Idiopathic granulomatous and necrotising inflammatory disorders of the canine central nervous system: a review and future perspectives

Granulomatous meningoencephalomyelitis, necrotizing meningoencephalitis, and necrotizing leukoencephalitis are common inflammatory conditions of the canine central nervous system. Although each disease has unique histopathological features, these canine disorders collectively seem to be aberrant immune responses directed against the central nervous system. A review of the neurological signs and general neurodiagnostic approach to canine meningoencephalitis is followed by an overview of the specific clinical and neuropathological features of granulomatous meningoencephalomyelitis, necrotizing meningoencephalitis, and necrotizing leukoencephalitis. The aetiopathogenesis of each disorder is explored including potential genetic, immunological, and environmental factors along with the current and prospective immunomodulatory therapies for meningoencephalitis.     

Infectious diseases of the central nervous system.

Neurologic disease is seen commonly in cats, with infectious causes accounting for 30-45% of cases. However, since a specific infection cannot be identified in 12-40% of these cases, it is essential that we try to understand these cases better in the hope that we can eventually identify the cause(s), and so determine how best to treat and/or prevent them.     

Spongy degeneration of the central nervous system in two canine littermates

Progressive dysmetria was observed at four months and six months of age in two female Labrador retriever littermates. Neurological examinations indicated a cerebellar disorder. Laboratory analyses were normal. The dogs were studied clinically until they were killed for necropsy at nine months and eleven months of age. Both dogs had normal brain size, shape, and calvarial symmetry; the older dog had body weight loss, reduced brain weight, and muscle atrophy. Microscopically, there were vacuoles, hypertrophied fibrous astrocytes, myelin loss, and prominent blood vessels, distributed symmetrically in the subcortical and deep white matter of all lobes of the cerebrum; in the folial and deep white matter of the cerebellum; in the tracts of some cranial nerves; in the thalamic area, midbrain and brainstem; and in the white matter of the spinal cord. There was no significant myelinolysis, inflammation, or axonal degeneration. Ultrastructurally, there were intramyelinic vacuoles with separation of lamellae at intraperiod lines and larger spaces formed by coalescence of ruptured vacuoles. Hypertrophied fibrous astrocytes had abundant glial filaments, edematous cytosol, membrane-bound crystalline inclusions, dilated cytocavitary systems, and abnormal mitochondria. The clinical, histological, and ultrastructural findings resembled those reported for the juvenile form of Canavan's disease (van Bogaert and Bertrand type) in children.     

Thrombocytosis and central nervous system involvement in a case of canine acute megakaryoblastic leukemia

This case report presents a 14‐month‐old female Poodle mix with acute megakaryoblastic leukemia based on a marked thrombocytosis, abnormal platelet morphology, circulating dwarf megakaryocytes, and blast cells in the blood. Bone marrow abnormalities included dysmegakaryopoiesis dygranulopoiesis, and an increased number of blast cells was observed in the blood. Extensive leukemic involvement was also found in the liver, spleen, lymph nodes, lungs, kidneys, and brain. The cytopathologic features of the abnormal circulating cells were highly suggestive of being megakaryocytic in origin, which was supported by negative myeloperoxidase staining and positive von Willebrand factor staining on immunocytochemistry (ICC). The neoplastic cells were also CD61 positive and had variable von Willebrand factor expression on ICC. Although there were only 25% blast cells in the bone marrow, which theoretically supported myelodysplastic syndrome, the hypothesis that this case represented acute myeloid leukemia of megakaryoblastic origin was confirmed by the continuous increase in circulating blast cell numbers during follow‐up visits and the extensive leukemic involvement of parenchymal organs.     

Granular cell tumor of the canine central nervous system: two cases.

Although pure granular cell tumors have been reported in various sites in the dog, only one tumor has been reported in the central nervous system. Two dogs presented with neurologic signs had brain lesions detected by magnetic resonance imaging in the area of the olfactory bulbs and frontal cortex. In both dogs, a clinical diagnosis of a granular cell tumor was made from tissues obtained from stereotactic biopsies guided by computed tomography. Surgical removal of the tumors was followed by histopathologic, ultrastructural, and immunocytochemical characterization. Although not conclusive, these studies indicated that the granular cells were not of leucocyte origin but may have been derived from the meninges. One dog died 12 months after surgery, and the other was alive 4 months later.     

Some diseases of the porcine central nervous system in new zealand

Extract

The purpose of this paper is to record and discuss those diseases of the porcine central nervous system (C.N.S.) which have been encountered at the Diagnostic Station of the Ruakura Agricultural Research Centre in the past nine years. It is based on approximately 200 cases. Most of the material was submitted by veterinarians from natural outbreaks of disease.     

