Allison C. Haley

Canine brain tumours: a model for the human disease?

Canine brain tumours are becoming established as naturally occurring models of disease to advance diagnostic and therapeutic understanding successfully. The size and structure of the dogs brain, histopathology and molecular characteristics of canine brain tumours, as well as the presence of an intact immune system, all support the potential success of this model. The limited success of current therapeutic regimens such as surgery and radiation for dogs with intracranial tumours means that there can be tremendous mutual benefit from collaboration with our human counterparts resulting in the development of new treatments. The similarities and differences between the canine and human diseases are described in this article, emphasizing both the importance and limitations of canines in brain tumour research. Recent clinical veterinary therapeutic trials are also described to demonstrate the areas of research in which canines have already been utilized and to highlight the important potential benefits of translational research to companion dogs.

Traumatic pneumocephalus in a dog

CASE DESCRIPTION A 17-month-old dog was evaluated because of progressive tetraparesis. The dog had a history of craniofacial trauma at 2 months of age. CLINICAL FINDINGS Results of a neurologic examination were suggestive of a lesion localized to the medulla. Computed tomography revealed extensive pneumocephalus extending throughout the ventricular system and into the cranial cervical subarachnoid space. TREATMENT AND OUTCOME Because of the deterioration in the dogs clinical condition, an emergency bilateral transfrontal craniectomy was performed. A large amount of pyogranulomatous material was found intraoperatively. Neurologic and computed tomographic abnormalities were no longer evident during a recheck examination 8 weeks after surgery. CLINICAL RELEVANCE Findings suggested that pneumocephalus should be considered in the differential diagnosis for dogs with neurologic signs of an intracranial abnormality, particularly if the dog has a history of craniofacial trauma.

Pharmacokinetic evaluation of immediate- and extended-release formulations of levetiracetam in dogs

OBJECTIVE To compare the pharmacokinetics of various formulations of levetiracetam after oral administration of a single dose to healthy dogs. ANIMALS 6 neurologically normal mixed-breed dogs. PROCEDURES A crossover study design was used. Blood samples for serum harvest were collected from each dog before and at various points after oral administration of one 500-mg tablet of each of 2 generic extended-release (ER) formulations, 1 brand-name ER formulation, or 1 brand-name immediate-release (IR) formulation of levetiracetam. Serum samples were analyzed to determine pharmacokinetic properties of each formulation by means of ultra-high-performance liquid chromatography with tandem mass spectrometry. RESULTS No dogs had clinically important adverse effects for any formulation of levetiracetam. All ER formulations had a significantly lower maximum serum drug concentration and longer time to achieve that concentration than did the IR formulation. Half-lives and elimination rate constants did not differ significantly among formulations. Values for area under the drug concentration-versus-time curve did not differ significantly between ER formulations and the IR formulation; however, 1 generic ER formulation had a significantly lower area under the curve than did other ER formulations. CONCLUSIONS AND CLINICAL RELEVANCE All ER formulations of levetiracetam had similar pharmacokinetic properties in healthy dogs, with some exceptions. Studies will be needed to evaluate the clinical efficacy of the various formulations; however, findings suggested that twice-daily administration of ER formulations may be efficacious in the treatment of seizures in dogs.

Ischemic stroke in Greyhounds: 21 cases (2007–2013)

OBJECTIVE To determine the prevalence of ischemic stroke in Greyhounds and determine whether affected dogs had coagulation abnormalities and hypertension. DESIGN Multi-institutional, retrospective study. ANIMALS 21 dogs. PROCEDURES Medical records (including diagnostic testing results) and MRI images of the brain were reviewed for Greyhounds with ischemic stroke that had been evaluated at 4 institutions. The proportion of Greyhounds with ischemic stroke was compared with the proportion of non-Greyhound dogs with ischemic stroke. Demographic information for dogs evaluated at each institution was obtained to determine the proportion of Greyhounds in the hospital populations. RESULTS 21 Greyhounds with ischemic stroke were identified. Abnormalities in coagulation were not identified in the 14 Greyhounds that underwent such testing. Systemic hypertension was identified in 6 of 14 Greyhounds that underwent such testing. No other abnormalities were identified by means of other routine diagnostic tests for Greyhounds. For all institutions combined, the prevalence of ischemic stroke in Greyhounds was 0.66% (21/3,161 Greyhounds). Greyhounds were significantly more likely to be evaluated because of ischemic stroke, compared with all other dog breeds combined (OR, 6.6; 95% confidence interval, 4.2 to 10.2). CONCLUSIONS AND CLINICAL RELEVANCE Results of this study suggested that Greyhounds were predisposed to ischemic stroke, compared with all other breeds combined. Coagulation abnormalities did not seem to contribute to ischemic stroke. Hypertension may have contributed to the development of ischemic stroke. Greyhounds with ischemic stroke should undergo measurement of systolic arterial blood pressure. Antihypertensive treatments may be warranted for such dogs.

