.

    In the meantime there is nothing stopping anyone from seeking out a clinic offering the “liberation procedure.”

  19. WilliamLawrenceUtridge says:

    @Edward,

    I have two familiy members with MS, so this isn’t an idle concern. However, everyone knows that MS has no established cure. We all know that drugs are flawed with side effects and incomplete efficacy.

    But that doesn’t mean CCSVI is automatically right, nor does it mean that a cure exists and it’s just not being shared.

    Science moves slowly, and this frustrates everyone, but the focus of most of the funding should always be on the best and most promising treatments. Science isn’t perfect, but it’s a lot better than the “trust me, I know it works” approach.

    Claiming “big pharma” is actively blocking cures to diseases is unwarranted, since it will almost certainly be “big pharma” that will eventually manufacture these causes. The reason these new “anti-CCSVI” studies are being reported is because the initial “miracle” reports of CCSVI were so heavily promoted – and the only thing the press likes more than a story about a miracle, is a story about how the miracle was a fraud.

    The fact that drugs are an incomplete cure or treatment doesn’t vindicate other proposed treatment. Big phrama would dearly, dearly love drugs that actually cure any disease because of their immense profitability. Until there is better evidence, the fact that we don’t have them is more rightly ascribed to science, medicine and biology being difficult and complicated rather than conspiracy and malice.

    IMHO.

  20. Edward Murray says:

    @ windriven
    > I am not aware of any MS drugs that claim to deliver a cure. The best on offer right now are drugs that can slow the progression and ameliorate some of the symptoms of the disease. Compared to a cure this may be cold comfort. But compared to the disease untreated?

    Agreed no one is claiming a cure, but I seriously question that any of the current DMDs can “slow the progression and ameliorate some of the symptoms,” with the exception of Tysabri. They mostly have a set of side effects that are pretty awful and no longer term evidence that they change the progress of the disease, regardless of what measure of efficacy they met to get regulatory authority approval.

    ITEM: Boggild et al, Multiple sclerosis risk sharing scheme: two year results of clinical cohort study with historical comparator.
    http://www.bmj.com/cgi/content/full/339/dec02_1/b4677?view=long&pmid=19955128

    “The outcomes so far obtained in the pre-specified primary analysis suggest a lack of delay in disease progression for all disease modifying treatments combined.”

    ITEM: Ebers et al, Analysis of clinical outcomes according to original treatment groups 16 years after the pivotal IFNB-1b trial.
    J Neurol Neurosurg Psychiatry. 2010 Aug;81(8):907-912. Epub 2010 Jun 19. http://jnnp.bmj.com/content/81/8/907.full

    “The original treatment assignment could not be shown to influence standard assessments of long-term efficacy.”

    @ windriven
    > One of the beauties of science is that the truth always comes out . . . If Zamboni’s therapy works, it will be proven and adopted. Period.

    I would say the history of science is that institutionally, it is a pretty good system for defending the status quo. (I’m not saying that’s bad since a high threshold eliminates a lot of nonsense.) I know it is early in the game, but I don’t think there is a penny of NIH money supporting research on CCSVI. We could very quickly figure out whether CCSVI is as prevalent in people with MS as Zamboni suggests. Probably an N=1,000 study by an independent group would do it. We will have cured cancer, AIDS and MS by the time that gets funded. A smaller study of the effectiveness of angioplasty could also go a long way to answering the question of whether treatment has merit. I don’t see that being funded any time soon.

    Science can take its time, but many people whose minds and bodies are deteriorating by the day in spite of all the wonderful disease modifying drugs available to them, find the risk of angioplasty to be minor compared with the potential benefit if CCSVI turns out to play a major role in MS and a far preferable alternative to the known side effects and lack of efficacy of today’s crop of DMDs.

    @ windriven
    > Look, scientists are by nature both curious and skeptical. The investigations will continue and a body of evidence will accrue that either supports or discredits the Zamboni intervention.

    I want to be respectful in answering this, but when I see two studies such as Doepp et al and Sundström et al being held up as indications that Zamboni’s proposition is not valid, I really wonder where the science is. Strictly in terms of the science, how can these studies judge Zamboni’s hypothesis when they don’t use his approach? Maybe they represent useful research in the advancement of science, but they don’t speak to Zamboni’s hypothesis when they don’t use his methods, at least I thought that was the way this is supposed to work.

    In answer to your other statement about IRB’s, all I know is watching from the sidelines, anyone who has found merit in CCSVI seems to be sidelined by their IRB and they have struggled to gain approval for further research, while these two studies were approved, done and published in what has to be record time of about 4-5 months! Add to that the fact that such minor studies are immediately picked up by major publications and touted as having undermined Zamboni tells me there is something going on here and it isn’t science.

    @ windriven
    > Perhaps Zamboni has discovered an incredible breakthrough. If so his work will be replicated and will redefine our understanding of the disease and its treatment. On the other hand all efforts at replicating his success may fail and it will become obvious that there was no breakthrough at all.

    > This is the way of science. It isn’t fast but it is sure. I hope you will read Dr. Novella’s post again, or at least the last 6 or so paragraphs.

    I sure wish that this were the way science worked!

    The reality is that existing funding organizations will plow the lion’s share and more of their funds into other research. Government and non-profits will continue to fund the expensive front end research for pharma and a few scraps may be thrown at CCSVI.

    Real CCSVI research will be funded by bake sales and patients paying researchers to look at their veins. (See BNAC’s CTEVD study.) Meanwhile, any negative study will be front page news.

    @ windriven
    > In the meantime there is nothing stopping anyone from seeking out a clinic offering the “liberation procedure.”

    Actually, almost every facility in the US and all of them in Canada that were offering treatment have been shut down. Not that I think there is a conspiracy of MS drug companies suggesting to neurologists that it would be a good idea to close down any treatment in facilities where they work. We know from history that drug company reps and executives never do things like that, unless of course, their sales are in jeopardy. :>)

  21. Dawn says:

    @Edward Murray: wow. Bitter at the world, much? And yeah, those conspiracy theories…you sound crazy, whether you really are or not. (I’d prefer to think not, actually).

    Look, I have an aunt and a very good friend with MS. My friend has had severe relapses lately. She’s looking at possibly being considered permanently disabled and unable to work at all at well under 60 years of age. She would LOVE (and we would love for her sake) something that could help her. However, we are talking about SURGERY here. You know, surgery, something that has as risk factors like infection and death? Let’s take a few steps back and look at things a little more dispassionately.

    First: no one is holding up the 2 studies and saying they disprove Zamboni’s findings. What they HAVE said is that they were not able to replicate his findings. Totally different thing. Maybe the 2 studies had issues that Zamboni didn’t. Maybe Zamboni is right and they are wrong. Maybe Zamboni is wrong and they are right.

    We are saying it is too early to tell and that no one should jump into having the surgery.

    Second: You think scientists wouldn’t love to be able to either prove or disprove Zamboni? World wide acclaim would go along with proof of his theory (those brave, maverick doctors) or those other, brave maverick doctors who risk their practices to prove him wrong. Scientists are suckers for things that can add to their publication records. But too many ‘disproven’ ideas look bad; you need to find new things, not only disprove someone else’s theories.

    Third: if you REALLY think neurologists have that much power, you are nuts. Hospitals that offer a successful surgery that isn’t done everywhere get LOTS of PAYING patients from all over the world. Money talks. No hospital administrator worth his/her salary would allow a medical department to over-rule a department that is bringing in TONS OF MONEY. (Ask almost any doctor – surgical departments usually get more respect and money than medical departments )

    Step back, take a deep breath, kiss your wife and be patient. Watch for clinical trials. I don’t know if you are in the US, Canada, or where. I know the NIH has a website that lists all clinical trials currently in process. Offer to participate in the clinical trials as they arise. If you are so sure this treatment works, have your wife join in a clinical trial and see what happens.

  22. Edward Murray says:

    @WilliamLawrenceUtridgeon
    > But that doesn’t mean CCSVI is automatically right, nor does it mean that a cure exists and it’s just not being shared.

    > Science moves slowly, and this frustrates everyone, but the focus of most of the funding should always be on the best and most promising treatments. Science isn’t perfect, but it’s a lot better than the “trust me, I know it works” approach.

    No dispute on this.

    But I think we also need to keep in mind that MS is a progressive disease that has devastating consequences. How much disability can you accept while science moves ahead? I think there are a number of people who see CCSVI as a much more intellectually satisfying explanation for MS than that it is an “auto-immune disease of unknown etiology.” They see the risks of treatment as minimal compared with the possible benefits and compared with current drug choices. The anecdotal evidence is quite compelling, even though most are well aware of the problems which occurred at Stanford, of the people who have been treated and not seen progress. Compare that with injecting yourself three times a week with an inflammatory cytokine that makes you feel as though you have the flu; which causes many to become suicidal; and which probably does little or nothing to slow the advancement of disability, along with monthly steroids for 5 days which is what my wife is being offered as the best that we can do.

    @ WilliamLawrenceUtridgeon
    > Claiming “big pharma” is actively blocking cures to diseases is unwarranted, since it will almost certainly be “big pharma” that will eventually manufacture these causes.

