The relationships of platelet-derived growth factor, microvascular proliferation, and tumor cell proliferation in canine high-grade oligodendrogliomas: Immunohistochemistry of 45 tumors and an AFOB-01 xenograft mouse model.

High-grade oligodendroglioma (HGOG) is the most common type of glioma in dogs and expresses platelet-derived growth factor receptor-α (PDGFR-α). Microvascular proliferation is often observed in HGOG. Therefore, the present study investigated the functional relationships between PDGFR-α, microvascular proliferation, and tumor cell proliferation in canine HGOG. The expression of PDGFR-α and PDGF-subunit A (PDGF-A) in tumor cells, as well as endothelial cells and pericytes of tumor-associated microvascular proliferations, in 45 canine HGOGs were examined immunohistochemically. Microvascular proliferation was observed in 24/45 cases (53%). PDGFR-α expression in tumor cells and microvascular proliferations was observed in 45/45 (100%) and 2/24 cases (8%), respectively. Furthermore, PDGF-A expression in tumor cells and microvascular proliferations was detected in 13/45 (29%) and 24/24 cases (100%), respectively. In vitro, stimulation of the canine HGOG cell line AOFB-01 with PDGF-A showed that the doubling time of AOFB-01 cells was significantly shorter with PDGF-A than without PDGF-A. Crenolanib (a PDGFR inhibitor) inhibited AOFB-01 cell proliferation. In vivo, the AOFB-01 xenograft mouse model was treated with crenolanib. Tumor xenografts were smaller in crenolanib-treated mice than in untreated control mice. PDGFR-α expression in tumor cells and PDGF-A expression in microvascular proliferations and tumor cells suggest autocrine and paracrine effects of PDGF-A in canine HGOG. The results of in vitro assays indicate that canine HGOG expresses functional PDGFR-α, which responds to PDGF-A. Therefore, PDGF-A produced by microvascular proliferations and tumor cells may promote the proliferation of PDGFR-α-expressing tumor cells in canine HGOG. PDGFR-α signaling has potential as a therapeutic target.

A review of primary central nervous system neoplasms of cats.

Primary central nervous system (CNS) neoplasms are uncommonly diagnosed in cats. The majority of primary feline CNS neoplasms described in the veterinary literature consist of meningioma and glioma occurring mainly in the brain and less often in the spinal cord. Although most neoplasms can be diagnosed based on routine histologic evaluation, less typical tumors need to be further characterized using immunohistochemistry. This review compiles the relevant information about the most common primary CNS neoplasms of cats available in the veterinary literature, aiming to serve as a converging source of information for the topic.

Immunohistochemical study of neural stem cell lineage markers in canine brains, gliomas, and a glioma cell line.

Neural stem cells (NSCs) produce neuron intermediate progenitor cells (nIPC), oligodendrocyte precursor cells (OPCs), and immature astrocytes. To confirm NSC lineages in the normal canine brain and the association of these cells with gliomas, an immunohistochemical study was conducted on fetal and adult canine brains, gliomas, and a glioma cell line. In fetal brains, glial fibrillary acidic protein (GFAP)- and nestin-immunolabeled NSC were observed in the ventricular zone, ß-3 tubulin- and/or neuronal nuclei (NeuN)-immunolabeled nIPC in the subventricular zone (SVZ), and platelet-derived growth factor receptor-α (PDGFR-α)- and OLIG2-immunolabeled OPC and GFAP- and OLIG2-immunolabeled immature astrocytes in the SVZ and intermediate zone. Ki-67 immunohistochemistry revealed that nIPC exhibited high proliferative activity. Quiescent nIPC and OPC were observed in adult brains. Among 58 glioma cases including 4 low-grade oligodendrogliomas (LGOGs), 48 high-grade oligodendrogliomas (HGOGs), 1 low-grade astrocytoma, and 5 high-grade astrocytomas (HGACs), immunohistochemical analyses revealed that oligodendrogliomas expressed PDGFR-α and OLIG2, whereas astrocytomas expressed GFAP and OLIG2. HGOG showed significantly higher immunohistochemical scores for NeuN and ß-3 tubulin than LGOG. The Ki-67 labeling index was high in PDGFR-α and NeuN-immunolabeled tumor cells, and low in ß-3 tubulin- and synaptophysin-immunolabeled cells. A HGOG cell line possessed the same immunohistochemical characteristics as HGOG. In this study, glioma cells with the OPC and IPC immunophenotypes had a higher Ki-67 labeling index, indicating their high proliferative activity. Furthermore, high-grade gliomas showed the characteristics of nIPC and neurons, which may suggest the pluripotent NSC lineage nature of these tumors.

