Chronic Degenerative Radiculomyelopathy: A Study of the Pathology and Pathogenesis

Veterinary science, Animal diseases

Johnston, Pamela Elizabeth Jean

University:University of Glasgow

关键词: Veterinary science, Animal diseases;   

Others  :  http://theses.gla.ac.uk/75879/1/13818615.pdf

来源: University of Glasgow

【 摘 要 】

Chronic degenerative radiculomyelopathy (CDRM) is a well-recognised neurodegenerative disease of unknown aetiology which affected large breed dogs, primarily the German shepherd dog (GSD). Previous studies had identified the major clinical signs of pelvic limb ataxia and weakness resulting from degeneration of tracts in spinal cord white matter. This clinical entity has been recognised since 1973, most reports concentrated on the clinical aspects of the disease and the pathology of the spinal cord. This project is the first to study a large number of affected dogs repeatedly throughout the course of disease. The previously reported clinical signs have been confirmed and the relationship between age of onset and rate of deterioration has been addressed for which no definite correlation was found. Clinical and pathological similarities between CDRM and neurodegenerative disorders due to vitamin E deficiency in horses and humans had implicated vitamin E as a potential factor in the aetiology of CDRM. This stimulated a study of serum vitamin E concentrations. Data presented in this thesis suggests that affected OSDs do not have significantly lower serum vitamin E concentrations than other breeds of dog. In contrast, OSDs with CDRM appear to have elevated levels of serum vitamin E in comparison with the general canine population. The pathology of the spinal cord is consistent with previously-described spinal cord pathology. However detailed examination of the brains of affected dogs revealed novel pathological changes in specific brain nuclei. Such changes included neurones with eccentric nuclei, chromatolytic neurones and neuronal loss often with an associated gliosis. These changes affected the red nucleus, lateral vestibular nucleus and lateral (dentate) nucleus to varying extents. Such changes were found consistently in CDRM dogs but only rarely in dogs with focal spinal cord lesions. Furthermore, gliosis in the red nucleus was found only in the dogs with CDRM. Due to the unusually high incidence of CDRM in one breed of dog and the discovery of at least two pairs of affected littermates, the investigation of a possible genetic factor was indicated. Following a literature search for diseases in other species with clinical and pathological similarities to CDRM, a working hypothesis was established; CDRM is caused by a CAG trinucleotide repeat expansion in an unknown gene. A number of molecular biological techniques were employed to test this theory, including the Repeat Expansion Detection (RED) technique. This work is still in progress but there is some evidence, still inconclusive, that CDRM may be the result of a trinucleotide repeat expansion.