Clinical features, comparative imaging findings, treatment, and outcome in dogs with discospondylitis: A multi-institutional retrospective study.

BACKGROUND: Limited recent data exists regarding discospondylitis in dogs. HYPOTHESIS/OBJECTIVES: (i) Describe the signalment, clinical and imaging findings, etiologic agents, treatment, and outcome of dogs with discospondylitis, (ii) determine diagnostic agreement between radiographs, CT, and MRI with regard to the presence of discospondylitis and its location, and (iii) determine risk factors for relapse and progressive neurological deterioration. ANIMALS: Three hundred eighty-six dogs. METHODS: Multi-institutional retrospective study. Data extracted from medical records were: signalment, clinical and examination findings, diagnostic results, treatments, complications, and outcome. Potential risk factors were recorded. Breed distribution was compared to a control group. Agreement between imaging modalities was assessed via Cohen's kappa statistic. Other analyses were performed on categorical data, using cross tabulations with chi-squared and Fisher's exact tests. RESULTS: Male dogs were overrepresented (236/386 dogs). L7-S1 (97/386 dogs) was the most common site. Staphylococcus species (23/38 positive blood cultures) were prevalent. There was a fair agreement (κ = 0.22) between radiographs and CT, but a poor agreement (κ = 0.05) between radiographs and MRI with regard to evidence of discospondylitis. There was good agreement between imaging modalities regarding location of disease. Trauma was associated with an increased risk of relapse (P = .01, OR: 9.0, 95% CI: 2.2-37.0). Prior steroid therapy was associated with an increased risk of progressive neurological dysfunction (P = .04, OR: 4.7, 95% CI: 1.2-18.6). CONCLUSIONS AND CLINICAL IMPORTANCE: Radiograph and MRI results could be discrepant in dogs with discospondylitis. Prior trauma and corticosteroids could be associated with relapse and progressive neurological dysfunction, respectively.

Rehabilitation Therapy for the Degenerative Myelopathy Patient.

Degenerative myelopathy is an inherited, progressive, neurodegenerative disorder affecting the spinal cord of dogs. There is no treatment of the disease. Physical rehabilitation is the only intervention that slows progression and prolongs quality of life. Further studies are needed to develop advanced treatment options and to better characterize the use of complementary therapeutic modalities in palliative care for these patients.

Agreement and differentiation of intradural spinal cord lesions in dogs using magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging is the method of choice for diagnosing spinal cord neoplasia, but the accuracy of designating the relationship of a neoplasm to the meninges and agreement among observers is unknown. OBJECTIVES: To determine agreement among observers and accuracy of diagnosis compared with histology when diagnosing lesion location based on relationship to the meninges. ANIMALS: Magnetic resonance images from 53 dogs with intradural extramedullary and intramedullary spinal neoplasms and 17 dogs with degenerative myelopathy. METHODS: Six observers were supplied with 2 sets of 35 images at different time points and asked to designate lesion location. Agreement in each set was analyzed using kappa (κ) statistics. We tabulated total correct allocations and calculated sensitivity, specificity, and likelihood ratios for location designation from images compared with known histologic location for lesions confined to 1 location only. RESULTS: Agreement in the first set of images was moderate (κ = 0.51; 95% confidence interval [CI], 0.43-0.58) and in the second, substantial (κ = 0.69; 95% CI, 0.66-0.79). In the accuracy study, 180 (75%) of the 240 diagnostic calls were correct. Sensitivity and specificity were moderate to high for all compartments, except poor sensitivity was found for intradural extramedullary lesions. Positive likelihood ratios were high for intradural extramedullary lesions and degenerative myelopathy. CONCLUSIONS AND CLINICAL IMPORTANCE: Overall accuracy in diagnosis was reasonable, and positive diagnostic calls for intradural extramedullary lesions and negative calls for intramedullary lesions are likely to be helpful. Observers exhibited considerable disagreement in designation of lesions relationship to the meninges.

Outcome of thoracolumbar surgical feline intervertebral disc disease.

