Magnetic resonance imaging and computed tomographic characteristics of a glioma causing calvarial erosion in a dog.

An 8-year-old female Boxer was examined for acute onset of seizures. On magnetic resonance imaging (MRI), an intra-axial mass with imaging features consistent with glioma was observed in the right cerebral hemisphere. A defect in the temporal bone adjacent to the mass was observed. Postmortem computed tomography (CT) confirmed temporal bone osteolysis and necropsy demonstrated a glioblastoma with associated calvarial erosion. Although occasionally described in human medicine, to our knowledge, this is the first description of a brain glioma causing calvarial erosion in a dog. Glioma should be included as a differential diagnosis for intracranial lesions that could cause bony changes in the skull.

Biochemical, histological and functional correction of mucopolysaccharidosis type IIIB by intra-cerebrospinal fluid gene therapy.

Gene therapy is an attractive tool for the treatment of monogenic disorders, in particular for lysosomal storage diseases (LSD) caused by deficiencies in secretable lysosomal enzymes in which neither full restoration of normal enzymatic activity nor transduction of all affected cells are necessary. However, some LSD such as Mucopolysaccharidosis Type IIIB (MPSIIIB) are challenging because the disease's main target organ is the brain and enzymes do not efficiently cross the blood-brain barrier even if present at very high concentration in circulation. To overcome these limitations, we delivered AAV9 vectors encoding for α-N-acetylglucosaminidase (NAGLU) to the Cerebrospinal Fluid (CSF) of MPSIIIB mice with the disease already detectable at biochemical, histological and functional level. Restoration of enzymatic activity in Central Nervous System (CNS) resulted in normalization of glycosaminoglycan content and lysosomal physiology, resolved neuroinflammation and restored the pattern of gene expression in brain similar to that of healthy animals. Additionally, transduction of the liver due to passage of vectors to the circulation led to whole-body disease correction. Treated animals also showed reversal of behavioural deficits and extended lifespan. Importantly, when the levels of enzymatic activity were monitored in the CSF of dogs following administration of canine NAGLU-coding vectors to animals that were either naïve or had pre-existing immunity against AAV9, similar levels of activity were achieved, suggesting that CNS efficacy would not be compromised in patients seropositive for AAV9. Our studies provide a strong rationale for the clinical development of this novel therapeutic approach as the treatment for MPSIIIB.

Development of learning objectives for neurology in a veterinary curriculum: part II: postgraduates.

BACKGROUND: Specialization in veterinary medicine in Europe is organized through the Colleges of the European Board of Veterinary Specialization. To inform updating of the curriculum for residents of the European College of Veterinary Neurology (ECVN) job analysis was used. Defining job competencies of diploma holders in veterinary neurology can be used as references for curriculum design of resident training. With the support of the diplomates of the ECVN and the members of the European Society of Veterinary Neurology (ESVN) a mixed-method research, including a qualitative search of objectives and quantitative ranking with 149 Likert scale questions and 48 free text questions in 9 categories in a survey was conducted. In addition, opinions of different groups were subjected to statistical analysis and the result compared. RESULTS: A return rate of 62% (n = 213/341) was achieved. Of the competencies identified by the Delphi process, 75% objectives were expected to attain expert level; 24% attain advanced level; 1% entry level. In addition, the exercise described the 11 highly ranked competencies, the 3 most frequently seen diseases of the central and peripheral nervous systems and the most frequently used immunosuppressive, antiepileptic and chemotherapeutic drugs. CONCLUSION: The outcomes of this "Delphi job analysis" provide a powerful tool to align the curriculum for ECVN resident training and can be adapted to the required job competencies, based on expectations. The expectation is that for majority of these competencies diplomates should attain an expert level. Besides knowledge and clinical skills, residents and diplomates are expected to demonstrate high standards in teaching and communication. The results of this study will help to create a European curriculum for postgraduate education in veterinary neurology.

Imaging diagnosis--Spinal epidural hemangiosarcoma in a dog.