Susceptibility artifact morphology is more conspicuous on susceptibility-weighted imaging compared to T2* gradient echo sequences in the brains of dogs and cats with suspected intracranial disease.

Susceptibility-weighted imaging (SWI) has been found to be more reliable in the detection of vessels and blood products than T2*-weighted gradient echo (GE) in several human brain diseases. In veterinary medicine, published information on the diagnostic usefulness of SWI is lacking. The aim of this retrospective observational study was to investigate the value of SWI compared to T2*-weighted GE images in a population of dogs and cats with presumed, MRI-based diagnoses grouped as neoplastic (27), cerebrovascular (14), inflammatory (14), head trauma (5), other pathologies (4), or that were normal (36). Areas of signal void (ASV) were assessed based on shape, distribution, number, and conspicuity. Presence of ASV was found in 31 T2*-weighted GE and 40 SWI sequences; the conspicuity of lesions increased in 92.5% of cases with SWI. A 44.7% increase in the number of cerebral microbleeds (CMBs) was identified within the population using SWI (110) compared to T2*-weighted GE (76). Linear ASV presumed to be abnormal vascular structures, as are reported in humans, were identified in 12 T2*-weighted GE and 19 SWI sequences. In presumed brain tumors, abnormal vascular structures were detected in 11 of 27 (40.7%) cases on T2*-weighted GE and in 16 of 27 (59.3%) cases on SWI, likely representing tumor neovascularization; amorphous ASV interpreted as presumed hemorrhages on T2*-weighted GE were diagnosed as vessels on SWI in five of 27 (18.5%) cases. Since SWI shows ASV more conspicuously than T2*-weighted GE, the authors advocate the use of SWI in veterinary patients.

Machine learning predicts histologic type and grade of canine gliomas based on MRI texture analysis.

Conventional MRI features of canine gliomas subtypes and grades significantly overlap. Texture analysis (TA) quantifies image texture based on spatial arrangement of pixel intensities. Machine learning (ML) models based on MRI-TA demonstrate high accuracy in predicting brain tumor types and grades in human medicine. The aim of this retrospective, diagnostic accuracy study was to investigate the accuracy of ML-based MRI-TA in predicting canine gliomas histologic types and grades. Dogs with histopathological diagnosis of intracranial glioma and available brain MRI were included. Tumors were manually segmented across their entire volume in enhancing part, non-enhancing part, and peri-tumoral vasogenic edema in T2-weighted (T2w), T1-weighted (T1w), FLAIR, and T1w postcontrast sequences. Texture features were extracted and fed into three ML classifiers. Classifiers' performance was assessed using a leave-one-out cross-validation approach. Multiclass and binary models were built to predict histologic types (oligodendroglioma vs. astrocytoma vs. oligoastrocytoma) and grades (high vs. low), respectively. Thirty-eight dogs with a total of 40 masses were included. Machine learning classifiers had an average accuracy of 77% for discriminating tumor types and of 75.6% for predicting high-grade gliomas. The support vector machine classifier had an accuracy of up to 94% for predicting tumor types and up to 87% for predicting high-grade gliomas. The most discriminative texture features of tumor types and grades appeared related to the peri-tumoral edema in T1w images and to the non-enhancing part of the tumor in T2w images, respectively. In conclusion, ML-based MRI-TA has the potential to discriminate intracranial canine gliomas types and grades.

The NRG3/ERBB4 signaling cascade as a novel therapeutic target for canine glioma.