    I know with every fiber of my body that those involved in the sales and marketing of current drugs are doing everything they possibly can to undermine CCSVI because that is the logical thing for them to do. Will that ever be proved? Who knows. It has been in quite a number of other cases.

    But I have not said that big pharma is blocking CCSVI regardless of my beliefs.

    @ WilliamLawrenceUtridgeon
    > The reason these new “anti-CCSVI” studies are being reported is because the initial “miracle” reports of CCSVI were so heavily promoted – and the only thing the press likes more than a story about a miracle, is a story about how the miracle was a fraud.

    Take a look at the US press and CCSVI. It didn’t exist until a month ago. The story was much bigger in Canada where an enterprising television reporter and producer jumped on it about a year ago.

    Other than that, the record is pretty clear that Zamboni was plodding along with peer-reviewed papers and presentations at scientific meetings.

    But what was different was a very active, patient-led examination of CCSVI through social media starting a little over a year ago. There are people on both sides of the issue discussing every aspect of this daily, including the conspiracies. :>)

    @ WilliamLawrenceUtridgeon
    > Big phrama would dearly, dearly love drugs that actually cure any disease because of their immense profitability. Until there is better evidence, the fact that we don’t have them is more rightly ascribed to science, medicine and biology being difficult and complicated rather than conspiracy and malice.

    Interested in a bridge in NY? :>)

    I have a slightly more cynical view. They are interested in patentable compounds that can get regulatory approval and command huge prices. Nice if patients have to take them month after month for life. They have a nice system in which government and non-profits take all the risks and then, when something is a safe bet, they take ownership.

    But what do I know? Maybe all my friends in pharmaceutical research are cynics.

  23. dr.cosa says:

    “However, we are talking about SURGERY here. You know, surgery, something that has as risk factors like infection and death? Let’s take a few steps back and look at things a little more dispassionately.”

    this is what i find so unusual, we equate surgery as a sort of catch all phrase, with all its implied risk.

    surgery is too broad a term.

    as others have pointed out previously, we need to consider the unique factors at play with CCSVI and why its attracting so much attention:

    MS is a disease that disproportionately affects industrialized nations in northern climates, which generally means that wealthier nations and their wealthier citizens are often affected meaning the vast resources of their medical institutions are better equipped to address the issue as opposed to diseases like Malaria and TB that are a greater threat to developing nations that often require outside funding and aid to tackle.

    much like how AIDS research commands considerable sums of money not because of how many people it kills (much less than malaria) but because it has the backing and support of developed nations, especially hollywood which can best spread the message.

    many with MS can either afford or obtain the funds needed to seek outside treatment, or have the political savy to band together under their perspective societies to demand action from state-sponsored medical systems.

    if this were a new and expensive drug with toxic side effects and suspect success there would be less support, but precisely because the testing (ultra sound) and the procedure (angioplasty) are relatively inexpensive compared to a lifetime of meds and care, and less risky than those attendant to immune suppression medication, it becomes a viable risk-reward situation.

    people are stubborn and at times immune to reason, and if given the chance to try an unproven and slightly risky procedure they may do so simply because the alternative treatments are as risky and currently are largely ineffective.

    Canada is at the forefront of investigating this procedure, each day more people undergo treatment and we can only hope sufficient data is collected to arrive at a more complete conclusion of the process at work, i would be suspect of studies that examine such small sample sizes.

    remember, a patient who dies during an angioplasty for this treatment will make front page news with daunting headlines about “the risks of this unproven treatment” yet you rarely hear about the thousands of ER admissions each year in Ontario alone for MS patients with life-threatening illness due to the current roster of MS medications, or those who are wheelchair bound and totally unsuccessful in their attempts at treatment. our society prefers the flashy in-your-face headlines and risks. its a shame.

    Canadian medical practitioners who are qualified can offer safe and largely low risk detection and treatment under the liberation protocol. it is well worth the expenditure to settle the issue in a definitive manner. this will also further advance the study and engineering of better stents to prevent migration as this procedure becomes more popular.

    it sure beats the host of vaguely effective medications on the market for MS sufferers.

    1 year should give us a great indication of what might lay ahead for the viability of liberation treatment.

  24. WilliamLawrenceUtridge says:

    “I think there are a number of people who see CCSVI as a much more intellectually satisfying explanation for MS than that it is an “auto-immune disease of unknown etiology.” They see the risks of treatment as minimal compared with the possible benefits and compared with current drug choices. The anecdotal evidence is quite compelling”

    Those same people, going off to India for this miracle treatment, could also die much sooner from the everything-resistant bacteria currently gnawing its way through hospitals in the UK, possibly for no benefit. Intellectual satisfaction is nice (so is anecdotal evidence), everyone loves a hypothesis that hangs together – but satisfying explanations are not necessarily right. If the benefits to the treatment is zero, then it’s essentially an expensive way to damage your nerve vessels and expose yourself to dangerous complications. Yes the adverse effects of current treatments are significant, but at least those come with some benefit – and are the reason that research continues. Hope is great, false hope is cruel and early death for no good reason is worse.

    “I know with every fiber of my body that those involved in the sales and marketing of current drugs are doing everything they possibly can to undermine CCSVI because that is the logical thing for them to do. Will that ever be proved? Who knows. It has been in quite a number of other cases.”

    I see your point as illogical and one based on hope, fear and frustration rather than evidence. Like all claims of conspiracy, it requires all doctors investigating CCSVI or MS in general to ignore the possible benefits to their patients and probably their loved ones with MS. Plus, it ignores everyone who could make money off of this treatment. Humans are irrational, so even if denying CCSVI is effective is “rational” (and that’s a stretch in my mind) I’m sure there are some interested in both the actual truth, and the best outcomes for people with MS – even if it cuts into profits. Most people in the company wouldn’t benefit from opposing CCSVI directly, though certainly some would like to see the profits continue and have the ability to exert force on other employees. But a conspiracy theory is ever unconvincing – easy to assert, hard to prove, and an assertion without proof is of little use to anyone.

    “Take a look at the US press and CCSVI. It didn’t exist until a month ago. The story was much bigger in Canada where an enterprising television reporter and producer jumped on it about a year ago.”

    Sounds like the press is being responsible for once and actually reporting the scientific mainstream – that this intervention is an unlikely one that is being investigated. Again, with no benefits conclusively proven, undergoing this operation is a leap off a cliff, hoping for there to be a bridge under you.

    “Other than that, the record is pretty clear that Zamboni was plodding along with peer-reviewed papers and presentations at scientific meetings.”

    Yes, but not many, particularly for a 53-year-old researcher. I see 13 publications on pubmed dating back to 2009 only, 14 on google scholar. His brief CV lists 10 http://www.fondazionehilarescere.org/cst/eng/cv_ZAMBONI_eng.doc

    “But what was different was a very active, patient-led examination of CCSVI through social media starting a little over a year ago. There are people on both sides of the issue discussing every aspect of this daily, including the conspiracies. :>)”

    Social media is very different from peer reviewed literature, which is a vicious, critical process designed to strip away hope, fear, despair and drama to leave only the truth. Slow, messy, ugly, but evidence-based and ultimately correct. The biases for research are myriad and easily lead to self-delusion, which is why peer review is so important. I’m most pissed off about the “surgical centers” springing up in medical tourism countries, fleecing patients and risking their lives based on desperate hope.

    “I have a slightly more cynical view. They are interested in patentable compounds that can get regulatory approval and command huge prices. Nice if patients have to take them month after month for life. They have a nice system in which government and non-profits take all the risks and then, when something is a safe bet, they take ownership.”

    Someone has to make it, and isn’t Zamboni doing the same thing? He may be seeking prestige (and hope, for his own wife with MS) rather than financial reward, but he’s still placing the evidence second. Companies can do very naughty things, but people do them also – and often with good intentions. Arguable which is worse. It is also the government which forces the research to be done, without which you would have companies and people manufacturing whatever drugs they wanted, with whatever safety precautions and purity/contaminants they felt like, and it would be people taking the risks along with their medicine. Perfect is the enemy of good, and research is good but not perfect.

  25. Edward Murray says:

    @ Dawn
    > However, we are talking about SURGERY here. You know, surgery, something that has as risk factors like infection and death? Let’s take a few steps back and look at things a little more dispassionately.

    I’m talking about a minimally invasive procedure done under mild sedation that lasts from around 1 to 4 hours and averages 1.5 hours. You are talking about SURGERY.

    IRs seem to have a pretty good handle on running wires through our veins without causing major problems and even experience with angioplasty and stenting of veins and have been doing all of this for decades.

    @ Dawn
    > First: no one is holding up the 2 studies and saying they disprove Zamboni’s findings. What they HAVE said is that they were not able to replicate his findings. Totally different thing. Maybe the 2 studies had issues that Zamboni didn’t. Maybe Zamboni is right and they are wrong. Maybe Zamboni is wrong and they are right.

