Miami Beach, FL - The International Symposium on Endovascular Therapy (ISET) 2011 kicked off last week with a full-house town-hall meeting dedicated to discussions on the possible link between chronic cerebrospinal venous insufficiency (CCSVI) and multiple sclerosis (MS), the main message being that randomized clinical trials are needed to ultimately determine whether balloon angioplasty of extracranial veins might cure or improve symptoms of the devastating disease.

Experts, speaking to a packed auditorium, warned that it's important to clearly define the link between CCSVI and MS and that interventionalists and MS experts must answer the remaining unknowns given the high level of public interest in the procedure and the new era of regulation and medical cost containment. One expert argued that if interventionalists are too gung-ho and the therapy doesn't work, works only in a small subset of patients, or causes significant complications, the ramifications will be felt across the whole community.

"I've worked for 20 years in a cost-control system, very bureaucratic, and you guys are now making your way into a similar situation," Canadian Dr Lindsay Machan (University of British Columbia, Vancouver) told the predominantly US audience. "I would really stress that there's a real danger zone here. It's a high-profile [procedure] that's getting a lot of press, and if we crap the bed on this, it's going to affect interventional and endovascular medicine in a big way."

CCSVI and MS explodes in 2009

For those who haven't yet heard, the field of MS research received a jolt in the past couple of years when Dr Paolo Zamboni (University of Ferrara, Italy) proposed the link between CCSVI and MS [1]. In his original article, published in 2009, Zamboni hypothesized that blockages in the extracranial veins—including blockages in main outflow routes, the jugular and azygous veins, among others—contribute to MS and that treatment targeting these veins, including balloon angioplasty, could halt the progression of MS and reduce patient symptoms. Since then, he as well as others have been treating MS patients with angioplasty, an approach that is controversial, to say the least.

The purpose of the town-hall meeting was to help shed some light on this contentious topic, with many interventional experts admitting that they simply don't have any answers right now. Dr James Benenati (Baptist Heart and Vascular Institute, Miami, FL) told heartwire that his office receives many calls every week from MS patients asking about treating CCSVI.

Speaking during the meeting, Benenati, the president of the Society of Interventional Radiologists (SIR), said that responsible interventionalists, as well as the professional societies, would likely agree there is evidence suggesting benefit in these patients, but the data are inconclusive. Most clinicians are supportive of the registries and trials, but SIR does not recommend interventionalists become involved in the treatment unless they are part of the investigative process. Benenati said that when he listens to patient testimonials he believes there are benefits in some patients but cautions that doctors have been fooled in the past.

There are many examples where endovascular medicine pioneered new procedures that were initially thought of as heresy and voodoo but turned out to be great procedures.

"We have to have an open mind," Benenati told heartwire. "There are many examples where endovascular medicine pioneered new procedures that were initially thought of as heresy and voodoo but turned out to be great procedures that are now part of mainstream medicine. Conversely, there are many examples, not just in endovascular medicine, but in all of medicine, where conventional wisdom and practice turned out to be not effective. Knowing that, while there is a tremendous amount of enthusiasm, some of which I share—and I have an open mind—we need to really investigate this very thoroughly."

In 2010, SIR issued an official statement in the Journal of Vascular and Interventional Radiology on the endovascular management of CCSVI in patients with MS, essentially concluding that the published literature was inconclusive in determining whether CCSVI was an important factor in the development and/or progression of MS and whether balloon angioplasty and/or stents were clinically effective [1].

Dr Ramon Quesada (Baptist Vascular and Cardiac Institute), like others, told heartwire that so little is known about the pathophysiology of the illness and corresponding treatment that randomized clinical trials are needed. He agreed with Benenati that patient advocacy is driving the interest in the procedure and that interventionalists, to his knowledge, aren't going out of their way to treat CCSVI in MS patients.

Confusion reigns

During his talk, Machan said that confusion reigns in Canada with regard to the treatment, but at least seven CCSVI and MS trials are under way. In the US, several centers are also conducting investigations, including some multiple-center studies, and patients can access the treatment if they are part of the clinical trial. Dr Michael Dake (Stanford University, Palo Alto, CA), who has performed the procedure, said follow-up research is under way, including tissue and animal studies, as well as clinical assessments using ultrasound and magnetic resonance venography. The bottom line, said Dake, is that interventionalists need to know whether, if an MS patient with CCSVI has the narrowed lesion treated, clinicians can objectively demonstrate an improvement in relevant parameters and MS symptoms.

At ISET, Dake presented preliminary data on 30 MS patients who underwent the procedure, with 1.86 lesions treated, on average. Over the course of two months of follow-up, said Dake, patients experienced a decrease in global symptoms, such as reduction in fatigue, sensitivity to heat, and "brain fog." Overall, patients experienced a 50% reduction in fatigue assessed by the modified fatigue impact scale (MFIS), with more mobile patients, measured by the expanded disability status scale (EDSS), benefiting the most.

Also speaking during the town-hall meeting, Dr Jack Burks, chief medical officer of the Multiple Sclerosis Association of America, said the CCSVI debate has been portrayed in the media as a turf battle, with MS patients and some interventionalists lining up against skeptical neurologists and MS societies. He said interventionalists who perform and push the benefits of CCVSI, in the absence of definitive evidence, are labeled "cowboys" and that the MS societies and neurologists are castigated as simply being afraid of losing their MS patient-care dollars.

"We need to work together to encourage a united message for the MS world," said Burks.

In working together, Burks said, clinicians need a multidisciplinary document and planning guide that defines superior CCSVI diagnostic tests and outcomes, defines treatment standards for the interventional procedures and successful outcomes, and establishes criteria for the diagnosis of MS. In addition, standards for qualified CCSVI specialists are needed, as are uniform institutional review board (IRB) requirements. Also unknown at this time are standards for follow-up care, such as who should treat the patient after the procedure—interventionalists, neurologists, or general practitioners—and what sort of imaging tests would be used.

During the session, Zamboni suggested the evidence of the many observational studies might be sufficient to convince interventionalists and MS experts of the treatment benefits, but the perception right now is that only a randomized, controlled, clinical trial will be good enough to convince the neurological community. Dr Martin Leon (Columbia University, New York), a member of the panel discussing the treatment, agreed. While registries might work, a randomized, controlled trial is needed to convince everybody, he said.

Machan reports speaking for, receiving honoraria from, and/or consulting for Cook, Boston Scientific, NDC, and Calgary Scientific. Benenati repots serving as the chief medical officer of Northpoint Domain and consulting/serving on the advisory boards of Abbott, Amaranth Medical, Biosphere, Cordis, Endovention, and WL Gore. Quesada reports speaking for, receiving honoraria from, and/or consulting for Abbott, Boston Scientific, Cordis, NMT, St Jude Medical, and AGA. Dake reports consulting for or serving on the advisory boards of Cytograft Tissue Engineering, CVRx, Endoluminal Sciences, NovoStent, Summit Life Sciences, TriVascular, Vatrix, WL Gore, Abbott, and Cook Medical. Burks reports speaking for, receiving honoraria from, and/or consulting for or serving on the advisory boards of Acorda, Bayer, Biogen, Novartis, Serono, Avanir, Allergan. Leon reports consulting for or serving on the advisory boards of Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Zamboni reports no conflicts of interest.

 Sources

1. Zamboni P, Galeotti R, Menegatti E, et al. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg 2009; 50:1348-1358.


2. Vedantham S, Benenati JF, Kundu S, et al. Interventional endovascular management of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: A position statement by the Society of Interventional Radiology, endorsed by the Canadian Interventional Radiology Association. J Vasc Interv Radiol 2010; 21:1335-1337.

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