Canadian study finds no blocked neck veins in MS patients, but CCSVI debate goes on
TORONTO — A long-awaited Canadian study has found no evidence that blocked neck veins or impaired blood flow are connected with multiple sclerosis, the most recent of several international trials that have called the hypothetical link with MS into question.
But instead of debunking the theory once and for all, the findings only appear to have fuelled the debate as to whether abnormal veins in the neck and chest are somehow involved with the progressive and debilitating neurological condition.
Zamboni dubbed the abnormality “chronic cerebrospinal venous insufficiency,” or CCSVI. He suggested it might be a cause of MS and that opening up the veins with balloon angioplasty, the same procedure used to unblock coronary arteries, could help relieve symptoms and might even stop progression of the disease.
In a study he performed on MS patients, Zamboni said specialized ultrasound testing showed neck vein anomalies in 100 per cent of subjects.
Since then, researchers around the world have conducted their own studies, using ultrasound and other imaging techniques, but none has come close to replicating Zamboni’s results.
The latest is the group from McMaster University in Hamilton, which used both ultrasound and MRI testing on 100 MS patients and 100 healthy control subjects. The study was blinded — meaning researchers did not know which subjects had MS and which ones had no neurological disease — until the data analysis was completed.
“When we broke the codes, we suddenly realized, my goodness gracious, there’s a very, very clear endpoint to this study — we have no evidence whatsoever of CCSVI,” said principal investigator Ian Rodger, professor emeritus in the department of medicine at McMaster.
“When we looked at the MRI (blood) flow and when we looked at the ultrasound flow, we saw again that there is nothing that differentiates the two sets of groups, MS from control,” Rodger said from Hamilton. “We saw no evidence at all of narrowing of the vessels, which is called stenosis or a blockage. We didn’t see reflux (blood backup).
“So at the end of the day, we had black-and-white information that suggested there’s no evidence of CCSVI.”
The researchers were careful to perform the ultrasound imaging using Zamboni’s method: two “very skilled” ultrasonographers and McMaster’s chief of radiology spent a week in Ferrara, Italy, learning his exact technique.
Rodger said the researchers wanted to avoid any suggestion that their ultrasounds differed from Zamboni’s, a criticism levelled at some previous studies to explain why their results contradicted the Italian doctor’s across-the-board positive findings.
The Canadian MS patients represented the spectrum of the disease: benign; relapsing and remitting; secondary progressive; and primary progressive. MRI scans of neck and chest veins were done as a means of validating ultrasound scans, which were both performed the same day.
Despite the somewhat surprising results, Rodger said the goal was to perform a rigorously controlled study.
“From the standpoint of a scientist, the best thing you can come out with is that it’s very clear one way or the other. And this is obviously remarkably clear.”
Some other researchers, however, don’t agree.
Neurologist Dr. Anthony Traboulsee of the University of British Columbia is heading a $6-million federally funded trial of vein-opening angioplasty — Zamboni’s so-called “liberation therapy” — among Canadian participants.
Traboulsee said ultrasound and MRI are not reliable tests to detect CCSVI on their own, but need to be used in conjunction with the gold standard test called catheter venography.
That test involves feeding a tube (catheter) through blood vessels from the groin area, up into the jugular and other neck and chest veins so they can be viewed from inside — not from the outside as is the case with ultrasound and MRI scans.
While the McMaster team is “very experienced” and their study was well-designed, said Traboulsee, “my concern is with the ultrasound.”
Widely varying results from ultrasound studies by research groups worldwide — including a University of Buffalo study that found 56 per cent of MS patients and 23 per cent of healthy controls had CCSVI — are a reflection of the subjective nature of interpreting ultrasounds, he said.
“I don’t think ultrasound is reliable to make definitive conclusions about Zamboni’s original theory or (in) any other papers that have come out since.”
Using catheter venography, his team has found CCSVI in close to 60 per cent of patients, he said of a soon-to-be published study.
Traboulsee said the McMaster results won’t affect the federal study, which will compare how patients given balloon angioplasty fare compared to those given a sham treatment.
“The Hamilton study is out of keeping with our findings, and we really don’t think it’s going to impact on how we’re going to continue to go forward,” he said, adding that enrolment has begun but results aren’t expected before 2016.
Meanwhile, MS patients worldwide continue to seek the liberation therapy in clinics in such countries as Poland, Bulgaria, India and Mexico. Included among those medical tourists are thousands of Canadians with MS: the unproven treatment is not offered in Canada.
An estimated 55,000 to 75,000 Canadians have MS, and the country has one of the highest rates of the incurable disease in the world. MS causes the destruction of myelin, the protective sheath around nerves throughout the body, leading to progressive physical and cognitive disability.