Epidemiology of Necrotizing Meningoencephalitis in Pug Dogs

Abstract

Background: Although the histopathologic features of necrotizing meningoencephalitis (NME) have been described previously, little information is available concerning the signalment, geographic distribution, seasonal onset, treatment, and survival of affected dogs.Animals: Sixty Pugs with NME and 14 contemporaneous control Pugs with other intracranial diseases (non-NME group). Methods: Pugs that were euthanized or died because of intracranial disease were prospectively obtained. All dogs had necropsy, histopathology, and testing for various infectious diseases and were subsequently divided into NME and non-NME groups. Signalment, geographic distribution, seasonal onset, treatment, and survival were compared between groups.Results: In Pugs with NME, median age at onset of clinical signs was 18 months (range, 4-113 months). A greater proportion of female dogs were present in the NME group (40/60) compared with the control group (6/14). Pugs with NME had a significantly lower mean weight (7.81 kg) than control Pugs (9.79 kg) (P 5 .012). Mean survival in Pugs with NME was 93 days (range, 1-680 days), with dogs receiving any form of treatment living significantly longer than those that were not treated (P 5 .003). Anticonvulsive drugs were the only treatment significantly associated with longer survival (P 5 .003).Conclusions and Clinical Importance: NME appears to be a common cause of intracranial signs in Pugs, based on the high proportion of NME dogs reported in this population. Pugs with NME are most commonly young adult female dogs. Although further investigation is needed to determine the optimal treatment of NME, anticonvulsive drugs appear to beneficially affect duration of survival.

Perspectives on Meningoencephalomyelitis of Unknown Origin

“…58,69,80,93 Although CSF analysis is more sensitive than MR imaging in identifying abnormalities consistent with inflammatory disease, normal CSF analysis has been described in cases with histopathologically confirmed inflammatory CNS disease. 5,16,58,75,80,107 Overall, CSF analysis is highly variable in the various types of MUOs but with little difference between these groups. 58,120 Other analyses of CSF have been studied for CNS inflammatory diseases, but lack disease specificity.…”

“…4 Dogs with NME commonly manifest forebrain signs, especially seizures, because of lesions in the cerebral cortex. 3,58,80,82 Other forebrain signs include lethargy, anorexia, central blindness, circling, and head-pressing. 78,80 Cervical spinal hyperesthesia may be evident depending on the extent of leptomeningitis.…”

“…3,58,80,82 Other forebrain signs include lethargy, anorexia, central blindness, circling, and head-pressing. 78,80 Cervical spinal hyperesthesia may be evident depending on the extent of leptomeningitis. 78 The hallmark of NME is extensive necrosis, which varies in severity from neuronal necrosis and gliosis in the early stage to gross cavitation of parenchyma in advanced disease.…”

“…138 Along with the wide range of age of onset and variable clinical course, this finding suggested the possibility of genetic modifiers or other influences contributing to the disease phenotype. 80,138 Genome-wide association studies identified CFA 12 near the dog leukocyte antigen (DLA) complex with the development of NME, 12,139 and this region was subsequently focused on the region containing DLA-DRB1, -DQA1, and -DQB1 genes. 12 Although the causative mutation had not been identified, fine mapping and candidate gene sequencing implicated linked-allelic homozygosity in the risk of developing NME.…”

Dog Leukocyte Antigen Class II–Associated Genetic Risk Testing for Immune Disorders of Dogs: Simplified Approaches Using Pug Dog Necrotizing Meningoencephalitis as a Model

“…Necrotizing meningoencephalitis in Pugs, formerly known as Pug dog encephalitis, is a progressive and fatal disease affecting 1-2% of Pugs, usually before 7 years of age. 9,27 There has been no laboratory evidence for an infectious cause, 27,32,35 and the etiology is now presumed to be immunologic. 9,35 Pug dog NME has been likened to fulminate atypical forms of human multiple sclerosis in its form and strong association to a specific human leukocyte antigen class II genotype.…”