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Abstract
Numerous idiopathic inflammatory disorders of the canine central nervous system (CNS) have been described over the past several decades. These include specific histopathological entities such as granulomatous meningoencephalomyelitis (GME) and necrotizing meningoencephalitis (NME) as well as those that lack a specific histological diagnosis, collectively referred to as meningoencephalomyelitis of unknown etiology (MUE). These idiopathic CNS disorders comprise a group of clinically challenging diseases that frequently carry a poor prognosis despite aggressive treatment. Although the etiopathogeneses of GME, NME and MUE are poorly understood, environmental (eg CNS infection) and genetic factors are suspected to contribute to disease development. To elucidate possible infectious and genetic etiopathogenic mechanisms, molecular screening tools were employed for pathogen detection in cases of GME, NME and MUE and genome-wide association (GWA) of single nucleotide polymorphisms was performed on cases of NME. Mycoplasma canis and was identified as a candidate etiological agent for GME and NME and La Crosse virus (LACV) as a candidate agent for MUE, while members of the genera Ehrlichia, Anaplasma, Rickettsia, Bartonella and Borrelia and viral groups adenovirus, alphavirus, bornavirus, bunyavirus, coronavirus, enterovirus, flavivirus, herpesvirus, paramyxovirus, parechovirus, polyomavirus and rhabdovirus species were determined to be infrequently associated with GME, NME and MUE. Additionally, GWA of Pug dogs with NME identified two loci strongly associated with disease development, including a 4.1 Mb region of dog leukocyte antigen class II. Although further research is needed to validate the role of M. canis and LACV in these disorders, these results support previous theories of multifactorial etiopathogeneses, where both environmental triggers and genetic susceptibility play an important role in disease pathogenesis. Moreover, the genetic risk loci identified in cases of NME provide important preliminary data to support in depth genetic analysis of this disease and other idiopathic meningoencephalomyelitides in numerous affected breeds.