OBJECTIVES: The aim of this study was to evaluate the outcome and prognosis of thoracolumbar feline intervertebral disc disease (IVDD) treated by surgical decompression. METHODS: This was a multi-institutional retrospective study evaluating the age, breed, sex, body weight, presenting complaint, neuroanatomic diagnosis at presentation, diagnostic imaging results, surgery performed and the overall outcome at discharge and at recheck. Bivariable associations between variables were assessed using the Kruskal-Wallis test (age and grade of IVDD at presentation) and Fisher's exact test (grade of IVDD at presentation and outcome). RESULTS: A total of 35 cats met the inclusion criteria for the study. The most frequently reported clinical sign was difficulty walking (54.2%). The majority of cats presented with an L4-S3 localization (57%). The most common site of intervertebral disc herniation (IVDH) was at L6-L7 (34%). The majority of feline patients that received surgery had a positive outcome at the time of discharge (62.5%; n = 20/32) and at the time of the 2-week recheck (91.3%; n = 21/23). No association was identified between the age of the patient and the grade of IVDD. No association was identified between the presenting grade of IVDD and the clinical outcome at the time of discharge or at the time of recheck evaluation. CONCLUSIONS AND RELEVANCE: Cats undergoing spinal decompressive surgery for thoracolumbar IVDH appear to have a favorable prognosis independent of the initial presenting grade of IVDD. A larger sample size and a longer length of follow-up is necessary to obtain statistical associations between the presenting grade of IVDD and overall clinical outcome.

Magnetization transfer and diffusion tensor imaging in dogs with intervertebral disk herniation.

BACKGROUND: Quantitative magnetic resonance imaging (QMRI) techniques of magnetization transfer ratio (MTR) and diffusion tensor imaging (DTI) provide microstructural information about the spinal cord. OBJECTIVE: Compare neurologic grades using the modified Frankel scale with MTR and DTI measurements in dogs with thoracolumbar intervertebral disk herniation (IVDH). ANIMALS: Fifty-one dogs with thoracolumbar IVDH. METHODS: Prospective cohort study. Quantitative MRI measurements of the spinal cord were obtained at the region of compression. A linear regression generalized estimating equations model was used to compare QMRI measurements between different neurological grades after adjusting for age, weight, duration of clinical signs, and lesion location. RESULTS: Grade 5 (.79 × 10-3 mm2 /s [median], .43-.91 [range]) and axial (1.47 × 10-3 mm2 /s, .58-1.8) diffusivity were lower compared to grades 2 (1.003, .68-1.36; P = .02 and 1.81 × 10-3 mm2 /s, 1.36-2.12; P < .001, respectively) and 3 (1.07 × 10-3 mm2 /s, .77-1.5; P = .04 and 1.92 × 10-3 mm2 /s, 1.83-2.37;P < .001, respectively). Compared to dogs with acute myelopathy, chronic myelopathy was associated with higher mean (1.02 × 10-3 mm2 /s, .77-1.36 vs. .83 × 10-3 mm2 /s, .64-1.5; P = .03) and radial diffusivity (.75 × 10-3 mm2 /s, .38-1.04 vs. .44 × 10-3 mm2 /s, .22-1.01; P = .008) and lower MTR (46.76, 31.8-56.43 vs. 54.4, 45.2-62.27; P = .004) and fractional anisotropy (.58, .4-0.75 vs. .7, .46-.85; P = .02). Fractional anisotropy was lower in dogs with a T2-weighted intramedullary hyperintensity compared to those without (.7, .45-.85 vs. .54, .4-.8; P = .01). CONCLUSION AND CLINICAL RELEVANCE: Mean diffusivity and AD could serve as surrogates of severity of spinal cord injury and are complementary to the clinical exam in dogs with thoracolumbar IVDH.

High-Frequency Irreversible Electroporation for Intracranial Meningioma: A Feasibility Study in a Spontaneous Canine Tumor Model.

