JAMA Neurology study delivers verdict on novel MS treatment
A new study published by JAMA Neurology delivers a verdict on a long-debated theory that MS can be treated by opening blocked veins: it's safe but "largely ineffective," and so cannot be recommended.
The treatment didn't reduce the patients' disability and only restored brain blood flow in about half of patients, according to lead author Dr. Paolo Zamboni and a committee of neurologists based in Italy.
Dr. Zamboni was the originator of the theory. He first proposed in 2009 that blocked veins might lead to some of the symptoms of MS. That set off a firestorm of interest by patients and scientists about the possibility that the disease, long labelled an immune disorder, could be linked to vein abnormality a condition Dr. Zamboni dubbed Chronic Cerebrospinal venous insufficiency, or CCSVI.
The JAMA study, dubbed "Brave Dreams," was designed to help answer the question: Could opening up those abnormal veins improve symptoms associated with MS?
The study was designed to be a large one, funded to treat 430 MS patients with either balloon angioplasty to open narrowed veins, or a placebo procedure.
However, after several years, researchers recruited only 115 patients.
The study reports that only six of the 15 MS clinics and centres that had agreed to participate in the study actually did.
Some patients in the study were reluctant to participate, unwilling to risk being in the placebo group and not receive the treatment.
"This was very tough for us," Dr. Zamboni told CTV News.
"Really the neurological community, asked for a double-blinded study, but in the meantime the neurologists rarely supported the study."
All of the patients in the study were diagnosed with CCSVI on ultrasound and with angiograms.
Balloon angioplasty corrected or restored blood flow in 53 per cent of patients treated for blocked veins. But it didn't seem to work on the others.
When scientists compared the effects on disability scores and brain scans, they reported no differences between the placebo and treatment groups.
"It's an unusual study," said Dr. George Ebers, a now-retired Canadian neurologist from Oxford University, who was asked to comment on the paper.
"You've got a study designed for some 400 people only able to enroll about 100. So it means it was very much underpowered to answer the questions. Yet it came up with this conclusion."
Despite the limitations in the study, he agreed with its conclusions.
"No one in the scientific world thought there were legs to this idea. I couldn't see any rationale to support the idea that venous narrowing is linked to MS," he said.
Dr. Maria Grazia Piscalgia, a neurologist in Ravenna, Italy, referred 28 of the 115 patients to the Brave Dreams study.
She told CTV News that eight of those patients received placebo angioplasty, while 20 were given the balloon angioplasty.
Of those 20 who received the treatment, 18 showed improvements in symptoms and fewer lesions on MRI scans for one year.
However, the data, when combined with all the other patients studied, showed no overall benefit.
"I believe that research in medicine, even if it leads to negative results, allows us to understand the diseases and care more precisely for the people who suffer from it," Dr. Piscaglia said in an email.
While clearly the therapy doesn't work on all patients, the study does note there appears to be a group of patients, who had fewer brain lesions, suggesting this group should be "further analyzed."
That research that could potentially explain cases like Tammy Lynn Tremblay. She was diagnosed with MS in 2006, and began losing strength, balance and vision.
"I would end up in a wheelchair. It was scary -- very scary," she said.
When drugs didn't stop her decline, the Ottawa scientist researched Zamboni's theory and went to Poland in 2010 for angioplasty, to open up blocked veins.
"The great thing is that I have never had any other MS episodes since and this was 2010. So, after seven years, if this is a placebo effect, it's a pretty good one."
Tremblay still holds out hope for her future.
"There is no cure for MS," she said. "I would still encourage them to pursue and investigate this possible avenue."