Canine glioma in the first year of life: 5 cases.

Most canine gliomas occur in adult and aged dogs, and reports in puppies < 12-mo-old are exceedingly rare. Here we describe the occurrence of gliomas in 5 dogs ≤ 12-mo-old. The affected patients (4 males, 1 female) were 3-12-mo-old (x̄ = 6.6-mo-old). None of the dogs were brachycephalic. Clinical signs consisted of dullness (2 cases), seizures (2 cases), vestibular signs, and deafness (1 case each). All patients were euthanized. Grossly, neoplasms were pale-tan or red, soft masses in the telencephalon (4 cases) or gelatinous leptomeningeal thickening in the brain and spinal cord (1 case). Neoplasms were classified as astrocytomas (3 cases) and oligodendrogliomas (2 cases) based on histology or histology and IHC. Our findings confirm that, while exceptionally rare, canine gliomas occur in the first year of life, and are clinically, morphologically, and immunohistochemically similar to gliomas in adult and aged dogs.

Neuronal Deposition of Amyloid-ß Oligomers and Hyperphosphorylated Tau Is Closely Connected with Cognitive Dysfunction in Aged Dogs.

BACKGROUND: Canine cognitive dysfunction (CCD) is a progressive syndrome recognized in mature to aged dogs with a variety of neuropathological changes similar to human Alzheimer's disease (AD), for which it is thought to be a good natural model. However, the presence of hyperphosphorylated tau protein (p-Tau) in dogs with CCD has only been demonstrated infrequently. OBJECTIVE: The aim of the present study was to investigate the presence of p-Tau and amyloid-ß oligomer (Aßo) in cerebral cortex and hippocampus of dogs with CCD, with focus on an epitope retrieval protocol to unmask p-Tau. METHODS: Immunohistochemical and immunofluorescence analysis of the cortical and hippocampal regions of five CCD-affected and two nondemented aged dogs using 4G8 anti-Aßp, anti-Aß1 - 42 nanobody (PrioAD13) and AT8 anti-p-Tau (Ser202, Thr205) antibody were used to demonstrate the presence of Aß plaques (Aßp) and Aß1 - 42 oligomers and p-Tau deposits, respectively. RESULTS: The extracellular Aß senile plaques were of the diffuse type which lack the dense core normally seen in human AD. While p-Tau deposits displayed a widespread pattern and closely resembled the typical human neuropathology, they did not co-localize with the Aßp. Of considerable interest, however, widespread intraneuronal deposition of Aß1 - 42 oligomers were exhibited in the frontal cortex and hippocampal region that co-localized with p-Tau. CONCLUSION: Taken together, these findings reveal further shared neuropathologic features of AD and CCD, supporting the case that aged dogs afflicted with CCD offer a relevant model for investigating human AD.

Case Report: Synucleinopathy Associated With Phalaris Neurotoxicity in Sheep.

Chronic intoxication with tryptamine-alkaloid-rich Phalaris species (spp.) pasture plants is known colloquially as Phalaris staggers syndrome, a widely occurring neurological disorder of sheep, cattle, horses, and kangaroos. Of comparative interest, structurally analogous tryptamine-alkaloids cause experimental parkinsonism in primates. This study aimed to investigate the neuropathological changes associated with spontaneous cases of Phalaris staggers in sheep with respect to those encountered in human synucleinopathy. In sheep affected with Phalaris staggers, histological, immunohistochemical, and immunofluorescence analysis revealed significant accumulation of neuromelanin and aggregated α-synuclein in the perikaryon of neurons in the cerebral cortex, thalamus, brainstem, and spinal cord. Neuronal intracytoplasmic Lewy bodies inclusions were not observed in these cases of ovine Phalaris staggers. These important findings established a clear link between synucleinopathy and the neurologic form of Phalaris plant poisoning in sheep, demonstrated in six of six affected sheep. Synucleinopathy is a feature of a number of progressive and fatal neurodegenerative disorders of man and may be a common endpoint of such disorders, which in a variety of ways perturb neuronal function. However, whether primary to the degenerative process or a consequence of it awaits clarification in an appropriate model system.

A Review of Proliferative Vascular Disorders of the Central Nervous System of Animals.

