Wallerian degeneration: history and clinical significance

The interruption of a peripheral nerve causes degenera- tion of the distal segment that is now known as ''Wallerian degeneration'' in honor of Augustus Waller (1) .W aller severed the glossopharyngeal and hypoglossal nerves of frogs and made microscopic observations on the distal nerves that were separated from their cell bodies in the brain stem. He described coagulation and curdling of the ''medulla'' into separate particles of various sizes. ''Medul- la'' may be equated with ''myelin.'' The secondary nature of myelin destruction was not realized until the more extensive studies of axons in Wallerian degeneration by Ranvier (2) and Ramon-y-Cajal (3). Waller made many other contribu- tions to the reaction of nerves to section and realized that the direction of traveling nerve impulses was not important. Rather, the separation of a fiber from its parent cell body was the critical process, and he anticipated the role of a ''trophic influence'' (4). The degeneration of the distal segment has also been termed ''direct'' Wallerian degener- ation. Axonal interruption in a peripheral nerve arising from the spinal cord causes a remarkable and reversible change in the corresponding anterior horn neurons known as ''axon reaction.'' The transient disturbance in the nerve cell is thought to cause ''indirect'' Wallerian degeneration in the proximal segment of the severed nerve. Interruption of fibers that reside entirely in the central nervous system (CNS) also causes distal degeneration but the fate of the parent neuron is quite different (Barron, this symposium). It may actually not be justified to use the term ''Wallerian'' for the unrecoverable destruction of the distal portions of long fiber tracts. Nevertheless, the term is widely used for CNS lesions, and modern imaging techniques readily show the permanent atrophy of the cerebral peduncle and the basis pontis after destruction of the corticospinal fibers at a higher level. Wallerian degeneration in the peripheral nervous system (PNS) and CNS are similar in that axonal destruction antedates the degeneration of mye- lin. However, the processes are very different in many other ways (reviewed in Ref. (5)). Contrary to expectation, Wallerian degeneration in the CNS is much slower than in the PNS though the age of the animal is important. Waller- ian degeneration in the CNS of neonatal mammals is as fast as in the PNS. In the PNS, the destruction of myelin begins after 24- 48 h. The sheath fragments into oblong ''ellipsoids'' (or ''digestion chambers'') that often contain residual axo- plasm. One end of the ellipsoid is located near the node of Ranvier, the other in the middle of the internode. Some authors thought that the most vulnerable sites in the internode were the Schmidt-Lantermann incisures, but ultrastructural studies did not confirm a preferential frag- mentation near or through these clefts. The longitudinal disruption of the axon-deprived myelin sheath was con- firmed by light and electron microscopy, freeze fracture,