Long-term computed tomography follow-up in great Danes with or without signs of osseous- associated cervical Spondylomyelopathy.

BACKGROUND: Osseous- associated cervical spondylomyelopathy (OA-CSM) has a high prevalence in Great Danes. In order to understand the progression of osseous changes, we aimed to perform a long-term computed tomographic (CT) follow-up study of Great Dane dogs with and without OA-CSM. Canine CSM is comparable to a common neurologic disease often diagnosed in older people termed cervical spondylotic myelopathy or degenerative cervical myelopathy, which is progressive in nature. The natural history of cervical spondylotic myelopathy in people has been well described, whereas there is scarce information on the natural history of canine OA-CSM. Our first goal was to evaluate if follow-up CT studies showed any changes compared to initial CT studies in Great Dane dogs with a diagnosis of OA-CSM. Our second goal was to establish whether clinically normal Great Danes went on to develop any vertebral changes or clinical signs consistent with OA-CSM. We enrolled Great Danes diagnosed with OA-CSM and clinically normal Great Danes who had previously participated in a prospective study. All dogs had clinical and CT follow-up evaluations. RESULTS: Twelve Great Dane dogs were investigated: six OA-CSM affected and six clinically normal dogs. The median time between CT studies was 28 months (OA-CSM dogs) and 25 months (normal dogs). On follow-up CT, two OA-CSM-affected dogs developed new sites of stenosis, and two clinically normal dogs developed new sites of stenosis (one each). Disc spaces most commonly affected were C4-C5, C5-C6 and C6-C7. New sites of foraminal stenosis were noted in two of the CSM-affected and four of the clinically normal dogs. Morphometric evaluation showed no statistically significant differences between the initial and follow-up CT studies in the OA-CSM affected or normal groups. CONCLUSION: Our long-term CT follow-up study documented progression of vertebral canal stenosis in four out of twelve dogs. The majority of dogs did not develop new sites of stenosis or show progression of vertebral lesions.

Comparison of angle, shape, and position of articular processes in Dobermans and Great Danes with and without cervical spondylomyelopathy.

BACKGROUND: Cervical spondylomyelopathy (CSM), also known as wobbler syndrome, affects mainly large and giant-breed dogs, causing compression of the cervical spinal cord and/or nerve roots. Structural and dynamic components seem to play a role in the development of CSM; however, pathogenesis is not yet fully understood. Physiologic and pathologic movements of the cervical spine depend on the morphology and morphometry of articular processes, as well as on intervertebral discs and vertebral column ligaments. Moreover, the characteristics of the articular processes affect motion and stability of the vertebral column. The goal of this study was to investigate the angle, shape, and position of the articular surfaces within the articular processes and compare them between Doberman Pinschers and Great Danes with and without cervical spondylomyelopathy. RESULTS: Magnetic resonance images were obtained for 60 dogs: 15 clinically normal Dobermans (Dob-N), 15 CSM-affected Dobermans (Dob-CSM), 15 clinically normal Great Danes (GD-N), and 15 CSM-affected Great Danes (GD-CSM). Angle, shape, and position (lateral distance) of the articular surfaces from the articular processes were analyzed from C2-3 to C7-T1. Results indicate that the mean angle was different between Dob-CSM and GD-CSM at C4-5, C5-6, and C6-7, and between GD-N and GD-CSM at C6-7. There were differences between Dob-N and GD-N, and between Dob-CSM and GD-CSM for the lateral distance at most locations, except C2-3. Compared with Great Danes, Dobermans generally had a greater proportion of concave caudal surfaces at C4-5, C5-6, and C6-7. Concave articular surfaces have been associated with greater axial rotation. This may explain the high proportion of disc-associated CSM in Dobermans compared to Great Danes. The differences between breeds suggest they may have different motion patterns in the caudal cervical vertebral column. CONCLUSIONS: Considering that no differences in angle, shape, or position of the articular surfaces within the articular processes were found between normal and CSM-affected dogs, their relevance appears to have a secondary role in the pathogenesis of CSM.

THE EFFECT OF ANGLE SLICE ACQUISITION ON COMPUTED TOMOGRAPHIC CERVICAL VERTEBRAL COLUMN MORPHOMETRY IN GREAT DANES.