Canine glioma is a common brain tumor with poor prognosis despite surgery and/or radiation therapy. Therefore, newer and more effective treatment modalities are needed. Neuregulin 3 (NRG3) has known to be a ligand of ERBB4. This study aimed to investigate the usefulness of the NRG3/ERBB4 signaling cascade as a novel therapeutic target in canine glioma. We found out that microRNA (miR)-190a was downregulated in canine brain tumor tissues, including glioma and meningioma. miR-190a directly targeted NRG3 and inhibited the growth of canine glioma cells. The level of p-Akt, which is a downstream target of ERBB4 signaling, was decreased by transfection with miR-190a. NRG3 silencing also suppressed cell growth and decreased the levels of p-Akt and p-ERK1/2, and NRG3 overexpression exhibited opposed effects in canine glioma J3T-1 cells. The mRNA level of erbb4 was significantly upregulated in glioma tissues compared with that in normal brain tissues and meningioma tissues. Furthermore, compared with gefitinib and lapatinib, afatinib exerted a greater inhibitory effect on the growth of canine glioma cells. In conclusion, NRG3/ERBB4 signaling is negatively regulated by miR-190a and contributes to the growth of canine glioma cells, indicating that it may be a promising therapeutic target in canine glioma.

Bovine intracranial neoplasia: A retrospective case series.

This case series describes the clinical and pathological findings of intracranial neoplasms in cattle, a rare entity. Data and archived tissues from 24 intracranial tumors were reviewed and investigated by immunohistochemistry for S100, glial fibrillary acidic protein, synaptophysin, pancytokeratin, vimentin, neuron-specific enolase, oligodendrocyte transcription factor 2, and isocitrate dehydrogenase 1. Ages of affected cattle ranged from 6 months to 14 years (5.7 ± 3.6 years; mean ± SD). Predominant clinical signs were altered mental state, central vestibular dysfunction, and cerebellar incoordination. Twelve gliomas, all high grade, were the most common tumors observed: oligodendrogliomas (n = 6), astrocytomas (n = 4), and undefined gliomas (n = 2). The oligodendrogliomas were located in the brainstem and extended into the ventricles, whereas all astrocytomas were located in the forebrain. Isocitrate dehydrogenase 1 gene mutation as described in humans was not detected. The 5 meningiomas exhibited microcystic, chordoid, atypical, papillary, and anaplastic subtypes. Metastatic carcinomas (n = 4) were the only secondary tumor type present, and these were located at the level of the medulla with infiltration of cranial nerves and in one case leptomeningeal carcinomatosis. In addition, 2 medulloblastomas and 1 choroid plexus carcinoma were diagnosed. Immunohistochemistry for vimentin and pancytokeratin was particularly useful to distinguish meningiomas and choroid plexus carcinoma (positive for vimentin only) from mestastatic carcinomas (positive for cytokeratin only) as all showed a papillary growth pattern. Overall, the morphological features were comparable with other species and the human and canine classifications could be applied.

Malignant Nerve Sheath Tumor of the Hypoglossal Nerve in a Maltese Dog.

A 4 yr old male Maltese dog presented with a 1 wk history of intermittent neck pain and progressive difficulty walking. Neurologic evaluation was consistent with a left-sided brainstem lesion. On oral examination, left lingual hemiatrophy was evident suggesting hypoglossal nerve involvement. A dumbbell-shaped extra-axial mass in the left side of the caudal fossa extending extracranially through the hypoglossal canal was detected by MRI. At postmortem histologic examination, the hypoglossal nerve was diffusely infiltrated by fusiform neoplastic cells arranged in Antoni A and Antoni B patterns. This is the first description of a malignant nerve sheath tumor selectively involving the hypoglossal nerve in a dog.

Prognostic histopathologic features of canine glial tumors.

Gliomas are relatively common tumors in aged dogs (especially brachycephalic breeds), and the dog is proving to be useful as a translational model for humans with brain tumors. Hitherto, there is relatively little prognostic data for canine gliomas and none on outcome related to specific histological features. Histologic sections of tumor biopsies from 33 dogs with glioma treated with surgical resection and immunotherapy and 21 whole brains obtained postmortem were reviewed. Tumors were diagnosed as astrocytic, oligodendroglial, or undefined glioma using Comparative Brain Tumor Consortium criteria. Putative features of malignancy were evaluated, namely, mitotic counts, glomeruloid vascularization, and necrosis. For biopsies, dogs with astrocytic tumors lived longer than those with oligodendroglial or undefined tumor types (median survival 743, 205, and 144 days, respectively). Dogs with low-grade gliomas lived longer than those with high-grade gliomas (median survival 734 and 194 days, respectively). Based on analysis of tumor biopsies, low mitotic counts, absence of glomeruloid vascularization, and absence of necrosis correlated with increased survival (median 293, 223, and 220 days, respectively), whereas high mitotic counts, glomeruloid vascularization, and necrosis correlated with poor survival (median 190, 170, and 154 days, respectively). Mitotic count was the only histological feature in biopsy samples that significantly correlated with survival (P < .05). Whole-brain analyses for those same histologic features had similar and more robust correlations, and were statistically significant for all features (P < .05). The small size of biopsy samples may explain differences between biopsy and whole-brain tumor data. These findings will allow more accurate prognosis for gliomas.

