ABSTRACT. Canine necrotizing meningoencephalitis (NME) and granulomatous meningoencephalomyelitis (GME) were compared pathologically. Gross observation exhibited lateral ventricular dilation and discoloration, malacia and/or cavitation of the cerebrum in NME. On the contrary, gross changes were milder in GME, except for occasional visible granulomatous mass formation. Histopathologically, the lesions of NME were distributed predominantly in the cerebral cortex and various degrees of inflammatory and necrotic changes were observed according to clinical stages. Besides, microscopic lesions of GME were mainly distributed in the white matter of the c erebrum, cerebellum and brainstem, which are characterized by perivascular cuffing, multiple granulomas and leptomeningeal infiltrates. Although macrophages and lymphocytes were predominant in the inflammatory lesions of both disorders, macrophages in GME transformed into epithelioid cells and exhibited more massive infiltration. Although lectin RCA-1-reactive cells were numerous in both disorders, lysozyme immunoreactive cells in NME were fewer than that in GME. Parenchymal infiltration of MAC387-positive cells was common in GME and limited in NME. The number of CD3-positive lymphocytes in the GME lesions tended to be greater than in NME, though the difference was not statistically significant. Morphological and immunohistochemical differences of the lesions, in particular, the characteristics of infiltrative macrophages may reflect these different pathogeneses of the two disorders. KEY WORDS: canine, granulomatous meningoencephalomyelitis, macrophage, necrotizing meningoencephalitis.J. Vet. Med. Sci. 65(11): 1233-1239, 2003 Canine necrotizing meningoencephalitis (NME) is a unique inflammatory disorder in small-sized breed dogs, especially in Pug dogs. The disease is histopathologically characterized by inflammatory changes consisting of lymphocytic, plasmacytic and histiocytic infiltrations and apparent parenchymal necrosis located mainly in the cerebral cortex [9,15,23]. The common clinical features are forebrain signs such as partial or generalized seizure, decreased consciousness, abnormal behavior, circling and ataxia [9,23]. The cause of NME is still unknown. However, our previous report showed that a certain autoantibody against a canine brain tissue was detected in the cerebrospinal fluid (CSF) and serum, which may suggest an autoimmune pathology in NME [25].The pathological features of NME are often compared with granulomatous meningoencephalomyelitis (GME) that is another inflammatory disease of unknown cause [5,8,23]. Although there are some differences such as breed predilection, the distribution of lesions and the presence or absence of necrotic foci, GME and NME show similar histological changes, i.e., meningitis and perivascular cuffing composed of mononuclear cells including lymphocytes and monocyte/histiocyte-lineages [5,8,23]. Kipar et al. [14] revealed lesions in GME are predominantly composed of CD3 antigen-positive T lymphocytes and a heterogeneo...

ABSTRACT. Histiocytic proliferative disorders in canine central nervous system (CNS) including granulomatous meningoencephalomyelitis (GME) and malignant histiocytosis were compared pathologically. Lesions of GME mainly existed in the white matter of the cerebr um, brainstem and cerebellum and consisted of characteristic perivascular cuffing, parenchymal granuloma and leptomeningeal infiltrates of mononuclear cells. In malignant histiocytosis, there were two histological patterns, diffuse proliferation of neoplastic histiocytes through the leptomeninges and neoplastic nodule formation in the parenchyma. Neoplastic histiocytes exhibited mild to severe cellular atypia and high ability of invasion into the brain parenchyma. Mitotic and phagocytic figures were also observed. Several histiocytic markers, including lysozyme, α1-antitrypsin and lectin RCA-1, revealed histiocytic origin of both inflammatory and neoplastic cells, however, those were not determinative for the discrimination between GME and malignant histiocytosis. CD3-and PCNA-positive cells existed in the lesions of both diseases. The number of CD3-positive cells in GME tended to be greater than in malignant histiocytosis, while the difference was not statistically significant.

