Remyelination of the CNS in multiple sclerosis is thought to be important to restore conduction and protect axons against degeneration. Yet the role that remyelination plays in clinical recovery of function remains unproven. Here, we show that cats fed an irradiated diet during gestation developed a severe neurologic disease resulting from extensive myelin vacuolation and subsequent demyelination. Despite the severe myelin degeneration, axons remained essentially intact. There was a prompt endogenous response by cells of the oligodendrocyte lineage to the demyelination, with remyelination occurring simultaneously. Cats that were returned to a normal diet recovered slowly so that by 3–4 months they were neurologically normal. Histological examination of the CNS at this point showed extensive remyelination that was especially notable in the optic nerve where almost the entire nerve was remyelinated. Biochemical analysis of the diet and tissues from affected cats showed no dietary deficiencies or toxic accumulations. Thus, although the etiology of this remarkable disease remains unknown, it shows unequivocally that where axons are preserved remyelination is the default pathway in the CNS in nonimmune-mediated demyelinating disease. Most importantly, it confirms the clinical relevance of remyelination and its ability to restore function.
The clinical and pathological details of a case of canine giant axonal neuropathy are presented. An 18-month-old alsatian had hind leg ataxia, weakness, hypotonia and loss of patellar reflexes. Electrophysiological studies demonstrated denervation of the distal hind leg muscles and abnormal nerve conduction velocities. Biopsy and post mortem examination of the peripheral nervous system (PNS) demonstrated large anoxal swellings, up to 28mu in diameter. Electron microscopy showed these swellings to be composed almost entirely of neurofilaments. Similar giant axons were found in the central nervous system (CNS) and the distribution of the lesions in the CNS and PNS was suggestive of a 'Dying Back' disease. The possible aetiology of this new canine condition is discussed.
Five Boxer dogs with a new neurological disease are described. There is a progressive ataxia and weakness, initially in the hind‐legs but later involving forelegs. The onset of signs is usually around 6 months of age although an older dog was affected. Proprioceptive function, muscle tone and tendon reflexes are diminished or absent while pedal reflexes and pain sensation are preserved. Muscle atrophy is minimal. The peripheral nerves are depleted in myelinated fibres. Nerve roots and, to a lesser extent, peripheral nerves show demyelination/remyelination changes and in the cervical ventral roots in particular, regenerative clusters are present. Forelimb muscles show evidence of re‐innervation. In the CNS numerous swollen axons are present. The dorsolateral and ventral columns of the spinal cord are affected throughout their length. In the brain a number of nuclei and tracts, particularly in the lower brain stem, are affected and the superior olives are severely involved. The cerebral cortex and subcortical white matter appear normal. Various portions of the auditory and optic pathways are affected pathologically as are a number of cranial nerves. The axonal swellings contain a number of organelles including smooth endoplasmic reticulum, disordered neurofilaments, vesicles and mitochondria. The disease may be specific to Boxer dogs and may be inherited.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.