Is CCSVI an entity and a subset of multiple sclerosis? – The jury is still out


Regula von Allmen, vascular research fellow, Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, UK, attended the VEITHsymposium where a session on chronic cerebrospinal venous insufficiency (CCSVI) was held. She wrote this article for Vascular News on the controversial subject, based on the discussions from New York.

Paolo Zamboni, professor at the University of Ferrara in Italy, launched a great debate in 2009 by claiming to have found the underlying condition for a very dreadful disease, multiple sclerosis. The CCSVI phenomenon was born.



Zamboni promoted a venoplasty-based therapy which he called the “liberation procedure”. In fact this approach is very tantalising because it brings multiple sclerosis down to a potentially curable disease and additionally it raises hope for the patients, which is also emphasised by the name of the procedure.



Multiple sclerosis is estimated to affect more than 400,000 people in the USA and more than two million people worldwide. It is typically a disease of young adults characterised by either a relapsing or progressive impairment in neurologic function resulting in significant disability. It is an inflammatory neurological disease widely considered to be autoimmune in nature, though its exact origins remain elusive.



The CCSVI hypothesis implies that venous congestion, as a result of insufficient venous drainage due to intra-luminal flow obstacles in the jugular veins, increases pericapillary iron deposition causing a subsequent autoimmune response and thus brain damage. This theory found its way immediately into the public consciousness. Moreover, it has also instigated one of the greatest disputes in medicine. There are as many opponents as proponents of it.



At the 38th VEITHsymposium in New York, USA, a whole session was assigned to the CCSVI controversy.


Zamboni opened this session with the topic “How can duplex identify large vein stenosis: An enthusiast’s view”. Zamboni explained that the most frequently noted intraluminal defects or abnormalities inside internal jugular veins, such as malformed or fixed valves, septa and webs may be detected in a high resolution B-mode ultrasound. He also emphasised that the assessment of the five criteria for CCSVI should be applied in supine and upright positions due to gravity induced hydrostatic gradient mechanisms. 

Moreover, “the localisation of the extracranial venous obstruction is not specific and can occur everywhere” as Michael Dake, chief of Interventional Radiology at Stanford University California, USA, and a clear proponent of CCSVI highlighted later on. Another interventionalist, Claudio Rabbia, chief of the Vascular and Interventional Department at Hospital Molinette of Turin, Italy, raised the question as to whether intravascular ultrasound should become standard to improve accuracy in pre- and postprocedural venous stenosis assessment.



The enthusiasts and budding enthusiasts found it interesting to learn that a consensus document regarding 2011 ultrasound-based criteria for screening for CCSVI will be published very soon in International Angiology, Functional Neurology as advertised and recommended by Zamboni: “This is a very important document ensuring more accurate and comparable results around centres”.



The core issue in the CCSVI debate is the controversy of how often internal jugular venous stenoses occur in the community. Zamboni reported a prevalence of 70% for CCSVI in multiple sclerosis patients versus 10% in control patients. These findings are combined results from 14 studies. Jean-Baptiste Ricco, professor of Vascular Surgery, University of Poitier, France, and editor-in-chief of the European Journal of Vascular and Endovascular Surgery, an opponent of the theory, stated in his introductory remarks that “there are a lot of negative studies from angiologists and neurologists reporting no difference in the presence of positive CCSVI criteria between multiple sclerosis patients and controls”. He concluded that “CCSVI does not seem to be a disease but a description of an anatomic variation”. He also raised concerns about the rapid worldwide popularity of the treatment, promoted by the help of social networks and by emotional testimonials from treated patients despite the lack of scientific evidence.

Manish Mehta, a vascular surgeon from the Vascular Group in Albany, USA, reported the Albany experience. They followed 100 multiple sclerosis patients (62% female, mean age 47 years) with CCSVI and venoplasty. The defined endpoints, evaluated preprocedurally and at one, three and every six months thereafter, consisted of a timed 25-foot walk, Multiple Sclerosis Quality of Life-54, and Modified Fatigue Impact Scale. The immediate success rate for the venoplasty procedure, defined as a less than 30% stenosis, was 82%. The results from 79 patients were available for a longer follow-up analysis, at a mean of 4.5 months. Mehta presented a restenosis and occlusion rate of 8% and 2% respectively, with no major complications or deaths. With regard to the endpoints, patients experienced statistically significant improvements in timed 25-foot walk, MSQOL-54, and MFIS, and over two-thirds of the patients reported alleviation in multiple sclerosis symptoms.


On the other side, it is evident that any possible treatment for what has been thought of as an incurable disease such as multiple sclerosis immediately gains popularity, as has happened in the past. Kieran Murphy, professor of Neuroradiology in Toronto, Canada, mentioned that even multiple bee stings and hyperbaric oxygen were believed to cure multiple sclerosis in the past and both theories were flawed. Murphy pointed out that the stories of amazing results from the new multiple sclerosis treatment could be more about the “placebo effect”. Placebo is a Latin word for “I shall please” and placebos can have a surprisingly positive effect.


In consequence, there is now an urgent need for a double-blinded randomised controlled trial for testing treatment effectiveness and getting level 1 evidence. Nelson Hopkins, professor and chairman of Neurosurgery, professor of Radiology from the University at Buffalo, the State University of New York, USA, presented the status of such a randomised trial launched in 2010, the PREMISE (Prospective Randomized Endovascular therapy in Multiple Sclerosis) trial. In its first phase, 10 multiple sclerosis patients with venous insufficiency underwent minimally invasive venous angioplasty to prove the safety of the procedure. In its second phase, 20 multiple sclerosis patients are randomised to either venous angioplasty or  “sham angioplasty” with insertion of a catheter but no inflation of the balloon. So far, 18 patients have been included in this phase. All patients are being followed for six months with an additional fMRI at the end of this stage. The defined endpoints assess safety of the procedure, efficacy of the procedure (restoration of venous outflow, change in relapse rate or disease progression and MRI parameters) and self reported improvement of quality of life.


Indeed, in the future a larger number of patients have to be studied in a blinded randomised controlled way to convincingly prove or disprove the association of CCSVI with multiple sclerosis.


Is CCSVI an entity and a subset of multiple sclerosis remains? The question remains. This CCSVI session at the 38th VEITHsymposium showed that there are still more questions than answers. We do now need a reliable scientific approach to ensure that a well-intentioned but possibly ineffective treatment is not used to take advantage of a vulnerable group of patients.