Computed tomography (CT) scans can be acquired with the transverse images aligned either parallel to the endplates or perpendicular to the vertebral canal. The purpose of this prospective cross-sectional study was to determine the effect of angle acquisition on CT morphometric evaluation of the cervical vertebral column of Great Danes with and without cervical spondylomyelopathy. Twenty-eight Great Danes (13 normal, 15 affected) were sampled. For each dog, a set of CT images was acquired with the transverse slices aligned parallel to the endplates and another one with the transverse images aligned perpendicular to the vertebral canal. For each different set, transverse slices from the cranial, middle, and caudal aspects of the individual vertebral bodies C2-C7 were measured. Height, width, transverse area, right dorsal to left ventral height (RDLV), and left dorsal to right ventral height (LDRV) were recorded by a single observer at each location. For both affected and control dogs, significant differences between the measurements obtained from the two sets of transverse images were found only at the cranial aspect of the vertebrae (P = 0.005, P < 0.001, P < 0.001, P = 0.005, and P = 0.010 for height, width, area, RDLV, and LDRV, respectively). Measurements for the middle and caudal aspects did not differ. The funnel-shape morphology of the cervical vertebral foramina in Great Danes with stenosis of their cranial aspect may be responsible for the significant differences found. Considering that the morphometric parameters were significantly affected by CT slice angle in the current study, authors recommend that a standardized scanning protocol be followed when morphometric evaluations using CT are planned.

Evaluation of traditional and novel radiographic vertebral ratios in Great Danes with versus without cervical spondylomyelopathy.

Great Danes are predisposed to osseous-associated cervical spondylomyelopathy (Wobbler syndrome). The first aim of this prospective study was to compare values measured using previously published intravertebral and intervertebral ratio methods and a novel ventrodorsal ratio method in radiographs of clinically normal and affected Great Danes. The second aim was to determine whether these ratios could be used as predictors of sites of spinal cord compression based on magnetic resonance imaging (MRI). Thirty dogs (15 normal, 15 affected) were prospectively enrolled. Lateral and ventrodorsal radiographs were obtained and six measurements were recorded from C3-T1. For each vertebral location, intravertebral ratios and intervertebral ratios were calculated from lateral views, and the ratio of the distance between the articular process joints vs. vertebral body width (novel ventrodorsal ratio) was calculated from ventrodorsal views. Values for these three ratios were compared, by vertebral location and dog group. Intravertebral and intervertebral ratios did not differ between dog groups. The ventrodorsal ratio was significantly smaller in affected Great Danes at C5-6 (P = 0.005) and C6-7 (P < 0.001). The ventrodorsal ratio was significantly associated with MRI presence of spinal cord compression. For each 0.1 unit increase in this ratio value, there was a 65% decrease in the odds of spinal cord compression being present at that site, independent of vertebral location (P = 0.002). Findings from this study supported use of the novel ventrodorsal ratio as an initial radiographic screening method for Great Danes with suspected cervical spondylomyelopathy.

Comparison of noncontrast computed tomography and high-field magnetic resonance imaging in the evaluation of Great Danes with cervical spondylomyelopathy.

Computed tomography (CT) provides excellent bony detail, whereas magnetic resonance (MR) imaging is superior in evaluating the neural structures. The purpose of this prospective study was to assess interobserver and intermethod agreement in the evaluation of cervical vertebral column morphology and lesion severity in Great Danes with cervical spondylomyelopathy by use of noncontrast CT and high-field MR imaging. Fifteen client-owned affected Great Danes were enrolled. All dogs underwent noncontrast CT under sedation and MR imaging under general anesthesia of the cervical vertebral column. Three observers independently evaluated the images to determine the main site of spinal cord compression, direction and cause of the compression, articular process joint characteristics, and presence of foraminal stenosis. Overall intermethod agreement, intermethod agreement for each observer, overall interobserver agreement, and interobserver agreement between pairs of observers were calculated by use of kappa (κ) statistics. The highest overall intermethod agreements were obtained for the main site of compression and direction of compression with substantial agreements (κ = 0.65 and 0.62, respectively), whereas the lowest was obtained for right-sided foraminal stenosis (κ = 0.39, fair agreement). For both imaging techniques, the highest and lowest interobserver agreements were recorded for the main site of compression and degree of articular joint proliferation, respectively. While different observers frequently agree on the main site of compression using both imaging techniques, there is considerable variation between modalities and among observers when assessing articular process characteristics and foraminal stenosis. Caution should be exerted when comparing image interpretations from multiple observers.

