Clinical relapses and disease activity on magnetic resonance imaging associated with viral upper respiratory tract infections in multiple sclerosis

Abstract

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 -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 eVects of interferon -1a, do not provide convincing evidence of increased blood-brain barrier breakdown or inflammation during periods of virally induced immune stimulation. (J Neurol Neurosurg Psychiatry 1998;64:736-741)

Systemic Inflammatory Response Reactivates Immune-Mediated Lesions in Rat Brain

“…Breakdown of the BBB has been reported in a clinical study by Edwards et al (1998) in MS patients during periods of infection. In contrast, in the more recent study by Buljevac et al (2002), peripheral infection did not appear to alter the number of contrast-enhancing lesions in MS patients, although changes in the spatial extent of existing lesions were not considered.…”

“…However, there is growing evidence that there may be a link between infection and relapse (Buljevac et al, 2002). A number of studies have shown that approximately one-third of MS relapses are preceded by a viral infection (Sibley et al, 1985;Andersen et al, 1993;Panitch, 1994;Edwards et al, 1998;Buljevac et al, 2002). Relapse in individuals with MS has also been associated with bacterial infections, such as those of the urinary tract, which appear to trigger relapse in as many as 30% of MS patients (Rapp et al, 1995).…”

“…A small number of magnetic resonance imaging (MRI) studies have been performed to investigate the effect of peripheral infection in MS, but the results have been inconsistent. Edwards et al (1998) reported that the number and the volume of enhancing lesions in MS patients increased during peripheral infection. However, others have reported no increase in the number of contrast-enhancing lesions despite worsening of neurological symptoms at the time of infection (Barkhof, 2002).…”

Activation of APCs Through CD40 or Toll-Like Receptor 9 Overcomes Tolerance and Precipitates Autoimmune Disease

“…Microbial infection is the environmental factor most strongly associated with exacerbations of MS as well as other autoimmune diseases (26,(61)(62)(63). Furthermore, mice that are transgenic for a myelin-specific TCR develop spontaneous EAE when housed in a nonsterile facility, but not in a sterile, specific pathogen-free facility (64).…”

Bystander CD8 T Cell-Mediated Demyelination After Viral Infection of the Central Nervous System

“…n certain autoimmune diseases, including diabetes, myocarditis, and herpes stromal keratitis, microbial infections often precede the onset of clinical disease (1)(2)(3)(4), or correlate with relapses, most notably in the case of multiple sclerosis (MS) 3 (5)(6)(7)(8). MS, a common chronic inflammatory disease of the CNS, is characterized by periodic relapses of neurological disease (9).…”