In disease, blood vessel proliferation has many salient roles including in inflammation, when granulation tissue fills superficial defects, or in the recanalization of an occluded blood vessel. Sometimes angiogenesis goes awry-granulation can be exuberant, and plexiform proliferation of vascular components can contribute to pulmonary hypertension. This review focuses on the diverse manifestations of pathologic vascular overgrowth that occur in the brain, spinal cord, and meninges of animals from birth until old age. Entities discussed include systemic reactive angioendotheliomatosis in which glomeruloid vascular proliferations are encountered in various organs including the central nervous system (CNS). The triad of CNS vascular malformations, hamartomas, and benign vascular proliferations are an especially fraught category in which terminology overlap and the microscopic similarity of various disorders makes diagnostic classification incredibly challenging. Pathologists commonly take refuge in "CNS vascular hamartoma" despite the lack of any unique histopathologic features and we recommend that this diagnostic category be abandoned. Malformative lesions that are often confusing and have similar features; the conditions include arteriovenous malformation, cavernous angioma, venous angioma, and capillary telangiectases. Meningioangiomatosis, a benign meningovascular proliferation with dual components, is a unique entity seen most commonly in young dogs. Last, accepted neoplastic conditions range from lower-grade locally acquired growths like hemangioblastoma (a tumor of mysterious interstitial stromal cells encountered in the setting of abundant capillary vasculature proliferation), the rare hemangioendothelioma, and the highly malignant and invariably multifocal metastatic hemangiosarcoma. Additionally, this review draws on the comparative medical literature for further insights into this problematic topic in pathology.

Plant poisoning leads to alpha-synucleinopathy and neuromelanopathy in kangaroos.

The pathogenesis of synucleinopathies, common neuropathological lesions normally associated with some human neurodegenerative disorders such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, remains poorly understood. In animals, ingestion of the tryptamine-alkaloid-rich phalaris pastures plants causes a disorder called Phalaris staggers, a neurological syndrome reported in kangaroos. The aim of the study was to characterise the clinical and neuropathological changes associated with spontaneous cases of Phalaris staggers in kangaroos. Gross, histological, ultrastructural and Immunohistochemical studies were performed to demonstrate neuronal accumulation of neuromelanin and aggregated α-synuclein. ELISA and mass spectrometry were used to detect serum-borne α-synuclein and tryptamine alkaloids respectively. We report that neurons in the central and enteric nervous systems of affected kangaroos display extensive accumulation of neuromelanin in the perikaryon without affecting neuronal morphology. Ultrastructural studies confirmed the typical structure of neuromelanin. While we demonstrated strong staining of α-synuclein, restricted to neurons, intracytoplasmic Lewy bodies inclusions were not observed. α-synuclein aggregates levels were shown to be lower in sera of the affected kangaroos compared to unaffected herd mate kangaroos. Finally, mass spectrometry failed to detect the alkaloid toxins in the sera derived from the affected kangaroos. Our preliminary findings warrant further investigation of Phalaris staggers in kangaroos, potentially a valuable large animal model for environmentally-acquired toxic synucleinopathy.

Schwannosis in Three Foals and a Calf.

Proliferation of ectopic Schwann cells within the central nervous system (CNS) parenchyma (schwannosis) in early life is most commonly associated with human neurofibromatosis type-2 and has been unrecognized in domestic animals. Three foals and a calf, 5 to 11 weeks old, with progressive neurological signs from birth were studied. Histologically, at multiple levels of the spinal cord, all animals had bilateral plaques of proliferative spindle cells, predominantly affecting the white matter adjacent to dorsal and ventral nerve roots and variably extending into the gray matter. Proliferating cells had strong intracytoplasmic immunoreactivity for the Schwann cell markers myelin protein zero and periaxin, highlighting the formation of peripheral nervous system (PNS) myelin within the spinal cord. In all cases, foci of disorganized neural tissue (glioneuronal hamartomas) were present, which in 2 cases formed a mass effect that resulted in syringohydromyelia. Neonatal presentation suggests a congenital maldevelopment of the nervous system, with spontaneous invasion of PNS-derived Schwann cells into the CNS.

An unusual lipomatous brain mass in a Golden Retriever dog.

A 9-year-old Golden Retriever dog was presented to the Veterinary Medical Center with a 3-week history of grand mal seizures and was subsequently euthanized. At autopsy, a discrete, firm, expansile mass was found in the right pyriform lobe, which compressed the ipsilateral hippocampus, thalamus, and cerebral cortex. Histologically, the mass was composed of well-differentiated adipose tissue supported by fibrous and mucinous stroma. Adipocytes exhibited strong immunoreactivity for vimentin and were negative for pancytokeratin (AE1/AE3), glial fibrillary acidic protein, neuron-specific enolase, and synaptophysin. These findings are most compatible with an intracranial lipomatous hamartoma, which is an extraparenchymal lesion that has been identified in several species. The current report describes an intracerebral lipomatous hamartoma in a veterinary species.

Giant axonal neuropathy-like disease in an Alexandrine parrot (Psittacula eupatria).

