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The p53 tumor suppressor gene (TP53) is the most frequently altered gene in human cancer. Mutation of the gene has been shown to be an important mechanism of p53 pathway inactivation in a variety of human brain tumors, particularly those of astrocytic origin. Genomic DNA from a series of 37 glial and 51 nonglial canine brain tumors was sequenced to determine the frequency of TP53 gene mutations involving exons 3-9. Exonic mutations were found in 3 of 88 tumors (3.4%) and specifically in 1 of 18 astrocytic tumors (5.5%). This is markedly lower than that reported in comparable human tumors, suggesting that alternative mechanisms of p53 inactivation are likely to be present if p53 function contributes significantly to oncogenesis in canine brain tumors.

Meningiomas are common primary brain tumors in dogs; however, little is known about the molecular genetic mechanisms involved in their tumorigenesis. Several tumor suppressor genes have been implicated in meningioma pathogenesis in humans, including the neurofibromatosis 2 (NF2), protein 4.1B (4.1 B), and tumor suppressor in lung cancer-1 (TSLC1) genes. We investigated the expression of these tumor suppressor genes in a series of spontaneous canine meningiomas using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) (NF2; n = 25) and western blotting (NF2/merlin, 4.1B, TSLC1; n = 30). Decreased expression of 4.1B and TSLC1 expression on western blotting was seen in 6/30 (20%) and in 15/30 (50%) tumors, respectively, with 18/30 (60%) of meningiomas having decreased or absent expression of one or both proteins. NF2 gene expression assessed by western blotting and RT-PCR varied considerably between individual tumors. Complete loss of NF2 protein on western blotting was not seen, unlike 4.1B and TSLC1. Incidence of TSLC1 abnormalities was similar to that seen in human meningiomas, while perturbation of NF2 and 4.1B appeared to be less common than reported for human tumors. No association was observed between tumor grade, subtype, or location and tumor suppressor gene expression based on western blot or RT-PCR. These results suggest that loss of these tumor suppressor genes is a frequent occurrence in canine meningiomas and may be an early event in tumorigenesis in some cases. In addition, it is likely that other, as yet unidentified, genes play an important role in canine meningioma formation and growth.

An acute to chronic idiopathic necrotizing meningoencephalitis was diagnosed in 5 Chihuahua dogs aged between 1.5 and 10 years. Presenting neurologic signs included seizures, blindness, mentation changes, and postural deficits occurring from 5 days to 5.5 months prior to presentation. Cerebrospinal fluid analyses from 2 of 3 dogs sampled were consistent with an inflammatory disease. Magnetic resonance imaging of the brain of 2 dogs demonstrated multifocal loss or collapse of cortical gray/white matter demarcation hypointense on T1-weighted images, with T2-weighted hyperintensity and slight postcontrast enhancement. Multifocal asymmetrical areas of necrosis or collapse in both gray and white matter of the cerebral hemispheres was seen grossly in 4 brains. Microscopically in all dogs, there was a severe, asymmetrical, intensely cellular, nonsuppurative meningoencephalitis usually with cystic necrosis in subcortical white matter. There were no lesions in the mesencephalon or metencephalon except in 1 dog. Immunophenotyping defined populations of CD3, CD11d, CD18, CD20, CD45, CD45 RA, and CD79a immunoreactive inflammatory cells varying in density and location but common to acute and chronic lesions. In fresh frozen lesions, both CD1b,c and CD11c immunoreactive dendritic antigen-presenting cells were also identified. Immunoreactivity for canine distemper viral (CDV) antigen was negative in all dogs. The clinical signs, distribution pattern, and histologic type of lesions bear close similarities to necrotizing meningoencephalitis as described in series of both Pug and Maltese breed dogs and less commonly in other breeds.

Vascular endothelial growth factor (VEGF) is an important regulator of tumor angiogenesis and vascular permeability, and has been implicated both in progression of central nervous system (CNS) tumors and development of vasogenic peritumoral edema. A retrospective study was done to characterize the levels of expression of the 3 major canine VEGF isoforms (VEGF(120), VEGF(164), VEGF(188)) in a variety of spontaneous canine CNS tumors using quantitative TaqMan reverse transcription real-time polymerase chain reaction. Presence and degree of peritumoral edema also were determined in sampled tumors using magnetic resonance imaging (MRI). Increased expression of VEGF relative to normal cerebral cortex tissue was seen predominantly in high grade astrocytic (grade IV) and oligodendroglial (grade III) tumors, with lower expression in low grade astrocytomas (grade II) and meningiomas (grade I). All 3 major VEGF isoforms were present; VEGF(164) was the predominant isoform, particularly in the tumors with the highest VEGF expression. Peritumoral edema was present in all tumor types; however, a significant association between the extent of peritumoral edema and the level of VEGF expression was not apparent.

