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

  1. Thanks Anne for keeping up your reporting on this issue. The sad part is that you have had to keep reporting on this issue. Many people with MS have lost their lives since the first W5 television program. It seems the vast majority of neurologists consider this an acceptable price for others to pay in order for them to defend their tunnel vision support of their pet & unproven MS theory.

  2. Maybe one day we can look forward to integrative patient-centered medicine rather than the egocentric theoretical one that currently exists to do nothing more than uphold the prevailing status quo…
    Thanks for the excellent reporting!

  3. Thank you Anne for keeping this in the news, they will get their heads out of the sand eventually!

  4. Thankyou so much from me here in the UK Anne . I appriciate lots too from ENGLAND

  5. I have just received copies of my medical reports from the MS Clinic at UBC. They document my “career” with MS that started when I was diagnosed in 1990, becoming secondary/progressive in the mid-’90′s which meant there was no treatment available for me and I would just continue to get worse. I had a score of 6 on the Expanded Disability Status Scale in 1995 and then 6.5 by 1998, which prevailed until I went to the U.S. for venous angioplasty on March 17, 2011–now I’m a 4! This procedure is the only thing that has given me any relief. I can’t imagine what state I’d be in if I hadn’t done my own risk/benefit analysis and left Canada for this treatment.

  6. My wife experienced mind blowing (to me) improvement after balloon angioplasty in August 2013 which I videoed. I had hoped for minor improvement due to the amount of propaganda in the air at the time. What I got was like nothing I had ever seen before. I put before and after videos on the web but my friends in the church of science refuse to even look at them! They prefer to believe studies of other parameters (that don’t measure patient improvement). I would happily get on the witness stand for McDonald. Joan Beal noted that the MS neurologists (and my church of science friends) would, if transported back in time, stand at Galileo’s shoulder and say “Jupiter has not moons because I cannot see them” all the while refusing to look through his telescope and calling his observations “anecdotes”. People have forgotten what science is all about. It was never (until now) a cult believing whatever a self appointed group of priests said. It was about reality. Why did my wife improve so massively? Why did I see a Mexican grandma hobble in clinging to her walker and walk out! after her surgery? If anybody spent a week in Newport beach, and just watched, they would know that angioplasty works for most people.

  7. Your rational and fact based approach is a breath of fresh air Anne. Perhaps you could facilitate a public debate? How you have my number on speed dial if you do.

  8. Since my first MRI 12 years ago, which I have a copy of, clearly stated there was vascular compromise, I opted to ignore the unsurprising backlash from the benefactors of the MS world and seek treatment. The results were documented improvement in eyesight and documented improvement on MRI, and though I believe restenosis has occurred I would not hesitate to make another attempt. That first MRI was at a time when there was nothing to hide, when CCSVI wasn’t a threat to the multi-billion dollar MS drug industry, when neurologists needn’t fret over being made to look like fools by a vascular specialist whilst clinging to a theory that has cost lives and billions of dollars and yielded nothing.

  9. Thank you Anne for this excellent summary of the CCSVI “news” of 2013. I agree with Dr Arata that your approach is a breath of fresh air. Your understanding of this important issue is outstanding. For many of us we are still improving (in my case with other complimentary therapies) 3 years on from our procedures.

  10. Thank you for this wonderful summary of the published research that gets media attention. Fortunately, there are a lot of intelligent and tireless advocates out there willing to challenge the status quo.

  11. Joining in on thanking you Anne, it truly is a breath of much needed fresh air. I wish I’d had access to this treatment earlier in my MS and that I didn’t have to pay for it out of country etc… What I got from my treatment was unexpected, I went in hoping but not expecting so to get anything was mind blowing. I’ve been a guinea pig and gone in with the same mindset for my past neurologist and oddly enough nothing happened from that but went into this the same way and it actually did some good! I know this helped me for a time (until I re-stenosed and even ended up with a blockage). And I’d do it again and again and again! Thank you Anne for staying on top of this and not allowing rhetoric to prevail.

  12. Great Article Anne! Thanks for cutting through the headline click-bait of “bad-news” to report on the TRUTH, which is way more complex than the nay-sayers would suggest. Jeff Beal – 4 years in treated

  13. Anne – your summary is incomplete on many levels, but your primary failure is not to distinguish between 1. attempts to show that craniocervical venous obstruction is more common in MS patients on the one hand, and 2. trials of venous balloon dilatation on the progression of MS on the other. In 2013, most serious reviews concluded that the first proposition was unlikely to be true.
    As for 2, you failed to identify a summary of randomized trials published in June 2013
    (J Neurol Neurosurg Psychiatry. 2013 Jun 18. Percutaneous transluminal angioplasty for treatment of chronic cerebrospinal venous insufficiency in people with multiple sclerosis: a summary of a Cochrane systematic review).

    This review did not identify any published trials but found there were six in progress. Of these six, two (both from the States) have been abandoned in 2013: one (from the Buffalo group) has been published in abstract form and therefore by the rules of randomized trials cannot be continued: and one from Australia had recruited 8 subjects by April 2013, and did not have financial support to continue. This leaves 2 (out of six) active trials of balloon dilatation: Traboulsee at UBC, and an Italian trial involving Zamboni. If this was a betting rather than a drinking game, I would not wish to bet the bank on the results of these two trials.