    Try Googling these studies: http://www.google.co.il/search?sourceid=chrome&ie=UTF-8&q=ccsvi+german+study+swedish+study

    Here’s a typical headline: “New studies question wide-spread hypothesis that CCSVI contribute to development of MS, Medical News Net.” This is from the Blackwell press release which has been picked up verbatim by a large part of the medical press: “The studies refuting the CCSVI theory with the first negative medical evidence on the subject, are available today in Annals of Neurology, a journal published by Wiley-Blackwell on behalf of the American Neurological Association.”

    How do you REPLICATE his findings without REPLICATING his methods?

    @ Dawn
    > Third: if you REALLY think neurologists have that much power, you are nuts. Hospitals that offer a successful surgery that isn’t done everywhere get LOTS of PAYING patients from all over the world. Money talks. No hospital administrator worth his/her salary would allow a medical department to over-rule a department that is bringing in TONS OF MONEY. (Ask almost any doctor – surgical departments usually get more respect and money than medical departments )

    So how do you explain the fact that the procedure been blocked at virtually every hospital that has offered it in the US and Canada? Who initiated the move to stop the treatment in these facilities? The Science Fairy?

    Here’s what happened at Stanford, courtesy of the associate director of the Stanford MS Center, Jeffry Dunn, MD:

    “If I can do anything to protect MS patients from the potentially devastating effects of false hopes or the risks of invasive and unproven treatment, I am happy to do so”

    “Most of you also are aware that a vascular surgeon on the campus here at Stanford University has been performing intravascular stenting on self-referred MS patients in what some have termed “The Liberation Procedure.” We are certain you are fielding questions regularly about this—and wondering what in the world is going on at Stanford. Effective immediately, this procedure has been SUSPENDED by the highest levels of medical leadership here on campus.”

    Dunn said, the MS pipeline is robust. “There are five oral medications now being tested in FDA phase-3 trials, and there are several other novel and emerging monoclonal antibody therapies that offer significant promise.”

    He’s a paid consultant or speaker for the following companies: Accorda Pharmaceuticals, Bayer Healthcare, Biogen Idec, EMD Serono, Gilead Sciences, Teva Neuroscience.

    Why would I be cynical? Why would I think people with a financial interest in MS drugs would be involved in blocking CCSVI?

    Must be nuts as you suggest.

    @ Dawn
    > Step back, take a deep breath, kiss your wife and be patient. Watch for clinical trials. I don’t know if you are in the US, Canada, or where. I know the NIH has a website that lists all clinical trials currently in process. Offer to participate in the clinical trials as they arise. If you are so sure this treatment works, have your wife join in a clinical trial and see what happens.

    We live outside the US and my wife has been treated.

    There is a single small clinical trial. I may not have the exact numbers, but something like 13,000 people tried to get into the trial which will be treating 30 MS patients in Buffalo. (Controlled Randomized EndovaScular Therapy (CRET) study for CCSVI. This will be a 6-month study that will evaluate the safety and preliminary efficacy of therapeutic angioplasty, and will include 30 patients with MS. http://bnac.net/newsletter/BNAC_Newsletter_02-04-2010.pdf)

    You asked in the beginning of your post if I am bitter at the world?

    Not at all. My wife has been treated. But I think it realistic to expect that science will take a back seat to money in the unfolding saga of CCSVI. There is honest skepticism about many aspects of the CCSVI hypothesis and certainly about the benefits of treatment. I respect that honest skepticism. I don’t see how research to answer those questions can advance when there is no funding for it and IRBs seem to make it quite difficult to get such research approved.

  26. windriven says:

    @EdwardMurray

    You said:”Actually, almost every facility in the US and all of them in Canada that were offering treatment have been shut down.”

    Dr. Cosa wrote: “Canada is at the forefront of investigating this procedure, each day more people undergo treatment …”

    One of you is correct and one of you isn’t. I have no idea which. But the fact remains either way that the procedure is obtainable given sufficient motivation.

    You also wrote: “The reality is that existing funding organizations will plow the lion’s share and more of their funds into other research. ”

    To which I can only point out that there are tens of thousands of MS sufferers in the United States and a number of large organizations dispensing MS research funds. Make your concerns known to the organizations dedicated to researching this disease.

    You can mount all manner of conspiracy theories, cursing the darkness as it were. Or you can band together with others who have MS, their friends and family, and make your voice heard. There is a lot of money raised every year for MS research; get some of it allocated to research on CCSVI.

    But don’t expect researchers who have spent their lives trying to understand this disease to simply drop everything and stand up to applaud a therapy with no carefully elucidated mechanism of action and no well designed independent studies replicating Zamboni’s success. This does not suggest a conspiracy. It is the normal inertia that any massive body exhibits when met with a change in force.

  27. Edward Murray says:

    @ WilliamLawrenceUtridgeon
    > Those same people, going off to India for this miracle treatment, could also die much sooner from the everything-resistant bacteria currently gnawing its way through hospitals in the UK, possibly for no benefit. Intellectual satisfaction is nice (so is anecdotal evidence), everyone loves a hypothesis that hangs together – but satisfying explanations are not necessarily right. If the benefits to the treatment is zero, then it’s essentially an expensive way to damage your nerve vessels and expose yourself to dangerous complications. Yes the adverse effects of current treatments are significant, but at least those come with some benefit – and are the reason that research continues.

    Agree completely. Sad that it is so difficult to get treatment in the US and Canada and even more disappointing that there is treatment without research. I think this is true even though CCSVI is mostly unproven and we don’t really know whether treatment provides any significant benefit. I say this because compared with the almost guaranteed risks of not treating (which I would argue is what you are doing with all the currently approved drugs, with the possible exception of Tysabri) the risk-benefit ratio is favorable. If there were good approved therapies, this would be different.

    @ WilliamLawrenceUtridgeon
    > Hope is great, false hope is cruel and early death for no good reason is worse.

    You write this about CCSVI treatment, but I would argue that it is a perfect description of life with the current meds at least in terms of false hope and a lot of suffering without benefit.

    @ WilliamLawrenceUtridgeon
    > I see your point as illogical and one based on hope, fear and frustration rather than evidence. Like all claims of conspiracy, it requires all doctors investigating CCSVI or MS in general to ignore the possible benefits to their patients and probably their loved ones with MS. Plus, it ignores everyone who could make money off of this treatment. Humans are irrational, so even if denying CCSVI is effective is “rational” (and that’s a stretch in my mind) I’m sure there are some interested in both the actual truth, and the best outcomes for people with MS – even if it cuts into profits. Most people in the company wouldn’t benefit from opposing CCSVI directly, though certainly some would like to see the profits continue and have the ability to exert force on other employees. But a conspiracy theory is ever unconvincing – easy to assert, hard to prove, and an assertion without proof is of little use to anyone.

    I probably am illogical, fearful and frustrated, but I make no claim that there is a conspiracy. I still think it very logical to expect that people who have a vested interest in the status quo, financial or intellectual, will do what they can to block something potentially disruptive of the status quo. For them to do otherwise would not make sense.

    @ WilliamLawrenceUtridgeon
    > Sounds like the press is being responsible for once and actually reporting the scientific mainstream – that this intervention is an unlikely one that is being investigated. Again, with no benefits conclusively proven, undergoing this operation is a leap off a cliff, hoping for there to be a bridge under you.

    The limited scientific and anecdotal evidence in my view absolutely merits going forward with treatment for some people willing to take the risks and hopefully advance our understanding of what if any role CCSVI plays in MS. This would be less true if current therapies provided real benefit and fewer side effects. It would be even more true if this could be done in the context of clinical trials aimed at doing the science.

    I believe this was the first public presentation of Zamboni’s hypothesis back in 2006: The Big Idea: Iron-dependent inflammation in venous disease and proposed parallels in multiple sclerosis, J R Soc Med 2006;99:589-593
    http://jrsm.rsmjournals.com/cgi/content/full/99/11/589

    @ WilliamLawrenceUtridgeon
    > Social media is very different from peer reviewed literature, which is a vicious, critical process designed to strip away hope, fear, despair and drama to leave only the truth. Slow, messy, ugly, but evidence-based and ultimately correct. The biases for research are myriad and easily lead to self-delusion, which is why peer review is so important. I’m most pissed off about the “surgical centers” springing up in medical tourism countries, fleecing patients and risking their lives based on desperate hope.

    Agree completely, although I think peer-review is currently up for reconsideration. :>)

    @ WilliamLawrenceUtridgeon
    > Someone has to make it, and isn’t Zamboni doing the same thing? He may be seeking prestige (and hope, for his own wife with MS) rather than financial reward, but he’s still placing the evidence second. Companies can do very naughty things, but people do them also – and often with good intentions. Arguable which is worse. It is also the government which forces the research to be done, without which you would have companies and people manufacturing whatever drugs they wanted, with whatever safety precautions and purity/contaminants they felt like, and it would be people taking the risks along with their medicine. Perfect is the enemy of good, and research is good but not perfect.

    Nothing to dispute there, although if you are talking FDA here, I think it is an agency which believes its mission is protecting manufacturers from the public, not the other way around. (Sorry, I just had to add that.)

