CCSVI 2013: ‘debunking,’ spin, and legal drama

Anne Kingston on the MS research that captured headlines in 2013

Dr. Paolo Zamboni. (THE CANADIAN PRESS/Nathan Denette)

If there were a drinking game that called for taking a shot whenever the term chronic cerebrospinal venous insufficiency—or CCSVI—appeared in 2013 in a headline alongside “debunked” or “death knell,” we all would have been plastered well before New Year’s Eve. Studies discounting the theory that a link exists between CCSVI and MS proposed by Italian vascular specialist Paolo Zamboni prevailed; “MS vein unblocking” was named by the CBC as one of the “top 6 news stories of 2013.” A clinical trial in Albany, NY, scheduled to include 86 Saskatchewan residents, was shut down in September due to lack of enrolment. CCSVI was declared a “fiasco,” even invoked as cautionary tale.

But a rear-view look at CCSVI in 2013 reveals a more complex picture—one in which positive studies were eclipsed by negative, clinical data was spun to fit prevailing wisdom, and rhetoric uttered unsupported by fact. There was glee that studies showed CCSVI is not the cause of MS, nor CCSVI treatment its “cure” (a claim Zamboni himself never made), and apparent disregard for the fact the treatment could offer some relief for those with extracranial venous blockages who exhibit neurodegenerative symptoms. Lost in the shuffle was emerging research on the role of blood flow, perfusion, and how luminal defects within the vein might impede flow and contribute to neurodegenerative conditions.

The first body blow to the CCSVI hypothesis appeared in March with the results from the first randomized CCSVI treatment trial, PREMiSe, at the University of Buffalo. Lead researcher Robert Zivadinov was one of the first MS neurologists to team up with Zamboni; his previous research revealed association between CCSVI and MS, though not to the extent Zamboni found it. Results were broadcast in a video released on the eve of the 2013 American Academy of Neurology meeting, where the findings were presented as a poster; CCSVI treatment was “safe,” they said, but it did not improve patient outcomes—and, in some cases, made them worse. Most media coverage of the 19-person study, which has not been published, failed to note that it didn’t meet its stated endpoint to improve venous flow, proving its conclusions moot. The first part of the PREMiSe trial, which did restore blood flow in subjects, was published—but didn’t receive press coverage, perhaps because its conclusions were more difficult to parse: It found that cerebral spinal fluid was moving faster through the brain, an improvement that continued a year past treatment.

Research that did receive ink was an MS Society-funded study in April that measured blood flow in teenagers with MS versus “normal” teens using ultrasound and MRI. A MS Society press release declared “minimal signs of CCSVI in children with MS.” Joan Beal, a high-profile CCSVI advocate since her husband, Jeff, experienced lasting improvements after CCSVI treatment in 2009, crunched the data; she found that teenagers with MS had 27 per cent less blood flow out their left internal jugular veins compared to “normals.” Yet the finding that children with MS have significantly reduced venous blood flow wasn’t noted by researchers themselves.

The year’s serious “debunking” of CCSVI began in August, when a McMaster University study that found no evidence of CCSVI in 99 adults with MS compared with 100 healthy controls was issued with a press release declaring CCSVI had been “debunked.” (The same day research out of Italy investigating the safety and efficacy of angioplasty to treat CCSVI was published but received virtually no media mention: it found blockages in 98 per cent of 1,200 subjects.)

In October, researchers published an Italian study announced at a meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in 2012. The study found CCSVI in only about three per cent of MS patients and in only slightly fewer healthy controls or patients with other neurological conditions. On its heels came University of British Columbia research published in The Lancet that found venous “narrowing” in 74 per cent of people with MS. But it also found similar narrowings in 66 per cent of unaffected siblings of people with MS and 70 per cent of healthy controls. So in other words, veins defined as “narrowed” are in fact the norm. The study used catheter venography, which the researchers billed as the “gold standard.” But as Zivadinov pointed out in a 2012 interview, there’s no “gold standard” yet in diagnosing CCSVI: “As a matter of fact, we are establishing standards, and catheter venography is [not a] gold standard for a number of reasons,” he said, referring to this study. As research is increasingly showing, it’s what’s within the vein intraluminally in terms of blockage, valves and blood flow that counts.

In reporting the UBC study, news editors didn’t even bother to get the Thesaurus out: “Zamboni MS vein theory debunked by study,” read one:” “Study debunks CCSVI: Narrowed neck veins found in people with and without MS” read another. Many headlines proclaimed, incorrectly, that the scanning studies discredited CCSVI treatment: “Controversial Treatment May Not Help MS Patients” and “Canadian study casts further doubt on liberation treatment for MS.” The CBC continued the thread announcing its top 6 health stories of 2013: “A series of studies in 2013 debunked Italian Paolo Zamboni’s belief that clearing blocked or narrowed neck veins could relieve symptoms of multiple sclerosis.”

But whether or not MS symptoms are relieved by CCSVI treatment has not been established beyond anecdotal reports. These reports suggest between one- and two-thirds of patients experience some benefit, which may or may not endure. Research in the U.S. (herehere and here) and Europe (here and here) conducted in 2013 concluded CCSVI treatment was safe, and resulted in physical and psychological improvements ranging from mild to significant. Zamboni has a clinical trial underway in Italy. In Canada, a four-centre treatment trial with 100 participants has commenced; results are expected in late 2015. Other research is apace.