An 8-year-old male Tibetan Terrier showed prolonged astasia, complete paralysis, ticlike signs, and seizure and died 2 months after the onset of symptoms. Histopathologically, there was moderate to severe infiltration of pleomorphic histiocytic mononuclear cells bilaterally in the basiarachnoidal and ventricular areas of the brain. The spinal dura mater, arachnoidal space, and leptomeninges were also affected by infiltrative proliferation of these mononuclear cells. The infiltrating cells had the morphologic characteristics of histiocytes but exhibited moderate pleomorphism and atypia, with abundant mitotic figures. With immunohistochemistry and lectin histochemistry, most of the infiltrating cells were positive for lysozyme and lectin RCA-1 and negative for glial fibrillary acid protein, suggesting that they were of monocytic/histiocytic-origin. Positive proliferating cell nuclear antigen immunostaining demonstrated that most nuclei of the histiocytic cells were in the S phase of the cell cycle, consistent with a proliferating population of cells. Based on these findings, the case was diagnosed as diffuse leptomeningeal malignant histiocytosis.

ABSTRACT. Neuroaxonal dystrophy (NAD) was examined in two Papillon dogs and a mix breed dog between Papillon and Chihuahua. In addition, cerebellar cortical abiotrophy (CCA) in a Papillon dog, which had similar clinical and magnetic resonance imaging (MRI) features to those of NAD, was also investigated. The common clinical symptoms of all dogs affected with NAD and CCA, were pelvic limb ataxia and cerebellar ataxia including intention tremor, head tremor, and hypermetria in the early onset. These clinical signs were progressed rapidly, and two dogs with NAD were euthanized by owner's request and the other two were died by aspiration pneumonia. MRI examinations and gross observations at necropsy revealed moderate to severe cerebellar atrophy in all cases of NAD and CCA. The most typical histological change of NAD was severe axonal degeneration with marked spheroid-formation in the dorsal horn of the spinal cords, the nuclei gracilis, cuneatus, olivalis and its circumference in the medulla oblongata. The spheroids were characterized as large eosinophilic or granular globes within the enlarged myelin sheaths, sometimes accompanied by moderate accumulation of microglias and/ or macrophages. In contrast, such spheroid formation was minimal in the brain of CCA. In the cerebellum, mild to moderate loss of the Purkinje and granular cells were recognized in three dogs with NAD, whereas these changes were more prominent in a dog with CCA. Although the clinical signs and MRI findings relatively resembled between NAD and CCA, the histopathological features considered to be quite differ, suggesting distinct pathogenesis and etiology. Since both NAD and CCA are proposed as the autosomal recessive hereditary disorders, careful considerations might be needed for the breeding of Papillon and Chihuahua dogs.

Canine Lafora disease (LD) is an autosomal recessive genetic disorder causing nonfatal structural epilepsy, mainly affecting miniature wirehaired dachshunds. Repeat expansion in the EPM2B gene causes a functional impairment of the ubiquitin ligase malin which regulates glycogen metabolism. Abnormally structured glycogen accumulates and develop polyglucosan bodies predominantly in the central nervous system. The authors performed a comprehensive clinical, genetic, and pathological study of 4 LD cases affecting miniature wirehaired dachshund dogs with EPM2B repeat expansions, with systemic distribution of polyglucosan bodies and accumulation of laforin and other functionally associated proteins in the polyglucosan bodies. Myoclonic seizures first appeared at 7-9 years of age, and the dogs died at 14-16 years of age. Immunohistochemistry for calbindin revealed that the polyglucosan bodies were located in the cell bodies and dendritic processes of Purkinje cells. Polyglucosan bodies were also positive for laforin, hsp70, α/β-synuclein, ubiquitin, LC3, and p62. Laforin-positive polyglucosan bodies were located in neurofilament-positive neurons but not in GFAP-positive astrocytes. In nonneural tissues, periodic acid-Schiff (PAS)-positive polyglucosan bodies were observed in the heart, skeletal muscle, liver, apocrine sweat gland, and smooth muscle layer of the urinary bladder. In the skeletal muscle, polyglucosan bodies were observed only in type 1 fibers and not in type 2 fibers. The results indicate that although the repeat expansion of the EPM2B gene is specific to dogs, the immunohistochemical properties of polyglucosan body in canine LD are comparable to human LD. However, important phenotypic variations exist between the 2 species including the affected skeletal muscle fiber type.