Dec 01 2017

Liberation Procedure for Multiple Sclerosis – The Final Chapter?

In 2009 an Italian neurosurgeon, Paolo Zamboni, published a controversial article in which he claimed that patients with multiple sclerosis (MS) suffered from blockage in the veins that drain blood from the brain, that this correlation was strong and the pattern suggested a causal relationship. He called his newly identified condition Chronic Cerebrospinal Venous Insufficiency (CCSVI). His article concluded:

CDMS is strongly associated with CCSVI, a scenario that has not previously been described, characterised by abnormal venous haemodynamics determined by extracranial multiple venous strictures of unknown origin. The location of venous obstructions plays a key role in determining the clinical course of the disease.

I first wrote about the resulting controversy in 2010. At the time I concluded that there was good reason to be skeptical, that there were many “red flags for crankery”, but that further research should be done to put the question to bed. There were many reasons to be skeptical, not the least of which is that an entirely vascular cause of MS went against decades of research showing that MS is an autoimmune disease. In that first article I also wrote:

Then one of two things will happen: either the new idea or treatment will fade, becoming little more than a footnote in the history of science, or a subculture will persist in believing in the treatment and will dismiss contrary evidence and mainstream rejection as a conspiracy. Which course the new idea will take seems to depend largely on the original scientist – if they accept the new evidence and abandon their claims, it will likely fade. If they refuse to give up in the face of new evidence, then a new pseudoscience will likely be born.

Well, here we are 8 years after Zamboni’s original publication. How has this drama played out?

Scientifically, the story is fairly typical. One researcher published an exploratory study with dramatic new claims. Most new claims in science will turn out to be false, and so we don’t get excited until we see independent replications. We can also assess plausibility to make predictions about how likely it is that the new finding will pan out. In this case the scientific community was very skeptical, and early replications were mixed, but mostly negative, and none as dramatic as Zamboni’s findings.

Over the last 8 years hundreds of studies on CCSVI have been done, exploring various aspects of these claims. The correlation between CCSVI and MS was studied, using various imaging techniques, and comparing MS patients of various types and severity, patient with other neurological disease, and healthy subjects. In the end it was found that there is no correlation between CCSVI and MS.

While the basic correlation was being studied, researchers were also studying treatment of CCSVI by opening up the blocked veins, an intervention called the liberation procedure. This kind of research takes years to complete. Early studies were negative, but this only motivated believers (Zamboni chief among them) to call for bigger better trials. Well – those trials have now been complete. Earlier this year a large Canadian study showed no benefit from the liberation procedure for MS patients.

And now we also have the results of a four-year study conducted by Zamboni himself, just published in JAMA Neurology. The results were completely negative, leading Zamboni himself to conclude:

Venous PTA has proven to be a safe but largely ineffective technique; the treatment cannot be recommended in patients with MS.

Now we will see what effect this has on the other side of the story – public perception and the reaction of the MS community. We will see if my prediction above comes true, if Zamboni’s admission that the liberation procedure does not work will allow the whole CCSVI affair to fade away. Alternatively, it may be that populist belief in CCSVI has already taken on a life of its own, and will survive after losing the support of its creator. It also remains to be seen if Zamboni will have the courage to stick by the results of his own research, or will backslide into maintaining some belief in CCSVI.

For now I give Zamboni credit for conducting a well-designed study, and for not spinning the results in his publication. He can fully redeem himself and even become a hero if he now campaigns against the monster he created, in the name of science and what’s best for patients. CCSVI is now a famous cautionary tale – what legacy in that tale will Zamboni ultimately make for himself?

The monster he created was substantial. His preliminary research, which should never have seen the light of day outside of wonky research journals for other experts, became a public sensation. News of a possible new treatment for MS spread throughout the MS community, with the usual exaggerations and anecdotes. The result was not pretty. Desperate patients understandably wanted access to a potential new treatment, and were largely unhappy when experts told them the treatment was not recommended. This led to conspiracy theories and general distrust between some patients and their MS doctors.

Of course all this was happening on the background of a general cultural movement in which expertise is easily dismissed, and trust of experts is threatened by memes spread on social media. It is hard to calculate the harm that was ultimately done to patients because of all this. We know that several patients died receiving the liberation procedure – so there was some direct measurable harm. But how many other patients had suboptimal treatment for their MS because of their faith in a highly implausible new theory that was crashing almost as soon as it was published? How much money was funneled to quack clinics, and all the ultimate harm that they do, by patients seeking out the liberation procedure?

Lessons from CCSVI

This is a cautionary tale, but I fear it will soon be forgotten. It’s not like this is the first time something like this has happened, and yet the cautionary tales of the past are not generally known. How many people remember the radioactive tonics of the early 20th century, or Abrams Dynomizer, or the countless other treatments that were popularized based upon flimsy preliminary evidence and ultimately were useless?

