Aug 23 2012

Yet Another Nail in the CCSVI Coffin

I have been following the story of chronic cerebrospinal venous insufficiency (CCSVI) as a new hypothesis for the cause of multiple sclerosis (MS). The idea comes from an Italian vascular surgeon, Dr. Zamboni, who claims that blockage of the veins that drain the brain are the primary cause of MS. His initial study on this question found 100% of MS patients he studied had this blockage.

There are numerous problems with this hypothesis, however. First, we have decades of research indicating that MS is an autoimmune disease. The immune system attacks the central nervous system, causing flares of inflammatory plaques that damage myelin (the insulation around axons) and disrupts the flow of signals. While we don’t understand everything about what causes the disease, what we do know does not square well with the notion that it is all being driven by venous blockage.

Zamboni’s idea has been met with appropriate skepticism by the neurological community, but at the same time it has been widely studied in just the few years since it was proposed. The community is doing its due diligence and not rejecting the idea out of hand. The studies coming in so far have been largely negative. No one has replicated Zamboni’s original results. Various studies just looking at the correlation between venous blockage and MS have had varied results, but nothing approaching Zamboni’s 100%. Some studies found no correlation, others a possible small correlation.

This left open the possibility that, while not a primary cause of MS, there may be a pathological association between MS and CCSVI. Perhaps, for example, MS inflammation causes CCSVI, which can then contribute to MS severity. So while Zamboni may not have revolutionized our understanding of MS, he may have found a contributing factor.

Even this lesser claim for CCSVI, however, is not fairing well. A recent  unblinded study looking at patients who went for the liberation procedure to open up the cerebral veins found no benefit. In fact, even in cases where the veins clot off completely there is no worsening of MS. Similarly a rat study in which rats with an experimental model of MS had their jugular veins ligated did not suffer any worsening of their MS compared to rats without the ligation.

Now we have yet another piece of evidence that indicates that CCSVI does not even contribute to MS severity. The researchers studied subjects with MS and healthy controls. First they established who had CCSVI, and they found:

The diagnosis of CCSVI was assigned by using specific color Doppler ultrasonographic criteria. Cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time were assessed with dynamic susceptibility contrast material–enhanced magnetic resonance imaging in normal-appearing white matter (NAWM) in 39 patients with MS. Of these, 25 had CCSVI and 14 did not. Twenty-six healthy control subjects were also evaluated, and of these, 14 had CCSVI and 12 did not.

That’s 64% of MS patients in the study with CCSVI, and 53% of healthy controls.  This is similar to other studies in that there may be a slightly higher incidence of CCSVI in MS, but not by much. They then looked at the effect of CCSVI on brain hemodynamics and on MS severity, and concluded:

The data support a role of CCSVI in cerebral hemodynamic changes, such as a decrease of CBV and CBF, regardless of the presence of MS. CCSVI had no effect on neurologic function and disability progression in patients with MS.

So – there may be a slight correlation between MS and CCSVI. CCSVI, whether in MS or healthy controls, does have an effect on blood flow in the brain. But – there does not appear to be any effect on MS severity.

This is just one study, and it is relatively small, so it’s not the last word on this score. However, it adds to the growing scientific literature on the questions of CCSVI showing that it is, at best, a small phenomenon in MS, it does not appear to contribute to MS severity, and treating it has no benefit.

In other words – CCSVI in MS appears to be a dead end.

In a perfect world the scientific evidence would be the final word and we would collectively move on. However, in addition to watching a new hypothesis go through the stages of scientific research, we are also watching a popular conspiracy theory evolve from this hypothesis. There is a populist pro-CCSVI movement, driven largely by MS patients who are not responding to standard treatment and are desperate for an alternative.  It is distressing how quickly they turned on the neurological community, accused them of  a conspiracy, of being in bed with (of course) “Big Pharma”, and of suppressing the truth.

There are many clinics now offering the liberation procedure, without any evidence that it helps or even that it does not cause net harm. There is a CCSVI Alliance to promote this diagnosis and its treatment. There is political pressure to fund more and more research into the treatment of CCSVI, despite its poor showing in existing research. There is a larger and larger disconnect between the scientific community and the pro-CCSVI community as the data comes in increasingly negative.

CCSVI is taking on a life of its own, ahead of, and in fact despite, the scientific evidence. There is a developing infrastructure and belief system that will not be easily dismantled. My fear and suspicion is that, once the scientific evidence against CCSVI is solid and complete enough that it is truly dead as a scientific hypothesis, it will live on in the fringe. It will become yet another “alternative” treatment with its devoted adherents.

If history is any guide, it’s possible it will survive for decades. Twenty years from now there will still be CCSVI institutions and practitioners exploiting MS patients with the false hope of the liberation procedure. They will be endlessly calling for more research to finally prove their claims correct, while finding reasons to dismiss existing negative research, and rewriting history to suit their conspiracy narrative. Meanwhile the memory of CCSVI will have mostly faded from mainstream medicine, and a new generation of neurologists will not even know what it is.

There are many examples of treatments that have followed a similar course: psychomotor patterning, chelation therapy for heart disease, laetrile, bee sting therapy for MS, facilitated communication, repressed memory syndrome, and others – all decades old. There are still older therapies that linger to a greater or lesser degree, and some that are even experiencing a resurgence: magnetic therapy, radio frequency therapy, energy medicine, homeopathy, iridology, and even classics like phrenology and blood letting still have their fringe adherents. These are all ideas discarded by science a century ago or longer.

