Progressive axonopathy: An inherited neuropathy of Boxer dogs. 3. The peripheral axon lesion with special reference to the nerve roots

Abstract

Progressive axonopathy is an autosomal recessive inherited neuropathy of Boxer dogs with lesions in the CNS and PNS. This paper describes the axonal changes in the lumbar and cervical nerve roots and tibial nerve. By 2 months of age the proximal paranodal areas of many larger diameter fibres show small axonal swellings, sometimes with attenuation or loss of the associated myelin sheath. Axoplasmic changes within swollen and non-swollen fibres include disorganization of the peripheral neurofilaments and small accumulations of vesicles and vesiculo-tubular profiles, particularly in the sub-axolemmal area. Occasional fibres, more often in the cervical roots, are massively distended with disorganized neurofilaments. The frequency of the membranous accumulations decreases with progression of the disease. Many axons show a markedly irregular or corrugated outline and are surrounded by an attenuated sheath. The peripheral axonal cytoskeleton is disorganized and misaligned, whereas the central structures maintain a more normal arrangement. Regenerating axonal clusters are common in the cervical ventral roots but occur infrequently in the lumbar roots. Similar axonal changes occur in the peripheral nerves but at a much lower frequency. Any membranous accumulations or cytoskeletal disorganization are more probable in the proximal tibial nerves, while the frequency of axonal degeneration and regeneration increases distally. The morphological appearances indicate gross disturbances in axon-sheath cell relationships and suggest that abnormalities in the transport of various axoplasmic organelles may be involved in the pathogenesis of the axonal lesion.