A chronic progressive neurological condition in an Alexandrine parrot (Psittacula eupatria) was manifest as intention tremors, incoordination, and seizure activity. Histology revealed large eosinophilic bodies throughout the central nervous system, and electron microscopy demonstrated that these bodies were greatly expanded axons distended by short filamentous structures that aggregated to form long strands. The presence of periodic acid-Schiff-positive material within the neuronal bodies of Purkinje cells and ganglionic neurons is another distinctive feature of this disease. The histological features of this case display some features consistent with giant axonal neuropathy as reported in humans and dogs. Based on investigation of the lineage in this case, an underlying inherited defect is suspected, but some additional factor appears to have altered the specific disease presentation in this bird.

MRI characteristics of fourth ventricle arachnoid diverticula in five dogs.

Intracranial arachnoid diverticula (cysts) are rare accumulations of cerebrospinal fluid (CSF) within the arachnoid membrane. The purpose of this retrospective study was to describe magnetic resonance imaging (MRI) characteristics of fourth ventricle arachnoid diverticula in a group of dogs. The hospital's medical records were searched for dogs with MRI studies of the brain and a diagnosis of fourth ventricle arachnoid diverticulum. Clinical characteristics were recorded from medical records and MRI studies were reinterpreted by a board-certified veterinary radiologist. Five pediatric dogs fulfilled inclusion criteria. Clinical signs included cervical hyperaesthesia, obtundation, tetraparesis, and/or central vestibular syndrome. In all five dogs, MRI findings were consistent with obstructive hydrocephalus, based on dilation of all ventricles and compression of the cerebellum and brainstem. All five dogs also had cervical syringohydromyelia, with T2-weighted hyperintensity of the gray matter of the cord adjacent to the syringohydromyelia. A signal void, interpreted as flow disturbance, was observed at the mesencephalic aqueduct in all dogs. Four dogs underwent surgical treatment with occipitalectomy and durotomy. A cystic lesion emerging from the fourth ventricle was detected in all four dogs during surgery and histopathology confirmed the diagnosis of arachnoid diverticula. Three dogs made excellent recovery but deteriorated shortly after surgery and were euthanized. Repeat MRI in two dogs revealed improved hydrocephalus but worsening of the syringohydromyelia. Findings from the current study supported theories that fourth ventricle arachnoid diverticula are secondary to partial obstruction of the central canal or lateral apertures and that arachnoid diverticula are developmental lesions in dogs.

Novel approach to temporal lobectomy for removal of a cavernous hemangioma in a dog.

OBJECTIVE: To report temporal lobe surgery for a cavernous hemangioma in a dog and outcome. STUDY DESIGN: Clinical report. ANIMALS: Dog (n = 1). METHODS: Magnetic resonance (MR) imaging was used to identify a temporal lobe mass in 9-year-old, male neutered Labrador Retriever that had a 12 hour history of seizures. An approach to the temporal lobe allowed preservation of the zygomatic arch and mass removal. RESULTS: The mass was confirmed as a cavernous hemangioma on histopathology. Repeat MR imaging at 13 months showed no recurrence of gross structural disease; however, the dog's anti-epileptic medication was administered for adequate seizure control. CONCLUSION: Temporal lobe surgery can be performed in the dog's for the management of temporal lobe mass lesions.

Feline spinal cord gliomas: Clinicopathologic and diagnostic features of seven cases

Intraparenchymal spinal cord tumors in the cat are rarely reported and often as single case reports. In the current study, the clinical, magnetic resonance imaging (MRI), histologic, and immunohistochemical features of 7 cases of intraparenchymal spinal cord tumors in the cat are described. All cats were domestic breed, ranged from 4 to 12 years of age (median 8 years), and included spayed females (5/7) and neutered males (2/7). The duration of clinical signs ranged from 2 weeks to 3 months. MRI revealed lesions that were hyperintense on T2-weighted images with variable contrast enhancement. All 7 tumors had histologic features consistent with glial origin: 3 were astrocytic (gemistocytic or fibrous), and 2 were oligoastrocytic. Single cases of oligodendroglioma and gliomatosis cerebri were also present in the study. Glial fibrillary acidic protein immunoreactivity was robust in the tumors that were predominately astrocytic, and the gliomatosis cerebri case had extensive BLA.36 and Iba1 immunoreactivity. Ki-67 immunoreactivity was variable and most abundant in the case of malignant oligoastrocytoma. The majority of peritumoral lymphocytes were CD3 positive. The current study expands upon the known reports of spinal cord neoplasia in the cat, confirms a caudal cervical segment predilection, and includes a report of gliomatosis cerebri in the spinal cord of a cat.