High-frequency irreversible electroporation is a nonthermal method of tissue ablation that uses bursts of 0.5- to 2.0-microsecond bipolar electric pulses to permeabilize cell membranes and induce cell death. High-frequency irreversible electroporation has potential advantages for use in neurosurgery, including the ability to deliver pulses without inducing muscle contraction, inherent selectivity against malignant cells, and the capability of simultaneously opening the blood-brain barrier surrounding regions of ablation. Our objective was to determine whether high-frequency irreversible electroporation pulses capable of tumor ablation could be delivered to dogs with intracranial meningiomas. Three dogs with intracranial meningiomas were treated. Patient-specific treatment plans were generated using magnetic resonance imaging-based tissue segmentation, volumetric meshing, and finite element modeling. Following tumor biopsy, high-frequency irreversible electroporation pulses were stereotactically delivered in situ followed by tumor resection and morphologic and volumetric assessments of ablations. Clinical evaluations of treatment included pre- and posttreatment clinical, laboratory, and magnetic resonance imaging examinations and adverse event monitoring for 2 weeks posttreatment. High-frequency irreversible electroporation pulses were administered successfully in all patients. No adverse events directly attributable to high-frequency irreversible electroporation were observed. Individual ablations resulted in volumes of tumor necrosis ranging from 0.25 to 1.29 cm3. In one dog, nonuniform ablations were observed, with viable tumor cells remaining around foci of intratumoral mineralization. In conclusion, high-frequency irreversible electroporation pulses can be delivered to brain tumors, including areas adjacent to critical vasculature, and are capable of producing clinically relevant volumes of tumor ablation. Mineralization may complicate achievement of complete tumor ablation.

Computed Tomography and Magnetic Resonance Imaging Are Equivalent in Mensuration and Similarly Inaccurate in Grade and Type Predictability of Canine Intracranial Gliomas.

While magnetic resonance imaging (MRI) is the gold-standard imaging modality for diagnosis of intracranial neoplasia, computed tomography (CT) remains commonly used for diagnosis and therapeutic planning in veterinary medicine. Despite the routine use of both imaging modalities, comparison of CT and MRI has not been described in the canine patient. A retrospective study was performed to evaluate CT and MRI studies of 15 dogs with histologically confirmed glioma. Multiple lesion measurements were obtained, including two-dimensional and volumetric dimensions in pre-contrast and post-contrast images. Similar measurement techniques were compared between CT and MRI. The glioma type (astrocytoma or oligodendroglioma) and grade (high or low) were predicted on CT and MRI independently. With the exception of the comparison between CT pre-contrast volume to T2-weighted MRI volume, no other statistical differences between CT and MRI measurements were identified. Overall accuracy for tumor grade (high or low) was 46.7 and 53.3% for CT and MRI, respectively. For predicted tumor type, accuracy of CT was 53.3% and MRI and MRI 60%. Based on the results of this study, both CT and MRI contrast measurement techniques are considered equivalent options for lesion mensuration. Given the low-to-moderate predictability of CT and MRI in glioma diagnosis, histopathology remains necessary for accurate diagnosis of canine brain tumors.

A case of stiff dog syndrome associated with anti-glutamic acid decarboxylase antibodies.

BACKGROUND: The stiff person syndrome (SPS) is a rare and debilitating autoimmune disorder with an unknown pathogenesis and variable clinical presentation that can present a diagnostic challenge. Although entities that clinically mimic stiff-person spectrum disorders (SPSD) have manifested in horses, they have not been reported in dogs. CASE PRESENTATION: We describe a 2-year-old beagle dog presented for progressive attacks of muscular rigidity and lordosis with superimposed spasms of the appendicular muscles triggered by tactile stimulation which resulted in marked gait impairment. Resting electromyography revealed continuous motor unit activity in the axial musculature. Compared to age-matched healthy beagle dogs, this patient had elevated glutamic acid decarboxylase antibody concentrations in serum and cerebrospinal fluid. CONCLUSION: This dog presented with phenotypic, electrodiagnostic, and immunologic criterion consistent with an SPSD, including elevated anti-GAD antibody titers, which we have termed the "stiff dog syndrome (SDS)". Durable clinical improvement was achieved with symptomatic and immunosuppressive treatments including baclofen, gabapentin, prednisone, and intravenous immunoglobulin.

Evaluation of magnetic resonance imaging for the differentiation of inflammatory, neoplastic, and vascular intradural spinal cord diseases in the dog.

