Immunohistochemical evaluation of fibrin/fibrinogen, d-dimers, and intravascular thrombosis in brains of dogs with meningoencephalitis of unknown origin.

Granulomatous meningoencephalitis (GME) and necrotizing encephalitides (NE) are the most common immune-mediated inflammatory diseases of the central nervous system in dogs. Activation of the fibrinolytic system in multiple sclerosis, a similar immune-mediated disease affecting the central nervous system in humans, seems to be related to disease progression. The aim of this study was to identify fibrin/fibrinogen and D-dimer deposition, as well as presence of intravascular thrombosis (IVT) in brains of dogs with a diagnosis of GME or NE. Immunohistochemical studies using antibodies against fibrin/fibrinogen and D-dimers were performed. Statistical analyses were performed to determine whether there were differences in the presence and location of fibrin/fibrinogen, D-dimers deposits, and IVT between GME and NE. Samples from sixty-four dogs were included in the study: 32 with a diagnosis of GME and 32 with a diagnosis of NE. Fibrin/fibrinogen depositions were detected in all samples and d-dimers were detected in 43/64 samples. IVT was present in 29/64 samples, with a significantly higher score in samples from dogs with NE than in samples from dogs with GME (P = 0.001). These data support hemostatic system activation in both diseases, especially NE. This finding might be related to the origin of the necrotic lesions seen in NE, which could represent chronic ischemic lesions. Further studies are needed to investigate the association between vascular lesions and the histopathological differences between GME and NE and the hemostatic system as a potential therapeutic target.

Tumour-to-Tumour Metastasis Phenomenon: Metastatic Prostatic Adenocarcinoma within an Anaplastic Oligodendroglioma in the Brain of a Dog.

A 10-year-old entire male French bulldog was presented following clusters of generalized tonic-clonic epileptic seizures. Neurolocalization was consistent with a lesion in the left forebrain. Magnetic resonance imaging of the brain revealed a large, ill-defined, intra-axial, space-occupying lesion at the level of the left temporal and parietal lobes, causing marked compression of the adjacent parenchyma. Computed tomography of the thorax and abdomen was consistent with disseminated metastatic disease. The dog was humanely destroyed and subjected to necropsy examination. Histological examination of the brain revealed a metastasis of prostatic carcinoma within an anaplastic oligodendroglioma in the left forebrain. To the author's knowledge, this is the first report describing clinical, imaging and histopathological features of an intracranial tumour-to-tumour metastasis in the brain of a dog.

Immunohistochemical expression of cyclooxygenase-2 (COX-2) is not associated with tumor grade in feline meningiomas.

Meningioma is the most common primary brain tumor in cats and occurs less frequently in the spinal cord. This study aimed to investigate cyclooxygenase-2 (COX-2) expression in feline meningiomas, and the possible association between COX-2 immunoreactivity and tumor grade using eight low-grade and seven high-grade meningiomas. All tumors (n=15/15) were immunoreactive to COX-2. The expression of COX-2 was not significantly correlated with tumor grade (P=0.22 and 0.34 for staining and intensity, respectively) but was significantly associated with necrosis (P=0.04 and 0.01 for staining and intensity, respectively). The findings in this study suggest that feline meningiomas express COX-2, but there were no differences in COX-2 immunoreactivity patterns between low- and high-grade meningiomas. However, the association between COX-2 expression and the presence of necrosis indicates a potential area for therapeutic intervention with selective COX-2 inhibitors.

Clinical Features, Imaging Characteristics, and Long-term Outcome of Dogs with Cranial Meningocele or Meningoencephalocele.

BACKGROUND: The term meningoencephalocele (MEC) describes a herniation of cerebral tissue and meninges through a defect in the cranium, whereas a meningocele (MC) is a herniation of the meninges alone. HYPOTHESIS/OBJECTIVES: To describe the clinical features, magnetic resonance imaging (MRI) characteristics, and outcomes of dogs with cranial MC and MEC. ANIMALS: Twenty-two client-owned dogs diagnosed with cranial MC or MEC. METHODS: Multicentric retrospective descriptive study. Clinical records of 13 institutions were reviewed. Signalment, clinical history, neurologic findings and MRI characteristics as well as treatment and outcome were recorded and evaluated. RESULTS: Most affected dogs were presented at a young age (median, 6.5 months; range, 1 month - 8 years). The most common presenting complaints were seizures and behavioral abnormalities. Intranasal MEC was more common than parietal MC. Magnetic resonance imaging identified meningeal enhancement of the protruded tissue in 77% of the cases. Porencephaly was seen in all cases with parietal MC. Cerebrospinal fluid (CSF) analysis identified mild abnormalities in 4 of 11 cases. Surgery was not performed in any affected dog. Seventeen patients were treated medically, and seizures were adequately controlled with anti-epileptic drugs in 10 dogs. Dogs with intranasal MEC and mild neurologic signs had a fair prognosis with medical treatment. CONCLUSION AND CLINICAL IMPORTANCE: Although uncommon, MC and MEC should be considered as a differential diagnosis in young dogs presenting with seizures or alterations in behavior. Medical treatment is a valid option with a fair prognosis when the neurologic signs are mild.

