Recent observations made using magnetic resonance spectroscopy to measure the axonal marker N-acetylaspartate have emphasized the fact that substantial axonal damage occurs in multiple sclerosis, in addition to demyelination. The axonal damage is present both in lesions and normal appearing white matter, progresses over time, and correlates with clinical disability. These observations, together with observations demonstrating that adaptations of sodium channels can restore conduction in demyelinated axons, have led to the hypothesis that axonal damage may be responsible for a significant proportion of the chronic disability that accrues in MS.