Vascular condition and MS share risk factors

U. BUFFALO (US) — People with a specific vascular condition, but no known neurological disease, display many of the same risk factors as people with multiple sclerosis, a new study shows.

The study, published in PLoS One, is the first to investigate risk factors for chronic cerebrospinal venous insufficiency (CCSVI ) in which blood flow from the central nervous system to the periphery is impaired. It has been hypothesized that this narrowing of veins restricts blood flow from the brain, altering brain drainage and possibly contributing to brain tissue injury that is associated with MS.

Yet, while CCSVI has generated intense interest among MS patients worldwide and independent scientific studies have suggested an association, none have found conclusively that the condition is associated with MS.

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For this reason, researchers decided that it was critical to determine the risk factors for CCSVI in individuals without neurological disease.

“Our results suggest that risk factors for CCSVI in this group of volunteers are remarkably similar to those of possible or confirmed importance to MS, but we do not yet understand the whole story,” says Robert Zivadinov, professor of neurology at the University at Buffalo and senior author on the study.

The study of 252 healthy volunteers “was designed to help provide scientists and the MS patient community with new information that, combined with the results of studies that are still ongoing at UB, will ultimately help explain CCSVI and its relationship to MS,” says Kresimir Dolic, a lead author on the study and radiologist at University Hospital in Split, Croatia who was a visiting fellow at UB when the study was conducted.

Common risk factors

The study found that CCSVI risk factors occurred more frequently in 1) those with a history of mononucleosis, i.e. infected with Epstein-Barr virus; 2) those with irritable bowel syndrome; 3) those who smoke or have a history of smoking.

“All three are confirmed risk factors for MS,” says second author Bianca Weinstock-Guttman, professor of neurology. According to the results, individuals with CCSVI were 2.7 times more likely than individuals without CCSVI to have infectious mononucleosis, 3.9 times more likely to have irritable bowel syndrome and 1.98 times more likely to have a history of smoking.

“Our finding that a risk factor that is highly significant for MS—Epstein-Barr virus, indicated by a history of infectious mononucleosis—is strongly associated with CCSVI, is important,” says Zivadinov. “This is the first time a connection has been found between Epstein-Barr virus and CCSVI.

“We know that Epstein-Barr virus is associated with an increased risk for MS,” he explains. “We also know that having mononucleosis when you are young increases the MS risk several-fold. So our finding that Epstein-Barr virus is also correlated with CCSVI is a novel finding that must be explored in future studies.”

In addition, individuals with heart disease—which is not a known MS risk factor—were 2.7 times more likely to have CCSVI, and those with heart murmurs, in particular, were 4.9 times more likely to have CCSVI.

The study also found a weak, protective effect from the use of dietary supplements—something the researchers note needs further explanation.  The team cautions the study was preliminary and the findings must be expanded upon and confirmed in further studies.

The volunteer subjects were part of the prospective Combined Transcranial and Extracranial Venous Doppler Evaluation study at UB. They were either independent individuals, or spouses or relatives of MS patients. The controls were purposely selected from different sources of recruitment, Zivadinov says.

“Spouses had no genetic similarity but may have shared environmental risk factors with MS patients, while relatives of MS patients had shared both genetic and environmental background,” he says. “However, no differences in risk factors or frequency of CCSVI were found according to the various sources of recruitment.”

All volunteers were screened for medical histories and underwent physical exams and Doppler sonography examinations of the neck; they also responded to an extensive environmental questionnaire. Individuals were considered to have CCSVI if they had at least two positive venous hemodynamic criteria on Doppler sonography.

The research was funded by the University at Buffalo, the Direct MS Foundation, and the Jacquemin Family Foundation.

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