Canine Gliomatosis Cerebri: Morphologic and Immunohistochemical Characterization Is Supportive of Glial Histogenesis.

Gliomatosis cerebri (GC) is a glioma subtype with diffuse neuroparenchymal infiltration without architectural distortion. GC was first used in human neuropathology and remained controversial until its elimination from the diagnostic lexicon in 2016. GC is currently defined as a diffuse growth pattern of glioma rather than a distinct entity. In this article, we characterize 24 cases of canine GC and classify these neoplasms as diffuse gliomas. Selected cases of canine GC were reviewed and immunolabeled for oligodendrocyte lineage transcription factor 2 (Olig2), glial fibrillary acidic protein (GFAP), and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase). The mean age of affected dogs was 7 years, and 9 were brachycephalic. Gross lesions (8 cases) consisted mainly of parenchymal swelling. Histologically, of the 24 cases, there was widespread infiltration of neoplastic cells with astrocytic (12 cases), oligodendroglial (8 cases), or mixed morphology (4 cases) in the brain (18 cases), spinal cord (4 cases), or both (2 cases). Secondary structures occurred across different tumor grades and were not restricted to high-grade neoplasms. Astrocytic neoplasms had moderate nuclear immunolabeling for Olig2 and robust cytoplasmic immunolabeling for GFAP. Oligodendroglial neoplasms had robust nuclear immunolabeling for Olig2, moderate or absent cytoplasmic immunolabeling for GFAP, and moderate cytoplasmic immunolabeling for CNPase. Tumors with mixed morphology had robust nuclear immunolabeling for Olig2 and variable cytoplasmic immunolabeling for GFAP and CNPase. Morphologic and immunohistochemical features confirmed a glial histogenesis for all tumors and allowed for their classification as diffuse, low- or high-grade astrocytoma; oligodendroglioma; or undefined glioma. Further research is needed to confirm or refute the hypothesis that canine GC represents an infiltrative growth pattern of canine glioma.

Feasibility and accuracy of 3D printed patient-specific skull contoured brain biopsy guides.

OBJECTIVE: Design 3D printed skull contoured brain biopsy guides (3D-SCGs) from computed tomography (CT) or T1-weighted magnetic resonance imaging (T1W MRI). STUDY DESIGN: Feasibility study. SAMPLE POPULATION: Five beagle dog cadavers and two client-owned dogs with brain tumors. METHODS: Helical CT and T1W MRI were performed on cadavers. Planned target point was the head of the caudate nucleus. Three-dimensional-SCGs were created from CT and MRI using commercially available open-source software. Using 3D-SCGs, biopsy needles were placed into the caudate nucleus in cadavers, and CT was performed to assess needle placement accuracy, followed by histopathology. Three-dimensional-SCGs were then created and used to perform in vivo brain tumor biopsies. RESULTS: No statistical difference was found between the planned target point and needle placement. Median needle placement error for all planned target points was 2.7 mm (range: 0.86-4.5 mm). No difference in accuracy was detected between MRI and CT-designed 3D-SCGs. Median needle placement error for the CT was 2.8 mm (range: 0.86-4.5 mm), and 2.2 mm (range: 1.7-2.7 mm) for MRI. Biopsy needles were successfully placed into the target in the two dogs with brain tumors and biopsy was successfully acquired in one dog. CONCLUSION: Three-dimensional-SCGs designed from CT or T1W MRI allowed needle placement within 4.5 mm of the intended target in all procedures, resulting in successful biopsy in one of two live dogs. CLINICAL SIGNIFICANCE: This feasibility study justifies further evaluation of 3D-SCGs as alternatives in facilities that do not have access to stereotactic brain biopsy.

Classification of neoplastic and inflammatory brain disease using MRI texture analysis in 119 dogs.

