A potential early clinical phenotype of necrotizing meningoencephalitis in genetically at‐risk pug dogs |
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Authors: | Rebecca Windsor Samuel Stewart Jessica Schmidt Mario Mosqueda Ignazio Piras Stefan M. Keller Briana Steinmetz Dori L. Borjesson Matthew Huentelman Chand Khanna |
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Affiliation: | 1. Ethos Veterinary Health, Woburn Massachusetts, USA ; 2. Ethos Discovery (501c.3.), San Diego California, USA ; 3. Neurogenomics Division, Translational Genomics Research Institute, Phoenix Arizona, USA ; 4. Department of Pathology, Microbiology, Immunology, University of California, Davis, Davis California, USA |
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Abstract: | BackgroundNecrotizing meningoencephalitis (NME) in the pug dogs is a fatal neuroinflammatory disease associated with rapid progression and poor response to conventional immunosuppressive therapy. Diagnosis is typically made after severe neurological abnormalities have manifested.Hypothesis/ObjectivePug dogs at genetic risk for NME might manifest neurological abnormalities before developing pathognomonic clinical signs of NME.AnimalsThirty‐six pug dogs less than 4 years of age asymptomatic for NME.MethodsProspective observational cohort study with germline genome‐wide genotyping. Neurological examinations were performed 4 weeks apart to document reproducible findings of central nervous system disease. Magnetic resonance imaging, cerebrospinal fluid analysis, and testing for infectious diseases were performed in all pugs with reproducible abnormalities detected on neurological examination.ResultsThe overall risk allele frequency in this cohort was 40%; 5 (14%) dogs were high risk, 19 (53%) dogs were medium risk, and 12 (33%) dogs were low genetic risk for NME. Reproducible abnormalities detected on neurological examination were identified in 8/24 (33%) genetically at‐risk dogs and 0/12 (0%) low risk dogs. Clinical abnormalities included multifocal spinal pain in 8/8, reduced menace response in 5/8, and lateralizing postural reaction deficits in 5/8 pugs. There was a strong association between genotype risk and the presence of this clinical phenotype (P = .03).Conclusions and Clinical ImportanceOur findings suggest the presence of a novel early clinical phenotype of NME in apparently asymptomatic genetically at‐risk pugs which might be used to plan early diagnostic and therapeutic clinical trials. |
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Keywords: | encephalitis immune inflammatory meningitis |
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