Phenotypic Abnormalities in Asymptomatic Pugs with Potential Early NME

Necrotizing meningoencephalitis (NME) is a devastating fatal disease that affects primarily Pug dogs, hence the term Pug Dog Encephalitis (PDE). Genetic risk factors for PDE have been thoroughly evaluated with a mutation on chromosome 12 within the dog leukocyte antigen (DLA II) locus representing the strongest identified genetic risk factor. Similar MHC II gene mutations have been associated with increased risk for multiple sclerosis (MS) in humans. In a previous study we prospectively evaluated germline risk for PDE coupled with assessment of systemic cytokine levels and lymphocyte subsets and identified an altered systemic inflammatory signature in genetic at-risk but asymptomatic Pugs which included elevations in IL-10 and reduced CD4+ T cells. In a follow-up study we evaluated cytokines in asymptomatic Pugs less than 4 years of age and performed serial neurological exams to identify any phenotypic abnormalities that may manifest prior to the presentation of fulminant neurological signs. MRI and CSF were evaluated in all neurologically abnormal Pugs with a multifocal CNS localization with reproducible neurological abnormalities. Dogs with MRI +/- CSF abnormalities were enrolled into a therapeutic trial with either cytarabine and prednisone or mesenchymal stem cells. Results from these studies and future investigations will be discussed.