Environmental Factors Associated with Disease Progression in Multiple Sclerosis after the First Demyelinating Event

Results from the multicenter SET study suggest that smoking, response to Epstein Barr virus, and other environmental factors contribute to disease progression in multiple sclerosis.

The first demyelinating event represents a crucial opportunity for the understanding of factors involved in conversion to multiple sclerosis (MS). Environmental factors in clinically isolated syndrome (CIS) have not been extensively investigated prospectively and their role in the MS disease course and progression is not well-characterized.

Dana Horakova, MD, PhD, from the Department of Neurology and Clinical Neuroscience, General University Hospital, Charles University, Prague, Czech Republic, gave a poster presentation on this topic during the “Multiple Sclerosis: Genetics and Environmental Influences” session at the American Academy of Neurology (AAN) 2013 Annual Meeting. Horakova and her collaborators at different centers investigated the associations of environmental risk factors in MS with clinical and MRI measures of progression in high-risk clinically isolated syndrome (CIS) after the first demyelinating event.

The clinical team analyzed data from a cohort of 211 CIS patients (age: 28.9 ± 7.8 years) enrolled in the Observational Study of Early Interferon beta 1-a Treatment in High Risk Subjects after CIS (SET) study, a multi-center study of high-risk CIS patients. Pre-treatment samples were analyzed for IgG antibodies against antigens on cytomegalovirus (CMV) and Epstein Barr virus (EBV), early nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA), early antigen-diffuse (EA-D), and also for vitamin D status (25 hydroxy-vitamin D3 level), smoking/nicotine exposure (cotinine level), and HLA DRB1*1501 status. The inclusion criteria specified evaluation within four months of the initial clinical demyelinating event, two or more brain MRI lesions, and the presence of two or more oligoclonal bands in cerebrospinal fluid.

All patients were treated first with methylprednisolone for CIS and then started on interferon beta-1a at baseline. Clinical and MRI assessments were obtained at baseline and at 6, 12, and 24 months, thereafter.

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 two-year period. The cumulative number of CEL and T2 lesions during the two-year period was greater for individuals in the highest quartile of anti-EBV VCA IgG antibody levels. The percent loss of brain volume was increased for patients in the highest quartile of anti-EBV VCA IgG antibodies.

In summary, anti-CMV positivity was linked to relapse in CIS patients, whereas anti-EBV VCA positivity was linked to progression of MS features on MRI.

Some environmental susceptibility factors for MS have been identified. Horakova says the goal is to be able to predict the degree of risk for an individual so that environmental or therapeutic interventions can be initiated prior to the event that precipitates the inflammatory demyelinating process that culminates in the first onset of clinical symptoms. The interval between the unobserved and unknown inciting event and CIS may be months or even years.