Time-of-flight magnetic resonance angiography of the canine brain at 3.0 Tesla and 7.0 Tesla.

OBJECTIVE: To evaluate the ability of 2-D time-of-flight (ToF) magnetic resonance angiography (MRA) to depict intracranial vasculature and compare results obtained with 3.0- and 7.0-T scanners in dogs. ANIMALS: 5 healthy Beagles. PROCEDURES: 2-D ToF-MRA of the intracranial vasculature was obtained for each dog by use of a 3.0-T and a 7.0-T scanner. Quantitative assessment of the images was obtained by documentation of the visibility of major arteries comprising the cerebral arterial circle and their branches and recording the number of vessels visualized in the dorsal third of the brain. Qualitative assessment was established by evaluation of overall image quality and image artifacts. RESULTS: Use of 3.0- and 7.0-T scanners allowed visualization of the larger vessels of the cerebral arterial circle. Use of a 7.0-T scanner was superior to use of a 3.0-T scanner in depiction of the first- and second-order arterial branches. Maximum-intensity projection images had a larger number of vessels when obtained by use of a 7.0-T scanner than with a 3.0-T scanner. Overall, image quality and artifacts were similar with both scanners. CONCLUSIONS AND CLINICAL RELEVANCE: Visualization of the major intracranial arteries was comparable with 3.0- and 7.0-T scanners; the 7.0-T scanner was superior for visualizing smaller vessels. Results indicated that ToF-MRA is an easily performed imaging technique that can be included as part of a standard magnetic resonance imaging examination and should be included in the imaging protocol of dogs suspected of having cerebrovascular disease.

MicroRNA expression in the cerebrospinal fluid of dogs with and without cervical spondylomyelopathy.

BACKGROUND: Osseous-associated cervical spondylomyelopathy (OA-CSM) is a common condition of the cervical vertebral column that affects giant dog breeds. MicroRNAs (miRNAs) are small RNAs that regulate gene expression, and recent data suggest that circulating miRNAs present in biological fluids may serve as potential biomarkers for disease. The miRNA profiles of cerebrospinal fluid (CSF) from healthy dogs and dogs clinically affected by OA-CSM have not been described. OBJECTIVE: To characterize the expression levels of miRNAs present in the CSF of normal Great Danes and identify differentially expressed miRNAs in the CSF of Great Danes clinically affected with OA-CSM. ANIMALS: Client-owned dogs: 12 control, 12 OA-CSM affected. METHODS: Cerebrospinal fluid samples were collected prospectively. MicroRNA expression was evaluated using the NanoString nCounter platform and quantitative real-time PCR. RESULTS: We identified 8 miRNAs with significant differential expression. MiR-299-5p and miR-765 had increased expression levels in the CSF of OA-CSM-affected dogs, whereas miR-494, miR-612, miR-302-d, miR-4531, miR-4455, and miR-6721-5p had decreased expression levels in OA-CSM affected dogs compared to clinically normal dogs. Quantitative real-time PCR was performed to validate the expression levels of 2 miRNAs (miR-494 and miR-612), and we found a 1.5-fold increase in miR-494 expression and a 1.2-fold decrease in miR-612 in the CSF of the OA-CSM affected group (P = .41 and .89, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Data generated from our study represent an initial characterization of the miRNA profile of normal canine CSF and suggest that a distinct CSF miRNA expression profile is associated with OA-CSM.

Proteomic analysis of cerebrospinal fluid in canine cervical spondylomyelopathy.

