Phenotypic and genotypic characterization of a myelopathy in pugs : A journey from ’wobbly pugs’ to pug dog myelopathyRohdin, Cecilia
Spinal cord disease, myelopathy, in dogs have several aetiologies, all characterised by their clinical presentation. Pugs with a thoracolumbar myelopathy (PDM) differ from most dogs by developing a form of myelopathy that shows little clinical variability. Most pugs with PDM show slowly progressive paraparesis and ataxia, absence of obvious spinal pain and a high prevalence of incontinence.
The overall aims of the thesis were to investigate the prevalence of PDM, to clinically and pathologically characterize this unique disorder in pugs and to explore underlying aetiologies. The importance of congenital vertebral malformations (CVMs) was examined using advanced diagnostic imaging. A potential contribution of an autoimmune aetiology was studied by analysing biomarkers in blood and cerebrospinal fluid. The necrotizing meningoencephalitis (NME) susceptibility dog leucocyte (DLA) class II risk was assessed and a genetic contribution to PDM was investigated by molecular genetics.
In summary, gait abnormalities were common in Swedish pugs and the character of the abnormal gait suggesting an underlying spinal cord disorder. The lack of association between presence, or type, of CVMs in the thoracolumbar vertebral column and neurological deficits, paraparesis and ataxia, suggested that other or additional factors were important for the development of PDM. Neuropathological examination showed that the clinical disease, PDM, was caused by the formation of profound meningeal fibrosis that interfered with the vascular supply to the spinal cord as well as caused obstruction of cerebrospinal fluid (CSF) flow with subsequent parenchymal spinal cord destruction. In addition a considerable number of PDM pugs presented with inflammation in the central nervous system. A contribution of the immunological system on the development of PDM was supported by the finding of anti-GFAP autoantibodies in the CSF of pugs with PDM. Our results also indicated that the DLA class II risk haplotype for necrotizing meningoencephalitis (NME), even in a heterozygous state, may cause a more severe PDM phenotype. The potential relevance of multiple candidate genes to the pathogenesis of PDM, including those implicated with bone homeostasis, the differentiation of cartilage, inflammation and fibrotic scar tissue formation, should be confirmed in future studies.
KeywordsKeywords: pug; ataxia; constrictive myelopathy; subarachnoid diverticula; caudal articular process; meningeal fibrosis; lymphohistiocytic inflammation; central nervous system; DLA class II
Published inActa Universitatis Agriculturae Sueciae
2022, number: 2022:74
ISBN: 978-91-8046-024-8, eISBN: 978-91-8046-025-5
Publisher: Swedish University of Agricultural Sciences