1. ¹Department of Neurology, Mayo Clinic, Scottsdale, Arizona
2. ²Department of Neurology, Mayo Clinic, Rochester, Minnesota

Correspondence: Dr. John H. Noseworthy, MD, FRCP(C), Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail: noseworthy.john@mayo.edu

Received 27 November 2000.

Abstract

Multiple sclerosis (MS) is an often disabling disease primarily affecting young adults that exhibits extraordinary clinical, radiological, and pathological heterogeneity. We review the following: (a) known environmental and genetic factors that contribute to MS susceptibility; (b) current knowledge regarding fundamental pathophysiological processes in MS, including immune cell recruitment and entry into the central nervous system (CNS), formation of the plaque, and orchestration of the immune response; (c) descriptive and qualitative distinct pathological patterns in MS and their implications; (d) the evidence supporting the causative role of direct toxins, cell-mediated and humorally mediated immune mechanisms, and the concept of a "primary oligodendrogliopathy" in demyelination and axonal injury; (e) the potential benefits of inflammation; (f) the prospects for remyelination; and (g) therapeutic implications and approaches suggested by putative pathophysiological mechanisms.