Feline ischemic myelopathy and encephalopathy secondary to hyaline arteriopathy in five cats.

Five cats presented with acute-onset neurological signs. Magnetic resonance imaging in four cats showed a T2-weighted hyperintense spinal cord lesion that was mildly contrast-enhancing in three cats. Owing to inflammatory cerebrospinal fluid changes three cats were treated with immunosuppression. One cat was treated with antibiotics. All cats improved initially, but were eventually euthanased owing to the recurrence of neurological signs. Histopathology in all cats showed hyaline degeneration of the ventral spinal artery, basilar artery or associated branches with aneurysmal dilation, thrombosis and ischemic degeneration and necrosis of the spinal cord and brain. Two cats also had similar vascular changes in meningeal vessels. Vascular hyaline degeneration resulting in vascular aneurysmal dilation and thrombosis should be a differential diagnosis in cats presenting with acute central nervous system signs.

Imaging diagnosis-malignant peripheral nerve sheath tumor presenting as an intra-axial brain mass in a young dog.

A 3-year-old Labrador retriever was presented with acute onset seizures. Magnetic resonance imaging demonstrated an intra-axial mass affecting the right temporal lobe of the brain. Surgical resection and histopathological findings were most consistent with a malignant peripheral nerve sheath tumor. After initial recovery, deterioration 3 months post surgery prompted euthanasia. Post-mortem revealed a mass protruding from the ventral surface of the temporal lobe, encroaching upon the optic chiasm and invading the brain. Histopathology findings were again consistent with malignant peripheral nerve sheath tumor. Although rare, this tumor should be included as a possible differential diagnosis for intra-axial brain masses in dogs.

Chronic hypertrophic ganglioneuritis mimicking spinal nerve neoplasia: clinical, imaging, pathologic findings, and outcome after surgical treatment.

OBJECTIVE: To report the clinical, imaging, pathologic findings, surgical planning, and long-term outcome after surgery in a dog with neurologic deficits because of a hypertrophic ganglioneuritis that compressed the spinal cord. STUDY DESIGN: Clinical report. ANIMAL: An 8-year-old male intact Yorkshire terrier. METHODS: The dog had ambulatory tetraparesis and neurologic examination was consistent with a C1-C5 myelopathy. Magnetic resonance imaging (MRI) revealed enlargement of the left C2 spinal nerve causing compression of the spinal cord. The main differential diagnosis was spinal nerve neoplasia with compression and possibly spinal cord invasion. On ultrasonography, there was enlargement of the spinal nerve and fine needle aspiration did not show evidence of neoplasia. Fascicular biopsy of the spinal nerve was consistent with enlargement because of chronic inflammation (hypertrophic neuritis). RESULTS: Hemilaminectomy followed by durotomy and rhizotomy allowed resection of an intradural-extramedullary mass that was the enlarged left C2 spinal nerve. Histopathology was consistent with a hypertrophic ganglioneuritis. Thirteen months later the dog remained free of clinical signs. CONCLUSION: Hypertrophic neuritis affecting the spinal nerves may be misdiagnosed as spinal nerve neoplasia that in dogs is usually malignant with a poor prognosis. Focal spinal nerve lesions with compression of the spinal cord evident on MRI may be inflammatory and are not necessarily a neoplastic condition.

Imaging diagnosis-magnetic resonance imaging features of a cerebral hemangioblastoma in a dog.

The magnetic resonance (MR) imaging features of a cerebral hemangioblastoma in a 9-year-old dog are described. Imaging revealed a well-defined contrast-enhancing lesion of the rostral forebrain that appeared extraparenchymal. Histopathology of the excised mass showed clusters of small blood vessels interspersed with interstitial cells staining positive for neuronal specific enolase, features consistent with a cerebral hemangioblastoma; the mass also appeared intraparenchymal after further immunohistochemistry study. This neoplasm should be considered a rare differential diagnosis for intracranial masses in dogs.

Differential expression of TAR DNA-binding protein (TDP-43) in the central nervous system of horses afflicted with equine motor neuron disease (EMND): a preliminary study of a potential pathologic marker.

