Epstein-Barr Virus May Be Associated with Progression of MS

Epstein-Barr Virus May Be Associated with Progression of MS

BUFFALO, N.Y. –

Epstein-Barr virus (EBV), the pathogen that causes mononucleosis, appears to play a role in the neuro-degeneration that occurs in persons with multiple sclerosis, researchers have shown at:

• the University at Buffalo and
• the University of Trieste, Italy,

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.

“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.

Written By:

Lois Baker

University at Buffalo

Release Date: March 2, 2009

Actual Abstract from :

the Journal of Neurology, Neurosurgery and Psychiatry and

Objective:

The aim was to determine whether the presence of anti-Epstein Barr virus (EBV) antibodies is associated with magnetic resonance imaging (MRI) measures of brain injury and neuro-degeneration in multiple sclerosis (MS) patients.

Methods:

A total of

• 135 MS patients (86 females; 49 males) underwent brain MRI and testing for antibodies against EBV.

The MRI measurements included

• gadolinium-enhancing (Gd) lesion volume,
• T1- and T2- lesion volumes and fractions of whole brain parenchyma (BPF), white matter (WMF) and gray matter (GMF).

The anti-EBV panel included anti-EBV early antigen (EA) IgG, anti-EBV nuclear antigen (EBNA) IgG and anti-EBV viral capsid antigen (VCA) IgG levels.

The relationships between antibody levels and MRI measurements were assessed in regression analysis.

Repeated measurements of anti-EBV VCA IgG and MRI measures were available for a subset of 50 patients after mean follow-up of 3.1 years.

Results:

The GMF (R2 = 0.24 for overall model and Standardized = -0.26, p = 0.002) and BPF (R2 = 0.39 for overall model and Standardized = -0.28, p < 0.001) showed negative associations with anti-EBV-VCA IgG levels. Higher decline in BPF was significantly associated with increased -3-year time point anti-EBV VCA IgG levels (p = 0.007).

Conclusions:

The results suggest that the presence of anti-EBV antibodies is associated with MRI markers of GM atrophy in MS and with increased loss of brain volume over 3-year follow-up.

Performed by:

¹ Buffalo Neuroimaging Analysis Center, United States
² UCO di Clinica Neurologica, Italy
³ SUNY University at Buffalo, United States
⁴ Cattinara Hospital, Trieste, Italy
⁵ Department of Clinical Medicine and Neurology of Trieste, Italy
⁶ State University of New York, United States

Robert Zivadinov ¹, Marino Zorzon ², Bianca Weinstock-Guttman ³, Maurizia Serafin ⁴, Antonio Bosco ⁵, Alessio Bratina ², Attlio Grop ⁵, Cosimo Maggiore ⁵, Maria Antonietta Tommasi ⁵, Bhooma Srinivasaraghavan ¹ and Murali Ramanathan ^6*

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.

Accepted 8 January 2009

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