Research: Towards a Viral Trigger of MS


OBJECTIVES: To investigate the associations of environmental MS risk factors with clinical and MRI measures of progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event.

METHODS: We analyzed 211 CIS patients (age: 28.9±7.8 years) enrolled in the SET study, a multi-center study of high-risk CIS patients. Pre-treatment samples were analyzed for IgG antibodies against cytomegalovirus (anti-CMV), Epstein Barr virus (EBV) early nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA), early antigen-diffuse (EA-D), 25 hydroxy-vitamin D3 and cotinine levels and HLA DRB1*1501 status. The inclusion criteria required evaluation within 4 months of the initial demyelinating event, 2 or more brain MRI lesions and the presence of two or more oligoclonal bands in cerebrospinal fluid. All patients were treated with interferon-beta. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24 months.

RESULTS: The time to first relapse decreased and the number of relapses increased with anti-CMV IgG positivity. Smoking was associated with increased number and volume of contrast-enhancing lesions (CEL) during the 2-year period. The cumulative number of CEL and T2 lesions during the 2-year period was greater for individuals in the highest quartile of anti-EBV VCA IgG antibodies. The percent loss of brain volume was increased for those in the highest quartile of with anti-EBV VCA IgG antibodies.

CONCLUSIONS: Relapses in CIS patients were associated with CMV positivity whereas anti-EBV VCA positivity was associated with progression on MRI measures, including accumulation of CEL and T2 lesions and development of brain atrophy.

                             Time to first relapse in all subjects

CMV is a common herpes virus that does not do much in healthy individuals, but can become life threatening in immunocompromised individuals. In this study people with a clinically isolated syndrome, i.e. the first diagnosed attack of MS (but could be due to other causes) were monitored. The first relapse was more related to whether there was evidence of an immune response to CMV and if you smoked this was associated with more disease activity as been by the number of MRI lesions, but those with a high antibody response to EBV progressed the most. Is this all just statisitcal chance or are viruses really part of the problem. The Prof Gs think so and this is why we have the Charcot project.

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