Magnetic resonance imaging is the primary method used to diagnose canine glial cell neoplasia and noninfectious inflammatory meningoencephalitis. Subjective differentiation of these diseases can be difficult due to overlapping imaging characteristics. This study utilizes texture analysis (TA) of intra-axial lesions both as a means to quantitatively differentiate these broad categories of disease and to help identify glial tumor grade/cell type and specific meningoencephalitis subtype in a group of 119 dogs with histologically confirmed diagnoses. Fifty-nine dogs with gliomas and 60 dogs with noninfectious inflammatory meningoencephalitis were retrospectively recruited and randomly split into training (n = 80) and test (n = 39) cohorts. Forty-five of 120 texture metrics differed significantly between cohorts after correcting for multiple testing (false discovery rate < 0.05). After training the random forest algorithm, the classification accuracy for the test set was 85% (sensitivity 89%, specificity 81%). TA was only partially able to differentiate the inflammatory subtypes (granulomatous meningoencephalitis [GME], necrotizing meningoencephalitis [NME], and necrotizing leukoencephalitis [NLE]) (out-of-bag error rate of 35.0%) and was unable to identify metrics that could correctly classify glioma grade or cell type (out-of-bag error rate of 59.6% and 47.5%, respectively). Multiple demographic differences, such as patient age, sex, weight, and breed were identified between disease cohorts and subtypes which may be useful in prioritizing differential diagnoses. TA of MR images with a random forest algorithm provided classification accuracy of inflammatory and neoplastic brain disease approaching the accuracy of previously reported subjective radiologist evaluation.

MRI of osteosarcoma metastases in the brain of an old English Sheepdog.

A 9-year-old, male neutered old English Sheepdog was presented for further investigation of altered mentation, impaired vision, and hemineglect syndrome of 10 days duration. An MRI study of the brain revealed multifocal, contrast-enhancing intra-axial lesions that had a stippled hypointense appearance in all sequences but lacked evidence of a strong signal void on T2* images. Histological examination of the brain postmortem confirmed the lesions were metastases arising from an osteosarcoma, which was later identified in the right humerus. To the authors' knowledge, these MRI characteristics of osteosarcoma metastases in the canine brain have not been previously reported.

Definitive-intent uniform megavoltage fractioned radiotherapy protocol for presumed canine intracranial gliomas: retrospective analysis of survival and prognostic factors in 38 cases (2013-2019).

BACKGROUND: Radiotherapy (RT) is currently considered the treatment of choice for presumed canine intracranial gliomas. However, variable therapeutic responses are described, due to heterogeneous populations and different radiation methods or protocols. Only one study dedicated to intracranial suspected glioma highlighted prognostic criteria. Determination or confirmation of specific clinical and imaging prognostic factors may guide the therapeutic management of these tumours. The objectives were to provide data on long-term clinical outcome (including quality of life, QoL) and to determine specific prognostic factors associated with survival time. We report a single-institution retrospective study, including all dogs with suspected symptomatic primary solitary intracranial glioma, treated with a complete uniform fractionated megavoltage radiation protocol of 15x3Gy over 5 weeks, between January 2013 and February 2019. Thirty-eight client-owned dogs were included. Medical records were retrospectively evaluated for median overall survival time (MST), clinical and imaging responses. Prognostic factors on survival were researched in terms of signalment, clinical presentation, tumour imaging characteristics and response following RT. Finally, the RT's impact on the dogs' clinical signs and Qol were evaluated by the owners. RESULTS: The disease-specific MST was 698 days (95% CI: 598-1135). Survival at 1 and 2 years were respectively 74.2 ± 7.4% and 49.0 ± 9.8%. Initial clinical signs were related to survival, as well as tumour characteristics such as cystic-pattern, mass effect and Tumour/Brain volume ratio. No significant adverse effect or radiotoxicity was observed. CONCLUSIONS: RT appears as a safe and effective treatment for canine intracranial gliomas, allowing long-term tumour control, improvement of life's quality and management of associated clinical signs. The initial clinical signs and MRI characteristics (Tumour/Brain volume ratio, cyst-like lesion and mass effect) may help predict the prognosis.

Onscreen-guided resection of extra-axial and intra-axial forebrain masses through registration of a variable-suction tissue resection device with a neuronavigation system.

