HONOLULU—A significant problem with the data relating Epstein-Barr virus infection to multiple sclerosis (MS) is that most are derived from adult studies. “It is difficult to effectively evaluate the association between Epstein-Barr virus and MS in adults because nearly all of us acquire Epstein-Barr virus by the time we reach adulthood,” Brenda L. Banwell, MD, told NEUROLOGY REVIEWS.

Perhaps the best way to examine the Epstein-Barr virus–MS link, then, is in children. “If Epstein-Barr virus is an important MS trigger, and from the literature it certainly appears to be, then we would expect children with MS to be Epstein-Barr virus–positive at an age when most children have not yet been exposed to the virus,” theorized Dr. Banwell, Director of the Paediatric Multiple Sclerosis Clinic at the Hospital for Sick Children in Toronto and lead author of a pilot study supporting that hypothesis. “We found a much higher rate of Epstein-Barr virus–seropositivity in children with MS compared to healthy age-matched kids,” related Dr. Banwell, who presented the study results at the 55th Annual Meeting of the American Academy of Neurology.

SEVERAL COMPARISON GROUPS

The 30 patients with MS in the study, who ranged from ages 4 to 18, were compared to age-matched controls randomly chosen from among children presenting to the emergency department with fever, rash, abdominal pain, pharyngitis, or an allergic reaction. The ratio of age-matched controls to patients was 3:1.

A group of healthy children who were bone marrow transplant donors also served as controls. These children were similar in age to the patients with MS but were not age-matched. The third control group consisted of children listed in the encephalitis registry at the Hospital for Sick Children. The encephalitis group showed no demyelination on MRI, Dr. Banwell noted.

Serum samples from all of the children were tested for Epstein-Barr virus capsid antigen, Epstein-Barr virus nuclear antigen, and Epstein-Barr virus early antigen. Serum from the 30 patients with MS and a random sample of 90 age-matched controls was also analyzed for other common viruses such as parvovirus B19, herpes simplex virus, cytomegalovirus, and varicella zoster.

INFECTION RATES

Eighty-three percent of the children with MS were Epstein-Barr virus–seropositive versus 48% of the bone marrow donors and 42% of the age-matched controls—both statistically significant differences; the Epstein-Barr virus infection rate was also much lower in the encephalitis group. There was no difference between the MS group and the random sample of age-matched controls in the rates of infection with the other viruses studied.

Although still significantly less likely than the MS group to be Epstein-Barr virus–seropositive, the children in the encephalitis group who had optic neuritis were more likely than the other control groups to be infected with Epstein-Barr virus. “Which is what one would predict given that optic neuritis is known to be a potential first presentation for multiple sclerosis,” remarked Dr. Banwell.

As she suspected, the study produced much more robust findings than similar adult studies and it suggests that Epstein-Barr virus, in particular, plays a pivotal role in the development of MS. The next step, said Dr. Banwell, is to validate the results in a much larger multicenter international study, a project that she is currently undertaking.

“But to go from where we are to a new therapeutic avenue will take multiple steps and many years,” she emphasized. “Down the road, though, if we were able to unravel the earliest triggers in MS biology, then clearly therapeutic strategies would be targeted at those initiating events.”

NR

—Timothy Begany

Suggested Reading
Ascherio A, Munger KL, Lennette ET, et al. Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study. JAMA. 2001;286:3083-3088.
Hernan MA, Zhang SM, Lipworth L, et al. Multiple sclerosis and age at infection with common viruses. Epidemiology. 2001;12:301-306.
Levin LI, Munger KL, Rubertone MV, et al. Multiple sclerosis and Epstein-Barr virus. JAMA. 2003;289:1533-1536.

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