A 6-year-old castrated German Shepherd Dog was presented with a 6-month history of progressive, nonpainful, left pelvic limb paresis. Magnetic resonance imaging revealed atrophy of left-sided epaxial and hypaxial muscles from L5-L7 and an enlarged L5 spinal nerve. Exploratory hemi-laminectomy revealed focally and cylindrically thickened L5 and L6 nerve roots. Histologic evaluation of a surgical biopsy specimen from the L6 dorsal nerve root, and the L5 nerve roots after later amputation revealed distended hypercellular fascicles. This distension was due to widely separated axons surrounded by concentric lamellations formed by neoplastic perineurial cells and their processes. These pseudo-onion bulbs were separated from each other by a basophilic myxoid stroma. The perineurioma cell processes were immunonegative for S-100 (alpha and beta chains) and collagen IV, but were immunoreactive for laminin. The central axons were also immunoreactive for NF-200 and S-100. The proliferative index of the perineurioma cells, as determined by MIB-1 immunoreactivity, was about 3%. Ultrastructurally, the widely separated, interdigitating perineurioma cell processes were connected by desmosomal-like junctional complexes to form continuous circles. Their processes were covered by a discontinuous basal lamina. Each centrally placed axon was normally, thinly, or completely unmyelinated and was surrounded by a normal Schwann cell. These morphologic and immunologic features distinguish this lesion from hypertrophic neuropathy and were consistent with intraneural perineurioma.

Although glioblastoma multiforme (GBM), a World Health Organization grade IV astrocytoma, is the most common primary brain tumor in humans, in dogs GBM is relatively rare, accounting for only about 5% of all astrocytomas. This study presents combined clinical, neuroimaging, and neuropathologic findings in five dogs with GBM. The five dogs, aged from 5 to 12 years, were presented with progressive neurologic deficits that subsequent clinical neurologic examination and neuroimaging studies by magnetic resonance imaging (MRI), localized to space occupying lesions in the brain. MRI features of the tumors included consistent peritumoral edema (n = 5), sharp borders (n = 4), ring enhancement (n = 3), heterogenous T2-weighted signal intensity (n = 3), iso- to hypointense T1-weighted images (n = 5), necrosis (n = 5), and cyst formation (n = 2). Two tumors were diagnosed clinically using a computed tomography-guided stereotactic biopsy procedure. At necropsy all the tumors resulted in, on transverse sections, a prominent midline shift and had a variegated appearance due to intratumoral necrosis and hemorrhage. Histologically, they had serpentine necrosis with glial cell pseudopalisading and microvascular proliferation, features which distinguish human GBM from grade III astrocytomas. Immunoreactivity of tumor cells for glial fibrillary acidic protein was strongly positive in all cases, whereas 60% and 40% of the tumors also expressed epidermal growth factor receptor and vascular endothelial growth factor, respectively. These canine GBMs shared many diagnostic neuroimaging, gross, microcopic, and immunoreactivity features similar to those of human GBMs.

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.

Existing reports concerning intervertebral disc disease (IVDD) have focused almost exclusively on dogs, although a small number of individual case reports of IVDD of cats has been published. The medical records of six cats with IVDD were reviewed. Radiographic studies confirmed narrowed intervertebral disc spaces, mineralised intervertebral discs, and one or more extradural compressive lesions of the spinal cord in each cat. All disc extrusions were located in the thoracolumbar region. Surgical decompression of the spinal cord was achieved in all cats by means of hemilaminectomy and removal of compressive extradural material confirmed to be degenerative disc material. Good to excellent neurological recovery was noted in five of the six cats included in this report. Based on this review, it appears that IVDD of cats has many similarities to IVDD of dogs, and that healthy cats with acute intervertebral disc extrusion(s) respond favourably to surgical decompression of the spinal cord., (Copyright 2001 European Society of Feline Medicine.)