OBJECTIVES: To describe a novel surgical technique in which neuronavigation is used to guide a tissue resection device during excision of forebrain masses in locations difficult to visualize optically. STUDY DESIGN: Short case series. ANIMALS: Six dogs and one cat with forebrain masses (five neoplastic, two nonneoplastic) undergoing excision with a novel tissue resection device and veterinary neuronavigation system. METHODS: The animals and resection instrument were coregistered to the neuronavigation system. Surgery was guided by real-time onscreen visualization of the resection instrument position relative to the preoperative MR images. Surgical outcome was evaluated by calculating residual tumor volume according to postoperative MRI. RESULTS: The technique was technically simple and led to the collection of diagnostic tissue samples in all cases. Postoperative MRI was available in six cases, two with gross-total resection, three with near-total resection, and one with subtotal resection. CONCLUSION: Neuronavigation-guided resection of intra-axial and extra-axial brain masses with the resection device resulted in gross-total or near-total resection in five of six animals with tumors otherwise difficult to visualize. Risk of brain shift limited absolute reliance on navigation images. CLINICAL SIGNIFICANCE: Real-time neuronavigation assistance is a feasible method for guidance and successful resection of brain masses that are poorly visualized because of intra-axial or deep location, tumor appearance, or hemorrhage.

Susceptibility weighted imaging at 1.5 Tesla magnetic resonance imaging in dogs: Comparison with T2*-weighted gradient echo sequence and its clinical indications.

Susceptibility weighted imaging (SWI) is a high resolution, fully velocity-compensated, three-dimensional gradient echo (GE) MRI technique. In humans, SWI has been reported to be more sensitive than T2*-weighted GE sequences in the identification of both intracranial hemorrhage and intra-vascular deoxyhemoglobin. However, published clinical studies comparing SWI to T2*-weighted GE sequences in dogs are currently lacking. The aim of this retrospective, observational study was to compare SWI and T2*-weighted GE sequences in a group of dogs with intracranial disease. Medical records were searched for dogs that underwent a brain MRI examination that included T2*-weighted GE and SWI sequences. The presence and appearance of non-vascular and vascular signal voids observed on T2*-weighted GE and SWI were compared. Thirty-two dogs were included with the following diagnoses: presumed and confirmed intracranial neoplasia (27), cerebrovascular accidents (3), and trauma (2). Hemorrhagic lesions were significantly more conspicuous on SWI than T2*-weighted GE sequences (P < .0001). Venous structures were well defined in all SWI sequences, and poorly defined in all dogs on T2*-weighted GE. Susceptibility weighted imaging enabled identification of vascular abnormalities in 30 of 32 (93.8%) dogs, including: neovascularization in 19 of 32 (59.4%) dogs, displacement of perilesional veins in five of 32 (15.6%) dogs, and apparent dilation of perilesional veins in 10 of 32 (31.3%) dogs. Presence of neovascularization was significantly associated with T1-weighted post-contrast enhancement (P = .0184). Hemorrhagic lesions and venous structures were more conspicuous on SWI compared to T2*-weighted GE sequences. Authors recommend adding SWI to standard brain protocols in dogs for detecting hemorrhage and identifying venous abnormalities for lesion characterization.

Definitive-intent intensity-modulated radiation therapy provides similar outcomes to those previously published for definitive-intent three-dimensional conformal radiation therapy in dogs with primary brain tumors: A multi-institutional retrospective study.

Radiotherapy with or without surgery is a common choice for brain tumors in dogs. Although numerous studies have evaluated use of three-dimensional conformal radiotherapy, reports of definitive-intent, IMRT for canine intracranial tumors are lacking. Intensity-modulated radiation therapy has the benefit of decreasing dose to nearby organs at risk and may aid in reducing toxicity. However, increasing dose conformity with IMRT calls for accurate target delineation and daily patient positioning, in order to decrease the risk of a geographic miss. To determine survival outcome and toxicity, we performed a multi-institutional retrospective observational study evaluating dogs with brain tumors treated with IMRT. Fifty-two dogs treated with fractionated, definitive-intent IMRT at four academic radiotherapy facilities were included. All dogs presented with neurologic signs and were diagnosed via MRI. Presumed radiological diagnoses included 37 meningiomas, 12 gliomas, and one peripheral nerve sheath tumor. One dog had two presumed meningiomas and one dog had either a glioma or meningioma. All dogs were treated in the macroscopic disease setting and were prescribed a total dose of 45-50 Gy (2.25-2.5 Gy per fraction in 18-20 daily fractions). Median survival time for all patients, including seven cases treated with a second course of therapy was 18.1 months (95% confidence of interval 12.3-26.6 months). As previously described for brain tumors, increasing severity of neurologic signs at diagnosis was associated with a worse outcome. Intensity-modulated radiation therapy was well tolerated with few reported acute, acute delayed, or late side effects.