An 8-year-old, male Boxer was examined for an acute onset of ambulatory paraparesis. Neurologic examination was consistent with a T3-L3 myelopathy. Myelography revealed an extradural spinal cord compression in the region of the T10-T13 vertebrae. On magnetic resonance (MR) imaging, a well-defined epidural mass lesion was detected. The mass was mildly hyperintense on T1-weighted, hyperintense on T2-weighted and STIR images compared to normal spinal cord and enhanced strongly and homogenously. Postmortem examination confirmed a primary epidural hemangiosarcoma. Findings indicated that the MRI characteristics of spinal epidural hemangiosarcoma may mimic other lesions including meningioma and epidural hemorrhages/hematomas of non-neoplastic etiology.

Imaging diagnosis: cranial cervical intraspinal schwannoma in a dog.

A 3-year-old, intact female Golden Retriever was presented with acute tetraplegia. Neurologic examination was consistent with a C1-C5 myelopathy. On magnetic resonance (MR) imaging a well-defined, extradural mass was detected within the spinal canal at the level of C1-C2. The mass was isointense to normal spinal cord gray matter on T1-weighted (T1W) images, hyperintense on T2-weighted (T2W), and gradient-echo (GE) images, and enhanced homogeneously after intravenous contrast administration. MR imaging features were mainly consistent with a meningioma. Surgical treatment was refused by the owners, and the dog was euthanized. Postmortem examination demonstrated that the intraspinal mass was a schwannoma.

Spinal meningiomas in dogs: description of 8 cases including a novel radiological and histopathological presentation.

Clinical, imaging, and histological features of 8 canine spinal meningiomas, including a cervical cystic meningioma with imaging and intraoperative features of an arachnoid cyst, are described. All meningiomas were histologically classified and graded following the international World Health Organization human classification for tumors. Six meningiomas were located in the cervical spinal cord. Myelography showed intradural/ extramedullary lesions in 3/4 cases. Magnetic resonance imaging revealed hyperintense intradural/extramedullary masses on pre-contrast T1-weighted and T2-weighted images with homogeneous contrast enhancement in 7/8 cases. One dog had a cerebrospinal fluid-filled subarachnoid cavity dorsal to the cervical spinal cord. A spinal arachnoid cyst was diagnosed on imaging, but the histopathological study of the resected tissue revealed a grade I meningothelial cystic meningioma. There were no differences in outcome associated with tumor grade and surgical treatment (6/8). Cystic meningioma should be considered in the differential diagnosis of intraspinal cystic lesions, and biopsy is necessary for definitive diagnosis.

Méningiome spinal chez les chiens : description de 8 cas incluant une nouvelle présentation radiologique et histopathologique. Les caractéristiques cliniques et histologiques et l'imagerie de 8 méningiomes spinaux canins, incluant un méningiome cystique cervical avec des caractéristiques intraopératoires et l'imagerie d'un kyste arachnoïde, sont décrites. Tous les méningiomes ont été classifiés histologiquement et ont été évalués en suivant la classification humaine des tumeurs de l'Organisation mondiale de la santé. Six méningiomes ont été repérés dans la colonne vertébrale cervicale. La myélographie a montré des lésions intradurales/extramédullaires dans 3 cas sur 4. L'imagerie par résonance magnétique a révélé des masses intradurales/extramédullaires hyperintenses sur les images précontraste pondérées T1 et pondérés T2 avec une augmentation de contraste homogène dans 7 cas sur 8. Un chien avait une cavité rachidienne remplie de liquide cérébrospinal dorsalement à la colonne vertébrale cervicale. Un kyste arachnoïde spinal a été diagnostiqué à l'imagerie, mais l'étude histopathologique du tissu réséqué a révélé un méningiome cystique méningothélial de grade I. Il n'y avait aucune différence au niveau des résultats associée au grade de la tumeur et au traitement chirurgical (6/8). Les méningiomes sclérokystiques devraient être considérés dans le diagnostic différentiel des lésions cystiques intraspinales et une biopsie est nécessaire pour un diagnostic définitif.(Traduit par Isabelle Vallières).