Spontaneously Arising Canine Glioma as a Potential Model for Human Glioma.

Human gliomas are malignant brain tumours that carry a poor prognosis and are composed of a heterogeneous population of cells. There is a paucity of animal models available for study of these tumours and most have been created by genetic modification. Spontaneously arising canine gliomas may provide a model for the characterization of the human tumours. The present study shows that canine gliomas form a range of immunohistochemical patterns that are similar to those described for human gliomas. The in-vitro sphere assay was used to analyze the expansion and differentiation potential of glioma cells taken from the periphery and centre of canine tumours. Samples from the subventricular zone (SVZ) and contralateral parenchyma were used as positive and negative controls, respectively. The expansion potential for all of these samples was low and cells from only three cultures were expanded for six passages. These three cultures were derived from high-grade gliomas and the cells had been cryopreserved. Most of the cells obtained from the centre of the tumours formed spheres and were expanded, in contrast to samples taken from the periphery of the tumours. Spheres were also formed and expanded from two areas of apparently unaffected brain parenchyma. The neurogenic SVZ contralateral samples also contained progenitor proliferating cells, since all of them were expanded for three to five passages. Differentiation analysis showed that all cultured spheres were multipotential and able to differentiate towards both neurons and glial cells. Spontaneously arising canine gliomas might therefore constitute an animal model for further characterization of these tumours.

Fibrinolytic activity in cerebrospinal fluid of dogs with different neurological disorders.

BACKGROUND: Fibrinolytic activity in cerebrospinal fluid (CSF) is activated in humans by different pathologic processes. OBJECTIVES: To investigate fibrinolytic activity in the CSF of dogs with neurological disorders by measuring CSF D-dimer concentrations. ANIMALS: One hundred and sixty-nine dogs with neurological disorders, 7 dogs with systemic inflammatory diseases without central nervous system involvement (SID), and 7 healthy Beagles were included in the study. Dogs with neurological disorders included 11 with steroid-responsive meningitis-arteritis (SRMA), 37 with other inflammatory neurological diseases (INF), 38 with neoplasia affecting the central nervous system (NEO), 28 with spinal compressive disorders (SCC), 15 with idiopathic epilepsy (IE), and 40 with noninflammatory neurological disorders (NON-INF). METHODS: Prospective observational study. D-dimers and C-reactive protein (CRP) were simultaneously measured in paired CSF and blood samples. RESULTS: D-dimers and CRP were detected in 79/183 (43%) and in 182/183 (99.5%) CSF samples, respectively. All dogs with IE, SID, and controls had undetectable concentrations of D-dimers in the CSF. CSF D-dimer concentrations were significantly (P < .001) higher in dogs with SRMA than in dogs with other diseases and controls. CSF CRP concentration in dogs with SRMA was significantly (P < .001) higher than in dogs of other groups and controls, except for the SID group. No correlation was found between blood and CSF D-dimer concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE: Intrathecal fibrinolytic activity seems to be activated in some canine neurological disorders, and it is high in severe meningeal inflammatory diseases. CSF D-dimer concentrations may be considered a diagnostic marker for SRMA.

Presumptive caudal cerebellar artery infarct in a dog: clinical and MRI findings.

Clinical signs and magnetic resonance imaging findings of a caudal cerebellar artery infarct are reported for the first time in a dog. Clinical signs were characterised by a peracute, non-progressive, right-sided central vestibular syndrome with paradoxical right-sided head tilt. Magnetic resonance images were consistent with a territorial, non-haemorrhagic, ischaemic lesion affecting the caudo-ventral part of the right cerebellar hemisphere, mainly involving the right paramedian lobe, the ansiform lobe and the caudal cerebellar peduncle. Bloodwork results were suggestive of an underlying hypercoagulable state, although the concomitant presence of a histologically confirmed mammary gland adenocarcinoma could have also been related to the cerebellar vascular obstruction through metastatic emboli formation. Posterior-inferior cerebellar artery infarction is the human equivalent of caudal cerebellar artery infarct in dogs.

Canine cutaneous spindle cell tumours with features of peripheral nerve sheath tumours: a histopathological and immunohistochemical study.