It already seems too late to nip the CCSVI machine in the bud. Scientists are doing all they can – researching the idea despite their skepticism, and far more than the idea merits, partly because of due diligence and partly because of the popular support for the hypothesis. Evidence will affect the attitude of the scientific community. It generally has little effect on believers and proponents.

Perhaps much of the fate of CCSVI will rest with Zamboni himself. If at some point he recants his claims in light of the scientific evidence, it may be enough to suck the wind out of the sails of CCSVI. The question is – will he have the courage to say that his idea was simply proven wrong by diligent scientific evidence, or will he cling to CCSVI as his legacy and become a cult hero to the medical fringe?

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8 responses so far

8 Responses to “Yet Another Nail in the CCSVI Coffin”

  1. mr. grieveson 23 Aug 2012 at 9:54 am

    The interesting thing about this most recent study is that it was published in a radiology journal and conducted almost entirely by radiologists. CCSVI proponents have been consistently demonizing neurologists (as you noted) while claiming that radiologists and vascular surgeons are the true experts in this emerging field. I am interested to see how the conspiracy theorists will spin this one.

    Your last point about Zamboni is something I have not considered and I think I agree – it may be the only way to really put a dent in support for CCSVI.

  2. elmer mccurdyon 23 Aug 2012 at 1:54 pm

    metaphors!

  3. petrossaon 23 Aug 2012 at 3:15 pm

    As for the final question of your piece, i go for the latter.
    Nothing human is foreign to scientists, vanity is also there.

    Better go to your grave as an unrecognized genius then as an admitted hoaxer.

  4. BillyJoe7on 23 Aug 2012 at 5:34 pm

    petrossa,

    I don’t think anyone is accusing Gamboni of hoaxing. He seems to genuinely believe in his hypothesis.

  5. BillyJoe7on 23 Aug 2012 at 5:46 pm

    The following is a link to the ABC Catalyst program that coincidentally aired last night in Australia:

    http://www.abc.net.au/catalyst/stories/3572695.htm

    It treats the proponents of this hypothesis as heroes. But with a twist. They propose that the underlying cause of ccsvi is mycoplasma infection and they propose curing it with antibiotics for twelve months. Yes, they have a cure for MS. And there are the usual anecdotal reports of sufferers being cured. There is an opposing mainstream view which is well put and a caution by the presenter at the end, but the main thrust of the program is to treat these proponents as brave mavericks likening them to the Western Australian scientist who overturned the accepted cause of peptic ulcers leading to the use of antibiotics to treat this condition.

  6. ccbowerson 23 Aug 2012 at 10:40 pm

    “…likening them to the Western Australian scientist who overturned the accepted cause of peptic ulcers leading to the use of antibiotics to treat this condition.”

    Of course they are missing the point… the data ended up supporting the role of H Pylori, and the medical community followed the data. Without supporting evidence, mavericks quickly become quacks

  7. SimonWon 24 Aug 2012 at 3:21 am

    Billy, the mycoplasma thing is interesting.

    We already know some mycoplasma are pathological, we know they can be hard to eradicate, and we know some cause symptoms similar to some (supposed) autoimmune diseases, and there is evidence that some mycoplasma can be the initial trigger for sensitising the immune system to self in some autoimmune diseases. Thus even if it is wrong it is likely that there will be the odd positive studies and compelling anecdotes or case studies – because some people in those will actually have infections with mycoplasma (or something else that clears up when they are having long courses of antibiotics) causing or exacerbating their symptoms unless it is specifically excluded in trial criteria. Always harder to dispel a hypothesis with a little bit of truth than one that is entirely fiction, and we struggle enough with the later.

  8. ccsvifabon 14 Oct 2012 at 6:34 pm

    On October 12, 2012 MedPage today had this item.
    “LYON, France — The largest study to date testing the venous-obstruction theory of multiple sclerosis failed to support it, leading the Italian Multiple Sclerosis Society to declare the theory dead.

    Reported here by leaders of the group, known by its Italian abbreviation AISM, the study of nearly 2,000 individuals with blinded central imaging analysis found the condition in only about 3% of MS patients and in only slightly fewer healthy controls or patients with other neurological conditions.The prevalence of CCSVI as determined under this process was as follows in the three groups of participants:

    MS patients: 3.26% (95% CI 2.38% to 4.45%)
    Healthy controls: 2.13% (95% CI 1.10% to 4.14%)
    Other neurological disorders: 3.10% (95% CI 1.58% to 6.44%)
    On the basis of these small values, and the lack of significant (P<0.05) differences between them, the AISM issued a statement declaring that "CCSVI is not a disease connected to multiple sclerosis."

    Moreover, it continued, "for people affected by MS, there is no need to carry out additional tests to diagnose CCSVI, nor is vein surgery required.

    The AISM is the first national MS society to make such a conclusive determination. In the U.S. and Canada, research on CCSVI commissioned by the major organizations in those countries is still under way, and no similar declaration is likely until those studies are completed."
    "Primary source: European Committee for Treatment and Research in Multiple Sclerosis
    Source reference:
    Comi G, et al "Chronic cerebro-spinal venous insufficiency (CCSVI) and global venous haemodynamics in multiple sclerosis: the CoSMo study" ECTRIMS 2012; Abstract 167

    Why such studies are still underway in North America (squandering precious research time and funding) after so many negative studies baffles me. I wonder what it will take for the CCSVI hypothesis to admit that it objectively fails?

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