Dural tear and myelomalacia caused by an airgun pellet in a cat.

An 8-year-old cat was presented with severe neurological deficits secondary to a traumatic cervical spinal cord injury caused by an airgun pellet. This report describes, for the first time, the myelographic findings of a dural rupture in a cat and also describes a bilateral Horner's syndrome in a cat.

Déchirure durale et myélomalacie causées par le plomb d'un pistolet pneumatique chez un chat. Un chat âgé de 8 ans a été présenté avec des déficits neurologiques graves secondaires à une blessure traumatique de la moelle épinière cervicale causée par le plomb d'un pistolet pneumatique. Ce rapport décrit, pour la première fois, les résultats myélographiques d'une rupture durale chez un chat et aussi un syndrome de Horner chez un chat.(Traduit par Isabelle Vallières).

Intracranial Granular Cell Tumours in Three Dogs: Atypical Magnetic Resonance Imaging Features and Immunohistochemical Study.

Intracranial granular cell tumours (GCT) are uncommon neoplasms of uncertain cellular origin that are rarely reported in dogs. This case series describes three aged dogs that presented with neurological signs in which magnetic resonance (MR) imaging revealed plaquelike extra-axial lesions that were hypointense on T2-weighted (T2w) images. The surgical biopsy of the lesions and necropsies were followed by histochemical characterisation with periodic acid-Schiff (PAS) staining and immunohistochemistry with ubiquitin, S-100, and SOX-10 to elucidate the cellular origin. The immunohistochemical study indicated that these intracranial GCTs were not of Schwann cell origin. In conclusion, GCTs should be considered a differential diagnosis of intracranial, extra-axial hypointense brain lesions on T2w MR images.

Paradoxical Vestibular Syndrome Caused by a Presumptive Cerebellar Infarction in a Rabbit.

A 6-year-old, female spayed rabbit (Oryctolagus cuniculus) presented with right paradoxical vestibular signs. Magnetic resonance imaging was performed and findings were consistent with an ischemic infarct of the cerebellum. The patient improved gradually and was free of clinical signs at the time this article was written. To the authors' knowledge this is the first case report of a paradoxical vestibular syndrome in a rabbit secondary to a presumptive ischemic infarct. Strokes should be included in the differential diagnosis of central vestibular syndrome in rabbits.

Performance of the Sysmex XN-V body fluid module for canine cerebrospinal fluid cell count.

BACKGROUND: Microscopic cell counts and nucleated cell identification are the "gold standard" for cerebrospinal fluid (CSF) assessments and are labor intensive and subject to operator variability. The use of automated methods could be an alternative to the current manual technique. OBJECTIVES: We aimed to assess the utility of the Sysmex XN-V body fluid (BF) module analyzer to count and differentiate nucleated cells in canine CSF and evaluate the accuracy and correlation between this and the manual method. METHODS: We prospectively analyzed 150 CSF samples from dogs using the Sysmex XN-V BF module and compared the results with those obtained using the manual counting method. We also evaluated the linearity, detection limits, and imprecision of the Sysmex XN-V BF module. RESULTS: The Sysmex XN-V BF module analyzer performance had a sensitivity of 92.59% and specificity of 94.30%. The lower limit of quantification for the total nucleated cell count (TNCC) was 0 cells/µL. A Pearson´s correlation coefficient of 0.945 was found between both methods for TNCC, with 0.997 and 0.940 for samples with TNCC >10 cells/µL and TNCC >5 cells/µL, respectively. The correlation coefficient for the mononuclear and polymorphonuclear differential cell count was -0.031 and -0.019, respectively, and it was 0.576 for the RBC count. CONCLUSIONS: The Sysmex XN-V BF module provides reliable TNCCs for canine CSF, even for samples with low cell numbers, but manual cytologic evaluation is still needed for differential cell counts.

Seven-year follow-up of durability and safety of AAV CNS gene therapy for a lysosomal storage disorder in a large animal.

