Evidence of Wallerian degeneration in normal appearing white matter in the early stages of relapsing-remitting multiple sclerosis

Abstract.

Objective: Wallerian degeneration in normal appearing white matter in early relapsing-remitting multiple sclerosis (RRMS), and its correlation with the number of relapses and disease duration. Background Recent pathological studies have demonstrated Wallerian degeneration in normal appearing white matter (NAWM) in multiple sclerosis (MS), in established RRMS, and in chronic MS. However, the presence of Wallerian degeneration early in the disease and its correlation with relapse and with disease duration has not been studied. Methods: We performed proton magnetic resonance spectroscopic imaging in 21 MS patients, and 4 healthy controls, age and gender matched, aged under 45 years, with a maximum of 4 years since first bout, and an EDSS score of less than 3.0. N-acetyl-aspartate (NAA) (an index of axonal integrity) was measured in the NAWM from the pons and the cerebellar peduncles. Results: We observed that the NAA levels were abnormally low in the NAWM in the early RRMS patients (p = 0.04, Student's t-test). The decrease in the NAA concentration correlated with disease duration in the two areas studied (p = 0.03 for pons and p = 0.04 for cerebellar peduncle); and with the number of previous relapses (Pearson's correlation = −0.582, p < 0.002). Conclusion: Wallerian degeneration measured by the NAA concentration at pons and cerebellar peduncles is present early in the disease and correlates with the number of relapses and disease duration.