Atypical meningeal granular cell tumor in a dog

A 10-year-old, female spayed Chihuahua dog was presented to the Veterinary Teaching Hospital at the University of Georgia for evaluation of seizures, abnormal mentation, and cervical pain of 2 months duration. On magnetic resonance imaging, there was generalized thickening of the meninges overlying the left cerebral hemisphere and along the falx cerebri. Despite symptomatic treatment, the dog remained neurologically affected. Consequently, the owners elected euthanasia. On gross examination, the meninges covering the left cerebral hemisphere were severely thickened and firmly adhered to the calvaria. On transverse section, the white matter of the left cerebral hemisphere was swollen, enlarged, and extended across the midline with resultant compression of the right cerebral hemisphere. Cytologic evaluation of an impression smear of the thickened meninges showed numerous large, spindloid to polygonal cells with abundant, amphophilic, vacuolated cytoplasm, present either in clusters or in individual cells. Histopathologic evaluation of the meninges revealed a poorly circumscribed and infiltrative, moderately cellular neoplasm, composed of vacuolated, spindloid to polygonal cells with marked anisocytosis and anisokaryosis, arranged in sheets, and occasionally separated by thick bands of connective tissue. Immunohistochemistry for vimentin revealed diffuse cytoplasmic staining of the neoplastic cells. Although the periodic acid–Schiff reaction was negative, ultrastructural findings showed numerous vesicles that were empty or that contained membranous or electron-dense material. Based on gross, microscopic, immunohistochemical, and ultrastructural changes, the meningeal neoplasm was diagnosed as an atypical granular cell tumor.

Prevalence of Effusion in the Tympanic Cavity in Dogs with Dysfunction of the Trigeminal Nerve: 18 Cases (2004–2013)

BACKGROUND Animals with disorders involving the trigeminal nerve or its nuclei in the brainstem can have effusion in the tympanic cavity ipsilateral to the side of the neurological deficits. The tensor veli palatini muscle (TVP), innervated by the mandibular branch of the trigeminal nerve, opens the pharyngeal orifice of the auditory tube. With denervation of the TVP, dysfunction of the auditory tube may occur, which could lead to effusion. HYPOTHESIS/OBJECTIVES To determine the prevalence of effusion in the tympanic cavity in dogs with disorders involving the trigeminal nerve. ANIMALS Eighteen client-owned dogs were evaluated retrospectively. METHODS Retrospective study. RESULTS Diagnostic imaging databases were searched for dogs having undergone magnetic resonance imaging (MRI) evaluation for signs referable to dysfunction of the trigeminal nerve. Signalment and neurological examination findings were recorded. The MRI study was evaluated for the presence or absence of effusion. MRI characteristics of the affected trigeminal nerve and the muscles of mastication were recorded. Based on the location of the trigeminal nerve lesion, dogs were divided into three categories: brainstem, trigeminal canal, or extracranial. Eighteen dogs met the inclusion criteria. Six of 18 dogs (33%) had effusion in the tympanic cavity ipsilateral to the affected trigeminal nerve. CONCLUSION AND CLINICAL IMPORTANCE A substantial proportion of dogs with a lesion affecting the trigeminal nerve had effusion in the tympanic cavity. This finding likely represents denervation of the TVP muscle, which may have led to dysfunction of the auditory tube.