The recent application of neuroimaging techniques in veterinary neurology has led to the accurate localization of many types of intracranial lesions but has also created a clinical need, particularly with brain tumors, for a specific intraoperative diagnosis. For human brain tumors, a smear technique has been used successfully for many years to provide an extremely rapid, highly accurate intraoperative diagnosis. In similar smear preparations of intracranial lesions, obtained either by computed tomography (CT)-guided stereobiopsy or from a craniotomy, we have described distinguishing cytologic features of some primary spontaneous nervous system tumors in 80 dogs and 13 cats. A final diagnosis was confirmed by evaluation of paraffin-embedded sections from the same sample and, when appropriate, by immunocytochemical staining. Preliminary findings indicate that, in dogs and cats, this procedure is useful for rapid, accurate intraoperative diagnosis of many primary nervous system tumors. The distinguishing features of the canine and feline tumors bear a remarkably close resemblance to their human counterparts.

Two oligodendrogliomas in two domestic cats involved mainly the rostral brain stem, midbrain, fourth ventricle, and cerebellum. Both cats were aged neutered males presenting with clinical neurologic deficits suggestive of a brain stem lesion. Magnetic resonance imaging of both tumors demonstrated lesions with a pattern of heterogeneous contrast enhancement and multifocal lesions in one cat. Routine cerebrospinal fluid analysis was normal in one cat and suggestive of an inflammatory disease in the other. Oligodendroglioma cells were seen in cytospin preparations of cerebrospinal fluid from both cats. In each cat, the tumors occurred intraventricularly in the midbrain and fourth ventricle with aggressive intraparenchymal infiltration. There was extensive growth into the basilar subarachnoid space of the midbrain and brain stem in one cat. One tumor was well differentiated, and the other was an anaplastic subtype. Immunostaining for several myelin- and oligodendroglia-specific antigens was negative with formalin-fixed tumors and with unfixed frozen samples from one cat. In both tumors, component cells of the intratumoral vascular proliferations were positive for human von Willebrand factor VIII antigen or smooth muscle actin. Immunocytochemical reactivity for glial fibrillary acidic protein identified both reactive astrocytes and a subpopulation of minigemistocytes in both tumors. Ultrastructurally, the tumor cells were unremarkable except for their prominent desmosomal junctions and paucity of microtubules.

Results of a neurological examination usually permit localisation of a vestibular disorder to either the central or peripheral parts of the vestibular system. Many different disorders located in the same part of the vestibular system will produce similar clinical signs. Therefore, additional diagnostic tests beyond a neurological examination are required in order to make an accurate diagnosis. The objectives of this review are to outline a diagnostic approach for disorders affecting the feline vestibular system, and to summarise the clinically important features of frequently diagnosed diseases affecting the vestibular system of cats., (Copyright 1999 W.B. Saunders Company Ltd.)

An understanding of the anatomy of the feline vestibular system is essential for interpretation of the clinical signs associated with vestibular dysfunction, for precise lesion localisation, and for accurate interpretation of results of diagnostic imaging. Appropriate recognition and interpretation of the clinical signs of vestibular disease is also an essential aspect of the precise diagnosis of the cause of vestibular dysfunction in cats. The objectives of this review are to provide an overview of the anatomy of the feline vestibular system, and to review the clinical signs of peripheral and central vestibular dysfunction of cats., (Copyright 1999 W.B. Saunders Company Ltd.)

Extracranial metastasis of primary central nervous system neoplasms is uncommon and has not been described in the dog. We report the clincopathologic features of intracranial meningioma with pulmonary metastasis in three dogs (case No. 1: 13-year-old castrated male Boxer dog; case No. 2: 14-year-old spayed female Dachshund; case No. 3: 6-year-old spayed female German Shepherd Dog). Case No. 1 presented with ataxia, lethargy, vomiting, and leaning and falling to the right, and had a transient remission following radiation and corticosteroid therapy; case No. 2 had a history of seizures that were unresponsive to primidone, left-sided postural reaction deficits, ataxia, and circling to the right; case No. 3 had only intermittent episodes of vomiting Computed tomography of case Nos. 1 and 2 revealed peripherally located homogeneous contrast-enhancing intracranial masses. Postmortem examination revealed intracranial masses with single or multiple pulmonary nodules in all three cases. Histologically, the intracranial and pulmonary masses were meningotheliomatous meningiomas with atypical features including brain infiltration, necrosis, nuclear atypia, prominent nucleoli, and moderate cell density. All of the primary meningiomas had low mitotic rates. The current interest in early diagnosis and aggressive clinical/surgical management of canine patients with meningioma and other primary central nervous system neoplasms will likely result in an increased detection of extracranial metastases.