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In Multiple Sclerosis Treatments, Hope Trumps Reason

The Science of Medicine

Steven Novella

Skeptical Inquirer Volume 36.1, January/February 2012

New ideas are presented in science and medicine all the time. This is healthy and necessary—we have to keep churning the pot so that new ideas can emerge and our thinking does not become calcified. But science is both a creative and destructive process, and most new ideas are weeded out by the relentless filtering process of research and peer review.

However, to patients suffering from an incurable disease a new idea represents one thing: hope. Science, by contrast, cares only about what works and is dispassionate, which is easily portrayed as heartlessness. Hopeful nonsense thus has a public relations advantage over pitiless science every time.

We are seeing this effect now with a new idea in the science of multiple sclerosis (MS). A lone Italian vascular surgeon, Paolo Zamboni, proposed that MS is not caused by an autoimmune process (the immune system attacking the nervous system) but rather by blockages in the veins that drain blood from the brain. He published his initial study that found a “dramatic” association between MS and these venous blockages (Zamboni et al. 2009). He called the condition chronic cerebrospinal venous insufficiency (CCSVI).

The paper set off a bitter controversy. Zamboni is suggesting that decades of MS research have been on the wrong track and that he has found the true cause—and potential cure—of MS with a simple diagnostic procedure. The press loved it—a lone maverick challenging the status quo with a bold new idea. Many patients with progressive and difficult-to-treat MS also loved it, for it provided hope of an effective treatment. (As an aside, there are several effective treatments for MS but not all types of MS or all patients respond.) When the neurological community treated Zamboni’s claims with (perfectly reasonable) skepticism, some patients began to weave conspiracy theories to explain the resistance. They wanted the new treatment, and they didn’t want stuffy neurologists getting in the way because their turf was being threatened by a surgeon (at least that is the narrative they told each other.) But science is pitiless and doesn’t care for narrative, turf, or good headlines.

Despite the low plausibility and the fact that Zamboni’s claims ran counter to the carefully accumulated MS research to date, many centers set about to replicate his findings. Replication is a key process in science. If a phenomenon is real, then it will be real in any lab. Zamboni’s findings were dramatic, so they should be easy to replicate.

Two years later we have several good replications. One study did produce similar findings to Zamboni, although the association was not as strong (Al-Omari and Rousan 2010). The next three, however, were all dead negative (Sundström et al. 2010; Doepp et al. 2010; Krogias et al. 2010). Skepticism mounted. Another study this year comparing MS patients to normal controls concluded, “This triple-blinded extra- and transcranial duplex sonographic assessment of cervical and cerebral veins does not provide supportive evidence for the presence of CCSVI in MS patients. The findings cast serious doubt on the concept of CCSVI in MS” (Mayer et al. 2011).

The largest replication to date (Zivadinov et al. 2011) found a small association between venous blockage and MS and concluded, “Our findings are consistent with an increased prevalence of CCSVI in MS but with modest sensitivity/specificity. Our findings point against CCSVI having a primary causative role in the development of MS.”

These findings are interesting. They do not entirely rule out a correlation between CCSVI and MS. However, the results are very ambiguous. There is a statistical correlation between MS and CCSVI, but there is also a correlation with other neurological diseases—with very different histories and probable causes from those of MS. CCSVI was also found in a quarter of healthy controls. So CCSVI is not specific to MS, and almost half of MS patients do not meet criteria for CCSVI.

To summarize all of the existing research on CCSVI and MS: The results are mixed with variable methodology used but are generally negative. No one has found the dramatic results first published by Zamboni. After a couple years of research, his implausible idea is not looking very good. At best we can say that there may be a small and inconsistent correlation between venous blockages and MS. If the correlation is true, it is also possible that these blockages are a result of MS, perhaps caused by inflammation, and are not necessarily a cause of MS.

Despite these largely negative findings, there are still many MS patients clamoring for treatment. The treatment of CCSVI is called the liberation procedure (essentially opening up the blocked veins, a procedure not without risk). Clinics are opening up offering the treatment to desperate patients—putting treatment ahead of the evidence or even using a treatment in the face of negative evidence, which is always a bad idea.

There are also calls, especially in Canada, for clinical trials of the liberation procedure. Such trials are not justified by the science that has been done so far, but because clinics are already offering the liberation procedure, this may force the hands of MS researchers. Before subjecting people to experimental medical interventions, ethics demands that we do sufficient basic science research to demonstrate that there is at least a reasonable chance of benefit. We have not crossed that line with CCSVI and the liberation procedure. Advocates of the procedure, however, are likely to succeed in making an end run around the usual safeguards of ethical medical research.

Those promoting CCSVI and the liberation procedure are likely to be portrayed by some in the media and by hopeful patients as brave mavericks. That is the hopeful, romantic, and sensational view. I suspect, however, that in the end the science will tell a different story.


Al-Omari, M.H., and L.A. Rousan. 2010. Internal jugular vein morphology and hemodynamics in patients with multiple sclerosis. International Journal of Angiology 29(2): 115–20.

Doepp, F., F. Paul, J.M. Valdueza, et al. 2010. No cerebrocervical venous congestion in patients with multiple sclerosis. Annals of Neurology 68 (2): 173–83.

Krogias, C., A. Schröder, H. Wiendl, et al. 2010. Chronic cerebrospinal venous insufficiency and multiple sclerosis. Critical analysis and first observation in an unselected cohort of MS patients. Der Nervenarzt 81(6): 740–46, DOI: 10.1007/s00115-010-2972-1.

Mayer, C.A., W. Pfeilschifter, M.W. Lorenz, et al. 2011. The perfect crime? CCSVI not leaving a trace in MS. Journal of Neurology, Neurosurgery and Psychiatry 82(4): 436–40.

Sundström, P., A. Wåhlin, K. Ambarki, et al. 2010. Venous and cerebrospinal fluid flow in multiple sclerosis—a case-control study. Annals of Neurology 68(2): 255–9.

Zamboni, P., R. Galeotti, E. Menegatti, et al. 2009. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry 80(4): 392–9.

Zivadinov, R., K. Marr, G. Cutter, et al. 2011. Prevalence, sensitivity, and specificity of chronic cerebrospinal venous insufficiency in MS. Neurology 77(July): 138–44.

Steven Novella

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Steven Novella, MD, is an assistant professor of neurology at Yale University School of Medicine. He is the host of the Skeptics’ Guide to the Universe podcast, author of the NeuroLogica blog, executive editor of the Science-Based Medicine blog, and president of The New England Skeptical Society.