FURTHER STUDIES OF THE CENTRAL NERVOUS SYSTEM IN CANINE GIANT AXONAL NEUROPATHY

Abstract

The CNS of 3 cases of canine giant axonal neuropathy (GAN) were examined. The axonal swellings were present in the distal portions of the spinal long tracts and their terminations in the cerebellar vermis; in the distal optic pathways; the nuclei of the habenulo-interpeduncular tract; certain thalamic relay nuclei and the cerebral cortex. The swelling were present both paranodally and internodally with the myelin sheath being attenuated or even absent. Excessive numbers of disordered 10 nm neurofilaments were the main constituent although mitochondria, membranous bodies, glycogen bodies and amorphous electron dense material also accumulated, particularly in the fasciculus gracilis. The neurotubules tended to form small subaxolemmal or intra-axonal islands. Complex interdigitations of oligodendroglia and axolemma were found in the affected areas. A small number of fibers in the rostral fasciculus gracilis showed marked proliferation of the smooth endoplasmic reticulum which may represent abortive attempts at regeneration. A small proportion of astrocytic processes were markedly enlarged with excessive whorling of the glial filaments. The accumulation of these various organelles in the non-terminal axon in the absence of mechanical obstruction suggests a defect in axoplasmic transport which may result from an energy failure as suggested in toxic neuropathies. The significance and pathogenesis of the glial filamentous changes and those reported in other cells in human GAN is at present uncertain.