Author: R.M. Clemmons DVM PhD Health -------------------------------------------------------------------------------- The Disease: Degenerative Myelopathy (DM) was first described as a specific degenerative neurologic disease in 1973. Since then, much has been done to understand the processes involved in the disease and into the treatment of DM. Hopefully, this will help you understand the problem and to explain further the steps that can be taken to help dogs afflicted with DM. The age at onset is 5 to 14 years, which corresponds to the third to sixth decades of human life. Although a few cases have been reported in other large breeds of dogs, the disease appears with relative frequency only in the German Shepherd breed, suggesting that there is a genetic predisposition for German Shepherd dogs in developing DM. The work presented here and by others on the nature of DM has been performed in the German Shepherd breed and it is my personal feeling that DM as described in the German Shepherd may only occur in that breed, the Belgium Shepherd and the Old English Sheepdog. It is currently not known whether the exact condition exists in other breeds of dogs. Many dogs may experience a spinal cord disease (myelopathy) which is chronic and progressive (degenerative); but, unless they are caused by the same immune-related disease which characterizes DM of German Shepherd dogs, the treatments described herein may be ineffectual. Diagnosis of DM is made by a history of progressive spinal ataxia and weakness that may have a waxing and waning course or be steadily progressive. This is supported by the neurologic findings of a diffuse thoracolumbar spinal cord dysfunction. Clinical pathologic examinations are generally normal except for an elevated cerebral spinal fluid (CSF) protein in the lumbar cistern. Electromyographic (EMG) examination reveals no lower motor unit disease, supporting the localization of the disease process in the white matter pathways of the spinal cord. DM diagnosis is, therefore, a process of elimination, exclusion and inclusion. The typical clinical presentation, presence of a normal EMG, presence of elevated CSF protein in the lumbar cystern (including changes which are reported here), the presence of altered immune-responses and the lack of significant compression on myelography all help confirm the diagnosis. The gross pathologic examination of dogs with DM generally is not contributory toward the diagnosis. The striking features being the reduction of rear limb and caudal axial musculature. The microscopic neural tissue lesions consist of widespread demyelination of the spinal cord, with the greatest concentration of lesions in the thoracolumbar spinal cord region. In severely involved areas, there is also a reduced number of axons, an increased number of astroglial cells and an increased density of small vascular elements. In the thoracic spinal cord, nearly all funiculi are vacuolated. Similar lesions are occasionally seen scattered throughout the white matter of the brains from some dogs, as well. Many patients have evidence of plasma cell infiltrates in the kidneys on throughout the gastrointestinal tract, providing a hint to the underlying immune disorder causing DM. During the past two decades, we, at the University of Florida, have provided important new insights into the pathoetiology of DM. Dogs afflicted with DM have depressed lymphocyte blastogenesis to plant mitogens. The depression of their cell mediated immune responses correlates with the clinical stage and severity of the disease. Furthermore, this suppression has been shown to be due to the genesis of a circulating suppressor cell. While the relationship of these findings and the onset of the clinical disease remains unclear, a great body of evidence suggests that DM is secondary to the activation of an autoimmune lymphocyte population that leads to subsequent immune attack upon their own neural tissues. Preliminary experiments have demonstrated that some dogs with DM exhibit antigen-binding cells specific to canine myelin basic protein. Immunoglobulins have been shown to be bound within lesions within the spinal cords of dogs with DM. These patients also show increased circulating immune-complexes in their sera. The antigens in these immune-complexes have been examined and appear to be unique seromarkers for DM. They have not been found to exist in patients who do not have DM. The release of antigens during the disease process could explain the immune deficits seen in DM and suggests that processing these immune-complexes by circulating macrophages leads to the development of the circulating suppressor cells that were previously noted. This provides a logical explanation for the presence of immune abnormalities in German Shepherd dogs with DM. Electrophoresis of immune-complexes demonstrates that the proteins present are inflammatory proteins which increase in inflammatory diseases of the dog nervous system. It is hoped that working with the antigens present in the immune-complexes will lead to a major breakthrough in our understanding of DM and that this also could lead to an early serodiagnostic test for the condition. However, the development of a serodiagnostic test will await the availability of antibodies specific to unique markers within the inflammatory proteins of DM dog immune-complexes. 2-Dimensional electrophoresis of CSF proteins indicates that the elevated proteins in the CSF of DM patients represent changes which are related to inflammation. While these changes are not specific for DM, the other conditions in which the inflammatory proteins have been found in CSF can be differentiated by clinical signs. The 2-dimensional electrophoresis of CSF proteins appears to be the most specific change seen in DM to date.
Posted on: Wed, 04 Sep 2013 01:59:42 +0000
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