Magnetic resonance imaging (MRI) is a common test for dogs with suspected intradural spinal cord lesions, however studies on diagnostic performance for this test are lacking. Objectives of this multi-institutional, retrospective, case-control study were to estimate sensitivity and specificity of MRI for (1) distinguishing between histopathologically confirmed intradural spinal cord disease versus degenerative myelopathy in dogs, (2) categorizing intradural spinal cord diseases as neoplastic, inflammatory, or vascular; and (3) determining tumor type within the etiologic category of neoplasia. Additional aims were to (1) determine whether knowledge of clinical data affects sensitivity and specificity of MRI diagnoses; and (2) report interrater agreement for MRI classification of intradural spinal lesions. Cases were recruited from participating hospital databases over a 7-year period. Three reviewers independently evaluated each MRI study prior to and after provision of clinical information. A total of 87 cases were sampled (17 degenerative myelopathy, 53 neoplasia, nine inflammatory, and eight vascular). Magnetic resonance imaging had excellent (>97.6%) sensitivity for diagnosis of intradural spinal cord lesions but specificity varied before and after provision of clinical data (68.6% vs. 82.4%, P = 0.023). Magnetic resonance imaging had good sensitivity (86.8%) and moderate specificity (64.7-72.5%) for diagnosing neoplasia. Sensitivity was lower for classifying inflammatory lesions but improved with provision of clinical data (48.1% vs. 81.5%, P = 0.015). Magnetic resonance imaging was insensitive for diagnosing vascular lesions (25.0%). Interrater agreement was very good for correctly diagnosing dogs with intradural lesions (ĸ = 0.882-0.833), and good (ĸ = 0.726-0.671) for diagnosing dogs with neoplasia.

Canine Butterfly Glioblastomas: A Neuroradiological Review.

In humans, high-grade gliomas may infiltrate across the corpus callosum resulting in bihemispheric lesions that may have symmetrical, winged-like appearances. This particular tumor manifestation has been coined a "butterfly" glioma (BG). While canine and human gliomas share many neuroradiological and pathological features, the BG morphology has not been previously reported in dogs. Here, we describe the magnetic resonance imaging (MRI) characteristics of BG in three dogs and review the potential differential diagnoses based on neuroimaging findings. All dogs presented for generalized seizures and interictal neurological deficits referable to multifocal or diffuse forebrain disease. MRI examinations revealed asymmetrical (2/3) or symmetrical (1/3), bihemispheric intra-axial mass lesions that predominantly affected the frontoparietal lobes that were associated with extensive perilesional edema, and involvement of the corpus callosum. The masses displayed heterogeneous T1, T2, and fluid-attenuated inversion recovery signal intensities, variable contrast enhancement (2/3), and mass effect. All tumors demonstrated classical histopathological features of glioblastoma multiforme (GBM), including glial cell pseudopalisading, serpentine necrosis, microvascular proliferation as well as invasion of the corpus callosum by neoplastic astrocytes. Although rare, GBM should be considered a differential diagnosis in dogs with an MRI evidence of asymmetric or symmetric bilateral, intra-axial cerebral mass lesions with signal characteristics compatible with glioma.

Evaluation of endothelin-1 and MMPs-2, -9, -14 in cerebrospinal fluid as indirect indicators of blood-brain barrier dysfunction in chronic canine hypothyroidism.

Chronic canine hypothyroidism is associated with blood-brain barrier (BBB) disruption. We hypothesized that this change is mediated by endothelin-1(ET-1) and matrix metalloproteinases (MMP) -2, -9, and -14, as evidenced by increased concentrations of these proteins in cerebrospinal fluid (CSF) compared to controls. CSF from 18 dogs, 9 controls and 9 with experimentally induced hypothyroidism was collected before and 6, 12, and 18 months after induction of hypothyroidism. Concentrations of ET-1 using an ELISA kit, and for MMP-2, -9, and -14 using gelatinase zymography were measured in CSF. ET-1 was undetectable in CSF of control and hypothyroid dogs at all time-points. Constitutively expressed MMP-2 was detectable in CSF samples in all dogs at all time-points. No other MMPs were detectable in CSF. No differences in CSF concentrations of ET-1 and MMP-2, 9, and 14 were found between hypothyroid and euthyroid dogs. Therefore, ET-1 and MMP-2, 9, and 14 are unlikely to be primary mediators of BBB damage in chronically hypothyroid dogs.

