What are we to make of the theory of CCSVI, that multiple sclerosis is caused by pressure from narrowed veins taking blood to the brain?
What are we to make of the theory of chronic cerebrospinal venous insufficiency (CCSVI), the theory that multiple sclerosis is caused by back pressure from narrowed veins taking blood back to the heart from the brain?
Professor Paolo Zamboni, a vascular surgeon from the University of Ferrara, Italy, has turned the multiple sclerosis world on its head in recent years, postulating that this back pressure leads to blood leakage around small veins in the brain, iron deposition from the blood and subsequent inflammation, producing the typical lesions of MS. Zamboni’s motivation in proposing this hypothesis is clear.
His wife, Elena Ravalli, was diagnosed with MS in 1995 at the age of 37, and Zamboni was a vascular surgeon who had previously published extensively about venous back pressure causing inflammation and ulcers in the legs. His research team’s many publications have led to people with MS world-wide clamouring for access to angioplasty to open these venous narrowings.
But in my view, it is difficult to say with any certainty whether CCSVI is a real entity, and if so, what causes it, whether it causes MS, and what role angioplasty has to play in it, without further research. Much of the initial optimism about CCSVI has been thrown into confusion by two recent publications in Annals of Neurology. These two publications, one from Germany and another from Sweden, through different methodologies, found no real evidence of venous obstruction in people with MS compared to people without MS.
The whole CCSVI issue is clouded by conflict of interest. Conflict of interest in this case is when a researcher, research group, or commentator have a vested interest in the subject under study and are therefore potentially biased. Conflict of interest can come from many sources; it is commonly financial, such as when a researcher stands to profit from the product being researched (such as when a drug company conducts a clinical trial of a new agent they have developed); but conflict of interest can also be related to career advancement, or prestige, or relationships that researchers have.
In 2009 Prof Zamboni and colleagues conducted research in 2009 which were published in the Journal of Vascular Surgery.
You can read the full paper via the pdf link below. In brief, the procedure is a short day-case procedure in which a catheter is inserted in the groin and threaded up into the venous system.
Narrowings of the veins exiting the brain are dilated via this route. The researchers found the procedure was safe, but with quite a high rate of re-narrowing of the veins at 18 months: about half the internal jugular vein narrowings that were dilated had narrowed again.
People with relapsing-remitting disease did best, with twice as many relapse-free after the operation than before, although half the patients who had the procedure still relapsed afterwards during follow up; the most worrying result reported was that there was no difference in the group’s relapse rate after the procedure. The number of people with new MRI lesions was considerably lower after the procedure.
People with progressive disease did not do as well as those with relapsing-remitting MS, and didn’t seem to get much benefit at all. All in all, the results look promising, although not nearly as dramatic as had been hoped, and warrant further study. It should be noted that this was not a controlled trial, and its main aim was to assess the safety of the vascular dilating procedure.
Many people with MS still had ongoing problems and new lesions after the procedure, and overall, the procedure had no effect on the annual relapse rate of the group.
From the point of view of a specialist medical practitioner of over 30 years’ experience, an academic medical researcher, and a person with MS, with my own peculiar conflict of interest, I make the following observations.
Zamboni developed an ultrasound technique for finding venous abnormalities in the brain, found some abnormalities only apparent with this technique which he termed CCSVI, developed the criteria for its diagnosis, and developed a treatment. Other researchers investigating the condition have either found a significantly different incidence of CCSVI in MS or not found it at all.
This raises the question of the extent of the un-blinded observer bias in the ultrasound assessments of the people with MS in the early studies, and hence the reliability and validity of those early conclusions.
Consequently, I don’t have any idea whether CCSVI exists or whether it has any role in causing MS. I just don’t think we yet have enough data on which to base an opinion about this, and much of the data are conflicting. Further, I have no opinion about whether venous angioplasty is likely to be of any benefit in MS, even if it is shown that a person has CCSVI. The fact that in the only formal study of the procedure there was no difference in relapse rate for the group before and after the procedure is of concern. Further, the single death from cerebral bleeding and the serious side effect of a venous stent migrating to the heart, need to be weighed against any potential benefit.
As a person diagnosed with MS, I hope there is something to the CCSVI theory and that effective treatments for MS might become available as a result; as an academic researcher, I have to say it is important for us to be patient while the medical research community goes about studying this issue
. Certainly at the moment, along with the original CCSVI researchers, I would not advise anyone with MS to try angioplasty, except in the context of a properly run research study. We simply don’t know if it would work and what the side effects are likely to be, particularly long term (what would happen if venous constrictions get worse after being ballooned open for instance?: it appears they often re-develop quite rapidly).