  28. Edward Murray says:

    @ windrivenon
    > You said:”Actually, almost every facility in the US and all of them in Canada that were offering treatment have been shut down.”

    Dr. Cosa wrote: “Canada is at the forefront of investigating this procedure, each day more people undergo treatment …”

    > One of you is correct and one of you isn’t. I have no idea which. But the fact remains either way that the procedure is obtainable given sufficient motivation.

    People from Canada are being treated, in Poland, in India, Costa Rica, a few in the US, some in Egypt, but I think I am completely correct in saying that there is not a single person being treated in Canada. Plenty of complaining about this here: http://www.facebook.com/pages/CCSVI-in-Multiple-Sclerosis/110796282297?ref=ts There are a few places offering treatment in the US, but many more that tried to offer it and then shut down.

    @ windrivenon
    > You can mount all manner of conspiracy theories, cursing the darkness as it were. Or you can band together with others who have MS, their friends and family, and make your voice heard. There is a lot of money raised every year for MS research; get some of it allocated to research on CCSVI.

    Can I do both, ie, curse the darkness and help fund research and understanding of CCSVI? :>)

    http://www.ccsvi.org/

  29. I love it – surgeons get blamed for doing too many procedures to make money. But now the medical doctors are being blamed for preventing surgeries to protect their drug profits. And drugs are evil, except when they are alternative – then they are supplements (even if they are industrial bleach or chelating agents).

    You can weave anything into a conspiracy theory – even mutually exclusive conspiracy theories. They don’t seem to have any relationship to reality.

    The fact is – medicine is not monolithic. There are varying interests. The reason hospitals are agreeing no to offer the liberation procedure is not to please neurologists (believe me – this just makes me laugh). It’s because the treatment is not evidence-based.

    Believe it or not, there are a few people in medicine who want to do the right thing for patients. Also – the people who are mostly setting the standard of care are salaried academicians who don’t make money directly off patient care.

    I have absolutely no dog in this hunt. I don’t get any money from pharmaceutical companies. I do not stand to benefit or be harmed in any way by how MS is treated. I am just reading the research.

    It’s more than cynical to make up and assume absurd conspiracy theories – it’s profoundly naive of how the medical system actually functions.

  30. Werdna says:

    “I still think it very logical to expect that people who have a vested interest in the status quo, financial or intellectual, will do what they can to block something potentially disruptive of the status quo. For them to do otherwise would not make sense|

    “Logical” is a poor word. It is far more logical for someone who is involved in a project (like I am at work) to give way to other projects which are likely to see better yield and even to yield some portion of resources to get more information if the outcome looks good. It is entirely illogical to preserve status quo if it is inferior to the alternative.

    It’s also unreasonable to assume that the cost/benefit works out in favor of blocking CCSVI. Large drug companies are diversified and sure they might spend some money to preserve some line of business it’s unreasonable to assume that they would spend *any* amount of money to do so.

    “So how do you explain the fact that the procedure been blocked at virtually every hospital that has offered it in the US and Canada? Who initiated the move to stop the treatment in these facilities? The Science Fairy?”

    In Canada there was no *move* nor is there any *block* it is the case of an existing approved procedure (angioplasty and stent placement) which can only be performed by medical doctors. MD’s can only be paid for these procedures by OHIP. These procedures are simply not approved for general use for the condition.

    If it was neither of these two things it could be done on a fee-for-service basis. For example PET scans and be done on-demand.

  31. dr.cosa says:

    Wernda said:

    “In Canada there was no *move* nor is there any *block*… MD’s can only be paid for these procedures by OHIP. These procedures are simply not approved for general use for the condition.”

    this is somewhat inaccurate, there is no Canadian medical system in a monolithic sense, it is a collection of separate but related provincial entities that can at time act very differently in the face of a specific condition or medication.

    the decision to perform Liberation treatment lies with the Hospitals themselves, it is the government agencies which decide if they will cover the costs. there are a host of treatments offered both in and out of hospital that aren’t covered by the provinces (ie: plastic surgery for non disfigurement/mastectomy reasons, alternative medicine, massage and physio therapy, etc) with some such as Alberta and Quebec offering extensive out of pocket treatments to those willing to pay.

    many MRI clinics are in fact private entities leasing space from hospitals in Ontario,

    the only move was to fund research treatment in Sask, other provences are watching and have not offered to reimburse it as of yet. this happens with a host of new drugs when they first come on line with it being funded in one province but not the other until several years later.

    luckily there are no shortage of ultrasound clinics that will gladly offer screening if they are qualified, and several doctors that perform liberation type treatments throughout the country.

    as ive said before, its not a case of drugs being universally bad and liberation treatment being risk free. i think we need to carefully met out the rationale when we speak to the current drugs on offer for MS which help some and hurt others vs. the reasonably safe procedures for liberation treatment that also help some but not others.

    once again i cant stress enough that it is not conspiracy theory to believe that some within the medical community posses untold influence to promote one protocol over another, and that if they happen to be paid vast sums from drug companies, it is fair to at least consider if their opinions are unbiased on the matter. (without unfairly implicating them)

    Dr. Novella I dont see anything in what you have written to indicate bias and you have treated the issue fairly. these discussions are critical.

    i think it does nothing for the cause of MS or medical science itself when we rely on phrasing and catch-all concepts to make our point. lets stop referring to angioplasty as “risky invasive surgery” to hammer home how dangerous it could be, or claiming that drug companies want everyone to be ill so they can push ineffective meds on the populace.

    its perfectly fair to point out the inadequacies of current MS treatment and the sorry outcomes for many who face not only declining health but difficulty securing basic daily care from cash strapped health agencies. these sorts of plights are what create a climate of desperation, and we do no service to seekers of treatment by obfuscating the issues with misleading descriptions.

    what makes Liberation treatment appealing is that it involves reasonably safe procedures that have been done for years in most modern medical systems, thus people seek treatment even if the research is still in its infancy because the risk reward is such that either you try or you continue to loose most of your mobility and livelihood. who would rather face a wheelchair and gradual decline in their bodily functions than the small chance of complications due to angioplasty and/or stent migration if it meant a %50 chance of success? what about a %30 chance?

    i think most people would risk much more for much less odds of success. this is why people are going nuts over the treatment.

  32. pmoran says:

    This is looming as another dispute that only well-controlled studies involving sham procedures can satisfactorily resolve.

  33. Edward Murray says:

    @ Werdna and @ dr.cosa

    I know almost nothing about the Canadian medical system.

    There are two widely publicized cases of IR’s being blocked from providing CCSVI treatment, I assume by the hospitals with which they are affiliated. One is Barrie’s Royal Victoria Hospital. The other in Victoria where the “Vancouver Island Health Authority” chastised an interventional radiologist for treating two patients with CCSVI.

    If it were a simple matter of paying for the procedure privately in Canada, then why are Canadians in large numbers paying large amounts of money to leave the country to get treatment in Poland, India, Costa Rica, and elsewhere?

    Other than the seven patients treated in Barrie and Victoria, I am not aware of anyone else being treated in Canada, but see on a daily basis on the web that Canadians are leaving the country for treatment.

  34. Dawn says:

    @Edward Murray and Dr Cosa: there is 1 truism in medicine: THERE IS NO SUCH THING AS MINOR SURGERY. All surgeries, no matter how “minor” carry the risk of infection, injury, and death. (What kind of dr are you, Dr Cosa, if you don’t know this?)

    Mr Murray: I’m glad you had your wife treated. At least you are putting your money where your mouth is. But you haven’t said whether she has displayed the great improvements that the surgery claims to allow. And, as we all know, MS has periods of waxing and waning. So, do you have documented, objective, clinical proof of her treatment and improvement? I won’t ask you to give it, I’m just asking if it really exists.

    And we all know that Facebook and the internet contain only the most reliable information on everything. No thanks. I’d rather trust peer-reviewed journal articles over Facebook. Anecdote, as is so often said, does not equal data.

  35. dr. cosa – what we need is a risk/benefit assessment. The treatment is not risk free (or negligible risk), therefore there should be a reasonable expectation of benefit before it is ethically justified outside a clinical trial.

    At this point, in my opinion, the procedure should only be done as part of an approved clinical trial.

    There is a case to be made for compassionate use. This is a point regarding CCSVI about which reasonable people can disagree. I do not think it meets the threshold for compassionate use – but admittedly, that’s my opinion.

    Hospitals and regulators will have to make the judgment call also.

  36. daedalus2u says:

    I agree with pmoran. There may be (very likely will be) a large placebo effect associated with this procedure. The amount of hype that has been generated by the press releases and the media will ensure that. This placebo effect may very well improve MS symptoms and that improvement may well last years.

    A large placebo effect is observed in other procedures, transmyocardial laser revascularization, using a laser to generate multiple voids through the heart muscle which (according to the idea) would become pathways for vessels. Postmortem analysis of treated hearts shows the holes were completely filled with scar tissue and there was no significant revascularization. Dr Gorski has written about various other treatments for angina; talc poudrage (the idea of sprinkling talc on the heart to cause inflammation leading to revascularization) and also grafting the internal mammary artery for heart revascularization. The last two procedures were adopted on the basis of open label trials which seemed to show good results. Later blinded trials showed that a sham procedure produced essentially equivalent results. Transmyocardial laser revascularization is surviving, but now with the added bells and whistles of growth factors and stem cells, and there are now alternative explanations of why it “works”, that the scar tissue stiffens the heart and makes it more efficient.

