Anyone following the latest CCSVI research can be forgiven for experiencing whiplash-induced confusion. On Wednesday, McMaster University released a scanning study in the journal PLOS ONE that found virtually zero relationship between multiple sclerosis and CCSVI, a condition characterized by narrowed neck and chest veins identified by Italian venous specialist Paolo Zamboni.
The research assessed 200 people—100 diagnosed with MS, 100 who had no history of the condition, or “normals,” using Doppler ultrasound and MRI. Only one participant, a man with primary progressive MS, met Zamboni’s ultrasound criteria for CCSVI. The finding represents a 180-degree swing from Zamboni’s contentious preliminary 2009 research that found a 100 per cent correlation between MS and CCSVI in 65 people with MS. The McMaster research contradicts other research (two examples here and here) that found most people with MS also had CCSVI — and also detected it in people not diagnosed with MS. It also eclipsed new research out of Italy investigating the safety and efficacy of angioplasty to treat CCSVI that found blockages in 98 per cent of 1,200 study subjects using ultrasound with venograms.
Certainly the McMaster findings are not without precedent: other studies, two here and here, found zero correlation. Yet the press release announcing the McMaster study framed it as the definitive take-down: “McMaster University study debunks controversial MS theory.” As with everything else surrounding “controversial” CCSVI, opinion on this one is divided. Zamboni, unsurprisingly, countered with a letter to the journal critiquing the study’s screening methodology as outdated and for replacing his protocols with those of researchers who’d reported negative results.
On the Facebook page CCSVI in Multiple Sclerosis, Joan Beal, a high-profile champion of CCSVI research and treatment, issued a more blistering rebuttal. People with MS who have benefitted from the CCSVI procedure, which does not benefit all who’ve had it, are speaking out. Another critic, surprisingly, is neurologist Anthony Traboulsee, the director of the MS Clinic at the University of British Columbia and principal investigator of the recently commenced Canadian CCSVI clinical trial. “We have seen the extremes—Zamboni’s 100 per cent is too good to be true, now the Hamilton’s results are too negative to be true,” he tells Maclean’s. ”It doesn’t make sense when you think about all of these folks travelling around the world to have something done; the radiologists must be seeing something.”
Ultrasound, the method pioneered and used by Zamboni, is problematic identifying CCSVI, says Traboulsee, who is not a vascular specialist. He prefers venography, a more intrusive scan conducted inside the veins using dye. “The ultrasound isn’t capturing what the catheter venography sees—that’s direct visualization. It’s going to be more accurate and sensitive for finding narrowings. In the study out of Hamilton, the ultrasound couldn’t detect what catheter venogram can detect. And why that is I really don’t know.” His research team at UBC is publishing a scanning study comparing ultrasound, MRI and venography in The Lancet within weeks. Employing venography, his team found most people with MS also exhibit CCSVI. Exactly how many is unclear. In an interview with the Ottawa Citizen earlier this week Traboulsee is quoted saying “maybe about 70 per cent have the narrowing.” Speaking to CTV yesterday, he said it was 60 per cent. “Both numbers are correct,” Traboulsee told Maclean’s but he declined to elaborate because of publication restrictions. “It will become much more clear when I can discuss my findings with you,” he says.
Ian Rodger, lead author of the McMaster study, admits the 100 per cent finding surprised him. Rodger, professor emeritus in the Michael G. DeGroote School of Medicine, invited Zamboni in February 2010 to participate in a two-day CCSVI seminar, the first in Canada. He stands by the research. “We have no axe to grind,” he says. “We went in completely open-minded and conducted it as authoritatively as we could.” They detected variations in the venous architecture and blood flow between normal and MS populations but nothing pathophysiological, he says. The study yielded a huge amount of data to be mined, says Rodger, whose group is preparing three more studies, including one evaluating Zamboni’s hypothesis that blood reflux created iron deposition in the brains of people diagnosed with MS. Rodger is critical of Zamboni research: “It seemed too good to be true. Now we can see the rigour early on was highly questionable.” He agrees ultrasound delivers inconsistent results: “It is operator-dependent. Pressing too hard can create compression that restricts the vein.” Rodger sees a “pendulum swing over the past 18 months”–from Zamboni’s 100 per cent correlation, to 56 per cent in a 2010 University of Buffalo, to his new study and others showing zero correlation. He’s trying to stay out of the politics that have underlined CCSVI for the past four years. But he does express surprise there hasn’t rethinking of the current Canadian clinical trial, in light of his research and a 2012 editorial in the Journal of Neurology that recommended MS patients not be treated for CCSVI.
Traboulsee says the McMaster trial hasn’t affected his thinking: “I don’t see it as even a hiccup.” He speaks of the more than 100 patients who’ve travelled out of country for CCSVI treatment interviewed for a UBC patient registry. ”There’s less perception of [CCSVI treatment] being a cure but interest in how it can help with quality of life and managing MS,” he says. The clinical trial design was based on patient responses, he says: “We were using that information for improvements we should measure. And these are things not measured on classic MS scales: hands feeling warmer, heads feeling clearer–the sort of responses that people report experiencing.” He expects results by 2015, at the earliest. Meanwhile, the quest for clarity continues.