Macrophages in central nervous canine distemper: friends or foes?

Brain macrophages play an important role in the CNS. We review some biological aspects of brain macrophages in vivo and in vitro. The criteria and methods used for the identification of these cells are considered. They include some morphological features such as the use of histochemical and immunocytochemical techniques for internal and surface components. In the second part of this review, we describe the role of brain macrophages in canine distemper encephalitis as proposed earlier by us. Studies in cultured dog glial cells infected with canine distemper virus (CDV) have shown that brain macrophages stimulated by anti-CDV antibodies will release reactive oxygen species as measured by chemiluminescence. This response depends on the presence of viral antigens on the surfaces of infected cells and is mediated by the interaction of antigen-bound antibodies with Fc receptors on brain macrophages. These observations support the hypotheses that brain macrophages may contribute to the damage of the white matter observed in canine distemper encephalitis.     

Assessment of the IgG index in dogs by indirect immunoenzimatic assays as diagnostic tool for inflammatory diseases of central nervous system

The IgG index measures the intrathecal immunoglobulin production and it is a useful tool for diagnosis of inflammatory diseases involving the central nervous system. This index is based on the precise quantification of albumin and IgG in canine cerebrospinal fluid and serum. Here, we report the development of an indirect competitive ELISAs for the detection of both antigens. Thirty-two dogs were included in this study, divided into three experimental groups. Group A was composed of 22 healthy animals, as determined by standard clinical examination. In group B, six animals, presented neurological pathologies associated with endogenous IgG production and, in group C four animals presented neurological diseases or symptoms not associated with intrathecal IgG production. Cerebrospinal fluid and serum samples were obtained from these animals. As expected, by using the indirect ELISAs proposed here, the IgG indexes obtained in healthy animals (A) were 0.371+/-0.252 (SD). In B and C, the values (3.002+/-1.897; 0.36+/-0.306, respectively), were in agreement with the pathologic conditions of the individuals in each group. Thus, the immunometric competition ELISA methods proposed here allow the discrimination of abnormal intrathecal IgG production, in a variety of inflammatory pathologic conditions of the central nervous system.     

Observations on diseases of the central nervous system of sheep in New Zealand

Extract

The purpose of this paper is to describe the salient features of the neurological conditions seen in sheep in New Zealand which are associated with changes in the central nervous system. Several of the conditions associated with perinatal mortality will be mentioned only briefly in this paper as the details will be included in a subsequent paper on ovine perinatal mortality. Some of the entities to be described have been reported before and are reviewed. Others are described here for the first time.     

Microarray analysis of differentially expressed genes of primary tumors in the canine central nervous system

The pathophysiologic similarities of many human and canine cancers support the role of the domestic dog as a model for brain tumor research. Here we report the construction of a custom canine brain-specific cDNA microarray and the analysis of gene expression patterns of several different types of canine brain tumor. The microarray contained 4000 clones from a canine brain specific cDNA library including 2161 clones that matched known genes or expressed sequence tags (ESTs) and 25 cancer-related genes. Our study included 16 brain tumors (seven meningiomas, five glial tumors, two ependymomas, and two choroid plexus papillomas) from a variety of different dog breeds. We identified several genes previously found to be differentially expressed in human brain tumors. This suggests that human and canine brain tumors share a common pathogenesis. In addition, we also found differentially expressed genes unique to either meningiomas or the glial tumors. This report represents the first global gene expression analysis of different types of canine brain tumors by cDNA microarrays and might aid in the identification of potential candidate genes involved in tumor formation and progression.     

Cryptococcosis of the central nervous system in a dog

A 3-year-old female German Shepherd Dog was evaluated for progressive mental obtundation and vestibular signs. Central nervous system cryptococcosis was diagnosed on the basis of growth of Cryptococcus neoformans in fungal culture of CSF, as well as detection of the organism in CSF via microscopy. Cryptococcal capsular latex antigen agglutination titer was 1:262,144 in CSF and 1:1,048,576 in serum samples. Imaging with magnetic resonance augmented diagnosis. The dog improved after long-term treatment with fluconazole. Fluconazole is useful in the treatment of CNS cryptococcosis, because it attains high concentration in the CNS. Long-term therapy is often required for resolution of clinical signs, and affected animals may require long-term follow-up with periodic evaluation of CSF via fungal culture and latex agglutination tests. Monitoring serum latex agglutination test results may provide a safe, less invasive means of monitoring response to treatment.