Blood-brain barrier dysfunction in canine epileptic seizures detected by dynamic contrast-enhanced magnetic resonance imaging.

OBJECTIVE: Dogs with spontaneous or acquired epilepsy exhibit resemblance in etiology and disease course to humans, potentially offering a translational model of the human disease. Blood-brain barrier dysfunction (BBBD) has been shown to partake in epileptogenesis in experimental models of epilepsy. To test the hypothesis that BBBD can be detected in dogs with naturally occurring seizures, we developed a linear dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) analysis algorithm that was validated in clinical cases of seizing dogs and experimental epileptic rats. METHODS: Forty-six dogs with naturally occurring seizures of different etiologies and 12 induced epilepsy rats were imaged using DCE-MRI. Six healthy dogs and 12 naive rats served as control. DCE-MRI was analyzed by linear-dynamic method. BBBD scores were calculated in whole brain and in specific brain regions. Immunofluorescence analysis for transforming growth factor beta (TGF-ß) pathway proteins was performed on the piriform cortex of epileptic dogs. RESULTS: We found BBBD in 37% of dogs with seizures. A significantly higher cerebrospinal fluid to serum albumin ratio was found in dogs with BBBD relative to dogs with intact blood-brain barrier (BBB). A significant difference was found between epileptic and control rats when BBBD scores were calculated for the piriform cortex at 48 hours and 1 month after status epilepticus. Mean BBBD score of the piriform lobe in idiopathic epilepsy (IE) dogs was significantly higher compared to control. Immunohistochemistry results suggested active TGF-ß signaling and neuroinflammation in the piriform cortex of dogs with IE, showing increased levels of serum albumin colocalized with glial acidic fibrillary protein and pSMAD2 in an area where BBBD had been detected by linear DCE-MRI. SIGNIFICANCE: Detection of BBBD in dogs with naturally occurring epilepsy provides the ground for future studies for evaluation of novel treatment targeting the disrupted BBB. The involvement of the piriform lobe seen using our linear DCE-MRI protocol and algorithm emphasizes the possibility of using dogs as a translational model for the human disease.

Cerebral cysts of ependymal or ventricular origin in a juvenile rhesus macaque (Macaca mulatta) with neurologic signs.

Naturally occurring neurologic disease in non-human primates may be attributable to a wide-range of causes, including infectious agents, congenital or acquired malformations, degenerative diseases, and, rarely, neoplasia. We report a case of ataxia and paresis in a juvenile rhesus macaque with ependymal-lined cerebral cysts.

Canine Cerebral Intravascular Lymphoma: Neuropathological and Immunohistochemical Findings.

Intravascular lymphoma (IVL) is a rare angiotropic large-cell lymphoma in which neoplastic lymphocytes proliferate within the lumina of small blood vessels in the absence of a primary extravascular mass or leukemia. This study included 10 cases of canine IVL restricted to the CNS. Dogs had an average age of 8 years and neurological signs mainly referred to brain involvement such as depression, seizures, and ambulatory deficits. Gross examination at necropsy showed focal extensive or multiple hemorrhagic areas mainly distributed in the telencephalon and diencephalon. Histopathologically, numerous veins and capillaries were filled with neoplastic lymphoid cells, accompanied by edema, hemorrhage, and thrombosis. Immunohistochemistry (IHC) for CD3, CD20, and PAX5 was performed to phenotype the neoplastic lymphocytes. IHC for CD44 and CD29 were used to investigate the pathogenetic mechanism leading to the intravascular aggregation of the neoplastic lymphocytes. The same IHC panel was applied to 8 cases of primary and metastatic canine CNS lymphoma in order to compare IVL immunoreactivity. Three IVLs were typified as T-cell, 3 as B-cell, and 4 as non-T non-B. Neoplastic lymphocytes showed marked expression of CD44 in all IVL cases, and CD29-immunolabeled cells were observed in 4 IVLs. CD44 immunoreactivity was consistent with the findings reported in human IVL, suggesting a predisposition to the formation of lymphocyte aggregates. CD29 was inconsistently immunonegative in canine IVL, confirming only partially the pathogenetic mechanism suggested for the human counterpart.