BACKGROUND Although the risk of clinical attacks of multiple sclerosis seems to be significantly increased with viral upper respiratory tract infections (URTI), serological evidence for the reported association remains controversial. In addition, although MRI is six to 10 times more sensitive than clinical exacerbations in indexing disease activity, any possible association between URTI and MRI activity has yet to be investigated. OBJECTIVES To examine the relation between URTI and disease activity, in multiple sclerosis patients participating in a placebo controlled trial of interferon beta-1a, as indexed both by clinical exacerbation rate and by the number and volume of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhancing lesions on MRI. "At risk" periods were defined around symptomatic URTI, with or without serological confirmation. RESULTS The relative risk of clinical relapse for serologically unconfirmed symptomatic URTI was 2.1 (p=0.004). Raised antiviral antibody titres conferred a relative risk of multiple sclerosis exacerbations that was 3.4 times higher than the "not at risk" periods (annual attack rates of 5.7 v 1.6, respectively, p=0.006). There was no definite relation between the number or the volume of active lesions on MRI and either symptomatic or serologically defined at risk periods. CONCLUSIONS These results confirm the previously reported association between viral infections and multiple sclerosis exacerbations and indicate that the relative risk may be even higher when viral infection is serologically confirmed. However, the results, perhaps because of the confounding effects of interferon beta-1a, do not provide convincing evidence of increased blood-brain barrier breakdown or inflammation during periods of virally induced immune stimulation.
Clinical relapses and disease activity on magnetic resonance imaging associated with viral upper respiratory tract infections in multiple sclerosis.