Comprehensive Immunohistochemical Studies on Canine Necrotizing Meningoencephalitis (NME), Necrotizing Leukoencephalitis (NLE), and Granulomatous Meningoencephalomyelitis (GME)

Abstract

In dogs, there are several idiopathic meningoencephalitides, such as necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME). Although they are often assumed to be immune mediated, the etiology of these diseases remains elusive. In this study, the histopathology of the lesions caused by these conditions and the inflammatory cell populations produced in response to them were examined among dogs affected with GME, NME, or NLE to understand their pathogeneses. The brain tissues of dogs with NME (n ¼ 25), NLE (n ¼ 5), or GME (n ¼ 9) were used. The inflammatory cells were identified by immunohistochemistry using antibodies against CD3, IgG, CD20, CD79acy, and CD163. In NME and NLE, malacic changes were located in the cerebral cortex, as well as the cerebral white matter and thalamus, respectively. The distribution of the brain lesions in NME and NLE was breed specific. In GME, granulomatous lesions that were mostly composed of epithelioid macrophages were observed in the cerebral white matter, cerebellum, and brainstem. Although the proportions of IgG-, CD20-, and CD79acy-positive cells (B cells) were not significantly different among the GME, NME, and NLE lesions, that of CD3-positive cells (T cells) was increased in GME. In NME and NLE, CD163-positive cells (macrophages) had diffusely infiltrated the cerebral cortex and white matter, respectively. However, in GME, CD163-positive cells accumulated around the blood vessels in the cerebral and cerebellar white matter. The distributions of these lesions were quite different among GME, NME, and NLE, whereas there were no marked differences in the proportions of inflammatory cells.

Perspectives on Meningoencephalomyelitis of Unknown Origin

“…GFAP 1 astrocytes distributed widely over cerebrum; CD3 1 lymphocytes scattered in meninges, perivascular cuffs, and brain lesions but less compared with GME; MAC-387 1 cells limited in NME but mainly in meninges and perivascular cuffs; lysozyme 1 cells faint compared with GME; expression of IFN-g and CXCR3 highest in NME compared with NLE and GME. CD1631 macrophages localized in active inflammatory lesions perivascular cuffs and brain parenchyma 1,76,77 Intralesional GFAP expression; CD3 1 T cells dominate in perivascular cuffing and in diffuse histiocytic and lymphocytic infiltrates; rare B cells; MAC-387 1 histiocytic cells were detected in lesions of Yorkshire terrier but few in French bulldog; IgG deposits in white matter associated with inflammation; faint labeling IgM and IgA; CD163 1 cells diffusely infiltrated the cerebral white matter 77,96,98 Abbreviations: CD, cluster of differentiation; FLAIR, fluid-attenuated inversion-recovery; GFAP, glial fibrillary acidic protein; GME, granulomatous meningoencephalomyelitis; IFN, interferon; IgA, -G, -M, immunoglobulin A, G, M; MHC, major histocompatibility complex; NLE, necrotizing leukoencephalitis; NME, necrotizing meningoencephalitis; T1W, T1-weighted; T2W, T2-weighted.…”

“…6 However, these findings differ from those of GME, in which macrophages represent the dominant cell type of infiltrating lesions. 76,77,88 …”

Cellular Microbiology of Mycoplasma canis

“…In canine NME, pathological findings consist of neuroparenchymal infiltration of lymphocytes and monocytes or histiocytes, with malacia and necrosis usually being localized in the cerebral cortex and subcortical region (58)(59)(60)(61). Similar pathologies have been attributed to other species of mycoplasmas that gained entry into the brain (62)(63)(64).…”

“…Canine GME is distinguished from NME by perivascular cuffing with lymphocytes, macrophages, and neutrophils as well as granulomatous lesions mainly in the cerebellum and brainstem, but both NME and GME are believed to share a pathogenesis (61). Although it did not occur frequently or consistently among cases of GME or NME, deposition of oxidized DAB throughout some vascular cuffs probed with anti-M. canis antibody (Fig.…”

MIP-3β/CCL19 is associated with the intrathecal invasion of mononuclear cells in neuroinflammatory and non-neuroinflammatory CNS diseases in dogs

“…For comparison, MUO was chosen as a disease group with a predominantly mononuclear pleocytosis within the CSF [1,25,26] despite the heterogeneity of the group. Examples of idiopathic inflammatory disorders of the CNS are NE and GME, in which a strong genetic component [27], occurrence of autoantibodies [28], and the distribution of lymphocytes and macrophages [29], suggest a strong involvement of mononuclear cells in the pathogenesis. A third group was analyzed.…”