    Conditions that are made worse by stress (such as angina and MS) should be expected to exhibit a large placebo effect. A large placebo effect was observed in various surgical techniques for heart revascularization. We should expect to see a large placebo effect in CCSVI for MS.

    Unless double blinded trials are very well done, it will be difficult to differentiate a therapeutic effect from a placebo effect. The “best” practitioners of CCSVI will be resistant to doing sham procedures because they “know” the real procedure is better. They may certainly believe this, but until they have data to demonstrate it, they can’t actually know it. The confidence in the procedure exuded by the charismatic developers and promoters of CCSVI will be a powerful placebo and difficult to simulate in other settings.

    The risk/benefit balance is difficult to analyze because humans don’t value potential gains and potential loses the same. Greg Laden blogged about research in monkeys showing the same effect.

    http://scienceblogs.com/gregladen/2010/08/laurie_santos_a_monkey_economy.php

    Monkeys (and humans) value a sure gain of 0.5 higher than a 50% chance of a gain of 0 or 1. But they value a 50% chance at a loss of 0 or 1 higher than a sure loss of 0.5. I think this is what is influencing the risk/benefit analysis that patients are doing. Is their initial state the pre-MS state where the MS is a loss that the procedure can mitigate and so prefer a 50% chance of something good or something bad, or is their initial state the post-MS state where a sure but modest gain is preferred over a 50% chance at a larger gain or no gain?

    I think this is also part of the “do everything that can be done” mentality that sometimes accompanies end of life medical decisions. Is death something to be avoided at all cost, including the cost of perhaps accelerating it? Or is death inevitable and the remaining lifespan to be used in as satisfactory a manner as possible?

  37. dr.cosa says:

    once again i appreciate your responses Dr. Novella, and a risk/benefit assessment is certianly a sound approach compared to some who choose to view it in such black/white terms (ie: risky surgery and death vs. shady drug company conspiracy)

    w/ respect to Canada’s medical system it currently takes upwards of several months to 1 year for an surgical consultation, thus people are rushing to other nations where they can obtain it almost immediately and at much lower costs.

    (i am not a doctor fyi, it is a long held dj moniker but i work in health care)

    people are currently able to obtain the specific type of ultrasound for CCSVI across the country at different clinics, i can speak to several locations in the Toronto area. there are an assortment of surgeons who are either willing to perform liberation treatment or have done so but faced backlash.

    part of the issue is should a surgeons time be spent performing procedures that are covered under health care plans for the public or perform out-of-pocket private surgeries? with limited resources in our system in Ontario the idea is that out-of-pocket should in no way limit or reduce resource availability of public services.

    (this is a hot issue in Ontario, with people going as far as to question why professional athletes on Toronto sports teams can obtain MRI’s in one day vs. the 3 month wait most of the public faces) Canadians spent untold millions seeking private medical treatments and tests outside the country with buffalo catering to southern ontario residents with same day MRI and CT scans. the idea that these are available in our country is secondary to the time frames involved.

    as noted people are naturally anxious and excited at even the vauge prospect of Liberation treatments success, and will go outside the grain of our current system to get it (ie: india, costa rica, poland).

    i believe there is a touch of xenophobia in some who seem to criticize clinics in places like India or Poland as if they inferior to Western medical clinics, or that they are predatory. we need to consider each individual clinic on its own merits, as there are a host of treatments and medications offered in the US that are not covered in Canada or are outright banned by our medical authorities but we dont cast them with the same brush.

    (consider medical marajuana treatment in California vs. draconian drug laws in oaklahoma or elsewhere, rational discussion should assert itself over a simple account of something being “illegal” in one place vs. another)

    lets examine each study and each surgeon on their own merits alongside their success and failures. some may decry the internet for fostering hype and hysteria, i would advance that despite some initial quackery that invades the debate, eventually some truth may begin to reveal itself as more people undergo the treatment and documentation is collected in a less haphazard manner than it is now.

  38. dr.cosa on why Canadians with MS are going elsewhere for the Zamboni intervention: “w/ respect to Canada’s medical system it currently takes upwards of several months to 1 year for an surgical consultation”

    That’s a very broad statement that needs qualifiers. My father was booked for Mohs surgery at a specialist hospital three weeks after his nose biopsy results came back. Three weeks from dermatologists office to OR is less than “several months to 1 year” for a consultation.

    It’s possible that with our horrible, evil, socialized medicine rationing and death panels that consultations for surgery with little indication (Zamboni intervention) are lower priority than surgery that we know will help (Mohs). Is that what you mean?

  39. Epinephrine says:

    @daedalus2u
    I agree that it’ll be hard to do a good blinded trial, I didn’t get into the issues when I mentioned it. Not only might it be difficult to get a surgeon to do the sham operations (if the surgeon is a believer in CCSVI), but it would be difficult to blind the surgeon to patient identity. I suspect that in most cases the surgeon also provides follow up, which couldn’t work with blinding, so you would need a separate investigator/medical team for follow up assessments, and one that doesn’t communicate directly with the surgeon preferably.

    If they do the trial right, though, it could work to disentangle the doubtless powerful placebo effect from the treatment effect. I’m glad that the Sask. government is pledging to fund clinical trials, but I really hope they do it right or it will be a complete waste of money/time/energy.

  40. Epinephrine says:

    @Alison Cummins
    I’ll second your comments. We have typically had short waits – my MIL had her mastectomy only a few weeks after diagnosis, my father had his biopsy followed by thyroidectomy (for thyroid cancer) in a couple of months. My eldest daughter was born with a club foot and was seen by her orthopedic surgeon a mere 4 days after birth.

    CIHI has reported on wait times, but it is very difficult to come up with precise numbers since there are differences in the way wait times are measured, and the effect that deferred surgeries have on the times. If your surgery for X can’t happen until you reach some target, should delays in reaching the target count as wait time? If you aren’t healthy enough for your surgery and it has to be delayed, does that count?

  41. dr.cosa says:

    allison,

    from the last part of your post it sounds as though you take any sort of criticism of the Canadian system as a Sara-Palin-esque attack. its disappointing that such an extreme approach is needed to consider the weaknesses in the Canadian system, no matter how sacrosanct you believe it to be.

    yourself and others are referring to singular examples of quick admission to surgery as if it qualifies your claim that there arent significant wait times yet would likley consider testimonials from Liberation Treatment patients to be anecdotal and too small a sample size.

    we need an objective and consistent approach to the issue, if we need to see large group sizes in carefully controlled studies to prove the merits of CCSVI then we need equally broad measures of understanding issues particular to the Canadian medical system, and consider why it is people are spending so much of their time and money obtaining MRI’s and CT scans across the border.

    wait times vary of course, and some are emergencies, but most would attest to the delays from seeing one’s FMD, to a referall to a specialist, from the specialist consultation to an actual recommendation for surgery to the procedure.

    yes, if its an emergency, or more serious the times can vary, but they are far too often longer than the averages due to the delays in obtaining scans and referrals to be reviewed.

    ontario wait times website:

    http://www.waittimes.net/surgerydi/En/What.aspx?View=0&Type=0&Modality=&ModalityType=

    a great example is lumbar spine neurosurgery wait times in toronto aprox 3-5 months wait time, that does not include the time from your family physician sees you to the point you see a specialist.

    http://www.waittimes.net/surgerydi/En/Data.aspx?view=0&Type=0&Modality=8&ModalityType=95&city=&pc=l5m1r6&dist=100&hosptID=0&str=&period=0&expand=0

  42. dr.cosa says:

    just to add to my above post, i have no interest in this devolving into a discussion of the merits of the Canadian system of health care, but i believe wait times are a salient issue for many

    the greater access and ease with which people with MS may be able to see a specialist, obtain the proper ultrasound and consider if blockages exist or not could help to stem the tide of suffers going across the border or traveling halfway around the world for actual treatments.

    part of the reason people dont want to dedicate more resources is precisely because of the rationing belief outlined by Allison that one surgery takes that resource away from another, hence the comparison to a known cure for a treatable disease being somehow more worthy of medical dollars than an unproven treatment.

    but at any given moment a large section of our medical resources are directed towards research, experimentation and a host of other medical fields that may be considered less than priority (ie: common fungal treatments vs. cancer therapy etc.) who ultimately makes the decision if and when to dedicate funds to something? Sask. made the call, is that to the detriment of all the other sick people in that Province? Was it purely political, or did their medical authorities see sufficient merit to at least warrant small-scale study?

  43. WilliamLawrenceUtridge says:

    In Canada, medical care is risk-based. If you’ve got an aneurism set to blow, you’ll bump some other poor sod out of an operating room. If you’re that poor sod getting a knee replacement, chances are you’re waiting a long time. One saves a life, the other makes a life better. In any situation with a public option, those are the choices you have to make. If I needed new knees, I’d curse the system for being stupid, but if I’m budgeting or triaging, I know where the priorities are.

