Page 242

~ enlarge ~

FIGURE 5.1 Demyelination and axonal degeneration in multiple sclerosis. (A) In a normal myelinated axon, the action potential (dashed arrow) travels, with high velocity and reliability, to the postsynaptic neuron. (B) In acutely demyelinated axons, conduction is blocked (black bar). (C) In some chronically demyelinated axons that acquire a higher-than-normal density of sodium channels, conduction is restored. (D) Axonal degeneration, by contrast, interrupts action potential propagation in a permanent manner. SOURCE: Waxman, SG, 1998.⁹⁹ Copyright 1998 Massachusetts Medical Society. All rights reserved. Reprinted with permission.

disability. Synapses are not formed onto axons, so that the excitotoxic theory of neuronal death, which almost certainly applies to diseases of gray matter such as stroke, may not play an important role in multiple sclerosis.⁸⁰

It is not yet known whether axonal injury is a consequence of demyelination, or the immune processes underlying demyelination, or is an independent process. There are some results suggesting that inflammation results in axonal damage in MS.^60,93 This provides an important angle for further investigation. Cytokines are likely candidates as mediators of inflammatory-induced axonal damage, and their possible role in MS should be investigated. Another approach is suggested by demonstrations that ion channels and exchangers together form a “final common