Immune-mediated demyelination--immunopathological basis for electrophysiological changes

A focal immune-mediated demyelinating lesion of peripheral nerve was produced by intraneural injection of antiserum to galactocerebroside, a major glycosphingolipid hapten common in CNS and PNS myelin. This model provides an excellent system for correlative studies of physiological and pathological alterations in the processes of demyelination, because the time course of such changes is predictable from animal to animal. Twenty minutes after antiserum injection, Schwann cells showed focal cytoplasmic outpouching and their external mesaxons opened. Between 1 and 8 h after injection "melting," splitting, vesiculation and vacuolation of myelin became increasingly prominent at paranodal regions and Schmidt-Lantermann clefts, with concomitant degenerative changes in Schwann cell cytoplasm. Disruption of myelin in the paranodal region with detachment of the outermost paranodal myelin loops from paranodal axon resulted in an increase in nodal surface area. This seems to be the most critical anatomical alteration responsible for the early changes in propagation of nerve impulses in this antibody-mediated demyelinating lesion. Between 8 h and 3 days axons became demyelinated progressively over several internodes by macrophage phagocytosis. The onset of clinical and saltatory conduction recovery from the lesion corresponded to the appearance of 2-8 myelin lamellae around each remyelinating axon.