    That CCSVI is not being paid for is not surprising. In fact, it is appropriate. Any idiot doctor who undertakes the operation, particularly if paid for by the public purse, will hopefully get a vicious smackdown from both regulatory agencies and hopefully any ethics board at their institution. This is not a proven treatment, and it’s simply waste to expend any resources but research on it. I understand that MS patients find it frustrating, but systems are not about individual patients – they are about masses of patients. Which means testing before treatment, conserving funds, and keeping an eye on the long-term. If this turns out to be a solid option, a good treatment decision, it will be integrated and kept until a better one shows up. Yes, time will be lost for people who didn’t get the treatment, and yes public health authorities will be castigated for not adopting it sooner – but hindsight is 20/20 and the same health authorities must be cold-hearted enough to know that the treatment may be worthless or even harmful.

    Decisions about H1N1 faced a similar quandry – move quickly in case it is deadly, or save money and hope no-one dies. In this case they made the wrong decision (possibly – my wife got what she thought was H1N1 and ended up being very miserable for a week and cursed she couldn’t get the vaccine sooner). The awful thing is those same decision makers can never win – if it’s a successful treatment they are cursed for not implementing it with lightning speed. If it’s a worthless treatment they are cursed for wasting valuable research dollars on it. And few appreciate what informs their decision making. Considering it’s only been months since this proposal hit public consciousness, it’s actually moving quickly in my mind. I give it a 90% chance of fizzling into a non-treatment that was oversold.

  44. Epinephrine says:

    @dr.cosa

    My anecdotes weren’t to refute the existence of greater wait times for some surgeries. I referred to CIHI’s report, and in fact I worked in the applied research and analysis directorate at Health Canada, and did some work with wait times. So, you found an example surgery with a 6 month wait. The numbers I mentioned aren’t oddities – 9 out of 10 patients in Ontario have breast cancer surgery within 34 days.

    As WilliamLawrenceUtridge mentions, there is triage involved.

    we need an objective and consistent approach to the issue, if we need to see large group sizes in carefully controlled studies to prove the merits of CCSVI then we need equally broad measures of understanding issues particular to the Canadian medical system, and consider why it is people are spending so much of their time and money obtaining MRI’s and CT scans across the border.

    First we need to determine if CCSVI is even a problem – the original research suggested that 100% of MS patients and 0% of controls had CCSVI, but that hasn’t been replicated. The Vancouver Coastal Health Research Institute is trying to get a study going using catheter venography to study the problem, since the results have been quite varied from different attempts to look for CCSVI.

    People spend their money on hope. It’s no mystery.

    On the subject of clinical trials; these things take time – one needs to secure funding, come up with a protocol, informed consent documents, submit it to research ethics boards, etc. You need more than just a group of people willing to have an operation.

    part of the reason people dont want to dedicate more resources is precisely because of the rationing belief outlined by Allison that one surgery takes that resource away from another, hence the comparison to a known cure for a treatable disease being somehow more worthy of medical dollars than an unproven treatment.

    Yes, somewhat. It’s the “unproven treatment” part. There isn’t even proof of a the problem the treatment is supposed to fix. And anecdotes don’t answer the very real question about the power of placebo surgeries.

    but at any given moment a large section of our medical resources are directed towards research, experimentation and a host of other medical fields that may be considered less than priority (ie: common fungal treatments vs. cancer therapy etc.) who ultimately makes the decision if and when to dedicate funds to something?

    The people putting money up? If you want government money to run a trial, you have to ask for it and get it approved, and that means showing why it should be funded. The MS society should be willing to step up to fund clinical trials, in which case it would be up to the funded research group to get REB approval. Money spent in one area does take away from money for another area.

    If you are talking about money spent developing drugs for fungus, then it’s drug companies, a separate source of funding – but they will have a different set of criteria as to what should be funded than a funding agency like the CIHR, or compared to a group with a specific interest, like the MS Society of Canada.

    @WilliamLawrenceUtridge

    Decisions about H1N1 faced a similar quandry – move quickly in case it is deadly, or save money and hope no-one dies. In this case they made the wrong decision

    I disagree, I don’t think it was the wrong choice – it was the right choice based on the available data. That it turned out to be less serious than was originally anticipated means that we got lucky, but it was still the right decision. It’s not the wrong decision to bother buckling up on a car trip in which you didn’t have an accident – it may not have been necessary that time, but it wasn’t “wrong.”

  45. WilliamLawrenceUtridge says:

    @Epinephrine

    I disagree, I don’t think it was the wrong choice – it was the right choice based on the available data. That it turned out to be less serious than was originally anticipated means that we got lucky, but it was still the right decision. It’s not the wrong decision to bother buckling up on a car trip in which you didn’t have an accident – it may not have been necessary that time, but it wasn’t “wrong.”

    Objectively, it was the wrong decision. H1N1 wasn’t unusually deadly (or at least I would venture not so deadly it was worth spending billions on it). But you are 100% correct, based on the information available at the time (the Manitoba study?) it appeared to be the best decision.

    And no matter what, all the vaccinations doubtless reduced the morbidity and mortality that accompany any influenza, seasonal or otherwise. The public does not appreciate that science is data-based not magic. It’s amazing just how much error will be tolerated for things like acupuncture and homeopathy, patently false, but let a scientist make a good decision on bad evidence (which would I suppose be a bad decision unless they got really lucky) and suddenly all research is worthless and we should get our auras adjusted.

    The CCSVI thing is the same – dangle some false hope and people trip over themselves to empty their wallets. God forbid it gets approval and ends up being harmful though…

    Public health officials can’t win.

  46. WilliamLawrenceUtridge says:

    Dog mand it, how do you work the quote tags?

  47. WilliamLawrenceUtridge says:

    Dam it

    Please remove the evidence of my humiliating inability to grasp basic premises or google “quote tag wordpress”.

  48. Chris says:

    Quotes:

    [blockquote]…. write stuff here…[/blockquote]

    Replace the square brackets with the less than and greater than signs, which are usually on the bottom row of the keyboard.

    Also, bolding is [b]…[/b], and italics is [i]…[/i], just remember to use the less than and greater than brackets instead.

  49. Edward Murray says:

    @ Dawn

    @Edward Murray and Dr Cosa: there is 1 truism in medicine: THERE IS NO SUCH THING AS MINOR SURGERY. All surgeries, no matter how “minor” carry the risk of infection, injury, and death. (What kind of dr are you, Dr Cosa, if you don’t know this?)

    But there is another truism: risk is only meaningful in the context of benefit. Just comparing intervention to treatment with interferon the risk-benefit seems enormously in favor of intervention, from my perspective and my weighting of the various factors.

    With interferon, I will be suicidal. I will spend a day after injection feeling nauseated. I will have flu-like symptoms for 24 hours after injection and as I look at the research, the benefits look much more like statistical games than anything real. I will be on an anti-depressant to deal with the suicidation and sleeping meds to deal with the sleep disruption caused by both. That will necessitate taking something for nausea. And then there are the constant headaches, neurological pain in my legs and all the other wonderful effects of MS which are not changed by the current MS drugs.

    Plus, I will see a continued downward spiral in my balance, vision, fatigue, Cog Fog and other things that may or may not be related to MS.

    The risks of a “minimally invasive procedure with mild sedation” which might restore balance, vision and eliminate constant migraines seem absolutely minimal compared with what I know about treatment with interferon and periodic monthly rounds of five days at one gram of methylprednisolone IV a day. Even if the only benefit were that it halted or slowed further progress, the best that other treatments offers, the risk-benefit ratio would be enormously in favor of intervention.

    I don’t think any of the MS DMDs claim to: stop fatigue, lessen cog fog, improve balance, stop choking, or otherwise change MS clinically. If tested over a short enough time frame, they reduce relapses marginally and cause changes in MRI’s, two things that don’t seem to have much clinical relevance to disability associated with MS which we know just marches on.

    @ Dawn
    > Mr Murray: I’m glad you had your wife treated. At least you are putting your money where your mouth is. But you haven’t said whether she has displayed the great improvements that the surgery claims to allow. And, as we all know, MS has periods of waxing and waning. So, do you have documented, objective, clinical proof of her treatment and improvement? I won’t ask you to give it, I’m just asking if it really exists.

    Since I am in contact with literally hundreds of people who have or are planning to have treatment, it may be more useful to provide a summary of what the results have been than to go into details of how my wife has responded, but I can say that having been treated, she is a strong proponent of “minimally invasive intervention.” :>)

    Dr. Gary Siskind who is doing treatment in Albany suggests that response is about 1/3rd miraculous, 1/3 moderate and 1/3 no improvement. There are a handful of people who have reported getting worse after intervention (mostly in terms of fatigue, cog fog and balance) and sadly, because they are traveling across the world for treatment, most have not gone back to find out why they had a negative response.

    The most consistent, though difficult to measure benefit of treatment, is in reduced fatigue and cog fog, probably the two most common impairments associated with MS. This seems a likely benefit of improving cerebral blood flow and something I would expect from treatment. It may all be placebo, but it is a benefit that seems to last among the group of people I know who are starting to hit their one year anniversary.

