In an article published this week in the journal Neurology, researchers from the University of Buffalo set out to determine the prevalence of chronic cerebrospinal venous insufficiency or CCSVI in 289 patients with MS compared to 163 normal subjects and 26 people with other neurological diseases. They were tested with transcranial and extracranial colour Doppler which is an accepted and non-invasive way of checking for blood flow in the veins draining blood from the brain to the heart.
Fifty-six percent of the patients with MS met the criteria for CCSVI - much less than the one hundred percent or so of the patients with MS in Zamboni's original study. Zamboni used five ultrasound criteria that have yet to be validated and reported that CCSVI can distinguish patients with MS from those who do not with something approaching one hundred percent sensitivity and one hundred percent specificity. Not only that, Zamboni's research published in 2009 in the Journal of Vascular Surgery, led him to suspect that CCSVI might be the cause of MS. The current study's conclusions make it highly unlikely that CCSVI is a primary cause of MS. That said, the researchers offered the possibility that CCSVI may contribute to the symptoms of MS.
The other result that will be disturbing to Zamboni treatment proponents is that blockages were also found in 23% of the normal subjects (i.e. no MS and no other neurological disease). Given the fact that as many as one in four normal individuals have CCSVI, it's entirely possible that CCSVI is not in any way associated with the symptoms of MS.
To researchers and others who are intellectually curious about the role of CCSVI in MS, these findings are highly significant. The study was adequately powered, rigorous, and well designed. Moreover, it follows smaller studies that have likewise cast doubt on Zamboni's original findings.
The implications appear to be clear. If CCSVI is the cause of MS symptoms, then angioplasty makes sense. But, if the CCSVI cannot be tied directly to MS symptoms, then it's hard to recommend a potentially risky procedure.
Since the study's publication earlier this week, I've spoken to a number of patients with MS who don't know what to think about the results. Likewise, I'm uncertain what to say to patients who have undergone angioplasty and have felt better consistently ever since. There are three possible explanations. The first is that for some reason, the treatment worked. This would not be the first time that a treatment worked and yet science was unable to explain why. A second possibility is that patients who feel better have benefited from a placebo effect. If that is the case, then the benefits should wane over time.
There is a third explanation that bears mention. MS is a disease that robs patients not only of their muscle strength but also of their will. Many MS patients speak of feeling like prisoners of their disease and of the medical system. I can well imagine patients feeling better following angioplasty - not because the treatment worked - but because going for it boosted the patient's sense of control over MS.
The current study will not derail the search for answers. As of June 2010, MS Societies in Canada and the U.S. have awarded seven grants totalling more than $2.4 million to study CCSVI. In addition, a final evaluation of the treatment cannot take place unless and until we see the results of prospective, randomized controlled clinical trials that take patients with both MS and CCSVI and randomize them to receive angioplasty or a matching placebo. As well, it can't be overstated that patients in such a study can only be evaluated using objective criteria by blinded observers who do not know whether the patient received angioplasty or not. In an accompanying editorial also published in Neurology, Fox and Rae-Grant exhorted fellow physicians to "neither jump on the bandwagon as it passes through town nor assiduously miss the parade."
Stay tuned. The story is not over yet.