Charcot-Marie-Tooth disease associated with hypertrophic neuropathy: a neuropathologic study of two cases

The neuropathologic features of two cases of Charcot-Marie-Tooth disease associated with hypertrophic neuropathy are described. The peripheral nerves had a loss of myelinated fibers, endoneurial fibrosis, and numerous onion-bulb formations. The most severe changes were seen in the distal nerves. In the older of the two patients, advanced changes were also observed in the proximal nerves and anterior roots and were associated with neuronal degeneration in the anterior horns and dorsal root ganglia. The muscles were the site of chronic denervation atrophy, which was most severe in the distal portions of the lower extremities. In one of the cases, the autopsy findings were complemented by sural nerve biopsy studies, which confirmed the presence of segmental demyelination and remyelination, axonal degeneration, and Schwann cell proliferation in the form of onion bulbs. Our observations support the concept of a primary neuronal abnormality in the hypertrophic type of Charcot-Marie-Tooth disease (HN-CMT). The disorder appears to initially involve the distal axonal processes but, with progression of the disease, also involves the proximal axons, eventually leading to degeneration and loss of neurons in the anterior horns and dorsal root ganglia. Onion-bulb formation generally parallels nerve fiber degeneration, suggesting that segmental demyelination and onion bulbs may occur secondary to axonal degeneration. The possibility of a concomitant Schwann cell abnormality cannot be excluded, however, on the basis of our postmortem studies.