Neuropathology of the spinal nerve roots, spinal cord, and brain in the first autopsied case of Charcot-Marie-Tooth disease 4F with a D651N mutation in the periaxin gene.

Charcot-Marie-Tooth disease (CMT) 4F is an autosomal recessive, hereditary peripheral neuropathy, mostly caused by mutations in the periaxin gene (PRX). This article reports neuropathological findings of the spinal nerve roots, spinal cord, and brain of a patient with CMT4F and a D651N missense mutation in PRX. The patient was a 74-year-old woman who had a history of peripheral neuropathy with onset at the age of 30 years. She also had a history of infantile paralysis at the age of 18 months. The most pronounced autopsy finding was diffuse enlargement of anterior and posterior nerve roots, accentuated at the lumbo-sacral levels. On microscopy, the swollen nerve roots showed a loss of large-diameter myelinated fibers and formation of numerous onion bulbs. Most of the onion bulbs lacked the central, regenerating thin myelin sheaths, and in large-diameter nerve fibers whose axons had been lost, collagen fibers occupied the center of the onion bulbs. Some nerve roots formed glial bundles at the proximal end. The spinal cord showed degeneration of the gracile fascicles, and the lumbar segment anterior horn showed an asymmetric neuronal loss with rarefaction of the neuropil. The brain did not show any notable changes except for multiple foci of a radial microcolumnar arrangement of neurons in the cerebral cortex. Degeneration of the lumbar segment anterior horn is most likely secondary to the anterior radiculopathy, but a localized circulatory disturbance is another possibility.