Delivery of adeno-associated viral vectors (AAVs) to cerebrospinal fluid (CSF) has emerged as a promising approach to achieve widespread transduction of the central nervous system (CNS) and peripheral nervous system (PNS), with direct applicability to the treatment of a wide range of neurological diseases, particularly lysosomal storage diseases. Although studies in small animal models have provided proof of concept and experiments in large animals demonstrated feasibility in bigger brains, there is not much information on long-term safety or durability of the effect. Here, we report a 7-year study in healthy beagle dogs after intra-CSF delivery of a single, clinically relevant dose (2 × 1013 vg/dog) of AAV9 vectors carrying the canine sulfamidase, the enzyme deficient in mucopolysaccharidosis type IIIA. Periodic monitoring of CSF and blood, clinical and neurological evaluations, and magnetic resonance and ultrasound imaging of target organs demonstrated no toxicity related to treatment. AAV9-mediated gene transfer resulted in detection of sulfamidase activity in CSF throughout the study. Analysis at tissue level showed widespread sulfamidase expression and activity in the absence of histological findings in any region of encephalon, spinal cord, or dorsal root ganglia. Altogether, these results provide proof of durability of expression and long-term safety for intra-CSF delivery of AAV-based gene transfer vectors encoding therapeutic proteins to the CNS.

Clinical features, diagnosis, and survival analysis of dogs with glioma.

BACKGROUND: Gliomas in dogs remain poorly understood. OBJECTIVES: To characterize the clinicopathologic findings, diagnostic imaging features and survival of a large sample of dogs with glioma using the Comparative Brain Tumor Consortium diagnostic classification. ANIMALS: Ninety-one dogs with histopathological diagnosis of glioma. METHODS: Multicentric retrospective case series. Signalment, clinicopathologic findings, diagnostic imaging characteristics, treatment, and outcome were used. Tumors were reclassified according to the new canine glioma diagnostic scheme. RESULTS: No associations were found between clinicopathologic findings or survival and tumor type or grade. However, definitive treatments provided significantly (P = .03) improved median survival time (84 days; 95% confidence interval [CI], 45-190) compared to palliative treatment (26 days; 95% CI, 11-54). On magnetic resonance imaging (MRI), oligodendrogliomas were associated with smooth margins and T1-weighted hypointensity compared to astrocytomas (odds ratio [OR], 42.5; 95% CI, 2.42-744.97; P = .04; OR, 45.5; 95% CI, 5.78-333.33; P < .001, respectively) and undefined gliomas (OR, 84; 95% CI, 3.43-999.99; P = .02; OR, 32.3; 95% CI, 2.51-500.00; P = .008, respectively) and were more commonly in contact with the ventricles than astrocytomas (OR, 7.47; 95% CI, 1.03-53.95; P = .049). Tumor spread to neighboring brain structures was associated with high-grade glioma (OR, 6.02; 95% CI, 1.06-34.48; P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with gliomas have poor outcomes, but risk factors identified in survival analysis inform prognosis and the newly identified MRI characteristics could refine diagnosis of tumor type and grade.

Diabetic neuropathy: electrophysiological and morphological study of peripheral nerve degeneration and regeneration in transgenic mice that express IFNbeta in beta cells.

Diabetic neuropathy is one of the most frequent complications in diabetes but there are no treatments beyond glucose control, due in part to the lack of an appropriate animal model to assess an effective therapy. This study was undertaken to characterize the degenerative and regenerative responses of peripheral nerves after induced sciatic nerve damage in transgenic rat insulin I promoter / human interferon beta (RIP/IFNbeta) mice made diabetic with a low dose of streptozotocin (STZ) as an animal model of diabetic complications. In vivo, histological and immunohistological studies of cutaneous and sciatic nerves were performed after left sciatic crush. Functional tests, cutaneous innervation, and sciatic nerve evaluation showed pronounced neurological reduction in all groups 2 weeks after crush. All animals showed a gradual recovery but this was markedly slower in diabetic animals in comparison with normoglycemic animals. The delay in regeneration in diabetic RIP/IFNbeta mice resulted in an increase in active Schwann cells and regenerating neurites 8 weeks after surgery. These findings indicate that diabetic-RIP/IFNbeta animals mimic human diabetic neuropathy. Moreover, when these animals are submitted to nerve crush they have substantial deficits in nerve regrowth, similar to that observed in diabetic patients. When wildtype animals were treated with the same dose of STZ, no differences were observed with respect to nontreated animals, indicating that low doses of STZ and the transgene are not implicated in development of the degenerative and regenerative events observed in our study. All these findings indicate that RIP/IFNbeta transgenic mice are a good model for diabetic neuropathy.

