Developmental and pathological changes at the node and paranode in human sural nerves.

The nodes and paranodes of peripheral nerve fibers are complex structures that are especially prone to artificial and pathological changes which have to be distinguished from normal developmental changes. Alterations during normal development are mainly caused by an increase in axonal diameter and myelin sheath thickness. The nodal, and paranodal axon diameters in human sural nerves reach their adult values at 3-5 years of age, simultaneously to the internodal diameter. The ratio between internodal and paranodal axon diameters remain relatively constant, with an average value of 1.8 to 2.0 (range: 1.6 to 2.5). Despite a considerable increase of the number of myelin lamellae, the length of the paranodal myelin sheath attachment zone at the axon does not increase correspondingly, because of (1) attenuation of the terminal myelin loops, (2) separation of some of these from the axolemma, and their piling up in the paranode. Separation of variable numbers of terminal myelin loops from the underlying axolemma results in the formation of the spines on the "double bracelet épineux" of Nageotte, while the transverse bands of these loops disappear. The adaptation of the paranodal myelin sheath to axonal expansion during development probably occurs by uneven gliding of the paranodal myelin loops simultaneously with internodal slippage of myelin lamellae. Artificial changes are caused by insufficient fixation or mechanical stress during excision and further handling (cutting, dedydrating, embedding) of nerves whereas pathological changes may be induced by a multitude of causes. An attempt to classify these changes is presented in Table 2.