Equine motor neuron disease (EMND) is a neurodegenerative disorder of unknown etiology affecting horses worldwide. Trans-Active Response DNA Binding Protein of 43 kDa (TDP-43) has been reported in the central nervous system (CNS) of several neurodegenerative conditions in humans including Amyotrophic Lateral Sclerosis (ALS) and assumed to play role in the disease. We examined whether horses afflicted with EMND express the TDP-43 in CNS. Ten horses with EMND and 6 controls of different ages and breed we enrolled. Detection of presence of TDP-43 protein in the CNS was analyzed by immunohistochemical staining using rabbit anti-human TARDBP (TDP-43) polyclonal antibody. Formalin fixed neuronal tissues from medulla, cervical, and lumbar spinal cord were harvested from EMND and from control horses. Sections were assigned randomly to TDP-43 treated or rabbit anti-IgG as control. Nuclear staining of TDP-43 was detected in one of the neural tissues of 75 % of EMND-positive and 0 of 0 % of control horses in the central nervous system (medulla, and/or cervical spinal cord and/or lumbar spinal cord). TDP-43 antibody was detected in the nucleus of EMND horses and no cytoplasmic staining was noted. As in ALS, there was no pattern of age clustering associated with the detection of TDP-43. This is the first report on the staining of TDP-43 in neuronal tissues of horses and suggests that TDP-43 may play a role in the pathogenesis of EMND. Further studies are needed to elucidate the etiologic role of this protein in the diseases.

Imaging diagnosis--spinal cord hemangioma in two dogs.

Intramedullary masses are a dilemma due to the limited access for a nonsurgical biopsy, thus, accurate imaging characterization is crucial. Magnetic resonance imaging findings of two confirmed canine thoracic intramedullary hemangiomas are described. A capillary hemangioma was of mixed intensity but predominantly T2-hyperintense and mildly T1-hyperintense to spinal cord with strong contrast enhancement. A cavernous hemangioma had a target-like appearance in both T1-weighted (T1w) and T2-weighted (T2w) images. In T2w images there was a small isointense center surrounded by a relatively large hyperintense area. In T1w images, there was a large isointense centre with a relatively small hyperintense periphery. Such characteristics should prioritize hemangioma as a consideration in a progressive myelopathy due to an intramedullary mass.

Paraneoplastic hypercalcemia in a dog with benign renal angiomyxoma.

An 11-year-old, male, neutered crossbred Collie dog was presented for a history of polydipsia and polyuria. Diagnostic investigations revealed total and ionized hypercalcemia and an increased concentration of parathyroid hormone-related peptide. Abdominal ultrasonography and contrast-enhanced computed tomography of the abdomen revealed a right-sided, cystic-appearing renal mass. Cytological examination of ultrasound-guided aspirates of the mass revealed high numbers of spindle cells. The mass was removed en bloc via an ureteronephrectomy. Histopathological examination of the mass revealed neoplastic spindle cells in loosely packed and interlacing streams within a myxomatous stroma. Immunohistochemical examination with vimentin, von Willebrand Factor, and alpha-smooth muscle actin confirmed the mass to be a renal angiomyxoma. A minority of the neoplastic spindle cells showed positive cytoplasmic parathyroid hormone-related peptide immunostaining. The hypercalcemia resolved following surgery, and the parathyroid hormone-related peptide concentration returned to within the reference interval. The dog was no longer polydipsic or polyuric 1 year following surgery. The present report describes a previously unreported renal neoplasm causing paraneoplastic hypercalcemia and highlights the possibility of paraneoplastic hypercalcemia being caused by a benign neoplasm.

Molecular detection of Canine distemper virus and the immunohistochemical characterization of the neurologic lesions in naturally occurring old dog encephalitis.

The current article describes a spontaneous case of old dog encephalitis (ODE) in a 7-year-old, intact, female Miniature Schnauzer dog from Londrina, Paraná, southern Brazil. Unlike conventional distemper encephalomyelitis, ODE is a poorly understood and extremely rare manifestation of Canine distemper virus (CDV) infection. The dog was presented with progressive clinical manifestations consistent with cerebral dysfunction. Briefly, histopathologic lesions were restricted to the forebrain and included chronic multifocal lymphoplasmacytic encephalitis with extensive perivascular cuffing, astrocytosis, and intranuclear inclusions within astrocytes and giant cells, with both intracytoplasmic and intranuclear inclusions. Immunohistochemistry (IHC) was used to identify the antigens of the nucleoprotein (NP) of CDV and to detect cluster of differentiation (CD)3, CD79a, macrophage (MAC) 387, glial fibrillary acidic protein, and vimentin to characterize the neuroparenchymal lesions. By IHC, CDV NP was demonstrated predominantly within neurons and astrocytes. Cells that formed perivascular cuffs and some astrocyte-like cells reacted intensely to vimentin. Reverse transcription polymerase chain reaction assay from brain sections further confirmed a role for CDV in this disease by the amplification and partial sequence analysis of the NP gene. These findings confirmed simultaneous detection of CDV in ODE by IHC and molecular assays. In addition, results of the current study could contribute to the neuropathologic characterization of this rare manifestation of CDV.