The question whether CCSVI is a real syndrome and its association with multiple sclerosis remains unanswered, therefore there is a need to implement a scientific trial to contribute to this lack of evidence. Machan commented, “To answer the question if the CCSVI syndrome is real, I still have absolutely no idea, but what I do know is that a sham controlled trial is urgently needed.” There are many problems surrounding this controversial topic, said Machan. Among those: “There is no consensus on criteria for diagnosis of venous stenosis in the upper body, we do not know what we are treating and we do not have a documented durable method to treat jugular venous stenosis.”
In September 2010, the Society of Interventional Radiology (SIR) published a statement endorsed by the Canadian Interventional Radiology Association which suggested the need for more rigorous clinical evidence to address CCSVI and its association with multiple sclerosis.
SIR stated, “At present SIR considers the published literature to be inconclusive on whether CCSVI is a clinically important factor in the development and/or progression of multiple sclerosis, and on whether balloon angioplasty and/or stent are clinically effective in patients with multiple sclerosis. SIR strongly supports the urgent performance of high-quality clinical research to determine the safety and efficacy of interventional multiple sclerosis therapies, and is actively working to promote and expedite the completion of the needed studies.”
Jim A Reekers, Michael J Lee, Anna Maria Belli and F Barkhof have also expressed the need for a small prospective, randomised trial, with a sham arm. In a commentary published in December 2010 in CVIR, the official journal of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), the authors commented “We believe that until real scientific data are available for CCSVI and balloon dilatation, this treatment should not be offered to multiple sclerosis patients outside of a well-designed clinical trial.”
Machan referred to Paolo Zamboni’s 2009 publication on endovascular treatment of CCSVI as the document that “set the fire” for all the controversy. Zamboni’s study stated that “CCSVI is strongly associated with multiple sclerosis.” In this study, 65 patients were treated with angioplasty and stenting in the jugular and azygous veins. The results showed that the treatment is safe and the clinical course positively influenced physical and mental quality of life parameters of the associated multiple sclerosis. This publication “set off a massive debate largely fuelled by the internet, social media and facebook. The multiple sclerosis community became very excited about CCSVI and there was an intense pressure overnight on neurologists to provide this service to patients. In interventional radiology this is very hot but controversial topic,” said Machan.
Machan also commented that since the publication of Zamboni’s article there are proponents and detractors of the proposed CCSVI-multiple sclerosis association. He noted that the general theme of comments used to support the perspective of proponents include the following. “There are now roughly 10,000 procedures done since November 2009 and unpublished reports typically note 70–90% patients are improved. ‘Can so many patients be having the same placebo effect?’ is a common refrain we hear… In British Columbia we have not treated patients but we have had over 1,000 patients going out of the country and coming back for further care and we have seen remarkable similarities in patient response such as decreased fatigue, brain fog and improvement in urinary function.”
Those who are in the detractors group note “The placebo effect is common in multiple sclerosis trials; there is more discussion on the Internet than in the literature, there has only been one publication on the therapy so far, and it is a single-centre study with no control group. There is no published level I or II evidence, and there are multiple centres that have been unable to reproduce the data from Zamboni’s initial reports, particularly for diagnosis.”
With regards to the last critique Machan commented on Christoph A Mayer et al’s article “The perfect crime? CCSVI not leaving a trace in multiple sclerosis”, he said that although this paper could not reproduce the ultrasound findings of Zamboni, “It did not use Zamboni’s criteria precisely.”
One of the main concerns around endovascular treatment of CCSVI is its safety. Machan said “There have been at least three deaths related to CCSVI, all of them related to stenting and subsequent anticoagulation or thrombolysis.” However, Machan also told delegates that a study presented at SIR 2011 by Kenneth Mandato, Albany Medical Center, New York, USA, on the safety of CCSVI showed positive outcomes. The single-centre, retrospective analysis evaluated the results of outpatient endovascular treatment of the internal jugular and azygous veins. Mandato and colleagues aimed to identify adverse events and complications in 247 procedures, performed in 231 patients (147 women and 84 men) between 25 and 70 years, within 30 days of the procedure. The results showed that in 99.2% of the procedures patients were discharged within three hours. Transient headache was present in 8.5% of the cases, neck pain in 15.8% and there were three cases of sustained cardiac arrhythmias during the procedure.
To conclude, Machan raised the question “What should we do as endovascular therapists?” He answered that four broad approaches are currently being taken: 1) Treatment of patients only within a trial; 2) Provision of treatment only for those patients who are deteriorating, despite maximal medical therapy under proper medical supervision; 3) Investigation and treatment of everyone but keeping stents to a minimum; 4) Or stand on the side until further data are available. Machan concluded that there is urgency to implement a sham controlled trial.
Questions
Roger Greenhalgh, CX programme chairman, proposed to Machan that at least three steps might have to be followed before the start of a CCSVI trial. At least three questions need to be answered, he said:
1) Does the condition exist? Is it recognisable?
2) How many patients have the abnormality in the vein?
3) What are the endpoints of the intervention?
