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1.  Cervical spondylomyelopathy in Great Danes: A magnetic resonance imaging morphometric study 
Morphometric investigations comparing normal and affected animals increase our understanding of spinal diseases in dogs. The aim of this study was to generate morphometric data for osseous-associated cervical spondylomyelopathy (CSM) in Great Danes (GDs). Magnetic resonance imaging (MRI) morphometric features of the cervical vertebral column of GDs with and without clinical signs of CSM were characterized and compared. Thirty client-owned GDs were prospectively enrolled, including 15 clinically normal and 15 CSM-affected GDs. All dogs underwent MRI of the cervical to thoracic vertebral column (C2–C3 through T1–T2). Areas of the cranial and caudal articular processes, and the height, width and areas of the vertebral canal and spinal cord were determined. Middle foraminal heights were measured. Intervertebral disc width was measured before and after traction. Intraobserver and interobserver agreement were calculated. CSM-affected GDs had larger areas of the caudal articular processes from C2–C3 through T1–T2. In CSM-affected GDs, the vertebral canal and spinal cord areas were significantly smaller at C5–C6 and C6–C7, the vertebral canal width was significantly narrower at C6–C7 and C7–T1, and the spinal cord width was significantly narrower at C5–C6 and C6–C7. Middle foraminal height was smaller in CSM-affected GDs from C3–C4 through C7-T1. Neutral intervertebral disc widths were smaller in CSM-affected GDs. It was concluded that the cervical vertebral canal dimensions are significantly different between normal and CSM-affected GDs. Absolute vertebral canal stenosis and severe foraminal stenosis involving the cervical vertebrae distinguish CSM-affected from clinically normal GDs. These findings are relevant to the pathogenesis of osseous-associated CSM and should be taken into consideration when performing imaging studies and planning surgery.
doi:10.1016/j.tvjl.2014.04.011
PMCID: PMC4169205  PMID: 24888675
Canine; Osseous-associated cervical; spondylomyelopathy; Spinal cord; Stenosis; Wobbler syndrome
2.  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.
doi:10.2460/javma.245.4.393
PMCID: PMC4213553  PMID: 25075822
3.  Kinematic Magnetic Resonance Imaging for Evaluation of Disc‐Associated Cervical Spondylomyelopathy in Doberman Pinschers 
Background
The dynamic component of disc‐associated cervical spondylomyelopathy (DA‐CSM) currently is evaluated using traction magnetic resonance imaging (MRI), which does not assess changes in flexion and extension of the cervical vertebral column. In humans with cervical spondylotic myelopathy, kinematic MRI is used to identify dynamic compressions.
Hypothesis/Objectives
To evaluate the feasibility and utility of kMRI in Doberman Pinschers with DA‐CSM using a novel positioning device. We hypothesized that kMRI would identify compressive lesions not observed with neutral positioning and change the dimensions of the spinal cord and cervical vertebral canal.
Animals
Nine client‐owned Doberman Pinschers with DA‐CSM.
Methods
Prospective study. After standard MR imaging of the cervical spine confirmed DA‐CSM, dogs were placed on a positioning device to allow imaging in flexion and extension. Morphologic and morphometric assessments were compared between neutral, flexion, and extension images.
Results
Flexion was associated with improvement or resolution of spinal cord compression in 4/9 patients, whereas extension caused worsening of compressions in 6/9 patients. Extension identified 6 new compressive lesions and was significantly associated with dorsal and ventral compression at C5‐C6 (P = .021) and C6‐C7 (P = .031). A significant decrease in spinal cord height occurred at C6‐C7 from neutral to extension (P = .003) and in vertebral canal height at C5‐C6 and C6‐C7 from neutral to extension (P = .011 and .017, respectively).
Conclusions and clinical importance
Our results suggest that kMRI is feasible and provides additional information beyond what is observed with neutral imaging, primarily when using extension views, in dogs with DA‐CSM.
doi:10.1111/jvim.13981
PMCID: PMC5089627  PMID: 27239003
Dynamic; Extension; Flexion; Wobbler
4.  Force Plate Gait Analysis in Doberman Pinschers with and without Cervical Spondylomyelopathy 
Background
The most accepted means of evaluating the response of a patient with cervical spondylomyelopathy (CSM) to treatment is subjective and based on the owner and clinician's perception of the gait.
Objective
To establish and compare kinetic parameters based on force plate gait analysis between normal and CSM-affected Dobermans.
Animals
Nineteen Doberman Pinschers: 10 clinically normal and 9 with CSM.
Methods
Force plate analysis was prospectively performed in all dogs. At least 4 runs of ipsilateral limbs were collected from each dog. Eight force platform parameters were evaluated, including peak vertical force (PVF) and peak vertical impulse (PVI), peak mediolateral force (PMLF) and peak mediolateral impulse, peak braking force and peak braking impulse, and peak propulsive force (PPF) and peak propulsive impulse. In addition, the coefficient of variation (CV) for each limb was calculated for each parameter. Data analysis was performed by a repeated measures approach.
Results
PMLF (P = .0062), PVI (P = .0225), and PPF (P = .0408) were found to be lower in CSM-affected dogs compared with normal dogs. Analysis by CV as the outcome indicated more variability in PVF in CSM-affected dogs (P = 0.0045). The largest difference in the CV of PVF was seen in the thoracic limbs of affected dogs when compared with the thoracic limbs of normal dogs (P = 0.0019).
