Multiple Sclerosis and CCSVI Share Risk Factors, UB Researchers Find

Studying individuals without neurological disease, researchers observed that risk factors for CCSVI—or chronic cerebrospinal venous insufficiency—occurred more frequently in people:

• with a history of mononucleosis
• with irritable bowel syndrome
• who smoke or used to smoke
  

“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 understand the whole story,” says Robert Zivadinov, MD, PhD, professor of neurology.

CCSVI, which is characterized by impaired blood flow from the central nervous system to the periphery, has generated worldwide interest among MS patients for the hypothesis that it may contribute to brain tissue injury in MS.

Independent scientific studies—including one of the largest to date being conducted by Zivadinov and UB colleagues—have suggested a connection between CCSVI and MS, but none have conclusively determined an association.

The UB study examined associations between CCSVI and demographic, clinical and environmental risk factors in 252 volunteers.

It found that people with CCSVI were:

• 2.7 times more likely than those without the condition to have infectious mononucleosis
• 3.9 times more likely to have irritable bowel syndrome
• 1.98 times more likely to have a history of smoking

“All three are confirmed risk factors for MS,” says Bianca Weinstock-Guttman, MD, professor of neurology and second author on the study.

Researchers observed, for the first time, a connection between CCSVI and Epstein-Barr virus, the cause of mononucleosis.

“We know that Epstein-Barr virus is associated with an increased risk for MS,” Zivadinov 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.”

UB researchers also found that individuals with heart disease—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 the condition.

The study’s additional finding of a weak, protective effect from the use of dietary supplements warrants further exploration, Zivadinov says.

He stresses that the study was preliminary, and that researchers must expand upon it and confirm its findings in future studies.

Study participants were part of the prospective Combined Transcranial and Extracranial Venous Doppler Evaluation at UB. They were either independent individuals, or spouses or relatives of MS patients.

Researchers purposely selected controls from different sources of recruitment, Zivadinov explains.

“Spouses had no genetic similarity but may have shared environmental risk factors with MS patients, while relatives of MS patients 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.”

Volunteers were screened for medical histories and underwent physical exams and Doppler sonography examinations of the neck. They also answered an extensive environmental questionnaire.

Individuals were considered to have CCSVI if they had at least two positive venous hemodynamic criteria on Doppler sonography.

The UB study was described in an article titled “Risk Factors for Chronic Cerebrospinal Venous Insufficiency (CCSVI) in a Large Cohort of Volunteers,” published Nov. 30 in PLoS One.

Kresimir Dolic, MD, served as a lead author. A radiologist at University Hospital in Split, Croatia, Dolic was a visiting MRI fellow at the Buffalo Neuroimaging Analysis Center (BNAC), part of UB’s Department of Neurology, where the study took place.

The BNAC and the Baird MS Center, both part of UB, as well as the Direct-MS Foundation and the Jacquemin Family Foundation, funded the research.