Annie V. Chen

Magnetic Resonance Imaging in Dogs with Neurologic Impairment Due to Acute Thoracic and Lumbar Intervertebral Disk Herniation

BACKGROUND Magnetic resonance imaging (MRI) is a correlate to physical examination in various myelopathies and a predictor of functional outcome. OBJECTIVES To describe associations among MRI features, neurological dysfunction before MRI, and functional outcome in dogs with disk herniation. ANIMALS One hundred and fifty-nine dogs with acute thoracolumbar disk herniation. METHODS Retrospective case series. Signalment, initial neurological function as assessed by a modified Frankel score (MFS), and ambulatory outcome at hospital discharge and >3 months (long-term) follow-up were recorded from medical records and telephone interview of owners. Associations were estimated between these parameters and MRI signal and morphometric data. RESULTS Dogs with intramedullary T2W hyperintensity had more severe pre-MRI MFS (median 2, range 0-4) and lower ambulatory proportion at long-term follow-up (0.76) than those dogs lacking hyperintensity (median MFS 3, range 0-5; ambulatory proportion, 0.93) (P=.001 and .013, respectively). Each unit of T2W length ratio was associated with a 1.9 times lower odds of long-term ambulation when adjusted for pre-MRI MFS (95% confidence interval 1.0-3.52, P=.05). Dogs with a compressive length ratio >1.31 (which was the median ratio within this population) had more severe pre-MRI MFS (median 3, range 0-5) compared with those with ratios < or =1.31 (median MFS 3, range 0-4; P=.006). CONCLUSIONS AND CLINICAL IMPORTANCE MRI features were associated with initial injury severity in dogs with thoracolumbar disk herniation. Based on results of this study, the T2W length ratio and presence of T2W intramedullary hyperintensity appear to be predictive of long-term ambulatory status.

Magnetic resonance imaging for the differentiation of neoplastic, inflammatory, and cerebrovascular brain disease in dogs

BACKGROUND The reliability and validity of magnetic resonance imaging (MRI) for detecting neoplastic, inflammatory, and cerebrovascular brain lesions in dogs are unknown. OBJECTIVES To estimate sensitivity, specificity, and inter-rater agreement of MRI for classifying histologically confirmed neoplastic, inflammatory, and cerebrovascular brain disease in dogs. ANIMALS One hundred and twenty-one client-owned dogs diagnosed with brain disease (n = 77) or idiopathic epilepsy (n = 44). METHODS Retrospective, multi-institutional case series; 3 investigators analyzed MR images for the presence of a brain lesion with and without knowledge of case clinical data. Investigators recorded most likely etiologic category (neoplastic, inflammatory, cerebrovascular) and most likely specific disease for all brain lesions. Sensitivity, specificity, and inter-rater agreement were calculated to estimate diagnostic performance. RESULTS MRI was 94.4% sensitive (95% confidence interval [CI] = 88.7, 97.4) and 95.5% specific (95% CI = 89.9, 98.1) for detecting a brain lesion with similarly high performance for classifying neoplastic and inflammatory disease, but was only 38.9% sensitive for classifying cerebrovascular disease (95% CI = 16.1, 67.0). In general, high specificity but not sensitivity was retained for MR diagnosis of specific brain diseases. Inter-rater agreement was very good for overall detection of structural brain lesions (κ = 0.895, 95% CI = 0.792, 0.998, P < .001) and neoplastic lesions, but was only fair for cerebrovascular lesions (κ = 0.299, 95% CI = 0, 0.761, P = .21). CONCLUSIONS AND CLINICAL IMPORTANCE MRI is sensitive and specific for identifying brain lesions and classifying disease as inflammatory or neoplastic in dogs. Cerebrovascular disease in general and specific inflammatory, neoplastic, and cerebrovascular brain diseases were frequently misclassified.

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.

Prospectively Recorded versus Medical Record‐Derived Spinal Cord Injury Scores in Dogs with Intervertebral Disk Herniation

BACKGROUND Validated spinal cord injury (SCI) scores have been established for veterinary species but are not uniformly used in practice. HYPOTHESIS/OBJECTIVES To determine the level of agreement of SCI scores at the time of admission versus those assigned from reconstructed medical records in a population of dogs with intervertebral disk herniation (IVDH). ANIMALS Eighty-six client-owned dogs with confirmed IVDH. METHODS Retrospective study. Medical records were reviewed for history, physical examination, neurologic examination, and recorded Modified Frankel score (MFS) and Texas spinal cord injury score (TSCIS) at the time of admission. Three raters, all board-certified neurologists, assigned MFS and TSCIS based on digitized abstracted medical records to each patient. These scores were then compared to the recorded score at the time of admission. RESULTS Actual agreement for MFS and TSCIS derived from medical records by the 3 raters compared to prospectively derived MFS and TSCIS was 77.9 and 51.2%, respectively. A kappa value of 0.572 (95% CI 0.450, 0.694; P < .001) and an ICC of 0.533 (95% CI 0.410, 0.646; P < .001) were calculated for MFS scores. A kappa value of 0.100 (95% CI 0.000, 0.222; P = .107), and an ICC of 0.503 (95% CI 0.377, 0.620; P < .001) were calculated for TSCIS scores. CONCLUSIONS AND CLINICAL IMPORTANCE Results showed that SCI scores recorded at the time of admission often do not agree with those retrospectively abstracted from medical records. Agreement was less when using the more complex TSCIS scale and therefore the MFS scale might be more appropriate for use in retrospective studies.

