ABSTRACT
Recent evidence suggests that the pathological substrate of permanent disability in multiple sclerosis (MS) is axonal loss1-4. While axonal loss appears to occur early on in the disease process, the mechanisms for axonal damage likely vary at different stages of the disease. In this chapter we review the evidence and potential mechanisms for both inflammatory-and non-inflammatory-mediated neural degeneration in MS. While this is a convenient manner in which to divide these topics, it should be recognized that there is probably a continuum of inflammatory and non-inflammatory neurodegenerative mechanisms occurring simultaneously in most patients. Therefore, our treatment strategies should be focused on addressing both aspects of the disease, not just one in isolation.