Still, it’s not surprising the “CCSVI-has-been-debunked” mindset prevails—to the point that CCSVI is now invoked as an example of how new alternative treatments don’t pan out. In November, for example, a Globe and Mail story outlined the debate over whether children with epilepsy could benefit from using medical marijuana. Toronto bioethicist Kerry Bowman used CCSVI as a cautionary tale: “But we’ve been down this road with other things, like [liberation therapy] for multiple sclerosis,” Bowman said. “You had people swearing that this has changed their lives and then it really did not hold up to randomized clinical trials.”

I emailed Bowman to ask which randomized clinical treatment trials he was referencing, since none have been published. “I think what I likely said is that they have not confirmed benefit,” he answered. “There are reportedly clinical trials running now but no one willing to discuss.” I responded by asking if he’d been misquoted. His response: “liberation therapy didn’t hold up to clinical trials…”

The phrase echoes an October editorial in Multiple Sclerosis Journal, “Goodbye to all of that: A short history of CCSVI” by Montreal neurologist Michael Rasminsky and Toronto radiologist Karel terBrugge. (Rasminsky is a former member of the MS Society’s medical advisory council; terrBrugge sits on it currently.) The piece is scathing in its dismissal of CCSVI, citing the studies that dismiss any CCSVI-MS link and suggests interest in investigating CCSVI is irrational (“It could be argued that such studies would have been unnecessary in a rational society, but they were unfortunately absolutely required in the hyper-connected society in which we live”) and declared CCSVI research a “fiasco,” asking: “What can be done to prevent such fiascos from occurring in the future?” (“Fiasco” terminology was also evoked in this April 2013 editorial that referred to the PREMiSe clinical trial, which was unsuccessful achieving its endpoints,  as “an outstanding, but small, trial.”)

Resistance to CCSVI among neurologists reached such a crescendo it’s now played out in courts, as we learned in November when Ontario’s Divisional Court gave the green light for a libel lawsuit filed by Barrie, Ont. vascular surgeon Sandy McDonald against Ottawa neurologist Mark Freedman (a good recap here.) McDonald was the first Canadian vascular surgeon to investigate CCSVI; he traveled to Ferrara, Italy to study CCSVI scanning and treatment. He conducted a small treatment trial on six patients before it was shut down; most experienced benefits, as broadcast on W5 in April 2010. His Barrie clinic continues to provide CCSVI scanning.

McDonald’s suit claims Freedman acted with “reckless disregard for the truth,” as part of a “continuing campaign to embarrass and vex the proponents of CCSVI.” It alleges Freedman, a former national medical advisor for the MS Society of Canada, libeled McDonald in emails to Ontario health minister Deb Matthews, copied to the Ontario College of Physicians and Surgeons. Freedman asserted McDonald “lured” patients to his imaging clinic, and defrauded the system by billing OHIP under another diagnosis. He also urged the ministry to investigate and shut down McDonald’s clinic because it was performing CCSVI diagnostic tests that “make a mockery” of the system. The College found that McDonald billed patients directly—not OHIP—and did nothing improper. In his defence, Freedman said he was worried about patients being drawn to undergo “a risky procedure” when it had no proven medical benefit. No date has been announced for the jury trial.

Scientific bias is always cause for concern, as Daniel Sarewitz elucidates in his 2012 essay “Beware the creeping crack of bias.” Certainly it has been evident in resistance to CCSVI from the outset —from the overt exclusion of vascular experts on the CCSVI “expert” panel convened by the Canadian Institute of Health Research (CIHR) to the more insidious mocking of Zamboni by displaying a Zamboni ice-clearing machine with his name on it in an allegedly educative video about CCSVI funded by the CIHR.

Yet the vascular link to MS dates back centuries, as confirmed in a 2013 metastudy that reviewed 132 papers written between 1839 and 2012 and concludes: “While the controversy over venous disease in MS is new, the observation of perivenular MS plaques and venous theories about MS pathogenesis are as old as the history of MS research.” Where the report gets it wrong, however, is that the controversy over venous disease in MS isn’t “new.” A fascinating 1988 study, “Social constructionism and medical sociology: a study of the vascular theory of multiple sclerosis,” required reading for anyone interested in medical politics, traces resistance within neurology to vascular hypotheses of MS decades before Zamboni coined CCSVI. Its focus is on the “power inequality on the production and assessment of knowledge about MS”. Translation: neurologists determine what research is valid, so much so that rigorous research outside of the still-unproven autoimmune theory of MS has been dismissed while less rigorous science supporting the current prevailing paradigm has been embraced.

But this year offered glimmers of change as neuroscientists recognized the importance of blood flow to MS. Research presented at a December conference in San Diego, “Blood-Clotting Protein May Offer Early Detection of Multiple Sclerosis,” revealed fibrin and hyper-coagulation are associated with MS, and other neurodegenerative disease, the focus of Zamboni’s work. At the 70th World Congress of the International Union of Phlebology in Boston this fall, an event not exactly buzzing with media, Zamboni expressed hope that that controversy between the vascular and the neurological communities can be solved by” multi-modality assessment” of CCSVI. After the year that we’ve seen, that seems optimistic. But without optimism, there is no progress.

Correction: Dr. Rasminsky’s name was misspelled in an earlier version of this article. Also, due to an editing error,  a quote was misattributed.

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