The loss of myelin from central axons is a prominent feature of the lesion of multiple sclerosis (MS), and a direct cause of the several conduction deficits which lead, in turn, to the symptoms associated with central demyelinating disease. This review of the conduction deficits will focus on experimentally demyelinated central axons, since in experimental lesions it is usually possible to determine the morphology of the axons with some certainty, whereas this is rarely possible in human demyelinating disease.
The conduction properties of central axons passing through a region of demyelination were reliably described for the first time by McDonald and Sears in their landmark studies of 1969 and 1970 (McDonald & Sears, 1969b, 1970a, b). These authors found that conduction along axons passing through long experimental demyelinating lesions (>5 mm in length) was often blocked at the site of the lesion, but that conduction could sometimes continue if the lesions were small. Where conduction occurred it was usually abnormal, and proceeded with a locally reduced velocity and a prolonged refractory period of transmission (RPT); the axons were also incapable of conducting trains of impulses at high frequency. These conduction abnormalities remain the hallmark of conduction in axons passing through demyelinating lesions in either the central or peripheral nervous systems.
Conduction block is believed to be the dominant cause of the most distressing symptoms of MS, such as paralysis, blindness and numbness (McDonald, 1975, 1986; Halliday & McDonald, 1977; Ulrich & Groebke-Lorenz, 1983; Waxman, 1988), and it was also the first conduction abnormality to be described in experimentally demyelinated central axons (McDonald & Sears, 1969a) (Fig. 10.1).