The nature of myelinated nerve fiber degeneration in dominantly inherited hypertrophic neuropathy

Morphometric studies were done on similar populations of nerve fibers from the saphenous nerve at midthigh and ankle levels of a patient with mild (case 1) and a patient with severe (case 2) dominantly inherited hypertrophic neuropathy to produce information on the nature of the fiber degeneration. Similar studies were done on control saphenous nerves. In case 1, compared to the proximal region, the distal portion had a higher incidence of demyelinated regions, a higher incidence of onion bulbs associated with myelinated fibers, a markedly decreased number of myelinated fibers, an abnormal frequency distribution of diameters of myelinated fibers with absence of large fibers, and a smaller slope of the regression line of myelin lamellae on area of axis cylinders. In case 2, both the proximal and distal levels showed histologic changes similar to those at the distal level in case 1. Regions of segmental demyelination were clustered, not random. From these data it is necessary to conclude that the decrease in number of fibers at the ankle level is the result not of selective disappearance of entire peripheral sensory neurons but of degeneration of the distal processes of these neurons. Present evidence does not favor the concept of a primary abnormality in the synthesis or maintenance of myelin. The primary defect is more likely to be in neurons. These observations are consistent with the hypothesis that, in this neuropathy, an unknown metabolic derangement in peripheral neurons leads to neuronal atrophy. In neuronal atrophy, the extremities of the cell are affected first and most severely. Segmental demyelination occurs secondary to axonal atrophy. The cycle of demyelination and remyelination on atrophic fibers leads to onion bulb formation. This explanation does not preclude a concomitant abnormality of Schwann cells.