Pug encephalitis

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MRI from a Pug with necrotizing meningoencephalitis, showing hyperintense regions (arrows) in the cerebrum[1]

Necrotizing meningoencephalitis of Pugs (Pug encephalitis) is a genetic immune-mediated disease of Pugs characterized by a progressive early-onset meningoencephalitis[2].

This dog has been reported in the Pug, Pekingese[3], Chihuahua[4], Yorkshire Terrier, Shih Tzu and Maltese breeds.

The genetic mutation has been localized to the dog leukocyte antigen class II on chromosome 12[5]. This mutations is similarly responsible for hypertrophic osteodystrophy in the Weimaraner, anal furunculosis in German shepherds and hypoadrenocorticism in the Nova Scotia Duck Tolling Retriever[6]. The mutations results in autoantibodies against glial fibrillary acidic protein +ve astrocytes[7].

This is a progressive and fatal disease affecting 1 – 2% of Pugs, usually before 7 years of age[8]. There has been no laboratory evidence for an infectious cause[9], and the etiology is now presumed to be immunologic.

Pug dog encephalitis 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.

Clinically affected pugs present as either an acute cases, with onset and progression of clinical signs occurring within 2 weeks[10], or a chronic form ranging from 4 to 6 months, showing various clinical signs with progressive ataxia, mental unresponsiveness, partial or full seizures, partial blindness[11], circling, ataxia and eventual recumbency, dementia and death.

Diagnosis is based on presenting clinical signs, histopathological evidence of perivacular encephalitis and exclusion of other causes of encephalitis.

Histopathologically, the affected regions show characteristic wide distribution of degenerated neurons with glial satellitosis and neuronophagia and prominent perivascular cuffing with lymphoid cells[12]. The encephalitis is usually restricted to the cerebrum in Pugs, whereas other parts of the brain and brainstem may be involved in other breeds[13].

DNA testing is considered a definitive diagnosis.

A differential diagnosis would include canine distemper virus, canine herpesvirus, rabies, tick-borne encephalitis and Toxoplasma spp infection.

Treatment with prednisolone (1 mg/kg every 24 hours) is sometimes successful in less severely affected cases, but death often ensues 2 - 12 months after first clinical signs[14].

References

  1. Texas A&M
  2. Pedersen N et al (2011) Dog leukocyte antigen class II-associated genetic risk testing for immune disorders of dogs: simplified approaches using Pug dog necrotizing meningoencephalitis as a model. J Vet Diagn Invest 23(1):68-76
  3. Cantile C et al (2001) Necrotizing meningoencephalitis associated with cortical hippocampal hamartia in a Pekingese dog. Vet Pathol 38(1):119-122
  4. Higgins RJ et al (2008) Necrotizing meningoencephalitis in five Chihuahua dogs. Vet Pathol 45(3):336-346
  5. Barber RM et al (2011) Identification of risk loci for necrotizing meningoencephalitis in Pug dogs. J Hered 102(1):S40-S46
  6. Safra N et al (2011) Expanded dog leukocyte antigen (DLA) single nucleotide polymorphism (SNP) genotyping reveals spurious class II associations. Vet J 189(2):220-226
  7. Shibuya M et al (2007) Autoantibodies against glial fibrillary acidic protein (GFAP) in cerebrospinal fluids from Pug dogs with necrotizing meningoencephalitis. J Vet Med Sci 69(3):241-245
  8. Greer KA et al (2009) Heritability and transmission analysis of necrotizing meningoencephalitis in the Pug. Res Vet Sci 86:438–442
  9. Levine JM et al (2008) Epidemiology of necrotizing meningoencephalitis in Pug dogs. J Vet Intern Med 22:961–968
  10. Uchida K et al (1999) Detection of an autoantibody from Pug dogs with necrotizing encephalitis (Pug dog encephalitis). Vet Pathol 36(4):301-307
  11. Beltran WA & Ollivet FF (2000) Homonymous hemianopia in a pug with necrotising meningoencephalitis. J Small Anim Pract 41(4):161-164
  12. Kuwabara M et al (1998) Magnetic resonance imaging and histopathology of encephalitis in a Pug. J Vet Med Sci 60(12):1353-1355
  13. Summer, BA et al (1995) Veterinary Neuropathology. Mosby, St.Louis. pp:95–188
  14. Kitagawa M et al (2007) A canine case of necrotizing meningoencephalitis for long-term observation: clinical and MRI findings. J Vet Med Sci 69(11):1195-1198