In vitro biomechanical evaluations of screw-bar-polymethylmethacrylate and pin-polymethylmethacrylate internal fixation implants used to stabilize the vertebral motion unit of the fourth and fifth cervical vertebrae in vertebral column specimens from dogs.

OBJECTIVE To determine the change in stiffness as evaluated by the dorsal bending moment of cervical vertebral specimens obtained from canine cadavers after internally stabilizing the vertebral motion unit (VMU) of C4 and C5 with a traditional pin-polymethylmethacrylate (PMMA) fixation implant or a novel screw-bar-PMMA fixation implant. SAMPLE POPULATION 12 vertebral column specimens (C3 through C6) obtained from canine cadavers. PROCEDURES A dorsal bending moment was applied to the vertebral specimens before and after fixation of the VMU of C4 and C5 by use of a traditional pin-PMMA implant or a novel screw-bar-PMMA implant. Biomechanical data were collected and compared within a specimen (unaltered vs treated) and between treatment groups. Additionally, implant placement was evaluated after biomechanical testing to screen for penetration of the transverse foramen or vertebral canal by the pins or screws. RESULTS Treated vertebral specimens were significantly stiffer than unaltered specimens. There was no significant difference in stiffness between vertebral specimen groups after treatment. None of the screws in the novel screw-bar-PMMA implant group penetrated the transverse foramen or vertebral canal, whereas there was mild to severe penetration for 22 of 24 (92%) pins in the traditional pin-PMMA implant group. CONCLUSIONS AND CLINICAL RELEVANCE Both fixation treatments altered the biomechanical properties of the cervical vertebral specimens as evaluated by the dorsal bending moment. There was reduced incidence of penetration of the transverse foramen or vertebral canal with the novel screw-bar-PMMA implant, compared with the incidence for the traditional pin-PMMA implant.

Loss of neurovirulence is associated with reduction of cerebral capillary sequestration during acute Babesia bovis infection

BackgroundSevere neurological signs that develop during acute infection by virulent strains of Babesia bovis are associated with sequestration of infected erythrocytes in cerebral capillaries. Serial passage of virulent strains in cattle results in attenuated derivatives that do not cause neurologic disease. We evaluated whether serial passage also results in a loss of cerebral capillary sequestration by examining brain biopsies during acute disease and at necropsy.FindingsCerebral biopsies of spleen intact calves inoculated intravenously with a virulent or attenuated strain pair of B. bovis were evaluated for capillary sequestration at the onset of babesiosis and during severe disease. In calves infected with the virulent strain, there was a significant increase in sequestration between the first and second biopsy timepoint. The attenuated strain was still capable of sequestration, but at a reduced level, and did not change significantly between the first and second biopsy. Necropsy examination confirmed the second biopsy results and demonstrated that sequestration identified at necropsy reflects pathologic changes occurring in live animals.ConclusionsLoss of neurovirulence after serial in vivo passage of the highly virulent T2Bo strain of B. bovis in splenectomized animals is associated with a significant reduction of cerebral capillary sequestration. Previous genomic analysis of this and two other strain pairs suggests that this observation could be related to genomic complexity, particularly of the ves gene family, rather than consistent gene specific differences. Additional experiments will examine whether differential gene expression of ves genes is also associated with reduced cerebral sequestration and neurovirulence in attenuated strains.

Vincristine-induced central neurotoxicity in a collie homozygous for the ABCB1Δ mutation

A six-year-old, neutered, female collie was presented to an oncology specialty service after developing tetraparesis and self-mutilation that progressively worsened while receiving chemotherapy for lymphoma. Neurologic examination revealed ataxia, paresis and diminished conscious proprioception in all limbs with entire spinal reflexes. Magnetic resonance imaging of the brain and spinal cord was normal. Electromyography of the limbs ruled out a vincristine-induced peripheral neuropathy. Cerebrospinal fluid analysis and cerebrospinal fluid and serum testing for Neospora and Toxoplasma were normal. Results of MDR1 genotyping revealed that the dog was homozygous for the ABCB1-1Δ (MDR1) mutation. This clinical presentation strongly resembled the effects seen from inadvertent intrathecal administration of vincristine in humans. Dogs that are homozygous for the ABCB1-1Δ (MDR1) mutation should not receive standard dosages of chemotherapy drugs known to be eliminated by P-glycoprotein, the gene product of ABCB1. Testing for this mutation is strongly recommended before chemotherapy initiation for at-risk breeds.

