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UW Launches Study of 'Zamboni Theory' of Multiple Sclerosis

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The University of Wisconsin School of Medicine and Public Health is one of three U.S. medical centers launching National MS Society studies of a controversial theory on the cause of multiple sclerosis.


Aaron Field, MD, associate professor of radiology, says the UW will use powerful magnetic resonance imaging (MRI) technology, some of it developed here, to test the so-called "Zamboni theory" of MS.


This theory turns conventional wisdom on its head. Most researchers believe that MS is an autoimmune condition, caused by the body's immune system attacking the myelin that lines the nerves.


But Paolo Zamboni, MD, of the University of Ferrara in Italy, has proposed that MS is instead primarily a vascular disease, with the nerve damage caused by blood backing up into the brain due to narrow neck veins. Dr. Zamboni treated his wife's MS by surgically clearing the veins in her neck.


Also called chronic cerebrospinal venous insufficiency (CCSVI) theory, the idea has drawn huge attention, especially in Canada, which has high rates of MS. In 2010, the National MS Society (USA) and MS Society of Canada gave $2.4 million to fund seven studies of the theory at leading medical centers in the U.S. and Canada.


"Currently, all the evidence for this theory has come from a small number of research groups; it is now critical for other investigators, working independently, to confirm or refute this evidence,'' says Field, the principal investigator for the study.


Dr. John Fleming, a neurologist and multiple sclerosis researcher, is a co-principal investigator, and says he hopes the trial will answer some of the questions his patients have about the theory.


"There is a lot of discussion about this theory in the world of multiple sclerosis, but few hard facts, so there will be a lot of interest in the results,'' Dr. Fleming predicts.


Dr. Field and collaborators will use an MRI scanner to generate highly detailed images of the head and neck veins in a group of MS patients, healthy volunteers, and patients with other neurological conditions.


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Additionally, using highly advanced MRI technology, researchers will measure the rate at which blood flows in the veins and look at the differences between people with and without MS. This approach is more anatomically complete and reliable than the ultrasound technology used by Dr. Zamboni, but UW researchers will also collect ultrasound images of subjects' neck veins.


"We will also study cause and effect, by looking at people who have had MS for more than ten years and those who are newly diagnosed,'' Field says. The MRI images will compare the blockage and brain lesions between the groups; if the theory is correct, those with more seriously blocked veins should show greater disease severity.


The UW trial is recruiting 112 people with MS - 56 healthy volunteers and 56 people with other neurological conditions. People interested in the trial can contact Amanda Kolterman, RN, in the Department of Radiology at or call (608) 263-0305.


Dr. Field emphasized that none of the seven trials are offering venoplasty, a procedure used to clear blocked veins that is similar to the more common angioplasty used to clear blocked arteries.


"First, we need to see if the Italian results can be duplicated before we start treating people based on a theory,'' he says. "If we obtain similar results, that would represent a powerful confirmation of this theory and lead toward a larger-scale trial of appropriate treatment targeting the abnormal veins."


The study will be "blind" during the research phase, so researchers and patients will not know what the scans of individuals show to avoid influencing the outcome. Participants and their physicians will have access to their scan results when the study is complete.