It is now a year since CTV’s W5 report on Dr. Paolo Zamboni and his CCSVI
(chronic cerebrospinal venous insufficiency) theory of multiple
sclerosis sent shock waves through the scientific and lay communities.
Would "tumultuous" be an appropriate adjective to describe the events of
the ensuing twelve months? I think so.
And if one had to identify the most important aspects of
this story, in what realm what would they lie? Medical? Political?
Social? Behavioral? Adversarial?
Ultimately, there are books to be written here! But for now, allow me, like Janus, to look back over the year that was, and ahead to the year that (hopefully) will be.
To begin, it is no understatement that Zamboni’s theory of MS came out of left field, evoking both an ill-informed, reflexive
dismissal of his hypothesis, and derogatory comments about him (it did
not help that the venoplasty treatment he developed to open blocked
veins was dubbed the "liberation procedure" by one of his colleagues).
"Who is this guy? Some obscure Italian? A vascular
surgeon? Not a neurologist? What does he know about MS? He treated his
own wife? His name is Zamboni? Ha ha ha!!"
Given the extremely icy reception Paolo Zamboni received from the medical establishment, his was an apt surname.
Within days of the W5 story, neurologists and MS Society
officials, longtime subscribers to the premise that MS is an autoimmune
disease, gave a unanimous thumbs-down to the possibility that
obstruction of venous drainage in the neck and/or chest caused blood to
back up and leak toxic iron from damaged thin-walled veins deep in the brain, killing nerve cells.
Some even went so far as to call CCSVI a hoax. Never mind that other researchers had shown that iron-rich MS plaques consistently form around veins and that the disease progresses in a "backwards"
fashion (compatible with retrograde blood flow) in tissues bordering
the venous system of the brain. It had to be a hoax. Period.
Then a remarkable thing happened. Patients pushed back
hard. Internet chat rooms on MS websites and Facebook lit up with
blistering comments aimed not only at neurologists, but at drug
companies and MS Societies as well. Given the marginal, or even negative, results of current drug therapies, how dare they dismiss Zamboni’s hypothesis without a shred of contrary evidence?
Soon, despite safety
warnings, and a lack of hard evidence that venoplasty worked, hundreds
of desperate MS patients, unable to get treatment in Canada, paid to go
to clinics abroad to have their veins "liberated". Many reported a rapid decrease in symptoms such as fatigue, headache, brain fog and cold extremities. Others posted "before and after" videos
on YouTube, showing dramatic improvements in balance and walking. Had
there ever been anything like this? Not that I could remember.
Realizing that they were rapidly falling out of step (not
to mention out of favour) with their constituency, the Canadian and
American MS Societies quickly changed course, becoming more conciliatory
and responsive. A call went out for CCSVI research proposals, with the
promise to fund successful applicants by June, 2010.
True to their word, seven grants, totaling $2.4 million, were awarded
to four Canadian and three American research teams. But there was a
problem: the studies would only assess vein anatomy; none would offer
treatment if blockage was found. Any future decision on funding clinical
trials would be put off until the findings of the first studies were
in.
But knowing that obtaining an answer could take up to
three years, and unwilling to wait for fear that, by then, their
symptoms could be much worse, angry and dissatisfied patients cranked up
the volume, demanding more immediate action.
"We hear you," the Canadian MS Society replied. Despite spending
only 22% of their $33.7 million budget to fund research, MSS officials
announced that they would join the federal Liberal Party in lobbying
Ottawa for $10 million to pay for treatment trials. In response, the
federal health minister, Leona Aglukkaq, convened a late-summer meeting
of "experts", selected by officials of the Canadian Institute of Health
Research and MS Society. Their mandate: to reach a consensus and advise
her.
But when that time came, the panel, which did not include
a single physician or scientist involved in the research, diagnosis or
treatment of CCSVI, recommended against clinical trials until the results of the anatomy studies were known. The optics were plainly bad….so bad that a Globe and Mail editorial encouraged the health minister to ignore the panel’s recommendation.
Luckily, there was already a plan B in the wings. A month
earlier, Saskatchewan’s premier, Brad Wall, had stepped up to the
plate. With the highest rate of MS in the country (and among the highest
in the world), he announced
that his province would fund a properly-designed clinical trial to
answer the question of whether unblocking veins is of benefit to
patients with the disease. Undeterred by the panel’s negative report,
Mr. Wall soon appointed his own group of expert advisors and pledged $5
million for an approved study to begin sometime in 2011.
Yet, even before the Saskatchewan study was announced,
clinical trials of CCSVI treatment had begun in the United States. The
University of Buffalo treated the first 10 patients in its new PREMiSe
(Prospective Randomized Endovascular therapy in Multiple Sclerosis)
study and is currently awaiting its institutional review board (IRB)
assessment before proceeding to the next twenty. A second IRB-approved
treatment study, involving vascular specialists associated with Albany Medical College, has recently commenced in Albany, NY.
The importance of these properly-designed clinical trials
of balloon venoplasty, with careful follow-up of patients, cannot be
overemphasized. Many worry about some of the out-of-country physicians
and centres that offer CCSVI treatment. What are their qualifications?
What do they really know? We generally hear about people who have had a
good outcome. How many have not? The latest reports of serious complications
following stenting in foreign clinics should cause us alarm. Indeed,
Dr. Zamboni himself has long warned against using stents, as well as
seeking treatment outside of clinical trials.
So where do we go from here? While I don’t claim to have a
crystal ball, I suspect that the next 12 months will bring heightened
attention to some of the controversies surrounding CCSVI.
For example, the interpretation of the data in a recent, widely-reported negative ultrasound study by Doepp and his colleagues, appears to have been effectively challenged by Dr. Zamboni. In a letter just published
in the Annals of Neurology, he pointed out that, as measured by the
German researchers, the change in blood flow through the neck veins when
going from the lying to upright position was 50% less in the 20 MS
patients than in the 56 normal controls tested.
In Zamboni’s opinion, this difference supported the
presence of CCSVI in the MS group. Using a Doppler ultrasound image for
illustration, he went on to note that, in his experience, abnormal
membranes (septa) and/or malformed valves inside neck veins were more
common than stenosis (narrowing) as a cause of obstructed blood flow.
"Clearly a complete understanding of the system is
required before drawing conclusions about the lack of venous
abnormalities, and this requires ultrasound, MRI and catheter
venography. This underscores the urgency of establishing an
internationally accepted protocol. In the attempt to achieve this…my
group is available to travel to Berlin and rescan with German colleagues
the entire series [using] the proposed methodology," he wrote. Touché.
Will Dr. Doepp accept Zamboni’s offer? I suspect that Dr. Sandy McDonald,
a Barrie, Ontario, cardiovascular surgeon who runs a private imaging
clinic, would urge him to do so. Before he and his colleagues traveled
to Ferrara last year to learn Dr. Zamboni’s ultrasound technique, they
"missed a lot of pathology," he told me a few months ago.
Dr. McDonald’s group has since scanned approximately 400
MS patients. Cautious by nature, he nonetheless believes that a very
high percentage appear to have significant, and often complex, vein
anomalies. As for normal subjects: "We also have done normals and find
they are indeed normal," he wrote in an e-mail last August. He is
currently reviewing all his data to confirm the findings in the hope of
publishing them.
Clearly, with the commitment of people like Sandy
McDonald and Brad Wall, each determined to find honest answers, the next
year should bring us closer to an understanding of CCSVI and how it may
be related to MS.
http://healthblog.ctv.ca/post/CCSVI-one-tumultuous-year-later-Where-do-we-go-from-here.aspx