STUDY DESIGN: Prospective study. OBJECTIVE: To identify proteins with differential expression in the cerebrospinal fluid (CSF) from 15 clinically normal (control) dogs and 15 dogs with cervical spondylomyelopathy (CSM). SUMMARY OF BACKGROUND DATA: Canine CSM is a spontaneous, chronic, compressive cervical myelopathy similar to human cervical spondylotic myelopathy. There is a limited knowledge of the molecular mechanisms underlying these conditions. Differentially expressed CSF proteins may contribute with novel information about the disease pathogenesis in both dogs and humans. METHODS: Protein separation was performed with 2-dimensional electrophoresis. A Student t test was used to detect significant differences between groups (P < 0.05). Three comparisons were made: (1) control versus CSM-affected dogs, (2) control versus non-corticosteroid-treated CSM-affected dogs, and (3) non-corticosteroid-treated CSM-affected versus corticosteroid-treated CSM-affected dogs. Protein spots exhibiting at least a statistically significant 1.25-fold change between groups were selected for subsequent identification with capillary-liquid chromatography tandem mass spectrometry. RESULTS: A total of 96 spots had a significant average change of at least 1.25-fold in 1 of the 3 comparisons. Compared with the CSF of control dogs, CSM-affected dogs demonstrated increased CSF expression of 8 proteins including vitamin D-binding protein, gelsolin, creatine kinase B-type, angiotensinogen, α-2-HS-glycoprotein, SPARC (secreted protein, acidic, rich in cysteine), calsyntenin-1, and complement C3, and decreased expression of pigment epithelium-derived factor, prostaglandin-H2 D-isomerase, apolipoprotein E, and clusterin. In the CSF of CSM-affected dogs, corticosteroid treatment increased the expression of haptoglobin, transthyretin isoform 2, cystatin C-like, apolipoprotein E, and clusterin, and decreased the expression of angiotensinogen, α-2-HS-glycoprotein, and gelsolin. CONCLUSION: Many of the differentially expressed proteins are associated with damaged neural tissue, bone turnover, and/or compromised blood-spinal cord barrier. The knowledge of the protein changes that occur in CSM and upon corticosteroid treatment of CSM-affected patients will aid in further understanding the pathomechanisms underlying this disease. LEVEL OF EVIDENCE: N/A.

Magnetic resonance imaging features of Great Danes with and without clinical signs of cervical spondylomyelopathy.

OBJECTIVE: To characterize and compare the MRI morphological features of the cervical vertebral column of Great Danes with and without clinical signs of cervical spondylomyelopathy (CSM). DESIGN: Prospective cohort study. ANIMALS: 30 Great Danes (15 clinically normal and 15 CSM-affected). PROCEDURES: All dogs underwent MRI of the cervical vertebral column (C2-3 through T1-2). Features evaluated included sites of subarachnoid space compression, spinal cord compression, or both; degree, cause, and direction of compression; MRI signal changes of the spinal cord; articular process (facet) joint characteristics; internal vertebral venous plexus visibility; and presence of extradural synovial cysts as well as presence and degree of intervertebral disk degeneration and foraminal stenosis. RESULTS: Clinically normal and CSM-affected dogs had 11 and 61 compressive sites, respectively, detected with MRI. All CSM-affected dogs had ≥ 1 site of spinal cord compression. No signal changes were observed in spinal cords of normal dogs, whereas 14 sites of hyperintensity were found in 9 CSM-affected dogs. Foraminal stenosis was present in 11 clinically normal and all CSM-affected dogs. The number of stenotic foraminal sites was significantly greater in the CSM-affected group, and severe stenosis appeared to be more common in this group than in the clinically normal group. Significant differences were identified between clinically normal and CSM-affected dogs with regard to amount of synovial fluid evident, regularity of articular surfaces, degree of articular process joint proliferation, and internal vertebral venous plexus visibility. CONCLUSIONS AND CLINICAL RELEVANCE: Abnormalities were detected with MRI in several clinically normal Great Danes. Severe spinal cord compression, number of stenotic foraminal sites, and signal changes within the spinal cord distinguished CSM-affected from clinically normal Great Danes.

MRI features of gliomatosis cerebri in a dog.

The features of gliomatosis cerebri involving the brainstem and cerebellum in a 3-year-old dog are described. In magnetic resonance (MR) images, there was diffuse loss of the cerebellar folia and cerebellar gray and white matter contrast. Multiple illdefined T2-hyperintensities were present in the cerebellar parenchyma. A poorly defined, T2-hyperintense mass effect was present ventral to the pons and rostral medulla. No contrast enhancement was noted. Cerebrospinal fluid (CSF) was normal. Postmortem examination was consistent with gliomatosis cerebri, based on compatible histopathology and immunohistochemical findings. Although rare, gliomatosis cerebri should be included as a differential for diffuse infiltrative central nervous system (CNS) lesions.