Acute postretinal blindness: ophthalmologic, neurologic, and magnetic resonance imaging findings in dogs and cats (seven cases).

OBJECTIVE: To describe the ophthalmologic, neurologic, and magnetic resonance imaging (MRI) findings of seven animals with acute postretinal blindness as sole neurologic deficit. METHODS: Medical records were reviewed to identify dogs and cats with postretinal blindness of acute presentation, that had a cranial MRI performed as part of the diagnostic workup. Only animals lacking other neurologic signs at presentation were included. Complete physical, ophthalmic, and neurologic examinations, routine laboratory evaluations, thoracic radiographs, abdominal ultrasound, electroretinography, and brain MRI were performed in all animals. Cerebrospinal fluid analysis and postmortem histopathologic results were recorded when available. RESULTS: Four dogs and three cats met the inclusion criteria. Lesions affecting the visual pathways were observed on magnetic resonance (MR) images in six cases. Location, extension, and MRI features were described. Neuroanatomic localization included: olfactory region with involvement of the optic chiasm (n = 4), pituitary fossa with involvement of the optic chiasm and optic tracts (n = 1), and optic nerves (n = 1). Of all lesions detected, five were consistent with intracranial tumors (two meningiomas, one pituitary tumor, two nasal tumors with intracranial extension), and one with bilateral optic neuritis that was confirmed by cerebrospinal fluid analysis. Histologic diagnosis was obtained in four cases and included one meningioma, one pituitary carcinoma, one nasal osteosarcoma, and one nasal carcinoma. CONCLUSIONS: Central nervous system (CNS) disease should be considered in dogs and cats with acute blindness, even when other neurologic deficits are absent. This study emphasizes the relevance of MRI as a diagnostic tool for detection and characterization of CNS lesions affecting the visual pathways.

Efficacy of medium chain triglyceride oil dietary supplementation in reducing seizure frequency in dogs with idiopathic epilepsy without cluster seizures: a non-blinded, prospective clinical trial.

BACKGROUND: Despite appropriate antiseizure drug (ASD) treatment, around two-thirds of dogs with idiopathic epilepsy (IE) have seizures long-term and 20-30per cent of affected dogs remain poorly controlled. METHODS: The current study aim is to test in a field trial the efficacy and tolerability of a commercially available diet enriched with 6.5per cent medium chain triglyceride (MCT) oil in dogs (n=21) with at least a tier 1 idiopathic epilepsy diagnosis, without cluster seizures, in 10 veterinary practices across Europe. Each dog's quality of life (QoL), ataxia, sedation and frequency and severity of seizures were recorded by owners throughout the study. RESULTS: The mean seizure frequency per month, averaged over the entire 84-day study, significantly (P=0.04) decreased 32per cent compared with the baseline monthly seizure frequency recorded during the month immediately before feeding the diet. Similarly, the seizure days rate (days/month) also declined (P<0.001) by 42per cent. QoL was reported as very good to excellent (>8.5/10) in 20 of the 21 dogs before starting the diet and this remained unchanged during the trial. CONCLUSIONS: This study demonstrates the use of a diet enriched with MCTs as an adjunct to ASD treatment may have some antiseizure properties for dogs diagnosed with IE, as demonstrated in previous studies.

Femoral mononeuropathy caused by a malignant sarcoma: two case reports.