There is a reason skeptics and promoters of science-based medicine recommend caution when new medical ideas are first proposed. We know from extensive history, and also from studying the medical literature quantitatively, that most new ideas will turn out to be wrong. We know that preliminary positive evidence is a very poor predictor of ultimate success. Anecdotes are inherently deceptive and cannot be relied upon to make conclusions. And plausibility matters – if a new idea goes against established principles, it is more likely to be wrong.

In medicine especially, all of this matters. Experts genuinely try to come up with a bottom line assessment of risk vs benefit with any intervention. With the liberation procedure it was clear that the probability of harm vastly exceeded the probability of benefit, which itself was tiny. It is dismissive and arrogant to wave away sober expert analysis with cheap conspiracy theories or claims of bias or protectionism.

It is in everyone’s best interest that we remain cautious in the face of preliminary evidence. Let the science work itself out. I know this is especially difficult for desperate patients or their loved-ones when faced with a serious illness without adequate treatment. But that is also already taken into consideration in the risk vs benefit analysis. We will give speculative or experimental treatments on a compassionate basis – but not anything. We still need to assess plausibility and the probability of harm vs benefit.

It was entirely clear that the liberation procedure for MS was not justified, even on a compassionate basis. The fact that the experts were correct in retrospect should not be brushed aside. However, I predict it will be for the next speculative treatment and the ones after that. Only with structural change to the way such information is disseminated and the practice of medicine is regulated can be prevent victims of the next liberation procedure.

7 responses so far

7 thoughts on “Liberation Procedure for Multiple Sclerosis – The Final Chapter?”

  1. Nidwin says:

    Interresting reading as I wasn’t aware of this or MS being the immune system attacking the CNS, thank you Dr Novella. I would probably qualify for MS because of the paresthesia, makes you always wonder.

    It still raises the question for publish or not publish. Because of early publishing other scientists could immediately react and investigate/replicate the claim. But it also leaves an open door for abuse and quackery as often seen with new extraordinary claims. 🙁

  2. Art Eternal says:

    At the University of Chicago, they studied the effects of swallowing pieces of radioactive fallout from the Nevada test sites, done by both hundreds of volunteers and staff. What were the long term effects?

  3. BillyJoe7 says:

    Nidwin,

    “I would probably qualify for MS because of the paresthesia…”

    This is a list of causes of paraesthesia: https://en.m.wikipedia.org/wiki/Paresthesia
    This is how MS is diagnosed: https://www.nationalmssociety.org/Symptoms-Diagnosis/Diagnosing-MS

    “…makes you always wonder”

    Or you could stop wondering, see a medical practitioner, and find out. 😉

  4. Germaine says:

    Another area of rampant fake medicine is the multi-billion dollar industry called dietary supplements, homeopathic products, neutraceuticals and whatever else helps move useless product. Myths there don’t die because there’s so much money to be made and the margins are generally quite good. That industry sells stuff like bogus immune system boosters (my fave quack immune booster is ‘Airborne’), fake memory treatments using 10 mg of a jellyfish protein, or in the case of homeopathic products, almost nothing at all except the package and whatever excipients and dosage form gets the sales job done.

    I wonder if studies have been done looking at the potency of the placebo effect vs cost of product vs slickness of packaging. Forget the blinded placebo, the unblinded placebo is the drug.

    For context: US dietary supplement sales projected at $37 billion by 2024 and global project at $278 billion by 2024. There’s gold in them ‘thar placebos. Yehaa!

  5. Drake says:

    Nidwin,
    I’m with BJ7: if you think your paresthesia may be an MS symptom, you might want to get that looked at. There are meds available that treat symptoms and slow progression in some forms of MS.

    In the comments on SN’s original post about Zamboni, one of the pro-Liberation commenters claimed the procedure had been performed on a Parkinson’s patient.

    PD patients are hardly immune from pursuing and promoting quack therapies. But I don’t recall having read anything about the ‘Liberation Procedure’ before–apparently it never caught on in the Parkinson’s community.

    Probably a good idea to be skeptical about any treatment that, like fashion and fads, is adopted by some communities and not others. With no rhyme or reason for either.

  6. FacelessMan says:

    Nidwin, the question isn’t to publish or not to publish. Of course you publish your results, but you make it clear that they are preliminary, not definitive and try to put them in their proper context in what we already know. And you don’t publish by press conference, but in a scientific journal, where other experts will evaluate your data and test your hypothesis without the public hype. Sure Zamboni published in a journal, but he sholud have skipped the press until we had more data.

  7. Nidwin says:

    No worries, I’m fine and I don’t suffer from anything. I haven’t seen a doctor in twenty+ Years and only take light paracetamol against fever once in a blue moon. I do get occasionally the seasonal feverish cold.

    My paresthesia is not illness or disease related, just the result of somethng that I’m able to do “stimulate” at will since my childhood. No need for a doctor on my side as I’m fine.

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