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.

Spinal cord injury secondary to electrocution in a dog.

A 13-year-old, female spayed, crossbreed dog of 32 kg was presented for evaluation of peracute onset of non-ambulatory tetraparesis after chewing an electrical wire. Neurological examination was consistent with a C1-C5 myelopathy. Magnetic resonance imaging revealed a focal intramedullary lesion over the C2-C3 vertebral bodies, which was confirmed to be an acute focal necrotising poliomyelopathy with subarachnoid and subdural haemorrhages on postmortem examination. This report describes the clinical, imaging and histopathological findings of this unusual type of spinal cord injury, and the effects of electrocution in the central nervous system of dogs.

Presumed brain infarctions in two dogs with systemic leishmaniasis.

Clinical signs and magnetic resonance imaging findings of multiple brain infarcts in two dogs infected with Leishmania spp. are reported. Clinical signs of intracranial dysfunction were peracute and there was no further deterioration. Magnetic resonance images of the brain were consistent with multifocal, non-haemorrhagic, ischaemic lesions. Routine serum biochemistry revealed hyperproteinaemia and hyperglobulinaemia. Serum antibody titres were highly positive for Leishmania infantum and Leishmania amastigotes were seen within bone marrow macrophages in both cases. Canine leishmaniasis can cause cerebrovascular alterations, such as vasculitis, that might predispose dogs to brain infarcts.

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.

Clinical findings in 10 foals with bacterial meningoencephalitis.

REASONS FOR PERFORMING THE STUDY: Bacterial meningoencephalitis is a severe complication in septic foals and there is scarce and often unclear information in the equine literature. OBJECTIVES: To report the most frequent clinical signs, clinicopathological findings, causative agents, treatments given and outcome of a group of foals with confirmed bacterial meningoencephalitis. METHODS: Foals aged < 6 months of age admitted to the Universitat Autonoma de Barcelona (2004-2009) with confirmed bacterial meningoencephalitis were retrospectively included in the study Diagnosis of bacterial meningoencephalitis was made by cerebrospinal fluid (CSF) culture, CSF analysis consistent with bacterial infection, observation of bacteria in CSF cytology or postmortem confirmation. RESULTS: Nine neonates and one 5-month-old foal were included. The most frequently observed clinical signs were alterations in mental status (10/10), recumbency (8/10), weakness (8/10), abnormal pupillary light reflexes (6/10), decreased suckling-reflex (6/9), seizures and/or nystagmus (4/10). Common clinicopathological alterations included hyperfibrinogenaemia (8/9), hyperlactataemia (7/7), and neutropenia (5/10) or neutrophilia (5/10). Most neonates (8/9) developed bacterial meningoencephalitis despite having a sepsis score near the cut-off value (median = 12). On CSF analysis, pleocytosis (9/9), increased total protein concentration (5/6) and intracellular bacteria (6/9) were detected. The most frequently isolated bacterium was Escherichia coil. Once bacterial meningoencephalitis was diagnosed, antimicrobial therapy was switched to third and fourth generation cephalosporins. CONCLUSIONS: The diagnosis of bacterial meningoencephalitis is established based on CSF analysis and culture. Clinical recognition of bacterial meningoencephalitis is difficult and can be easily overlooked. Moreover, severe sepsis is not necessary to develop bacterial meningoencephalitis. POTENTIAL RELEVANCE: CSF analysis should be considered more often in sick newborn foals with signs indicative of central nervous system (CNS) involvement. Cerebrospinal fluid (CSF) cytology and culture would help to confirm or rule out unnoticed bacterial meningoencephalitis, and to choose appropriate antimicrobial therapy

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.

A novel spongiform degeneration of the grey matter in the brain of a kitten.

A young female domestic short-hair cat presented with neurological signs consistent with a multifocal encephalic lesion (depressed mental status, head tilt to the right, cervical ventroflexion, head tremors, tetraparesis, conscious propioceptive deficits in all four limbs and visual deficits). No gross lesions were seen at necropsy. On light microscopical examination lesions were found only in the brain and cervical spinal cord. A generalized vacuolation of the grey matter of the brain was observed. Special staining techniques, immunohistochemistry, lectin affinity histochemistry and ultrastructural studies were performed to characterize the lesion; preservation of the white matter and a reactive astrogliosis were demonstrated. Feline retroviruses and PrPsc were not detected. Ultrastructurally, a dilatation of intracytoplasmic membrane-bounded organelles with membrane disruption and dendritic and somatic swelling was found in astrocytes and neurons. The age of the animal and histological changes suggested a novel, possibly congenital, spongiform degeneration of the brain and cervical spinal cord.

Electrically induced blink reflex and facial motor nerve stimulation in beagles.

Electrophysiologic assessment of the blink reflex test and the muscle-evoked potentials evoked by stimulation of the facial nerve were performed in 15 healthy adult Beagles before and after supraorbital (trigeminal) and facial anesthetic nerve blocks performed by lidocaine injections. Unilateral electrical stimulation of the supraorbital nerve elicited 2 ipsilateral (R1 and R2) and a contralateral (Rc) reflex muscle potential in orbicularis oculi muscles. Electrical stimulation of the facial nerve elicited 2 muscle potentials (a direct response [D] and a reflex faciofacial response [RF]) in the ipsilateral orbicularis oculi muscle. Anesthetic block of the left supraorbital nerve resulted in bilateral lack of responses upon left supraorbital nerve stimulation, but normal responses in right and left orbicularis oculi muscles upon right supraorbital stimulation. Right facial anesthetic block produced lack of responses in the right orbicularis oculi muscle regardless the side of supraorbital nerve stimulation. Results of this study demonstrate that the blink reflex can be electrically elicited and assessed in dogs. Reference values for the blink reflex responses and for the muscle potentials evoked by direct facial nerve stimulation in dogs are provided. The potential usefulness of the electrically elicited blink reflex test in the diagnosis of peripheral facial and trigeminal dysfunction in dogs was demonstrated.