CCSVI
Chronic cerebrospinal venous insufficiency (CCSVI) is a condition that was discovered in 2010 by an Italian Vascular Surgeon named Paolo Zamboni. Dr. Zamboni found that in up to 91% of patients with multiple sclerosis (MS), the veins that drain blood from the brain and spine were blocked. These blockages prevented normal blood flow out of the brain and spine, presumably causing an increase in venous pressure inside of the brain.

It's caused by a narrowing in the veins (stenosis) that drain the brain and the spine. Blood takes longer to return to the heart, and it can reflux back into the brain and spine or cause oedema and leakage of red blood cells and fluids into the tissues of the brain and spine.

Blood that remains in the brain too long creates a delay in deoxyginated blood leaving the head (slowed perfusion). This can cause hypoxia which is a lack of oxygen in the brain. Plasma and iron from blood deposited in the brain tissue can also be very damaging leading to iron along with other unwelcome cells crossing the crucial brain-blood barrier.

It's felt by some that this may be an early step in the disease process causing MS, and early work suggests that these lesions may respond to angioplasty.
A Controversial Hypothesis
A December 22, 2009 article in Medscape Medical News discusses the controversial hypothesis proposes that narrowing in the major veins draining the brain may be an early step in the disease process causing MS, and early work suggests that these lesions may respond to angioplasty. A pilot, open-label study published in December 2009 in the Journal of Vascular Surgery by lead author Paolo Zamboni, MD, director of the Vascular Diseases Center at the University of Ferrara, Italy, showed in a series of 65 patients that endovascular treatment of strictures in the extracranial cerebrospinal veins was safe in MS patients and may provide neurologic benefit (Zamboni P, et al. J Vasc Surg. 2009;50:1348-1358).

Dr. Zamboni emphasized that their work is preliminary and urgently requires replication. "What we know is that MS is very complex and multifactorial," Dr. Zamboni told Medscape Neurology at that time. "We have identified an unknown factor and possible treatment for that factor."

Already, work to discover the prevalence of CCSVI in MS patients is under way, and treatment trials are being planned.

"We are interested in more research because obviously [these are] very preliminary findings about CCSVI. The society is certainly inviting investigators to apply for grant funding so that we can further investigate this and provide the appropriate guidance for people with MS," Patricia O'Looney, MD, vice president of biomedical research at the NMSS in New York City, told Medscape Neurology.

There has been a great deal of public interest, particularly in Canada, where media reports and a documentary profiled Dr. Zamboni and colleagues' work and MS rates are among the highest in the
world.

"People with MS have been pursuing this and perhaps having unnecessary surgery, which carries a risk to it because it is invasive, but also we want to respond to any possible clue that may help us help people with MS or help us understand it."
The Great Debate: CCSVI and MS
This has given birth to a great debate: Does CCSVI exist? And if so, is it linked with MS?

The current research on CCSVI has provided results that are wildly contradictory. Consider the following:
● CCSVI's existence and association with MS has received broad support from a wide range of studies.
● The existence of CCSVI has been refuted (and thus any association with MS dispelled) by a wide range of studies.
● A smaller group of studies suggests that CCSVI may exist, but that it may be a consequence of MS as opposed to a contributor.

With the current contradictory research, no truly definitive statements about CCSVI can currently be made. However, a careful review of the studies does reveal important trends, and hints at where and how research should proceed.

Only two studies have explored treatment effectiveness. Both were "open label" (not scientifically conclusive), and both found similar results (that treatment may help, but that more research is needed before any conclusions can be drawn). Thus, no contradictions in treatment data currently exist.

Results from the several CCSVI clinical trials currently underway will emerge over the next twelve months (around the end of 2012), and then there should be treatment data to consider. Till that time, clear research data doesn't exist. When the data is presented, hopefully it will bring clarity into the debate over the existence of CCSVI and its connection to MS.

A May 6, 2011 article in Medscape Medical News shows the results of a cohort study examining the prevalence of CCSVI suggest that the condition appears to be elevated in patients with MS but probably doesn't take a causative role in the disease.

Researchers from the University of Buffalo found an increased prevalence in MS over other neurologic conditions and healthy controls but with only "modest" sensitivity and specificity, they note.

"Based on our findings, we don't think CCSVI could be a cause of MS," lead study author Robert Zivadinov, MD, PhD, from the Buffalo Neuroimaging Analysis Center and the Jacobs Neurological Institute at the University of Buffalo, New York, told Medscape Medical News.

Within MS patients, the prevalence of CCSVI actually appears to increase with disease severity, from 38% in those with first clinical onset to up to 90% in those with progressive disease, he added. "So clearly, at this time we cannot exclude completely that CCSVI is playing a role in the first clinical attack...but as a unique factor to be the cause of this disease, I don't think that's the case."

The paper, first released last year, was published online April 13 and will appear in the July 12 issue of Neurology.