Meningoencephalomyelitis of unknown origin (MUO) is a heterogeneous group of overlapping central nervous system inflammatory diseases of unknown cause. This article highlights the current understanding of MUO and its phenotypic variants encountered in clinical practice. Diagnostic evaluation of presumptive MUO includes lesion distribution on magnetic resonance imaging and ruling out other acquired diseases. Recent evidence provides further knowledge of immune-mediated processes that underlie the pathogenesis of MUO. Current empiric treatment options include corticosteroids and other adjunctive immunomodulating therapies. As the understanding of neuroimmunology and genetic influences on these disorders evolves, a more targeted treatment approach is becoming attainable.

Perspectives on meningoencephalomyelitis of unknown origin.

Meningoencephalomyelitis of unknown origin (MUO) encompasses a group of idiopathic, most likely immune mediated, inflammatory central nervous system diseases that cause clinical, diagnostic and treatment challenges to veterinary neurologists. Clinical criteria for obtaining this presumptive diagnosis are currently available, and multiple treatment protocols have previously been investigated in small (prospective or retrospective) case series. As this group of diseases is considered fatal if left untreated, the identification of clinically usable prognostic indices could be of great value. This review provides an overview of recent developments in the clinical presentation, diagnostic findings, possible prognostic factors, treatment and outcome in dogs diagnosed with MUO.

Clinical presentation, diagnostic findings, prognostic factors, treatment and outcome in dogs with meningoencephalomyelitis of unknown origin: A review.

Background
Granulomatous meningoencephalomyelitis (GME) and necrotizing meningoencephalitis (NME) are common inflammatory conditions of the central nervous system of dogs. Infectious pathogens, particularly viruses, are suspected to contribute to the etiopathogenesis of GME and NME.

Hypothesis
Broadly reactive PCR might aid in the identification of infectious agents in GME and NME.

Animals
Sixty-eight client-owned dogs evaluated by necropsy at 1 university referral hospital.

Methods
A mixed prospective/retrospective case-control study was performed. Brain tissue prospectively collected at necropsy from GME, NME, and control cases was evaluated by broadly reactive polymerase chain reaction (PCR) for adenoviruses, bunyaviruses, coronaviruses, enteroviruses, flaviviruses, herpesviruses, paramyxoviruses, and parechoviruses. In addition, these tissues were retrospectively evaluated for the presence of mycoplasmas by PCR, culture, and immunohistochemistry (IHC).

Results
Brain tissue was collected from 11 GME and 27 NME cases and 30 controls. Viral nucleic acids were not identified in the 6 GME cases, 25 NME cases, and 2 controls evaluated by viral PCR. Mycoplasma canis was identified by Mycoplasma genus PCR in 1/5 GME and 4/25 NME cases and subsequently was cultured from 4/5 GME and 4/8 NME cases as well as 2/9 controls. The IHC did not detect M. canis in any of the 11 GME and 27 NME cases or 14 controls evaluated with strain PG14 polyclonal antiserum.

Conclusions and Clinical Importance
The negative results suggest that viral pathogens are not common in the brain tissue of dogs with GME and NME. Further investigation is warranted to determine the importance of M. canis in cases of GME and NME.

https://www.onlinelibrary.wiley.com/doi/epdf/10.1111/j.1939-1676.2012.00954.x

Broadly reactive polymerase chain reaction for pathogen detection in canine granulomatous meningoencephalomyelitis and necrotizing meningoencephalitis.

Due to their unique population structure, purebred dogs have emerged as a key model for the study of complex genetic disorders. To evaluate the utility of a newly available high-density canine whole-genome array with >170,000 single nucleotide polymorphisms (SNPs), genome-wide association was performed on a small number of case and control dogs to determine disease susceptibility loci in canine necrotizing meningoencephalitis (NME), a disorder with known non-Mendelian inheritance that shares clinical similarities with atypical variants of multiple sclerosis in humans. Genotyping of 30 NME-affected Pug dogs and 68 healthy control Pugs identified 2 loci associated with NME, including a region within dog leukocyte antigen class II on chromosome 12 that remained significant after Bonferroni correction. Our results support the utility of this high-density SNP array, confirm that dogs are a powerful model for mapping complex genetic disorders and provide important preliminary data to support in depth genetic analysis of NME in numerous affected breeds.

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Identification of Risk Loci for Necrotizing Meningoencephalitis in Pug Dogs

In dogs, there are several idiopathic meningoencephalitides, such as necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME). Al...

https://journals.sagepub.com/doi/pdf/10.1177/0300985811429311

Comprehensive immunohistochemical studies on canine necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME).

Necrotizing meningoencephalitis (NME) is a disorder of Pug Dogs that appears to have an immune etiology and high heritability based on population studies. The present study was undertaken to identify a genetic basis for the disease. A genome-wide association scan with single tandem repeat (STR) markers showed a single strong association near the dog leukocyte antigen (DLA) complex on CFA12. Fine resolution mapping with 27 STR markers on CFA12 further narrowed association to the region containing DLA-DRB1, -DQA1 and, -DQB1 genes. Sequencing confirmed that affected dogs were more likely to be homozygous for specific alleles at each locus and that these alleles were linked, forming a single high risk haplotype. The strong DLA class II association of NME in Pug Dogs resembles that of human multiple sclerosis (MS). Like MS, NME appears to have an autoimmune basis, involves genetic and nongenetic factors, has a relatively low incidence, is more frequent in females than males, and is associated with a vascularly orientated nonsuppurative inflammation. However, NME of Pug Dogs is more aggressive in disease course than classical human MS, appears to be relatively earlier in onset, and involves necrosis rather than demyelination as the central pathobiologic feature. Thus, Pug Dog encephalitis (PDE) shares clinical features with the less common acute variant forms of MS. Accordingly, NME of Pug Dogs may represent a naturally occurring canine model of certain idiopathic inflammatory disorders of the human central nervous system.

M. Wallace

Papers

Necrotizing meningoencephalitis of Pug Dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis