Stephanie A. Thomovsky

Vaccination for Invasive Canine Meningioma Induces in Situ Production of Antibodies Capable of Antibody-Dependent Cell-Mediated Cytotoxicity

Malignant and atypical meningiomas are resistant to standard therapies and associated with poor prognosis. Despite progress in the treatment of other tumors with therapeutic vaccines, this approach has not been tested preclinically or clinically in these tumors. Spontaneous canine meningioma is a clinically meaningful but underutilized model for preclinical testing of novel strategies for aggressive human meningioma. We treated 11 meningioma-bearing dogs with surgery and vaccine immunotherapy consisting of autologous tumor cell lysate combined with toll-like receptor ligands. Therapy was well tolerated, and only one dog had tumor growth that required intervention, with a mean follow up of 585 days. IFN-γ-elaborating T cells were detected in the peripheral blood of 2 cases, but vaccine-induced tumor-reactive antibody responses developed in all dogs. Antibody responses were polyclonal, recognizing both intracellular and cell surface antigens, and HSP60 was identified as one common antigen. Tumor-reactive antibodies bound allogeneic canine and human meningiomas, showing common antigens across breed and species. Histologic analysis revealed robust infiltration of antibody-secreting plasma cells into the brain around the tumor in posttreatment compared with pretreatment samples. Tumor-reactive antibodies were capable of inducing antibody-dependent cell-mediated cytotoxicity to autologous and allogeneic tumor cells. These data show the feasibility and immunologic efficacy of vaccine immunotherapy for a large animal model of human meningioma and warrant further development toward human trials.

Canine Intervertebral Disc Fenestration Using a Vacuum‐Assisted Tissue Resection Device

OBJECTIVEnDescribe the use and feasibility of a novel vacuum-assisted tissue resection device (VRD) for canine intervertebral disc fenestration, and compare the effectiveness of manual fenestration to the VRD.nnnSTUDY DESIGNnRandomized prospective study.nnnANIMALSnCanine cadavers (n = 15).nnnMETHODSnA cadaveric lumbar spine study was performed to compare the use of manual fenestration to a novel VRD for intervertebral disc fenestration. Both fenestration groups were compared to a control group. Effectiveness of fenestration was assessed by calculating a ratio of remaining nuclear weight postfenestration to total nuclear volume. Fenestrated discs with lower ratios were indicative of greater removal of nucleus pulposus.nnnRESULTSnThere was a statistically significant reduction in mean ratio (±SD) of remaining nuclear weight to volume with both fenestration groups compared to controls (0.39 ± 0.07; P < .001). There was an improved ratio using the VRD (0.23 ± 0.09) compared to manual fenestration (0.30 ± 0.10); this was not statistically significant (P = .069). It was technically difficult to fenestrate the disc spaces at L5-L6 and L6-L7 because of location and anatomy, resulting in a statistically significant increase in the median ratio of nuclear weight-to-volume ratios in both manual and VRD fenestration groups when compared to the more cranial L4-L5 disc spaces, 0.32 ± 0.08, and 0.35 ± 0.08 versus 0.25 ± 0.13 at L4-L5 (P = .026 and P = .004, respectively).nnnCONCLUSIONSnThe VRD is a feasible instrument for canine intervertebral disc fenestration. It is at least as effective as manual fenestration, and provides additional safety features.

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

We describe histopathologically confirmed intracranial metastasis of cutaneous lymphoma. In magnetic resonance (MR) images there was a heterogeneous, contrast-enhancing, extraaxial mass in the right parietal and piriform lobes at the level of the optic chiasm. Our MR imaging findings are consistent with reports in humans in that lymphoma masses have indistinct borders that are iso- to hyperintense relative to adjacent gray matter on T2-weighted images. Our report varies from findings in humans in that the mass was extraaxial, whereas masses reported in humans are intraaxial. Contrast enhancement can be heterogeneous, as in our report, or homogeneous.

MEDULLOBLASTOMA IN A GRIZZLY BEAR (URSUS ARCTOS HORRIBLIS)

Abstract:u2003 A 3-yr-old female spayed grizzly bear (Ursus arctos horribilis) was evaluated for seizure activity along with lethargy, inappetence, dull mentation, and aggressive behavior. Magnetic resonance (MR) examination of the brain revealed a contrast-enhanced right cerebellar mass with multifocal smaller nodules located in the left cerebellum, thalamus, hippocampus, and cerebrum with resultant obstructive hydrocephalus. Cerebrospinal fluid analysis revealed mild mononuclear pleocytosis, with differentials including inflammatory versus neoplastic processes. Blood and cerebrospinal fluid were also submitted for polymerase chain reaction and agar gel immunodiffusion to rule out infectious causes of meningitis/encephalitis. While awaiting these results, the bear was placed on steroid and antibiotic therapy. Over the next week, the bear deteriorated; she died 1 wk after MR. A complete postmortem examination, including immunohistochemisty, revealed the cerebellar mass to be a medulloblastoma. This is the only case report, to the authors knowledge, describing a medulloblastoma in a grizzly bear.

Successful Long-Term Use of Itraconazole for the Treatment of Aspergillus Diskospondylitis in a Dog

A 5-year-old spayed female German shepherd dog was admitted with a history of generalized stiffness. Neurologic examination revealed mild paraparesis with multifocal spinal pain. Spinal radiographs and magnetic resonance imaging revealed diskospondylitis at L6-7 and multiple sites throughout the thoracolumbar spine. Biopsy of the intervertebral disk at L6-7 revealed a positive culture for Aspergillus species, and the dog was placed on itraconazole indefinitely. Clinical signs were significantly improved after two weeks of itraconazole. The dog was reevaluated 8 years later for unrelated reasons. No spinal pain was detected. Spinal radiographs revealed a fused L6-7 disk space and collapsed and sclerotic disk spaces at multiple sites. Itraconazole was tolerated by the dog with normal yearly liver enzyme values. To our knowledge, this is the first reported case of successful long-term use of itraconazole for the treatment of Aspergillus diskospondylitis in a dog.

SPINAL CORD COMPRESSION IN TWO RELATED URSUS ARCTOS HORRIBILIS

Two 15-yr-old grizzly bear littermates were evaluated within 9 mo of each other with the symptom of acute onset of progressive paraparesis and proprioceptive ataxia. The most significant clinical examination finding was pelvic limb paresis in both bears. Magnetic resonance examinations of both bears showed cranial thoracic spinal cord compression. The first bear had left-sided extradural, dorsolateral spinal cord compression at T3-T4. Vertebral canal stenosis was also observed at T2-T3. Images of the second bear showed lateral spinal cord compression from T2-T3 to T4-T5. Intervertebral disk disease and associated spinal cord compression was also observed at T2-T3 and T3-T4. One grizzly bear continued to deteriorate despite reduced exercise, steroid, and antibiotic therapy. The bear was euthanized, and a necropsy was performed. The postmortem showed a spinal ganglion cyst that caused spinal cord compression at the level of T3-T4. Wallerian-like degeneration was observed from C3-T6. The second bear was prescribed treatment that consisted of a combination of reduced exercise and steroid therapy. He continued to deteriorate with these medical therapies and was euthanized 4 mo after diagnosis. A necropsy showed hypertrophy and protrusion of the dorsal longitudinal ligament at T2-T3 and T3-T4, with resulting spinal cord compression in this region. Wallerian-like degeneration was observed from C2-L1. This is one of few case reports that describes paresis in bears. It is the only case report, to the authors knowledge, that describes spinal magnetic resonance imaging findings in a grizzly bear and also the only report that describes a cranial thoracic myelopathy in two related grizzly bears with neurologic signs.

Fungal Infections of the Central Nervous System in Small Animals: Clinical Features, Diagnosis, and Management

Small animal mycoses vary geographically. Different clinical presentations are seen in animals with infection of the central nervous system (CNS), including multifocal meningoencephalomyelitis, intracranial lesions that accompany sinonasal lesions, rapidly progressive ventriculitis, or solitary granuloma of the brain or spinal cord. Systemic, nasal, or extraneural clinical signs are common but, especially in granuloma cases, do not always occur. Surgery may have a diagnostic and therapeutic role in CNS granuloma. There have been recent advancements in serology. Fluconazole, voriconazole, and posaconazole cross the blood-brain barrier, but voriconazole is neurotoxic to cats. Liposomal and lipid-encapsulated formulations of amphotericin B are preferred.

Canine (Pet Dog) Tumor Microsurgery and Intratumoral Concentration and Safety of Metronomic Chlorambucil for Spontaneous Glioma: A Phase I Clinical Trial

OBJECTIVEnMetronomic (daily low-dose) chlorambucil requires further study before use in human patients with glioma. The aim of this study was to investigate distribution and safety of metronomic chlorambucil in naturally occurring canine glioma.nnnMETHODSnEight client-owned (pet) dogs with newly diagnosed spontaneous glioma were prospectively enrolled. Chlorambucil was administered preoperatively at 4 mg/m2 every 24 hours for ≥3 days and continued postoperatively until death or dose-limiting adverse events. Chlorambucil concentrations in the surgical glioma specimen, cerebrospinal fluid, and serum were analyzed. Dogs additionally received lomustine postoperatively. Dogs were monitored for seizures, myoclonus, cytopenias, and tumor recurrence.nnnRESULTSnComplete microsurgical resection was achieved in 7 oligodendrogliomas and 1 astrocytoma (6 high grade, 2 low grade). Median surgical glioma specimen chlorambucil concentration was 0.52 ng/g (range, 0-2.62 ng/g), or 37% (range, 0%-178%) of serum concentration. Median cerebrospinal fluid concentration was 0.1 ng/mL (range, 0-0.3 ng/mL). Chlorambucil was not associated with increase in seizure activity. Six dogs displayed prolonged seizure-free intervals. There was no myoclonus. Three dogs developed asymptomatic thrombocytopenia after 8-12 months of chlorambucil. Median progression-free survival was 253 days (range, 63-860 days). Median overall survival was 257 days (range, 64-860 days).nnnCONCLUSIONSnThe presence of intratumoral chlorambucil indicated an altered blood-brain barrier that varied from case to case. Despite sporadic previous reports of neurotoxicity, prolonged seizure-free intervals supported a high safety margin at this dose in this species. Metronomic chlorambucil was well tolerated. Spontaneous canine glioma offers a robust preclinical model.

Objective measurements of the atlantoaxial joint on radiographs performed without flexion can increase the confidence of diagnosis of atlantoaxial instability in toy breed dogs

Toy breed dogs are overrepresented for atlantoaxial instability. Radiography is a standard diagnostic test, however published toy breed-specific radiographic measurements are lacking and diagnosis remains largely subjective. Aims of this retrospective, diagnostic accuracy study were to describe normal values and determine whether some quantitative radiographic criteria strongly support a diagnosis of atlantoaxial instability specific to toy breed dogs. Neutral lateral and ventrodorsal radiographs of 102 toy breed dogs (92 control, 10 affected) were reviewed. The median C1-C2 overlap (the distance of overlap between the C2 spinous process and the dorsal arch of C1) was +4.65xa0mm in control dogs and -5.00xa0mm in atlantoaxial instability cases. A C1-C2 overlap ≤xa0+1.55xa0mm was the most sensitive (100%) and specific (94.5%) radiographic measurement in the diagnosis of atlantoaxial instability. Three relative measurements were performed: the ventral atlantodental interval to dorsal atlantodental interval ratio, the dens/C2 ratio, and the C1-C2 angle. These three relative measurements had good specificity (94.5, 86.9, and 98.9%, respectively), lower sensitivity (80.0, 66.7, and 60.0%, respectively), and were not influenced by body weight (Pxa0>xa00.05). Absolute measurements (including absolute dens length and atlantoaxial distance) were significantly correlated with body weight (Pxa0<xa00.05) diminishing their utility in the diagnosis of atlantoaxial instability. Decreased C1-C2 overlap strongly supports atlantoaxial instability. The ventral atlantodental interval/dorsal atlantodental interval ratio, dens/C2 ratio, and C1-C2 angle may provide further support but may be normal in individual cases.Toy breed dogs are overrepresented for atlantoaxial instability. Radiography is a standard diagnostic test, however published toy breed-specific radiographic measurements are lacking and diagnosis remains largely subjective. Aims of this retrospective, diagnostic accuracy study were to describe normal values and determine whether some quantitative radiographic criteria strongly support a diagnosis of atlantoaxial instability specific to toy breed dogs. Neutral lateral and ventrodorsal radiographs of 102 toy breed dogs (92 control, 10 affected) were reviewed. The median C1-C2 overlap (the distance of overlap between the C2 spinous process and the dorsal arch of C1) was +4.65xa0mm in control dogs and -5.00xa0mm in atlantoaxial instability cases. A C1-C2 overlap ≤xa0+1.55xa0mm was the most sensitive (100%) and specific (94.5%) radiographic measurement in the diagnosis of atlantoaxial instability. Three relative measurements were performed: the ventral atlantodental interval to dorsal atlantodental interval ratio, the dens/C2 ratio, and the C1-C2 angle. These three relative measurements had good specificity (94.5, 86.9, and 98.9%, respectively), lower sensitivity (80.0, 66.7, and 60.0%, respectively), and were not influenced by body weight (Pxa0>xa00.05). Absolute measurements (including absolute dens length and atlantoaxial distance) were significantly correlated with body weight (Pxa0<xa00.05) diminishing their utility in the diagnosis of atlantoaxial instability. Decreased C1-C2 overlap strongly supports atlantoaxial instability. The ventral atlantodental interval/dorsal atlantodental interval ratio, dens/C2 ratio, and C1-C2 angle may provide further support but may be normal in individual cases.

Myositis, Ganglioneuritis, and Myocarditis with Distinct Perifascicular Muscle Atrophy in a 2-Year-Old Male Boxer

A 2-year-old male, intact Boxer was referred for chronic diarrhea, hyporexia, labored breathing, weakness and elevated creatine kinase, and alanine aminotransferase activities. Initial examination and diagnostics revealed a peripheral nervous system neurolocalization, atrial premature complexes, and generalized megaesophagus. Progressive worsening of the dog’s condition was noted after 36u2009h; the dog developed aspiration pneumonia, was febrile and oxygen dependent. The owners elected humane euthanasia. Immediately postmortem biopsies of the left cranial tibial and triceps muscles and the left peroneal nerve were obtained. Postmortem histology revealed concurrent myositis, myocarditis, endocarditis, and ganglioneuritis. Mixed mononuclear cell infiltrations and a distinct perifascicular pattern of muscle fiber atrophy was present in both muscles. This is a novel case of diffuse inflammatory myopathy with a distinct perifascicular pattern of atrophy in addition to endocarditis, myocarditis, and epicarditis.