Faculty Bibliography

BACKGROUND: Pediatric multiple sclerosis (MS) is a rare disorder with significant consequences. Quantitative MRI measurements may provide significant insights, however multicenter collaborative studies are needed given the small numbers of subjects. The goal of this study is to demonstrate feasibility and evaluate lesion volume (LV) characteristics in a multicenter cohort of children with MS. METHODS: A common MRI-scanning guideline was implemented at six member sites of the U.S. Network of Pediatric MS Centers of Excellence. We included in this study the first ten scans performed at each site on patients meeting the following inclusion criteria: pediatric RRMS within 3 years of disease onset, examination within 1 month of MRI and no steroids 1 month prior to MRI. We quantified T2 number, T2-LV and individual lesion size in a total of 53 MRIs passing quality control procedures and assessed gadolinium-enhancing lesion number and LV in 55 scans. We studied MRI measures according to demographic features including age, race, ethnicity and disability scores, controlling for disease duration and treatment duration using negative binomial regression and linear regression. RESULTS: The mean number of T2 lesions was 24.30 +/- 19.68 (range:1-113) and mean gadolinium-enhancing lesion count was 1.85 +/- 5.84, (range:0-32). Individual lesion size ranged from 14.31 to 55750.60 mm3. Non-white subjects had higher T2-LV (unadjusted pT2-LV = 0.028; adjusted pT2-LV = 0.044), and maximal individual T2-LV (unadjusted pMax = 0.007; adjusted pMax = 0.011) than white patients. We also found a trend toward larger mean lesion size in males than females (p = 0.07). CONCLUSION: Assessment of MRI lesion LV characteristics is feasible in a multicenter cohort of children with MS.

BACKGROUND: As remote infections with common herpes viruses are associated with modulation of the risk of multiple sclerosis (MS), we hypothesized that antibody concentrations against these viruses may further modify risk. As many common viruses are first encountered during childhood, pediatric MS offer a unique opportunity to investigate more closely their influence on susceptibility. Our aim was to determine if MS patients who were positive for these viruses had higher levels of antibodies to these viruses. We also assessed whether human leukocyte antigen (HLA)-DRB1*1501 genotype influenced viral antibody levels. METHODS: Antibody response levels toward Epstein Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV)-1, and HLA-DRB1*1501 status were determined in pediatric MS patients (n=189) and controls (n=38). Multivariate analyses were used, adjusted for age, gender, race, ethnicity and use of disease-modifying therapies. RESULTS: The antibody concentrations against EBV (Epstein-Barr nuclear antigen 1 (EBNA-1), viral capsid antigen (VCA) and early antigen (EA)), CMV and HSV-1 were similar between pediatric MS patients and controls positive for seroconversion against the virus of interest. EBNA-1 humoral responses were higher in HLA-DRB1 positive individuals (p=0.005) whereas other viral humoral responses were similar in HLA-DRB1 positive and negative individuals. CONCLUSION: Among those positive for EBNA-1, MS patients did not have higher levels of antibody response to EBNA-1: however, titers for EBNA-1 were higher in those who were HLA-DRB1 positive. This suggests that genotype might influence the humoral response to EBV. Whether other genotypes influence antibody response to other viruses remains to be determined.