Pure axonal neuropathy: nerve xenografts and clinicopathological study of a family with peripheral neuropathy, hereditary ataxia, focal necrotizing encephalopathy, and spongy degeneration of brain.
Three family members had the unusual combination of severe peripheral neuropathy, atypical hereditary ataxia, spongy degeneration of cerbral hemispheres, and cerebellar and brainstem foci of necrotizing encephalopathy, proved pathologically in one autopsied case. A sural nerve from a patient, devoid of myelinated fibers, was transplanted into thymectomized, lethally irradiated, and bone marrow reconstituted adult mice. A normal number of myelinated fibers was present in the grafts eleven weeks later. Eighteen weeks after grafting, mice were reconstituted with syngeneic thymus to return immunocompetence. Schwann cells in the graft were rejected and axons became totally denuded of myelin after thymus reconstitution. The peripheral neuropathy is thus due to axonal disease since human Schwann cells were capable of normally myelinating regenerating mouse axons. A puzzling feature after rejection was the absence of myelin debris containing macrophages in the grafts. It is suggested that part of the rejection process in this model is mediated by antibody rather than by cellular mechanisms.