Granulomatous Meningoencephalomyelitis

Granulomatous meningo-encephalomyelitis (GME) is a sporadic, idiopathic inflammatory disease of the CNS of dogs and, rarely, cats.  This disease appears to have a worldwide distribution, with recent reports coming from the USA, Australia, New Zealand, and Europe.

Signalment and Clinical Signs:  Most cases of GME occur in small breed dogs, especially in Pug dogs, although any breed may be affected.  The majority of confirmed cases occur in young to middle-age dogs, with a mean age around five years.  GME occurs in both sexes; however, there appears to be a higher prevalence in females.  The onset of disseminated GME is acute, with a progressive course over a 1-8 week period, and dogs with focal GME tend to have a longer clinical course.  Common clinical signs include incoordination, ataxia and falling, cervical hyperesthesia, head tilt, nystagmus, facial and/or trigeminal nerve paralysis, circling, visual deficits, seizures, depression and titanic spasms.  An infrequently reported ocular form of GME appears to be related to lesions localized in optic nerves and optic chiasm resulting in visual impairment, uveitis, and abnormal papillary reflexes.  A hyperemic and edematous optic disk may be seen on opthalmological examination, vessels may be dilated, and focal hemorrhage may be present.  Occasionally, ocular and neurological signs may be seen concurrently in the affected animals.

Etiopathogenesis: The cause of GME is unknown.  Immunohistochemical studies have indicated that many lymphocytic/lymphoblastic cells are immunoglobulin bearing.  The recent report of IgE positive cells in perivascular cuffs in two dogs with GME lends credence to a possible underlying immunopathological perturbation.  Results of an immunomorphological study further suggested a T cell-mediated delayed-type hypersensitivity of an organ-specific autoimmune disease as a possible pathogenic mechanism for this unique lesion.  It is also possible that GME represents an altered host response to an infectious agent.

Diagnosis:  A tentative diagnosis of GME may be suggested by signalment data, clinical course of the disease, and clinical signs.  Hematology, serum chemistry, and urinalysis are usually normal.  GME must be distinguished from other granulomatous lesions in the brain that are associated with known   infectious agents as well as from other CNS disorders including sporadic necrotizing meningoencephalitis and granulomatous leptomeningitis in beagles associated with E. coli.  The most useful diagnostic aid is cerebrospinal fluid (CSF) analysis.  In most GME cases, CSF is abnormal with mild to pronounced pleocytosis, ranging from 50-900/ųl.  Cells are predominantly mononuclear, including lymphocytes (60-90%), monocytes (10-20%) and variable numbers of large anaplastic mononuclear cells with abundant lacy cytoplasm.  While neutrophils typically comprise 1-20% of the cell type differential, they may be the predominant cell type on rare occasions.  Protein in CSF is usually mildly to moderately elevated, ranging from 40-400 mg/dl.  CSF pressure may be normal or increased.  A combination of CSF and MRI findings may also be useful, the latter being characterized by isointense lesions in T1-weighted images.  Although infrequently performed, a brain biopsy can be a very useful diagnostic test in animals with focal lesions.

Pathology:  Lesions associated with GME are restricted to the CNS.  In brain and/or spinal cord, soft, grey, oval lesions with irregular or well-defined margins occasionally can be discerned on gross sectioning, especially with large focal lesions.  Sometimes, the cut section of the CNS has a granular, mottled appearance with finger-like projections.  Meninges may appear thickened and cloudy, and occasionally optic nerves are grossly enlarged.  Internal hydrocephalus may be present in some dogs.  Microscopic lesions are usually widely distributed through the CNS, but primarily in the white matter of the cerebrum, caudal brain stem, cerebellum, and cervical spinal cord.  The lesions are characterized by a dense aggregation of mesenchymal cells arranged in a whirling perivascular pattern.  These perivascular cuffs are composed of histiocytes and varying numbers of predominantly CD3 antigen-positive lymphocytes, monocytes, and plasma cells set in nets of reticulin fibers.  Aggregates of histiocytic cells (granulomatous nodules), sometimes with an apparent epitheloid differentiation, appear to develop eccentrically from a previously formed lymphocytic cuff and may also be seen at the center of the most severe lesions.  Granulomatous lesions may compress and invade adjacent CNS parenchyma, resulting in necrosis, glial cell reaction, and edema.  Coalescence of granulomatous lesions from a large number of adjacent blood vessels may produce a true space occupying mass.  Focal lesions most commonly occur in the brain stem, especially in the pontomedullary region, and cerebral white matter.  Large, focal lesions usually produce signs suggestive of a single, space-occupying mass, with signs varying according to the location of the lesions.  These lesions can usually be detected using CT or MRI imaging techniques.

Treatment and prognosis:  Prognosis for permanent recovery is poor.  Shortest survival periods, ranging from several days to weeks, are seen with the disseminated and ocular forms.  Longer survival periods of from 3-6 months are more suggestive of a focal lesion.  Some dogs die from aspiration pneumonia secondary to megaesophagus.  Long-term therapy is generally unsatisfactory, although temporary remission of signs is often achieved with corticosteroid administration, such as oral prednisone.  Most dogs will require continued therapy to prevent recurrence of signs.  Improvement may last for several days, week, or months, although most eventually succumb to the disease.  Part of the temporary improvement may be related to a reduction in mast cell function in dogs receiving glucocorticoid medication.  Cessation of glucocorticoid therapy is invariably associated with rapid and dramatic clinical deterioration.  The ocular form of GME may be treated initially with repositol retrobulbar glucocorticoid in conjunction with oral prednisone therapy.

-by Domenico Bianco, ECFVG Student

-edited by Dr. Angela Smith, ADDL  Graduate student