Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability

Objective: To assess axonal damage and its contribution to disability at di fferent stages of multiple sclerosis (MS). Background: Recent in a vivo imaging and in situ pathologic studies have de monstrated that substantial axonal damage accompanies the inflammatory lesi ons of MS. However, the relation of axonal damage to the duration of MS and its contribution to disability at different stages of the disease remain p oorly defined. Design: We performed proton magnetic resonance spectroscopic imaging in 88 patients with a wide range of clinical disability and disease duration to m easure N-acetylaspartate: (NAA, an index of axonal integrity) relative to c reatine (Cr) in a large central brain volume that included mostly normal-ap pearing white matter on magnetic resonance imaging. Results: We observed that the NAA/Cr values were abnormally low in the earl y stages of MS, even before significant disability (measured using the Expa nded Disability Status Scale [EDSS]) was evident clinically, and declined m ore rapidly with respect to EDSS at lower than at higher EDSS scores (P<.00 1). The correlation of NAA/Cr values with EDSS score was significantly (P<. 03) stronger in patients with mild disability (EDSS score <5, Spearman rank order correlation=-0.54, P<.001) than in patients with more severe disabil ity (EDSS score greater than or equal to5, Spearman rank order correlation= -0.1, P<.9). When similar analyses were performed in patients with MS group ed for duration of disease, the subgroup with early disease duration (<5 ye ars) also showed central brain NAA/Cr resonance intensity ratios significan tly lower than healthy controls (P<.001). Conclusion: Cerebral axonal damage begins and contributes to disability fro m the earliest stages of the disease.