Necrotizing meningoencephalitis (NME) is a fatal immune-mediated neuroinflammatory disease that predominately affects smaller dog breeds. The Pug is one breed that is most commonly associated with the disease in which it’s often referred to as Pug Dog Encephalitis. The disease is characterized by severe inflammation and necrosis of the brain (overwhelmingly affecting the cerebrum) and typically results in rapid neurological deterioration and death. NME shares several important similarities with multiple sclerosis (MS) in humans including: genetic risk loci (within the major histocompatibility complex class II region), female sex predisposition, young age of onset, and an immune-mediated pathogenesis. These parallels have positioned NME as a comparative model for MS in humans.
NME in dogs, historically, has been recognized as a fatal disease with an acute to subacute onset of clinical signs and rapid progression. Seizures are the most common clinical sign seen in dogs with NME and, by the time of presentation, most with fulminant disease have irreversible brain necrosis. While fulminant disease associated with brain necrosis does occur in humans with MS, it is rare. Most forms of MS in humans follow a far more indolent clinical course, progressing over 30 to 40 years. That form of disease is characterized by a prolonged preclinical phase during which MRI lesions and brain pathology accumulate before neurological disability becomes apparent.
Emerging evidence - as seen in genetically at-risk Pugs - suggests that a comparable preclinical or early inflammatory phase may also exist in dogs with NME. Investigators identified a distinct and reproducible constellation of neurological abnormalities in young, apparently healthy Pugs that were at genomic risk for NME, but that were absent in low-risk dogs. These findings were documented through structured screening of over 250 Pugs across multiple studies. These specific clinical signs include:
- Multifocal spinal hyperesthesia / pain
- Menace response / visual processing deficits (often unilateral)
- Delayed or absent paw placement reflexes (often unilateral)
- Proprioceptive ataxia / loss of balance
These abnormalities were found to be reproducible, progressive over time, and often lateralized. They also mirror the earliest reported symptoms of MS in humans: sensory disturbances (sensations of “pins and needles”), proprioceptive deficits leading to tripping, and visual processing abnormalities. The striking similarity between early canine and human clinical phenotypes supports the hypothesis that there may be early manifestations of NME or, alternatively, a less aggressive immune-mediated neuroinflammatory condition within the same disease spectrum.
A definitive diagnosis of NME requires postmortem histopathology, however MRI and cerebrospinal fluid (CSF) findings can be helpful in signaling neuroinflammatory disease. This was demonstrated in those studies of young, healthy Pugs who were genetically at-risk for NME and also confirmed to be free of other congenital structural abnormalities commonly seen in the breed (e.g., hydrocephalus, Chiari-like malformation, and syringomyelia). In the final analysis, detection of preclinical or early forms of NME (or variant) may be possible through screening that includes: history and owner-reported observations of the dog, thorough physical and neurological examination, neuroimaging (brain MRI), and CSF analysis. Earlier diagnosis could provide the opportunity for earlier intervention – before fulminant disease and cerebral necrosis ensues.
Despite advances in MS therapeutics there is no cure, and many treatments carry serious side effects. While disease-modifying therapies may reduce inflammatory activity in early MS, neuroregeneration and remyelination of axons do not occur with current standard treatments (e.g. corticosteroids, immunosuppressants, interferon-β, and monoclonal antibodies). Similarly, standard immunosuppressive therapy for NME remains largely ineffective once necrosis has developed. Median survival times in affected dogs is approximately 6–7 months after diagnosis. This therapeutic failure underscores the critical importance of identifying disease earlier in its course, before irreversible brain damage occurs.
Recognition of a potential preclinical or early inflammatory stage of NME represents a paradigm shift in how this disease may be approached diagnostically and therapeutically. Identifying genetically at-risk dogs with early neurological abnormalities, supported by MRI and CSF changes, offers a rare opportunity to further explore possible biomarkers of disease, earlier treatment interventions, and improve survival in affected dogs.
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References:
1. Intravenous allogeneic mesenchymal stromal cell therapy in 13 Pugs with presumptive early necrotizing meningoencephalitis. JAVMA 2025. Vol 263(11); pp 1-10. https://doi.org/10.2460/javma.25.05.0354
2. A potential early clinical phenotype of necrotizing meningoencephalitis in genetically at-risk pug dogs. J Vet Intern Med. 2022. Vol 36(4):1382–1389. https://doi.org/10.1111/jvim.16444
3. An early clinical phenotype of necrotizing meningoencephalitis in the Pug reveals similarities to multiple sclerosis in humans. AJVR 2023. Vol 85(1). https://doi.org/10.2460/ajvr.23.07.0164
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