Pharmacokinetics of oral rufinamide in dogs

The objective of this study was to determine the pharmacokinetic properties and short-term adverse effect profile of single-dose oral rufinamide in healthy dogs. Six healthy adult dogs were included in the study. The pharmacokinetics of rufinamide were calculated following administration of a single mean oral dose of 20.0 mg/kg (range 18.6-20.8 mg/kg). Plasma rufinamide concentrations were determined using high-performance liquid chromatography, and pharmacokinetic data were analyzed using commercial software. No adverse effects were observed. The mean terminal half-life was 9.86 ± 4.77 h. The mean maximum plasma concentration was 19.6 ± 5.8 μg/mL, and the mean time to maximum plasma concentration was 9.33 ± 4.68 h. Mean clearance was 1.45 ± 0.70 L/h. The area under the curve (to infinity) was 411 ± 176 μg · h/mL. Results of this study suggest that rufinamide given orally at 20 mg/kg every 12 h in healthy dogs should result in a plasma concentration and half-life sufficient to achieve the therapeutic level extrapolated from humans without short-term adverse effects. Further investigation into the efficacy and long-term safety of rufinamide in the treatment of canine epilepsy is warranted.

Clinical features and magnetic resonance imaging characteristics of diskospondylitis in dogs: 23 cases (1997–2010)

OBJECTIVE To describe the signalment, clinical features, and most common MRI characteristics in dogs with diskospondylitis and investigate whether a correlation exists between the degree of spinal cord compression and neurologic status of the patient. DESIGN Retrospective case series. ANIMALS 23 dogs. PROCEDURES The medical records and imaging database of the Veterinary Teaching Hospital at Washington State University were retrospectively cross-referenced for cases of diskospondylitis in dogs from 1997 through 2010. Signalment, clinical signs, MRI characteristics, and results of bacteriologic cultures of urine, blood, CSF, or intervertebral disk material were reviewed. RESULTS On T2-weighted sequences, vertebral endplates were most often of mixed signal intensity, whereas the vertebral body was hypointense. The intervertebral disk space was most often hyperintense on T2-weighted and short tau inversion recovery sequences and of mixed signal intensity on T1-weighted sequences. Paravertebral soft tissue hyperintensities were noted commonly on T2-weighted and short tau inversion recovery sequences. Heterogenous contrast enhancement of endplates and intervertebral disk spaces also occurred commonly, whereas contrast enhancement of vertebral bodies and paravertebral soft tissues was uncommon. Intramedullary spinal cord intensity was noted at 10 of 27 sites on T2-weighted sequences. Static spinal cord compression occurred in 17 of 23 dogs, and a significant direct correlation was found between the percentage of spinal cord compression and the patient neurologic score. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that diskospondylitis in dogs has a characteristic MRI appearance, and in some patients, MRI may aid in the identification of severe spinal cord compression, which could warrant surgical intervention.

Intracranial pressure and cardiopulmonary variables during isoflurane or sevoflurane anesthesia at various minimum alveolar concentration multiples in normocapnic dogs

OBJECTIVE To compare effects of isoflurane and sevoflurane on intracranial pressure and cardiovascular variables at 1.0, 1.5, and 2.0 times the minimum alveolar concentration (MAC) in mechanically ventilated normocapnic dogs. ANIMALS 6 healthy male Beagles. PROCEDURES The individual MAC was determined for each agent with an electrical stimulus. After a minimum of 1 week, anesthetic induction by use of a mask with one of the inhalation anesthetics selected randomly was followed by mechanical ventilation and instrumentation for measurement of intracranial pressure and cardiovascular variables. Heart rate; systolic, mean, and diastolic arterial blood pressures; central venous pressure; mean pulmonary arterial pressure; pulmonary artery occlusion pressure; cardiac output; intracranial pressure (ICP); core body temperature; end-tidal inhalation anesthetic and carbon dioxide concentration; and arterial blood gas values were measured after attaining equilibrium at 1.0, 1.5, and 2.0 MAC of each inhalation anesthetic. Cardiac index, systemic vascular resistance, pulmonary vascular resistance, and cerebral perfusion pressure (CPP) were calculated. RESULTS Mean ICP did not differ within and between anesthetics at any MAC. Compared with equipotent concentrations of isoflurane, the CPP and mean values for systolic, mean, and diastolic arterial blood pressures were increased at 2.0 MAC for sevoflurane, whereas mean values for mean and diastolic arterial blood pressures and systemic vascular resistance were increased at 1.5 MAC for sevoflurane. CONCLUSIONS AND CLINICAL RELEVANCE Although ICP was similar in healthy normocapnic dogs, CPP was better maintained during 2.0 MAC for sevoflurane, compared with isoflurane.