Safety and feasibility of the NanoKnife system for irreversible electroporation ablative treatment of canine spontaneous intracranial gliomas.

OBJECT: Irreversible electroporation (IRE) is a novel nonthermal ablation technique that has been used for the treatment of solid cancers. However, it has not been evaluated for use in brain tumors. Here, the authors report on the safety and feasibility of using the NanoKnife IRE system for the treatment of spontaneous intracranial gliomas in dogs. METHODS: Client-owned dogs with a telencephalic glioma shown on MRI were eligible. Dog-specific treatment plans were generated by using MRI-based tissue segmentation, volumetric meshing, and finite element modeling. After biopsy confirmation of glioma, IRE treatment was delivered stereotactically with the NanoKnife system using pulse parameters and electrode configurations derived from therapeutic plans. The primary end point was an evaluation of safety over the 14 days immediately after treatment. Follow-up was continued for 12 months or until death with serial physical, neurological, laboratory, and MRI examinations. RESULTS: Seven dogs with glioma were treated. The mean age of the dogs was 9.3 ± 1.6 years, and the mean pretreatment tumor volume was 1.9 ± 1.4 cm(3). The median preoperative Karnofsky Performance Scale score was 70 (range 30-75). Severe posttreatment toxicity was observed in 2 of the 7 dogs; one developed fatal (Grade 5) aspiration pneumonia, and the other developed treatment-associated cerebral edema, which resulted in transient neurological deterioration. Results of posttreatment diagnostic imaging, tumor biopsies, and neurological examinations indicated that tumor ablation was achieved without significant direct neurotoxicity in 6 of the 7 dogs. The median 14-day post-IRE Karnofsky Performance Scale score of the 6 dogs that survived to discharge was 80 (range 60-90), and this score was improved over the pretreatment value in every case. Objective tumor responses were seen in 4 (80%) of 5 dogs with quantifiable target lesions. The median survival was 119 days (range 1 to > 940 days). CONCLUSION: With the incorporation of additional therapeutic planning procedures, the NanoKnife system is a novel technology capable of controlled IRE ablation of telencephalic gliomas.

Acute adverse events associated with ventral slot decompression in 546 dogs with cervical intervertebral disc disease.

OBJECTIVE: To report the frequency, types, and risk factors for acute perioperative adverse events (AEs) in dogs that had ventral slot decompression (VSD) for cervical intervertebral disc disease (IVDD). DESIGN: Retrospective, case-control study. ANIMALS: Dogs (n = 546) with cervical IVDD treated by VSD; 54 cases experiencing AE and 492 controls. METHODS: Historical, clinical, diagnostic, operative, and outcome data were collected. AE were graded using a Spine Adverse Events Severity (SAVES) system. Associations between the development of AE and hypothesized risk factors were analyzed using bi- and multi-variable analyses. RESULTS: AE were observed in 54 dogs (9.9%). Minor AE (SAVES Grade 1-2) occurred in 3.5% (19 dogs) and major (SAVES Grades 3-5) AE in 6.4% (35 dogs). Deterioration in neurologic status (n = 13), persistent pain (12), and intraoperative hemorrhage (7) were common major AE. NSAID administration, surgeon experience, C7-T1 disc location, and intraoperative hypotension were significantly associated with AE in multivariate analyses. Improvement of AE occurred in 48/54 (88.9%) of cases, although reoperative neurosurgery was required in 48.5% (17/35) of dogs experiencing major AE. Dogs with major AE had significantly longer hospitalization and worse outcomes than dogs with minor AE or controls. No fatal AE occurred, although 0.7% (4/546) of dogs were euthanatized postoperatively. CONCLUSIONS: AE occurred in 9.9% of dogs that had VSD, and were significantly associated with perioperative hypotension, C7-T1 disc extrusions, surgeon experience, and NSAID usage. Identification of a major postoperative AE is an indication for immediate diagnostic imaging studies, as 50% of dogs experiencing major AE required reoperation.