Epstein-Barr virus may be associated with progression of multiple sclerosis

Epstein-Barr virus (EBV), the pathogen that causes mononucleosis, appears to play a role in the neurodegeneration that occurs in persons with multiple sclerosis, researchers at the University at Buffalo and the University of Trieste, Italy, have shown.

Multiple sclerosis (MS) is an autoimmune disease that can cause major disability. There currently is no cure.

"This study is one of the first to provide evidence that a viral agent may be related to the severity of MS disease process, as measured by MRI," said Robert Zivadinov, M.D., Ph.D., associate professor of neurology in UB's Jacobs Neurological Institute (JNI) and first author on the study.

The research appears in the Online First section of the Journal of Neurology, Neurosurgery and Psychiatry and is available at http://jnnp.bmj.com/cgi/rapidpdf/jnnp.2008.154906v1.

"A growing body of experimental evidence indicates that past infection with EBV may play a role in MS," said Zivadinov, "but the relationship of EBV and the brain damage that can be seen on MRI scans had not been explored."

The study involved 135 consecutive patients diagnosed with MS at the Multiple Sclerosis Center of the University of Trieste. Evaluations of the MRI scans were carried out at the University of Trieste and at the JNI's Buffalo Neuroimaging Analysis Center (BNAC), which Zivadinov directs.

The Buffalo researchers measured total brain volume, as well as the decrease in gray matter, at baseline and three years later.

Results showed that higher levels of anti-EBV antibody measured at the beginning of the study were associated with an increased loss of gray matter and total brain volume over the three-year follow-up.

The researchers now are carrying out prospective longitudinal studies in patients who experienced a condition called "clinically isolated syndrome," a first neurologic episode that lasts at least 24 hours, and is caused by inflammation/demyelination in one or more sites in the central nervous system. If a second episode occurs, the patient is diagnosed with MS.

The study will investigate the relationship of anti-EBV antibody levels to development of gray matter atrophy, neurocognitive function and disability progression over time.

UB and Trieste researchers also are investigating interactions between environment, certain genes and EBV antibodies and the association with MRI injury in MS. A paper on this work is "in press" in the Journal of Neuroimmunology.

Marino Zorzon, M.D., from the University of Trieste, is second author on the Journal of Neurology, Neurosurgery and Psychiatry study. Murali Ramanathan, Ph.D., from the UB School of Pharmacy and Pharmaceutical Sciences and the JNI, is co-corresponding author with Zivadinov. The BNAC and JNI are located in Kaleida Health's Buffalo General Hospital.

Additional contributors to the study are Bianca Weinstock-Guttman, M.D., from UB; Maurizia Serafin, M.D., from Cattinara Hospital in Trieste; and Antonio Bosco, M.D., Ph.D., Alessio Bratina, M.D., Cosimo Maggiore, M.D., Attilio Grop, Maria Antonietta Tommasi, M.D., all from the University of Trieste, and Bhooma Srinivasaraghavan, from the BNAC.

The study was supported in part by the Consortium for International Development of the University of Trieste, Italy. The researchers also gratefully acknowledge additional support from the National Multiple Sclerosis Society and a Pediatric MS Center of Excellence Center Grant.

The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. The School of Medicine and Biomedical Sciences is one of five schools that constitute UB's Academic Health Center. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.