Development and Use of an Interactive Computerized Dog Model to Evaluate Cranial Nerve Knowledge in Veterinary Students

In veterinary medicine, the cognitive skills necessary to interpret neurological disorders from text-based case descriptions may not translate into the diagnostic capabilities required for clinical neurological patients. As live animals exhibiting certain specific neurological disorders are infrequent during a students exposure to clinics, students may graduate without the experience necessary to make an accurate diagnosis in the field. To address this, we have developed a computerized simulated dog head that can exhibit cranial nerve dysfunctions and respond to specific testing procedures in a clinically accurate manner. To evaluate whether this type of model could add value to traditional student assessments, we created a multiple-choice quiz system with three types of questions: standard text-based cases, videos of an expert performing an examination of the simulated dog, and an interactive version requiring the student to perform an appropriate examination of the simulated dog to uncover the lesion localization. In an experiment conducted with 97 freshman veterinary students who had recently been taught cranial nerve anatomy and function, we found that examination performance decreased with the need for interactivity compared to memorization of fact, while satisfaction increased. Students were less likely to identify the correct disorder when they had to conduct the examination of the virtual dog themselves, revealing an inadequacy in traditional neuroanatomical teaching. However, students overwhelmingly supported the use of interactive question for assessment. Interestingly, performance on text-based questions did not correlate significantly with interactive or video questions. The results have implications for veterinary teaching and assessment within the classroom and in clinical environments.

Treatment of canine meningoencephalomyelitis of unknown aetiology with mycophenolate mofetil and corticosteroids: 25 cases (2007–2012)

Abstract The use of mycophenolate mofetil (MMF) for a variety of immune‐mediated diseases in veterinary medicine has been described. However, there is only a small number of cases documenting its use in dogs with meningoencephalomyelitis of unknown aetiology (MUE). We hypothesized that the use of MMF and corticosteroids in dogs with MUE results in comparable survival data to other published treatment protocols and is associated with limited adverse effects. A retrospective study of medical case records of dogs clinically diagnosed with MUE recorded signalment, neuroanatomic localization, magnetic resonance imaging findings, cerebrospinal fluid analysis results, medications administered, follow‐up neurologic examinations, survival and adverse events. Variables were compared between dogs which were treated with MMF within 30 days of diagnosis (immediate group) vs. dogs in which MMF therapy was started >30 days after diagnosis (delayed group). Twenty‐five cases of MUE were identified. The overall median survival time from diagnosis was 731 days (range 43–1672 days). After 1 month of MMF treatment, 92% of dogs showed improvement on a neurological examination. There was no significant effect of any recorded parameter on survival, including delayed vs. immediate initiation of MMF treatment. Dogs with delayed treatment had significantly lower clinical remission rates than dogs with immediate treatment at 6 months after starting MMF. Adverse events were identified in two cases (8%) and were characterized by mild gastrointestinal signs (vomiting and decreased appetite). Administration of MMF appears safe in dogs with MUE. The use of MMF results in comparable survival times to alternate immunosuppressive protocols.

Evaluation of cytospin precision in low cellularity canine cerebrospinal fluid

The cell count and differential of cerebrospinal fluid (CSF) cytologic examination classify CSF as inflammatory or not. The cytospin cell yield is related to cell count, but to our knowledge a relationship has not been characterized and cytospin precision is undocumented in any species. The objective of our study was to calculate intra-assay precision of cellular yield and differential on cytocentrifuged canine CSF, determine the factors that may affect precision, and predict the number of cytospins necessary to confirm mild neutrophilic pleocytosis. Ten concurrent replicate cytospins were created from nonhemorrhagic CSF, obtained from 60 dogs in other terminal studies, with either a manual or calibrated pipetting technique. Up to 500 cells per cytospin were counted and classified on each slide. Coefficient of variation (CV), multiple regression, and probabilities were calculated for relationships between cell yield and independent factors including technique, total nucleated cell count, cell differential, and total protein. Manual and calibrated pipetting had similar CVs (average 31%) for total cell yield, but the calibrated technique had fewer foamy macrophages. CV for neutrophil percentage among low cellularity samples with any neutrophils was 146%. Probability based on linear regression showed that 1 cytospin is sufficient to identify samples with >3% neutrophils. Occasional neutrophils, eosinophils, mitotic figures, phagocytic cells, and ependymal cells were seen in many low cellularity canine CSF samples. Canine CSF cytospin cell yield and differential evaluations are imprecise. Calibrated rather than manual pipetting is recommended.