    • In 2013 vascular researchers continued to elucidate the connection between CCSVI and MS, showing higher prevalence of CCSVI in those with MS, and benefit of venoplasty. As Anne’s article shows us- linking to the1988 review on social constructivism and the vascular connection to MS- the disregard for vascular research goes back decades. Your comment on “most serious reviews” betrays this prejudice. It’s time to work together to understand cerebral perfusion and the impact of the venous system. The collaborative work of the ISNVD is essential.

      Phlebology 2013 Dec. “Objective duplex ultrasound evaluation of the extra cranial circulation in MS” The current findings support the view that the early symptomatic benefits observed after venoplasty for stenoses in the extracranial venous circulation may be the result of increased cerebral perfusion.

      Phlebology 2013 Dec. “Blood pressure normalization post jugular venous balloon angioplasty” Balloon angioplasty corrects blood pressure deviation in multiple sclerosis patients undergoing internal jugular vein dilation. Further studies should investigate the association between blood pressure deviation and internal jugular veins narrowing, and whether blood pressure normalization affects Patient’s clinical outcomes.

      Phlebology 2013 Nov. “Prevalence of CCSVI in MS, a blinded sonographic evaluation” Chronic cerebrospinal venous insufficiency is a haemodynamic condition strongly associated with multiple sclerosis and is not found in normal controls. The addition of M-mode ultrasound to the diagnostic protocol allows improved observation of venous valve abnormalities.

      Vascular and Endovascular Surgery 2013 Nov. “Meta-Analysis of the Correlation Between CCSVI and MS” In all, 19 studies were identified from January 2005 through February 2013. The meta-analysis demonstrated a correlation between CCSVI and MS.

  14. Thank you Anne for keeping INTELLIGENT debate alive in regards to CCSVI! I would be in a wheelchair by now if I hadn’t gotten treated! My secondary-progressive MS had me chained to my walker whenever I went out, which wasn’t often and I was on CPP disability for four years. I haven’t used my walker since the day I got treated, I have returned to work full-time and gotten off CPP disability and I bought myself a bicycle and signed up for a Bollywood dance class! Even my neuro when I last saw him in the summer said my MS is now “stable” and he even asked me if I still want to see him! CCSVI may not work for everyone, but it worked an absolute miracle for me!

  15. Thanks Anne for reporting on the ongoing political game that continues to roadblock CCSVI testing and treatment in Canada. It is truly a shame that the MS Neuro’s and the MS Society continue to do everything in their power to ignore, discredit and disrespect the ongoing PROPER studies to satisfy their own self serving interests. It angers me to know that so many people with MS and other Neurological conditions could be helped with symptom improvement and yet they are still waiting 4 years later, while a small, uninformed yet powerful group controls their destiny.Here’s hoping 2014 will be the year that MS Neuro’s and the MS Society put their patients needs before their own profits.

  16. Thank you for continuing to spread the truth. As the 2nd of 6 to receive the treatment in Barrie ,I am aghast at the continued denial of this safe and effective procedure. I would have died several years ago without it. I now live a life without the pain ,and many other symptoms of MS. For those 2/3 of us whom this procedure has returned our quality of life, we applaud you. We will never turn our back on our fellow MSers. We will continue to spread this truth until our dieing day if necessary. By the way I was secondary progressive when diagnosed.

  17. BRILLIANT BRILLIANT BRILLIANT reporting Anne!! THANK YOU THANK YOU THANK YOU!!! I HAVE HOPE!!!

  18. Thank you to Anne Kingston for her continuing journalistic excellence!!!

  19. Thank you Anne for keeping CCSVI real and unbiased. MS hit my family two fold with my daughter and myself being diagnosed in 2001. Both of us had treatment-my daughter in 2010 and myself in 2012. Both of us had positive results. My daughter returned to her teaching career and I have been symptom/relapse free for over a year. We both got our lives back. Big Pharma makes tons of money off of MS patients. They stand to lose the most so I can well imagine the lobbying that goes on behind closed doors not to mention the ego’s that are being deflated on the neurologists. To put it in simple terms-why would you send an electrician to fix a plumbing problem ? This debate is not going away.

  20. Your effort is priceless, thank you so much. This is what I need to read when I’m in despair about my situation an my future.
    Humble greetings from Denmark

  21. Maybe, hostessing a public debate (suggested by Dr. Arata) is an option worth seriously considering Anne. It should be televised of course; with representation from both sides.

  22. Bless you Anne for keeping a weather eye on the situation and I could not agree with you more, even in Italy where you would have thought they had a vested interest in being fair, the research done by the CosMo study was skewed against the possibility of positive result. There is too much vested interest in this not succeeding for anything positive to happen until the power of neurologists, commercial interests, government funding is put under the microscope. How long that will take is anyone’s guess, but some major disaster will likely be the only trigger for proper investigation of these vested interests… Sad world.

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