    Probably the next most common immediate benefit is in balance. This is easily tested before and after intervention with standard balance tests and if you are interested, a series of before and after videos on YouTube. One of the people treated the same day as my wife, a Canadian woman, was able to walk the day after intervention, something she had not been able to do for 6 years, mainly because of balance problems. Before intervention, she could stand as long as she was holding on to something to prevent her from falling, but if she tried moving without a walker, her balance sent her straight to the floor. My wife’s balance has only improved slightly, but has gotten progressively better with time. Prior to intervention, she fell once a day. She has not fallen since, but if she extends her hands and closes her eyes, she falls. She can’t walk heel to toe. Dr. Siskind’s 1/3 rule seems about right for this. Some people are getting up out of the wheelchair and walking, some are falling less and some see no change.

    Vision improvements are probably the next most common immediate benefit, again following the 1/3 rule. People are going from blurry, double vision to HD vision in terms of clarity and color. Others see better, but the improvement is not dramatic. There have been a number of cases of people announcing to their IR on the table that they can see. These are people who could not see prior to intervention. My wife, whose visual problems are not typical for MS, has not seen any measurable improvement.

    Elimination or reduction in headaches, a common MS disability, seem to follow a 50-50 rule. About half the people who have headaches pre-intervention say they mostly go away while the other half see only minor or even no change. This was my wife’s most important improvement: The total elimination of multiple, daily, severe migraines which were her most debilitating problem with MS.

    As part of her treatment, she did a full neuro exam before and 24 hours after intervention. It showed no change. She did a series of before physical baseline tests and is doing monthly follow ups. The tests show quantitative improvement in balance that subjectively she does not see. Because of improvements in fatigue, cog fog and headaches, she shows about a 25% improvement in MS Quality of Life measured by the MS QLI survey.

    Other reported changes have to do with choking, numbness, warmth, heat tolerance and spacticity. My wife has stopped choking on her foods, previously a daily occurrence, but none of the other problems were issues for her and my impression is that this is a 50-50 thing where about half of those being treated see improvements while half do not.

    I want to stress two things: First, I don’t think anyone involved in this medically is making wild claims in terms of benefits. At best, they are saying it appears to provide some benefits for some people and we need more research to find out what is real and what isn’t and especially to find out why some respond better than others.

    Second, most of the benefits are immediate, although there are also slow improvements over time. For example, someone who has been in a wheelchair for years is not getting up and running a marathon. But they are able to walk farther and farther as they regain strength in their legs. The immediate change is in their balance that lets them stand without falling over.

    A LOT of research to be done on this and it is sad that so many are being treated without data being collected, probably around 50 people a day now.

    There is discussion of creating a registry and a group of patients have put the MS QLI online so that everyone doing treatment can have a way to do a standard neurological self-assessment before and after for whatever that is worth.

    I think a key question about intervention is whether it stops progress in the disease. Anecdotally, everyone I know of who saw immediate benefit has seen the benefits continue for up to a year now, unless they were found to have restenosis. These same people are showing either reductions or no change in lesions on their follow-up MRI’s. And I don’t know of any who have had a clinically significant relapse.

    Restenosis is running between 30%–59% and provides real insight into the effects of intervention. I don’t know of anyone who has been found to have restenosis on a routine follow-up who wasn’t already aware there was a problem because of deterioration in their “MS” or is it CCSVI symptoms?

    In other words, as far as I know, 100% of the cases of restenosis were found because of a deterioration in MS/CCSVI-related symptoms prompted the patients to be re-examined and none have been found on scheduled re-examinations alone.

    I think that points to the fact that there is clearly an effect and since the patients have no way of knowing that there is restenosis until they are examined, I think it suggests that some part of the changes people are seeing are not simply placebo, although there is likely a very large placebo effect, thanks to social networking building expectations. :>)

    Respected IR’s who have gotten involved are all seeing problems in the veins of people they are treating which they are are unlike anything they have seen before and they too are as surprised by the benefits as skeptics.

    It may all turn out to be mass delusion of patients and serious medical professionals, or something that seems near miraculous at a small scale which will unravel when tested on a large scale or with a different patient population, but I don’t think CCSVI fits into the category of laterile, EDTA, bee sting therapy, and those sorts of scams, even though in some cases, the blind are seeing and people are getting up out of their wheelchairs.

    I don’t claim any of my impressions are anything other than that. I fully support the need to research every aspect of CCSVI. But I do think that the anectodal evidence is such that it warrants giving CCSVI serious attention to see what’s real and what isn’t and find out why some respond dramatically while others don’t seem to respond at all or only modestly.

    While we can criticize tools like Facebook and forums such as ThisIsMS where patients are reporting on their progress or lack of progress, they can be useful.

    Among those reporting on the effects of treatment I know a neuro-ophthalmologist, an ophthalmologist, a urologist, three cardiac surgeons, two veterinarian, a number of nurses and physicians assistants, including one who specialized in care of neonates with venous problems plus a number of other serious people who have nothing to gain from promoting CCSVI.

    There is much more we don’t know about all of this than we do, especially for those of us immersed in the online discussions CCSVI. :>)

  50. Edward Murray says:

    @ Steven Novella
    > At this point, in my opinion, the procedure should only be done as part of an approved clinical trial.

    I can accept that this is a reasonable position for a medical professional, government official or insurance administrator to take, but wonder how patients should view this and whether that difference in perspective is valid?

    First, this is a progressive disease. You don’t know when you are going to wake up and not be able to walk. When your mind is going to slip away. When you are going to choke so badly that you need a feeding tube. When you will be completely blind. When the MS hug gets so bad you have to be on a respirator.

    Secondly, you are painfully aware of the side effects and lack of any real clinical benefit of current treatments and the misery of doing five days of steroids periodically.

    Thirdly, you see literally hundreds of people who have gotten treatment reporting on the benefits on a daily basis, something you have NEVER seen with ANY MS drug. Something that has not happened with any other alternative treatment such as stem cells, bee sting, or any other MS therapy over the years that you have had MS.

    Finally, you know that although there are 2.5 million or so people with MS, the only current clinical trial involves 30 patients and it is extremely unlikely that anyone is going to fund much beyond this in the near future.

    As a patient, do you just sit back and wait for an RCT where you might be part of the sham treatment group, or do you weigh the risks and take your chances on a treatment which might provide major benefits and halt further progress of the disease that is robbing you of life?

  51. Edward Murray says:

    @ daedalus
    > I agree with pmoran. There may be (very likely will be) a large placebo effect associated with this procedure.

    Is there some sinister reason that CCSVI has a large placebo effect, but this isn’t seen with any of the MS DMDs, or even any of the woo-woo treatments that have been suggested for MS over the years?

    Why is CCSVI showing such a large placebo effect?

    I don’t know of any IRs involved in CCSVI treatment who are adverse to doing sham treatment, although there are questions about how to do this since every patient knows that you can feel that balloon inflating and feel the pain after treatment thanks to social networking where all the intimate details of these interventions are posted, complete with venography graphics and YouTube before and after videos.

    There are a lot of questions about how you do an RCT at this stage when there is no standard for treatment.

    But again, why does CCSVI have such a dramatic placebo effect and other treatments don’t show this effect?

  52. Epinephrine says:

    @Edward Murray (x3)

    If the benefits are as big as you claim, it should have no trouble at all in a clinical trial. While it might seem like a long time, it’s (as you agree) the responsible thing for regulators to do. Patients should view it the same way they view the testing of every medication and treatment – a way to ensure that they don’t suffer harm, and that money isn’t wasted on treatments that don’t work.

    You asked about the placebo effect, why it would be stronger. I think this has been at least partially addressed, but the type of placebo makes a big difference. Capsules work better than tablets, injections work better than capsules, and surgeries have the biggest placebo effects of them all. The type of symptom plays a part; pain responds well to placebo, as do more subjective conditions. A quick search located an article(1) by La Mantia et al. (2002) suggesting that MS responds well to placebo. I don’t, however, have a subscription to the Italian Journal of Neurological Sciences.

    I think it’s quite fair to say that it is a big concern. Parkinson’s Disease sufferers can show pretty impressive objective improvements, and clinicians who are not blinded to placebo can end up “seeing” improvements in many diseases, including MS.

    (1) L. La Mantia, M. Eoli, A. Salmaggi and C. Milanese (2002) Does a placebo-effect exist in clinical trials on multiple sclerosis? Review of the literature. The Italian Journal of Neurological Sciences. 17(2), 135-139

  53. Epinephrine says:

    Oh, as to how to do the blinding? Use sedation/anaesthesia to ensure patients can’t tell which surgery they are having. If the feeling of a balloon inflating is important, do so in a safe manner next to the vein. A sham surgery still involved the incision and insertion; when our lab did sham surgeries on rats (not for placebo effect, to test whether it was the ischemia or some trauma during the surgery that produced an effect) everything except the ligation of the carotid arteries was replicated. It’s not just a cut – you duplicate the whole surgery as best you can, missing only the element you want to test.

