A decade ago, a physician in Italy proposed an unorthodox but intriguing theory: that the intermittent autoimmune attacks that occur in multiple sclerosis are triggered by narrowed veins in the head and neck.
Since then, tens of thousands of MS patients around the world have undergone balloon angioplasty to widen their veins. Clinics from California to Bulgaria have sprung up to provide the "liberation therapy," even as studies have increasingly poked holes in it and neurologists have frowned on it.
Now, the first large, rigorous clinical trial of vein-widening, or venoplasty, has shown that it is no better than a sham for treating multiple sclerosis. The results of the study, conducted in four Canadian cities and led by the University of British Columbia and Vancouver Coastal Health Research Institute, were presented Wednesday at the annual meeting of the Society for Interventional Radiology in Washington.
"We've got this tension between science and social media, where people will put these compelling stories, saying, 'I've had this treatment, and I feel dramatically better,' " said study co-leader Anthony Traboulsee, a neurologist who directs the MS clinic at the University of British Columbia. "I hope these findings from a carefully controlled 'gold standard' study will persuade people with MS not to pursue liberation therapy, which is an invasive procedure that carries the risk of complications, as well as significant financial cost."
Patients like Janet Grieco, 60, of Chalfont, are unlikely to be swayed.
Dissatisfied with the marginal benefits, high costs, and serious side effects of standard MS drugs, Grieco has had venoplasty seven times since 2010 — the first three at Lankenau Hospital in Wynnewood, before officials there scuttled the treatment as unproved for MS.
Venoplasty "is for relief, not a cure," said Grieco, who says she believes the procedures improved her walking ability and mental sharpness. "I'm doing great. I wouldn't hesitate to have it again."
But the new study could deter the treatment if insurers end coverage that Grieco and some U.S. patients have relied on.
Venoplasty "is an expensive procedure, about $8,000, depending whether you go to a private clinic. Insurers base a lot of their coverage on studies. Insurers are not going to pick it up anymore," predicted Sharon Richardson, a Denver MS patient. She has had venoplasty twice and is president of a patient advocacy group called CCSVI Alliance.
The group's name is short for "chronic cerebrospinal venous insufficiency," the terminology coined by Paolo Zamboni, a vascular specialist at Italy's University of Ferrara. While trying to help his wife's MS, he discovered that the three main veins that channel blood from the brain back to the heart — the jugulars and the azygos — are often twisted or constricted in MS patients.
He posited that blood backs up in the brain, creates new drainage patterns to compensate for the slow-flowing veins, and leaves behind iron that irritates delicate brain tissue. In theory, this signals immune cells to seep out of the blood and try to mop up the toxic deposits.
Zamboni's maverick work offered an explanation for the central mystery of MS: why immune cells run amok, attacking nerves and causing progressive disability, usually over the course of decades. An estimated 2.3 million people worldwide, including 400,000 in the United States, are living with the varied and unpredictable symptoms, including weakness, numbness, blurred vision, and problems with walking, balance, and continence.
"It was a reasonable theory, a bold theory," said Traboulsee. "Our goal was to take Dr. Zamboni's observation and validate it with a stringent study. We couldn't validate it, and that's unfortunate, but that's science."
To prevent the biases of patients and doctors from undermining the study, the researchers randomly assigned half the patients to a sham procedure, the surgical equivalent of a placebo. Although all 104 participants had a tube, or catheter, threaded into their blocked veins, only 49 had their vessels widened by inflating the balloon tip. Neither the patients nor the doctors who evaluated their results knew who had the fake procedure.
Assessments — variously including brain MRIs, vein imaging, standard MS evaluations, and patients' self-evaluations — were done 72 hours after the procedure and four more times over a year. There were no significant differences between the two groups, providing "the most definitive debunking of the claim that patients could achieve dramatic improvements from a one-time medical procedure," said a study news release.
Even before the latest study, researchers around the world were finding fault with the CCSVI concept. Poor vein drainage does not bother everyone who has it, and some studies have found it is common in healthy people as well as those with neurological conditions other than MS. Not all MS patients get better after venoplasty, and their veins often re-narrow within a year.
Paulette O'Leary, 48, of Toronto, was turned away for venoplasty at Lankenau in 2010, but went on to undergo the procedure twice at Albany State Medical Center in New York. She said she now sometimes needs crutches and gets Botox shots for urinary control.
"I don't think [venoplasty] made a difference in me," she said this week. "But I think it does work for some people."
Patients in the Canadian study had no serious complications related to the treatment. But safety has been an issue. In 2012, the U.S. Food and Drug Administration issued a warning that liberation therapy had caused side effects including stroke, blood clots, and death.
That alert sharply curtailed the availability of the procedure, according to patients and medical groups.
The new study, which has not yet been published in a journal, was funded with $5.4 million from the Canadian national and provincial governments and the MS Society of Canada.
In the U.S., the National MS Society's executive vice president, Bruce Bebo, wrote in an email that results "suggest that treating CCSVI may not have benefits for people living with MS."