Multiple sclerosis after infectious mononucleosis

Background: Infectious mononucleosis caused by the Epstein-Barr virus has been associated with increased risk of multiple sclerosis. However, little is known about the characteristics of this association. Objective: To assess the significance of sex, age at and time since infectious mononucleosis, and attained age to the risk of developing multiple sclerosis after infectious mononucleosis. Design: Cohort study using persons tested serologically for infectious mononucleosis at Statens Serum Institut, the Danish Civil Registration System, the Danish National Hospital Discharge Register, and the Danish Multiple Sclerosis Registry. Setting: Statens Serum Institut. Patients: A cohort of 25 234 Danish patients with mononucleosis was followed up for the occurrence of multiple sclerosis beginning on April 1, 1968, or January 1 of the year after the diagnosis of mononucleosis or after a negative Paul-Bunnell test result, respectively, whichever came later and ending on the date of multiple sclerosis diagnosis, death, emigration, or December 31, 1996, whichever came first. Main Outcome Measure: The ratio of observed to expected multiple sclerosis cases in the cohort (standardized incidence ratio). Results: A total of 104 cases of multiple sclerosis were observed during 556 703 person-years of follow-up, corresponding to a standardized incidence ratio of 2.27 (95% confidence interval, 1.87-2.75). The risk of multiple sclerosis was persistently increased for more than 30 years after infectious mononucleosis and uniformly distributed across all investigated strata of sex and age. The relative risk of multiple sclerosis did not vary by presumed severity of infectious mononucleosis. Conclusions: The risk of multiple sclerosis is increased in persons with prior infectious mononucleosis, regardless of sex, age, and time since infectious mononucleosis or severity of infection. The risk of multiple sclerosis may be increased soon after infectious mononucleosis and persists for at least 30 years after the infection.