The Lancet: “Gold standard” imaging study reveals no association between venous narrowing and multiple sclerosis

The results, published in The Lancet, call into question the basis for a controversial theory that MS is associated with a disorder which proponents call chronic cerebrospinal venous insufficiency (CCSVI).  Supporters of this theory, originally published by Zamboni and colleagues in 2009, claim that MS arises where narrowing of the extracranial veins (the veins which lead from the brain to the heart) leads to venous blockages and flow abnormalities, and that some people with MS can be effectively treated by angioplasty treatments to widen the veins, sometimes called the liberation procedure.

While controlled research into whether angioplasty treatment has any beneficial effects for MS patients is ongoing, results from imaging studies examining the association between venous narrowing and MS have so far been inconclusive.

Funded by the MS Society of Canada as part of a series of research projects investigating CCSVI, Dr Anthony Traboulsee at the University of British Columbia and Vancouver Coastal Health in Vancouver, Canada, and Dr Katherine Knox at the University of Saskatchewan in Saskatoon, Canada and colleagues set out to examine the extracranial veins of 79 people with MS, 55 of their unaffected siblings, and 43 unrelated healthy volunteers (controls), using both ultrasound and catheter venography.  Catheter venography is a more complicated and invasive procedure than ultrasound, and involves taking an x-ray of the vein after injecting it with a special dye.

“Until now, most studies of venous narrowing have used ultrasound imaging to establish whether venous narrowing is present.  While ultrasound is a relatively simple and inexpensive way of looking at veins, it’s not necessarily the most accurate imaging technique, so in our study, we also used catheter venography – usually thought of as the gold standard of venous imaging – to measure whether any narrowing of the veins was present,”** explains Dr Traboulsee.

By comparing the width of extracranial veins with a normal reference segment of vein, taken from below the jaw, the researchers used catheter venography to show that at least two thirds of each of the study groups had narrowing of the extracranial veins greater than 50%.  Venous narrowing was present in 74% of people with MS, 66% of their unaffected siblings, and 70% of the unrelated controls; the differences in rates of venous narrowing between the groups were not statistically significant.

Using the overall criteria for CCSVI proposed by Zamboni and colleagues*, the researchers found that just one of the people with MS tested positive, as did one of the MS patients’ siblings, and one of the unrelated healthy volunteers.

However, the researchers also found that Zamboni’s ultrasound criteria for CCSVI did not reliably pick up venous narrowing as shown by catheter venography, with ultrasound picking up venous narrowing in just two fifths (42%) of cases confirmed by the more accurate imaging technique.

According to Dr Traboulsee, “Our results confirm that venous narrowing is a frequent finding in the general population, and is not a unique anatomical feature associated with multiple sclerosis.  This is the first study to find high rates of venous narrowing in a healthy control group, as well as the first to show that the ultrasound criteria usually used to ‘diagnose’ CCSVI are unreliable, so if there is a connection between venous narrowing and MS, it remains unknown, and it would certainly appear to be much more complicated than current theories suggest.” Writing in a linked Comment, Dr Friedemann Paul and Dr Mike Wattjes suggest that the new results should sound a “death knell” for the hypothesis of CCSVI as a disease entity. “If chronic cerebrospinal venous insufficiency actually existed, the ultrasound findings of this study and previous studies would suggest that up to half of the general and otherwise healthy population should be judged to be seriously ill because of venous insufficiency of the cervical veins. The fact that some changes in the venous system have been described in association with multiple sclerosis does not imply causality.”

“A lively discussion has emerged recently as to whether funding of chronic cerebrospinal venous insufficiency research is, or was, a waste of valuable time, money, and intellectual energy. The work by Traboulsee and colleagues should be viewed as the definitive conclusion to this discussion. Although it is laudable that the Multiple Sclerosis Society of Canada and other sources have funded this seminal study, which would probably not have received funding otherwise, now it is absolutely clear that no reason exists to allocate any further resources to chronic cerebrospinal venous insufficiency research, be they financial or intellectual.”

Further Information

Link to article:

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61747-X/abstract

Comment by F. Paul and Mike P. Wattjes:

Chronic cerebrospinal venous insufficiency in multiplesclerosis: the final curtain