A 9-year old miniature poodle and a 6-year old American Staffordshire terrier were evaluated for slowly progressive lameness and atrophy of the left pelvic limb. Neurological examinations of both animals were consistent with femoral nerve lesions. In both cases, neoplastic masses were identified within the left psoas muscle, invading the left femoral nerve or, in one case, its nerve roots. Ultrasound-guided fine needle aspirate and histopathological examination of the masses revealed that these were malignant sarcomas. Femoral mononeuropathies are very rare in dogs, and most descriptions of femoral nerve lesions are caused by traumatic injuries. Descriptions of neoplastic processes affecting the femoral nerve are limited to peripheral nerve sheath tumours (PNST). These cases provide the first descriptions of malignant neoplasms other than PNSTs that infiltrate the femoral nerve or its nerve roots and cause unilateral femoral mononeuropathy and lameness of obscure origin.

Juvenile-onset polyneuropathy in American Staffordshire Terriers.

BACKGROUND: The only hereditary neurologic disorder described so far in American Staffordshire Terriers is adult-onset cerebellar degeneration secondary to ceroid lipofuscinosis. We have seen several dogs with a newly recognized neurological disease characterized by locomotor weakness with or without respiratory signs and juvenile onset consistent with degenerative polyneuropathy of genetic origin. OBJECTIVES: To characterize a novel polyneuropathy in juvenile American Staffordshire Terriers. ANIMALS: Fourteen American Staffordshire Terriers presented with clinical signs consistent with juvenile-onset polyneuropathy at 5 veterinary hospitals between May 2005 and July 2017. METHODS: Case series. Dogs were included retrospectively after a diagnosis of degenerative polyneuropathy had been confirmed by nerve biopsy. Clinical, pathological, electrophysiological, histological data, and outcome were reviewed and a pedigree analysis performed. RESULTS: All dogs displayed clinical signs of neuromuscular disease with generalized motor and sensory involvement, associated with focal signs of laryngeal paralysis (10/14 dogs) and megaesophagus (1/14 dogs). Histopathological findings were consistent with degenerative polyneuropathy. Follow-up was available for 11 dogs, and 3 dogs were euthanized shortly after diagnosis. In these 11 dogs, the disease was slowly progressive and the animals maintained good quality of life with ability to walk. Pedigree analysis was mostly consistent with an autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: Juvenile polyneuropathy, associated with laryngeal paralysis, is a newly described entity in American Staffordshire Terriers, and results from degenerative neuropathy. When surgery for laryngeal paralysis is performed, lifespan may be similar to that of normal dogs even though affected dogs have locomotor disturbance.

Presence of neural progenitors in spontaneous canine gliomas: A histopathological and immunohistochemical study of 20 cases.

Gliomas are the most common primary brain tumours in humans and are associated with a poor prognosis. An accurate animal model of human glioma tumorigenesis is needed to test new treatment strategies. Dogs represent a promising model because they develop spontaneous diffusely-infiltrating gliomas. This study investigated whether spontaneous canine gliomas contain cancer stem cells previously identified in all grades of human gliomas. Twenty spontaneous cases of canine gliomas were graded according to the human WHO classification. The expression of different markers of lineage differentiation was evaluated with immunohistochemistry as follows: nestin and CD133 for neural stem cells, doublecortin for neuronal progenitor cells, Olig2 for glial progenitor cells, glial fibrillary acidic protein, vimentin and S-100 for mature glial cells, and NeuN and ßIII-tubulin for mature neurons. Gliomas were characterised as follows: five grade II (oligodendrogliomas); nine grade III (seven anaplastic oligodendrogliomas, one anaplastic astrocytoma, one anaplastic oligoastrocytoma); six grade IV (glioblastomas). Immunohistochemical evaluation revealed that (1) nestin and CD133 were expressed in all grades of gliomas with a higher proportion of positive cells in high-grade gliomas; (2) the expression of S-100 protein and Olig2 did not differ substantially between astrocytic and oligodendroglial tumours, and (3) all gliomas were negative for mature neuron markers. The results demonstrated the presence of undifferentiated neural progenitors in all grades of spontaneous canine gliomas, confirming the relevance of this animal model for further studies on cancer stem cells.