JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

February 2023

N-M26

Signalment (JPC #140798): 11-year-old Jack Russell terrier.

HISTORY: This dog had a 3-week history of severe behavioral changes. CSF analysis showed elevated WBC count. There were no gross lesions.

HISTOPATHOLOGIC DESCRIPTION: Cerebrum with lateral ventricle and hippocampus: Multifocally, primarily within the white matter and extending into the adjacent gray matter and meningeal vasculature, there is perivascular cuffing with expansion of Virchow-Robins space by concentric layers of epithelioid macrophages, lymphocytes, and plasma cells. Adjacent neuroparenchyma has a mild gliosis consisting of increased numbers of reactive astrocytes with large, vesiculate nuclei (astrocytosis) and fewer microglial cells with rod-shaped nuclei (microgliosis). Diffusely, endothelial cells are hypertrophied (reactive) and vessel walls are often transmigrated by previously described inflammatory cells.

MORPHOLOGIC DIAGNOSIS: Cerebrum: Meningoencephalitis, perivascular, lymphohistiocytic, multifocal, moderate, Jack Russell terrier, canine.

CONDITION: Granulomatous meningoencephalitis/meningoencephalomyelitis (GME)

GENERAL DISCUSSION:

Granulomatous meningoencephalitis (GME) is a sporadic disease of young to middle aged small breed dogs (e.g. terrier and toy breeds)
Etiology is unknown, but an immune-mediated process is suspected
Primarily affects the white matter
Two forms seen:
- Focal: Affects primarily thalamus and brainstem, better mean survival time
- Disseminated: No specific predilection

PATHOGENESIS:

Unknown
Inflammatory infiltrates consist primarily of T lymphocytes and activated macrophages; may indicate immune-mediated response

TYPICAL CLINICAL FINDINGS:

Signs vary with location and severity of lesion
Mature dog with progressive neurologic dysfunction often suggestive of a multifocal lesion
CSF evaluation often reveals marked elevated protein (beta globulin) and marked leukocytosis, variable components; lymphocytic, mixed, or neutrophilic

TYPICAL GROSS FINDINGS:

Variable, often no gross lesions
If present, often gray-white discoloration of white matter of brain or spinal cord
Lesions predominate in the white matter

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Multifocal distribution of perivascular accumulations of primarily lymphocytes, plasma cells, and macrophages, mainly within the white matter
Lower numbers of multinucleated giant cell, and epitheloid macrophages also seen
Astrogliosis seen as a secondary reaction
In areas of severe cuffing, inflammatory cells may spill over into adjacent white matter
Chronic cases may have increased amounts of collagen and reticulin in perivascular space

ADDITIONAL DIAGNOSTIC TESTS:

CSF analysis: Increased protein and leukocytosis
Cytology: well-differentiated lymphocytes, plasma cells, and macrophages

DIFFERENTIAL DIAGNOSIS:

Canine distemper encephalitis (N-V11): Mononuclear perivascular cuffing; predilection for white matter; viral inclusions IN/IC in glial cells and neurons; viral antigen in tissue with IHC, generally has Decreased beta globulins in CSF
Fungal (blastomycosis, cryptococcosis), bacterial (Mycobacteria spp., Nocardia spp.), protozoal, or algal (protothecosis) encephalitis: Perivascular and parenchymal changes; identification of organisms in tissue
Lymphoma: Previously classified as neoplastic reticulosis
- A monomorphic population of cells that generally do not infiltrate the surrounding white matter parenchyma
Central malignant histiocytosis: Previously classified as neoplastic reticulosis
- Lesions are focal to multifocal and most often in the cerebrum
- Similar to GME with whirling of neoplastic cell around blood vessels; however, meninges are diffusely involved and neoplastic nodules may form in the parenchyma, away from blood vessels
- Typically less differentiated with high mitosis and variable numbers of lymphocytes and macrophages that may mimic an inflammatory lesion
Necrotizing meningoencephalitis of the pug and other small breeds
- “Pug dog encephalitis” also commonly reported in Maltese, Pekingese, Shih Tzu and Chihuahua
- Predominately within the cerebral cortex gray matter often bilateral but asymmetric
- Similar inflammatory component to GME but more extensive necrosis with fewer histiocytes, less perivascular distribution
Necrotizing leukoencephalitis of Yorkshire terriers
- Similar histopathologic lesions but more necrotic and affects brainstem and cerebrum, less perivascular distribution

COMPARATIVE PATHOLOGY:

No direct correlates (idiopathic causes of GME) outside the dog, but many infectious causes of granulomatous meningoencephalitis in other species.

REFERENCES:

Cantile C, Youssef S. Nervous System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:362, 393-394.
De Lorenzi D, Mandara MT. The Central Nervous System. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 4^th ed. St. Louis, MO: Elsevier; 2023:517, 530-531.
Levine GJ, Cook JR. Cerebrospinal Fluid and Central Nervous System Cytology. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:221.
Miller AD, Porter, BF. Nervous System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:979-980.