Unraveling MUO in Dogs: From Breed Susceptibility to Immune-Mediated Pathways

Among canine neurological conditions, Meningoencephalitis of Unknown Origin (MUO) remains one of the most challenging to diagnose and manage. Once considered a vague, catch-all term for non-infectious encephalitis, MUO is now recognized as a spectrum of immune-mediated inflammatory diseases of the central nervous system (CNS), including Granulomatous Meningoencephalomyelitis (GME) and Necrotizing Encephalitides (NME/NLE^)1. 

Although the exact cause is unclear, increasing evidence supports an autoimmune origin, where the dog’s own immune system attacks the brain and spinal cord. 

What Exactly is MUO? 
MUO refers to a presumed immune-mediated inflammation of the brain, sometimes extending to the spinal cord. 
Dogs commonly present with seizures, ataxia, circling, blindness, cranial nerve deficits, or behavioural changes, depending on the lesion’s location¹. 

It remains a diagnosis of exclusion, made only after infectious causes have been ruled out using serology, CSF analysis, or PCR testing². 

Clinical Tip: When a small-breed dog under six years presents with acute neurological signs and no fever, MUO should be considered an important differential^3,4. 

Histopathologically, MUO is characterized by mononuclear infiltrates, perivascular cuffing, and areas of necrosis, especially in necrotizing variants⁵. 

Inside the Immune Storm 
MUO is now viewed as an autoimmune CNS disease driven by abnormal T-cell activity. Studies indicate that Th17 cells and cytokines such as IL-17 and IFN-γ play a major role in driving inflammation and neuronal damage⁶. 

Lesions show lymphocytic and macrophagic infiltration with demyelination, often resembling multiple sclerosis in humans⁷. 
MRI typically shows multifocal, asymmetric T2/FLAIR hyperintensities, while CSF findings reveal lymphocytic pleocytosis and elevated protein⁸. 

Clinical Note: MRI combined with CSF analysis remains the most reliable method for early MUO detection³. 

MUO vs. Infectious Encephalitis — Quick Comparison 
Both MUO and infectious encephalitis can present similarly. Differentiating them early helps guide correct treatment⁹. 

MUO — Key Features 

• No systemic fever 

• Signs vary with lesion site 

• Common findings: Altered mentation, cranial nerve and proprioceptive deficits, ataxia, seizures 

• CSF: Lymphocytic pleocytosis 

• MRI: Multifocal lesions 

• Infectious testing: Negative 

Infectious Encephalitis — Key Features 

• May have fever 

• Overlapping neurological signs (ataxia, seizures, cranial nerve deficits) 

• CSF: Neutrophilic or mixed response 

• PCR or serology: May be positive 

• Possible exposure history — tick bites, travel, or local outbreaks 

Clinical Reminder: Always rule out infectious causes before initiating corticosteroids. Early immunosuppression may mask infection and complicate diagnosis. 

Breed Predispositions & Genetic Factors 
Certain small and toy breeds show consistent patterns of MUO, suggesting a heritable immune predisposition. 

• In Pugs, necrotizing meningoencephalitis (NME) has a strong association with DLA/MHC class II haplotypes (DRB1-010011, DQA1-00201, DQB1-01501), supporting an autoimmune genetic link^3,11. 

• Maltese and Chihuahuas also exhibit MHC II–linked risks, indicating a shared immune mechanism³. 

• GME is less clearly linked to genetics but may involve similar autoimmune pathways in predisposed small breeds. 

Table 1. MUO Subtypes, Histopathology, and Breed Predispositions^3,10 

Clinical Insight: 

• Young toy breeds → often necrotizing forms (NME/NLE) with genetic-immune basis. 

• Middle-aged small breeds → commonly GME, an immune-mediated variant. 

Reflective Insight 
MUO is no longer the vague “mystery inflammation” it was once thought to be. It represents a complex but decipherable immune disorder that rewards early recognition and evidence-based interpretation. Understanding its genetic and immunologic framework helps clinicians approach each case with greater confidence and helps patients achieve a better long-term outcome. 

References 

1. Cornelis I, Van Ham L, Gielen I, De Decker S, Bhatti SF. Clinical presentation, diagnostic findings, prognostic factors, treatment and outcome in dogs with meningoencephalomyelitis of unknown origin: a review. The Veterinary Journal. 2019 Feb 1;244:37-44. 

2. Bach FS, Cray C, Burgos AP, Junior JA, Montiani-Ferreira F. A comparison between neurological clinical signs, cerebrospinal fluid analysis, cross-sectional CNS imaging, and infectious disease testing in 168 dogs with infectious or immune-mediated meningoencephalomyelitis from Brazil. Frontiers in veterinary science. 2023 Oct 25;10:1239106. 

3. Nessler JN, Tipold A. Of potential new treatment targets and polythetic approach in meningoencephalitis of unknown origin: a review. Frontiers in veterinary science. 2024 Oct 15;11:1465689. 

4. Barber R, Downey Koos L. Treatment with cytarabine at initiation of therapy with cyclosporine and glucocorticoids for dogs with meningoencephalomyelitis of unknown origin is not associated with improved outcomes. Frontiers in Veterinary Science. 2022 Jun 10;9:925774. 

5. Robinson KE. Transcriptomic evaluation of granulomatous and nectrotizing meningoencephalitis of dogs. University of Georgia, Athens, Georgia. 2020:80. 

6. Barber R, Barber J. Differential T-cell responses in dogs with meningoencephalomyelitis of unknown origin compared to healthy controls. Frontiers in Veterinary Science. 2022 Aug 4;9:925770. 

7. Zdora I, Raue J, Söbbeler F, Tipold A, Baumgärtner W, Nessler JN. Case report: Lympho-histiocytic meningoencephalitis with central nervous system vasculitis of unknown origin in three dogs. Frontiers in veterinary science. 2022 Aug 24;9:944867. 

8. Levitin HA, Lampe R, Hecht S. Case report: meningoencephalomyelitis of unknown etiology manifesting as a bilateral cranial polyneuropathy in 3 dogs. Frontiers in Veterinary Science. 2020 Jun 12;7:326.  
9. Patterson A. Meningoencephalomyelitis of Unknown Origin in Dogs. Vet Ir J Small Animal. 2023 Nov; (Small Animal Continuing Education) 
10. Oshima A, Ito D, Katakura F, Miyamae J, Okano M, Nakazawa M, Kanazono S, Moritomo T, Kitagawa M. Dog leukocyte antigen class II alleles and haplotypes associated with meningoencephalomyelitis of unknown origin in Chihuahuas. Journal of Veterinary Medical Science. 2023;85(1):62-70.

Related Experts

Dr. Hamid Shah

BVSc, MS, PhD PPAM – Pet Practitioners Association of Mumbai

Veterinary