Magnetic resonance spectroscopy of the canine brain at 3.0 T and 7.0 T.

The purpose of this study was to evaluate the feasibility of proton magnetic resonance spectroscopy (1H MRS) to study the concentration of metabolites in the brain of dogs at 3.0 and 7.0 T. Four healthy male beagles were scanned using 3.0 T and 7.0 T human magnetic resonance imaging (MRI) units. The results obtained showed that all dogs had excellent quality spectra for a small (1 cm3) and large (8 cm3) voxel at 3.0 T, whereas only 2 dogs had high quality spectra at 7.0 T due to insufficient water suppression. 1H MRS at 3.0 T appears to be a reliable method to study metabolite concentrations in the canine brain. The development of more advanced water suppression techniques is necessary to improve the results at 7.0 T.

Presumptive meningoencephalitis secondary to extension of otitis media/interna caused by Streptococcus equi subspecies zooepidemicus in a cat.

A 5-year-old castrated male domestic longhair cat was presented with neurological signs consistent with a central vestibular lesion and left Horner's syndrome. Computed tomography images revealed hyperattenuating, moderately contrast-enhancing material within the left tympanic bulla, most consistent with left otitis media/interna. Marked neutrophilic pleocytosis was identified on cerebrospinal fluid analysis. Streptococcus equi subspecies zooepidemicus (SEZ) was isolated from the cerebrospinal fluid. Intracranial extension of otitis media/interna is relatively infrequent in small animals. There are no reports of otitis media/interna caused by SEZ in dogs or cats. This is the first report of otitis media/interna and presumptive secondary meningoencephalitis caused by SEZ in a cat.

Cerebral vascular hamartoma in a geriatric cat.

An 11-year-old castrated male domestic medium hair cat was presented with neurological signs consistent with a right thalamocortical lesion. Computed tomography (CT) images revealed a heterogeneously, hyperattenuating, poorly contrast enhancing intra-axial mass within the right lateral ventricle. The histological diagnosis at post-mortem examination was vascular hamartoma with hemorrhage and necrosis. This is the first report of a vascular hamartoma affecting the thalamocortex in a geriatric cat. Also, this is the first time that CT images of a feline cerebral vascular hamartoma have been reported.

Magnetic resonance imaging of the canine brain at 3 and 7 T.

Magnetic resonance (MR) imaging of the canine brain is commonly acquired at field strengths ranging from 0.2 to 1.5 T. Our purpose was to compare the MR image quality of the canine brain acquired at 3 vs. 7 T in dogs. Low-resolution turbo spin echo (TSE) T2-weighted images (T2W) were obtained in transverse, dorsal, and sagittal planes, and high-resolution TSE T2W and turbo spin echo proton density-weighted images were obtained in the transverse and dorsal planes, at both 3 and 7 T. Three experienced reviewers evaluated 32 predetermined brain structures independently and without knowledge of field strength for spatial resolution and contrast. Overall image quality and evidence of artifacts were also evaluated. Contrast of gray and white matter was assessed quantitatively by measuring signal intensity in regions of interest for transverse plane images for the three pulse sequences obtained. Overall, 19 of the 32 neuroanatomic structures had comparable spatial resolution and contrast at both field strengths. The overall image quality for low-resolution T2W images was comparable at 3 and 7 T. High-resolution T2W was characterized by superior image quality at 3 vs. 7 T. Magnetic susceptibility and chemical shift artifacts were slightly more noticeable at 7 T. MR imaging at 3 and at 7 T provides high spatial resolution and contrast images of the canine brain. The use of 3 and 7 T MR imaging may assist in the elucidation of the pathogenesis of brain disorders, such as epilepsy.

Imaging diagnosis--Hemorrhagic meningioma.

An 8-year-old Labrador Retriever developed acute central vestibular signs. An extra-axial mass was detected on MR images ventral to the brainstem. The mass was both T1- and T2-hypointense; there was also thin-rimmed patchy contrast enhancement. These findings were nonspecific, but the extreme T2-hypointensity was notable and suggested a hemorrhagic mass. The histologic diagnosis was anaplastic meningioma with acute hemorrhage. These findings document an unusual appearance of a meningioma in MR images due to intratumoral hemorrhage.