In veterinary medicine, the term peripheral nerve sheath tumour is usually restricted to neoplasms that are closely associated with an identified nerve. Thirty-three cases of canine cutaneous tumours previously classified as spindle cell tumours with features resembling peripheral nerve sheath tumours were examined. Two histological patterns were identified: dense areas of spindle shaped cells resembling the Antoni A pattern and less cellular areas with more pleomorphic cells resembling the Antoni B pattern. Immunohistochemically, all tumours uniformly expressed vimentin and 15/33 (45.4%) had scattered and patchy expression of S-100. Laminin expression was found in 25/33 (75.7%) tumours and collagen IV labelling occurred in 14/33 (42.4%). Expression of protein gene product 9.5 was detected in 31/33 (93.9%) of tumours and neuron specific enolase labelling was present in 27/33 (81.8%). Glial fibrillary acidic protein was only expressed within the cytoplasm of some large multinucleated cells in one tumour. These findings suggest that any cutaneous tumour with one of the two histopathological patterns described above should be described as a cutaneous peripheral nerve sheath tumour and that expression of S-100, laminin and collagen IV may be used to define a schwannoma.

Histological and immunohistochemical study of 30 cases of canine meningioma.

This report describes the incidence, location and histopathological and immunohistochemical features of 30 canine meningiomas, of which 22 were intracranial, three were retrobulbar and five were located in the spinal canal. Nine types of meningioma were diagnosed: transitional (9), meningothelial (5), psammomatous (3), anaplastic (3), fibroblastic (2), angioblastic (2), papillary (2), microcystic (1) and meningiomas arising from the optic nerve (3). One of the optic nerve tumours had a granular cell component. All tumours were examined immunohistochemically with antibodies against vimentin, S100, neuron-specific enolase (NSE), cytokeratin (CK) and glial fibrillary acidic protein (GFAP). Vimentin was demonstrated in all tumours, and concentric whorls of cells showed more intense labelling than did bundles of fibroblastic cells. S100 labelling was detected in all tumours except a single angioblastic meningioma. The intensity of labelling for S100 was lower than that for vimentin, and bundles of fibroblastic cells showed particularly strong positivity. NSE labelling was highly variable, but most tumours displayed moderate positivity. CK expression was observed in five of the 30 meningiomas, and was stronger in areas of microcystic differentiation. Most of the tumours were GFAP-negative, but two fibroblastic meningiomas were strongly positive.

Electrically induced blink reflex in horses.

The electrically induced blink reflex was studied electromyographically in 21 healthy adult, detomidine-sedated horses. Using surface electrodes, the supraorbital nerve was electrically stimulated at the supraorbital foramen. The responses were recorded from the ipsilateral and contralateral orbicularis oculi muscles with concentric needle electrodes inserted in the lateral aspect of the ventral eyelids. Ipsilateral and contralateral recordings were made on successive stimulations of the same side of the face, maintaining a constant stimulus intensity. The electromyographically recorded responses consisted of an early R1 response in the orbicularis oculi muscle ipsilateral to the side of stimulation, a bilateral late response (ipsilateral R2 and contralateral Rc) and a third, R3 response, in the ipsilateral orbicularis oculi muscle. All the responses were polyphasic muscle potentials of variable duration and peak to peak amplitudes. The reflex latency of the R1 response was, as in man, fairly stable. The R2 response showed greater variability both within and between individual horses. The Rc response was recorded in only 13 of the 21 horses and showed a slightly longer latency than the corresponding R2. The R3 response, which is significantly related to pain sensation in man, appeared in 19 horses and showed the greatest variability in latency.

Neospora caninum infection in a Napolitan mastiff dog from Spain.

Fetal neosporosis-associated myeloencephalitis was diagnosed in a 4-month-old Napolitan mastiff dog from Spain. Neospora caninum tachyzoites and tissue cysts were observed in lesions in the central nervous system and the diagnosis was confirmed by immunohistochemical staining with anti-N. caninum monoclonal and polyclonal antibodies.

Malignant epithelioid schwannoma affecting the trigeminal nerve of a dog.

A malignant epithelioid schwannoma was diagnosed affecting the trigeminal nerve of an 11-year-old dog. Neurologic abnormalities included an altered mental status, ataxia, left head tilt, postural reaction deficits of all four limbs, a pronounced left masticatory muscle atrophy, and absent left facial sensation. Histologically, a densely arranged epithelioid population with a very high mitotic index was surrounded by a spindle-shaped cell proliferation characteristic of schwannomas. Both cell populations stained positively for vimentin, but only spindle cells were occassionally positive for S-100 protein. The histologic and immunohistochemical features of this tumor were consistent with those found in human epithelioid schwannomas.