Granulomatous meningoencephalomyelitis

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Section showing characteristic perivascular cuff lesion around a blood vessel associated with granulomatous meningoencephalomyelitis[1]

Primary granulomatous meningoencephalomyelitis (GME) is a common immune-mediated neurological disease of the dog.

Secondary granulomatous meningoencephalomyelitis has also been recorded due to primary fungal and protozoan pathogens.

Primary GME is a central nervous system disorder is characterized by focal or multifocal non-suppurative granulomatous lesions within the white matter of the brain and cervical spinal cord, characterised by dense aggregates of inflammatory cells arranged in whorling patterns around blood vessels[2].

Like Greyhound meningoencephalitis and necrotizing meningoencephalitis (Pugs, Maltese Terriers, Pekingese, Yorkshire Terriers), this disease is thought to be either an immune-mediated disease or caused by infectious pathogens[3].

Mycoplasma canis has been identified with PCR analysis of postmortem brain samples from affected dogs[4] and immunohistochemical studies have shown a preponderance of anti-T cell receptor complex antibodies[5].

Clinically affected dogs usually present with a brief history (3 - 5 days) of progressive neurological symptoms such as behavior abnormalities, seizures, compulsive pacing, circling, or cranial nerve abnormalities may be observed. Choroiditis, retinal detachment, and secondary glaucoma may lead to blindness. Severely affected dogs usually progress to tetraparesis and absent postural reflexes.

The antemortem diagnosis of these disorders is clinically challenging. Blood tests, CSF analysis and imaging are often inconclusive and histopathology is often required for a definitive diagnosis. When there is no definitive histopathological diagnosis, the terminology meningoencephalitis of unknown etiology (MUE) may be used[6].

Histologically, lesions consist of perivascular cuffs distributed within the CNS but they occur most commonly within the white matter of the cerebrum, cerebellum, caudal brainstem or cervical spinal cord[7]. Comparable lesions may also be observed in grey matter and there may be lesions involving the vasculature of leptomeninges or choroid plexus. These perivascular cuffs comprise principally macrophages and occasional lymphocytes, monocytes, plasma cells, neutrophils and multinucleate giant cells[8].

A differential diagnosis would include meningoencephalitis caused by Cryptococcus spp, neospora caninum, canine distemper virus, Histoplasma capsulatum, Coccidioides immitis, Cladophialophora bantiana, Aspergillus spp, Fusarium spp, Sporobolomyces roseus[9] and Balamuthia mandrillaris[10].

Although radiation therapy[11] and pharmacotherapy with azathioprine, cytosine arabinoside[12][13], cyclosporine[14], procarbazine and prednisolone[15] has been shown to alleviate clinical symptoms in the short-term, this disease is rapidly progressive with poor survival times after clinical onset.

References

  1. O'Neill, G et al (2005) Granulomatous meningoencephalomyelitis in dogs: A review. Irish Veterinary Journal 58:86-92
  2. Schatzberg SJ (2010) Idiopathic granulomatous and necrotizing inflammatory disorders of the canine central nervous system. Vet Clin North Am Small Anim Pract 40(1):101-120
  3. Kang, MH et al (2009) 7.0-Tesla Tesla magnetic resonance imaging of granulomatous meningoencephalitis in a Maltese dog: a comparison with 0.2 and 1.5-Tesla. J Vet Med Sci 71(11):1545-1548
  4. Barber RM et al (2012) Broadly reactive polymerase chain reaction for pathogen detection in canine granulomatous meningoencephalomyelitis and necrotizing meningoencephalitis. J Vet Intern Med 26(4):962-968
  5. Park ES et al (2012) Comprehensive immunohistochemical studies on canine necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME). Vet Pathol 49(4):682-692
  6. Schatzberg SJ (2005) An update on granulomatous meningoencephalitis, necrotizing meningoencephalitis and necrotizing leukoencephalitis. 23rd ACVIM Proceedings pp:351–353
  7. Braund KG (1985) Granulomatous meningoencephalomyelitis. J Am Vet Med Assoc 186:138-141
  8. Braund KG et al (1978) Granulomatous meningoencephalomyelitis in six dogs. J Am Vet Med Assoc 172:1195-1200
  9. Saey V et al (2011) Granulomatous meningoencephalitis associated with Sporobolomyces roseus in a dog. Vet Pathol 48(6):1158-1160
  10. Hodge PJ et al (2011) Another case of canine amoebic meningoencephalitis--the challenges of reaching a rapid diagnosis. Parasitol Res 108(4):1069-1073
  11. Munana KR & Luttgen PJ (1998) Prognostic factors for dogs with granulomatous meningoencephalomyelitis: 42 cases (1982-1996). J Am Vet Med Assoc 212:1902-1906
  12. Menaut P et al (2008) Treatment of 11 dogs with meningoencephalomyelitis of unknown origin with a combination of prednisolone and cytosine arabinoside. Vet Rec 162(8):241-245
  13. Nuhsbaum MT et al (2002) Treatment of granulomatous meningoencephalomyelitis in a dog. Vet Ophthalmol 5:29-33
  14. Adamo FP & O'Brien RT (2004) Use of cyclosporine to treat granulomatous meningoencephalitis in three dogs. J Am Vet Med Assoc 225:1211-1216
  15. Platt SR (2002) Recommendations for corticosteroid use in neurological diseases. In 20th Annual ACVIM Forum. Edited by Davenport DJ, Lester GD. Dallas: American College of Veterinary Internal Medicine; pp:370-372