  54. daedalus2u says:

    It isn’t the treatment that exhibits the placebo effect, it is the disease that responds to the placebo effect. Certain types of diseases and disorders are more susceptible to placebos because the physiology that is responsible for the disorder is more easily influenced by the placebo effect.

    Disorders that are exacerbated by stress are disorders that will be especially susceptible to placebos.

    MS is a disorder that is exacerbated by stress; so it is going to be a disorder that is especially susceptible to placebos. There is a book about the use of CAM with MS. Some of these CAM modalities have effects mediated only through the placebo effect, they are effective on MS, MS is a disorder that is susceptible to the placebo effect.

    http://books.google.com/books?id=5uZkix66afgC&lpg=PR9&ots=3ZzRf3C4hZ&dq=Complementary%20and%20alternative%20medicines%20and%20dietary%20interventions%20in%20multiple%20sclerosis%3A%20what%20is%20being%20used%20in%20South%20Australia%20and%20why&lr&pg=PP1#v=onepage&q&f=false

    That is why the placebo treatments for angina were effective; angina is a disorder that is made worse by stress, angina is especially susceptible to the placebo effect.

    My understanding of this is informed through my research on nitric oxide physiology. One of the most universal and generic “stress responses” is a lowering of the basal NO level. Virtually every organism exhibits this, certainly every eukaryote does. MS is one of the long term consequences of a low basal NO level on susceptible individuals. A lowering of basal NO levels increases the sensitivity of mast cells to degranulation. I think this is one of the mechanisms at play in MS and migraine, the increased neuroinflammation due to mast cell degranulation in the brain. When a mast cell degranulates, there is a burst of ROS, which lowers NO levels local to the mast cell. This potentiates adjacent mast cells, and allows for a robust immune response. It also allows for a propagation of mast cell degranulation. I suspect that this may be one of the things that happens in migraine to trigger the spreading depression.

    I suspect that your adverse reaction to interferon is to the wrong “balance” of pro and anti-inflammatory cytokines. Neuroinflammation produces the symptoms you mention, depression, brain fog, insomnia, neurogenic pain. If you are having those symptoms from interferon, I think it is very likely not helping and is making things worse (my non-medical opinion based only on my understanding of NO physiology). But where in the brain those things are happening is critical.

  55. JMB says:

    But again, why does CCSVI have such a dramatic placebo effect and other treatments don’t show this effect?

    I think that Dr Crislip’s post may provide some insight into the marked variability of placebo effect.

    http://www.sciencebasedmedicine.org/?p=6485

    Also note Dr Gorski’s comment,

    Actually, the placebo effect from surgery alone has confounded trials of coronary artery bypass, leading to the questioning of whether it is as effective as we have traditionally believed.

    Your observation,

    Thirdly, you see literally hundreds of people who have gotten treatment reporting on the benefits on a daily basis, something you have NEVER seen with ANY MS drug. Something that has not happened with any other alternative treatment such as stem cells, bee sting, or any other MS therapy over the years that you have had MS.

    is reason why this a priority research topic. Comparing how different countries support this research may be revealing. I have heard that research that is at the clinical trial stage in the USA is hampered because of medical liability. I would not be surprised if the Stanford program is at risk from medical liability. Stents are approved for use in arteries not veins. I have already seen adds on TV by lawyers advertising for victims of migration of stents. I remember a prediction made over ten years ago that we were going to see many, if not most, advances in medicine developed and tested in other countries, because of medical liability in the USA. That may be what is now unfolding.

    However rapidly the research is completed, I suspect the most reliable results will still be years away.

  56. Edward Murray says:

    @ daedalus
    < It isn’t the treatment that exhibits the placebo effect, it is the disease that responds to the placebo effect. Certain types of diseases and disorders are more susceptible to placebos because the physiology that is responsible for the disorder is more easily influenced by the placebo effect.

    This makes complete sense, though the treatment must also play a role with surgery having more effect than say an oral pill.

    But this still doesn't explain what is happening with CCSVI versus say autologous stem cell transplant where there are two surgical interventions. The MS community is quite active in following all new treatments and what is happening in terms of the reaction to CCSVI is very unique.

  57. Edward Murray says:

    @ Epinephrine

    > Oh, as to how to do the blinding? Use sedation/anaesthesia to ensure patients can’t tell which surgery they are having. If the feeling of a balloon inflating is important, do so in a safe manner next to the vein. A sham surgery still involved the incision and insertion; when our lab did sham surgeries on rats (not for placebo effect, to test whether it was the ischemia or some trauma during the surgery that produced an effect) everything except the ligation of the carotid arteries was replicated. It’s not just a cut – you duplicate the whole surgery as best you can, missing only the element you want to test.

    That is FAR easier said than done.

    The problem here is NOT that you need to inflate the balloon DURING surgery since you can sufficiently sedate the patients so that they don’t know whether a balloon was inflated or not DURING the surgery.

    The problem is that people know they are supposed to feel a little pain from the venoplasty AFTER the sedation wears off so you need to cause that pain if your really want to blind the patient. Does everyone gets low-dose heparin? Plavix? Do you lie to the patient when someone does a post-intervention Doppler and tell them that the venoplasty was successful? How does that work with a blinded u/s technician or does the technician need to be blinded?

    You also have the problem that you have with testing the DMDs.

    People expect awful side effects from current classes of drugs so if they don’t have them, they know they are probably in the placebo arm. Here, with the expectation pretty universal that there will be immediate benefits, people may well figure out that they were in the placebo arm if their condition does not improve.

    Depending on how far you go trying to blind the patients, you are going to be pushing up against some ethical and practical issues with this that suggest to me that maybe another approach can be constructed that accomplishes the same goal.

    Don’t ask me what that approach is, but there have to be many situation like this where something other than an RCT has been done and provided scientifically useful data.

    There are certain things we need to know with scientific certainty about the CCSVI hypothesis. Is it prevalent in MS populations and not in controls?

    Then the issue is whether venoplasty provides any benefit.

    Do we really care how much of the benefit is placebo as much as needing to know whether there are clinically relevant changes that improve the quality of life of the patient. All the details of that can be teased out later.

    We need neurologists who are blinded to whether someone has been treated or not to measure whether there are clinically significant changes. It seems easier to get patients to remain silent about whether they have been treated or not than to blind patients and treat them with sham surgery. We might lose the ability to measure the full extent of the placebo effect, but is that really important? Won’t that be obvious over the long run?

    Lots of interesting issues.

  58. daedalus2u says:

    Another approach would be to use an agent that pharmacologically triggers the placebo effect, for example topical application of the bacteria I am working with. Then you do the trial in 3 legs, CCSVI alone, the bacteria alone, and the combination.

    The difference between the bacteria alone and the combination is the actual therapeutic effect of CCSVI. Because topical application of the bacteria I am working with is so benign, you could do that to everyone so they could be their own control and they could start it now without access to the surgery team to do the CCSVI.

    Because applying the bacteria doesn’t introduce metal internally, you could still do MRIs to measure blood flow and neuroinflammation so you could get instrumental measures of end points not just the subjective experiences of the patients. Because the whole point is to induce a placebo-like effect, there is no need to blind anyone as to the bacteria. If the waiting list is a couple months, that should be time enough for a NO/NOx mediated placebo-like effect to produce a response. MRIs would need to be repeated just before the surgery anyway, so you wouldn’t need to do a bunch of extra MRIs.

  59. Dawn says:

    @Edward Murray: Not everyone gets “awful side effects from current classes of drugs so if they don’t have them, they know they are probably in the placebo arm.” What drugs are you talking about? MS drugs? You complain about the side effects of interferon that (I am guessing) your wife has experienced – my friend and my aunt have no such side effects. (Interferon caused some other issues with Cynthia but my Aunt Lucia has had no issues at all with it).

    {I just noticed that both names end in “a”…maybe having a name ending in “a” makes you more susceptible to MS?}

    You cannot blind the U/S technicians easily. Since patients will have had before/after screens, they will see an objective improvement in blood flow if there is one. However, that would be only one part of improvement. Clinical testing of other symptoms, compared to the before status AND over time would be important since as I have said before, the disease has waxing and waning periods.

  60. joanb says:

    Steven–this is the reason I brought Dr. Zamboni’s research to Stanford University–to see if there was any scientific merit. I found two doctors at Stanford, one a researcher, one a cardio-thoracic doctor, who both agreed there might something there. One of them tested my husband for CCSVI in April 2009. He was found to have two completely occluded jugular veins, a tangle of collaterals and slowed blood flow thru his brain. The decision was made to undergo angioplasty, and my husband was treated at Stanford a month later–NOT for MS–but for severe venous insufficiency which was creating diffuse cerebral hypoxia.

    It is now eighteen months since that procedure and he is still free of the MS fatigue that crippled him, working full days, no more heat intolerance, no more urgent bladder, biking, hiking, skiing at high altitude, living a full and active life. His recovery may be anecdotal, but to our family, that is all that matters. And that is why I write about CCSVi and advocate for more patients and caregivers. Please come to http://www.ccsvi.org to learn more.

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