Conclusions and Clinical Importance
The CV of PVF in all 4 limbs, especially the thoracic limbs, distinguished clinically normal Dobermans from those with CSM. Other kinetic parameters less reliably distinguished CSM-affected from clinically normal Dobermans.
doi:10.1111/jvim.12025
PMCID: PMC4025962  PMID: 23278957
Cervical vertebral instability; Dog; Kinetic; Wobbler
5.  Three-Dimensional Kinematic Gait Analysis of Doberman Pinschers with and without Cervical Spondylomyelopathy 
Background
The optimal treatment of cervical spondylomyelopathy (CSM) is controversial, with the owner’s and clinician’s perception of gait improvement often being used as outcome measures. These methods are subjective and suffer from observer bias.
Objectives
To establish kinematic gait parameters utilizing digital motion capture in normal Doberman Pinschers and compare them with CSM-affected Dobermans.
Animals
Nineteen Doberman Pinschers; 10 clinically normal and 9 with CSM.
Methods
All dogs were enrolled prospectively and fitted with a Lycra® body suit, and motion capture was performed and used to reconstruct a 3-D stick diagram representation of each dog based on 32 reflective markers, from which several parameters were measured. These included stride duration, length, and height; maximal and minimal spinal angles; elbow and stifle flexion and extension; and maximum and minimum distances between the thoracic and pelvic limbs. A random-effects linear regression model was used to compare parameters between groups.
Results
Significant differences between groups included smaller minimum (mean = 116 mm; P = .024) and maximum (mean = 184 mm; P = .001) distance between the thoracic limbs in CSM-affected dogs. Additionally, thoracic limb stride duration was also smaller (P = .009) in CSM-affected dogs (mean = 0.7 seconds) when compared with normal dogs (mean = 0.8 seconds). In the pelvic limbs, the average stifle flexion (mean = 100°; P = .048) and extension (mean = 136°; P = .009), as well as number of strides (mean = 2.7 strides; P = .033) were different between groups.
Conclusions and Clinical Importance
Our findings suggest that computerized gait analysis reveals more consistent kinematic differences in the thoracic limbs, which can be used as future objective outcome measures.
doi:10.1111/jvim.12012
PMCID: PMC4157597  PMID: 23194100
Cervical instability; Digital motion capture; Dog; Wobbler
6.  Morphological changes of the caudal cervical intervertebral foramina due to flexion-extension and compression-traction movements in the canine cervical vertebral column 
BMC Veterinary Research  2015;11:184.
Background
Previous studies in humans have reported that the dimensions of the intervertebral foramina change significantly with movement of the spine. Cervical spondylomyelopathy (CSM) in dogs is characterized by dynamic and static compressions of the neural components, leading to variable degrees of neurologic deficits and neck pain. Studies suggest that intervertebral foraminal stenosis has implications in the pathogenesis of CSM. The dimensions of the cervical intervertebral foramina may significantly change during neck movements. This could have implication in the pathogenesis of CSM and other diseases associated with radiculopathy such as intervertebral disc disease. The purpose of this study was to quantify the morphological changes in the intervertebral foramina of dogs during flexion, extension, traction, and compression of the canine cervical vertebral column. All vertebral columns were examined with magnetic resonance imaging prior to biomechanic testing. Eight normal vertebral columns were placed in Group 1 and eight vertebral columns with intervertebral disc degeneration or/and protrusion were assigned to Group 2. Molds of the left and right intervertebral foramina from C4-5, C5-6 and C6-7 were taken during all positions and loading modes. Molds were frozen and vertical (height) and horizontal (width) dimensions of the foramina were measured. Comparisons were made between neutral to flexion and extension, flexion to extension, and traction to compression in neutral position.
Results
Extension decreased all the foraminal dimensions significantly, whereas flexion increased all the foraminal dimensions significantly. Compression decreased all the foraminal dimensions significantly, and traction increased the foraminal height, but did not significantly change the foraminal width. No differences in measurements were seen between groups.
Conclusions
Our results show movement-related changes in the dimensions of the intervertebral foramina, with significant foraminal narrowing in extension and compression.
doi:10.1186/s12917-015-0508-4
PMCID: PMC4545818  PMID: 26245514
Cervical spondylomyelopathy; Disc degeneration; Dog; Spinal cord; Wobbler syndrome
7.  “Disk extension beyond the interspace”: an investigation into an alternative nomenclature in diagnostic imaging for displaced canine intervertebral disk material 
BMC Veterinary Research  2015;11:110.
Background
Displacement of canine intervertebral disk material can be seen directly in diagnostic imaging modalities such as magnetic resonance imaging and computed tomographic imaging. Canine intervertebral disk herniation can be differentiated into Hansen type 1 and 2 categories by clinical appearance, but anular- and nuclear disk material cannot be distinguished in computed tomographic images. Therefore, we hypothesized that the “Disk extension beyond the interspace”-nomenclature that describes the displacement by the disk contour might aid diagnosis. The aim of this study was to test the reliability of the “Disk extension beyond the interspace”-nomenclature in the evaluation of canine intervertebral disks via magnetic resonance and computed tomographic imaging.
Results
Magnetic resonance and computed tomographic images of 144 intervertebral disks of 43 dogs were evaluated by 3 observers with different degrees of experience from 2 institutions retrospectively. A substantial intraobserver agreement was found, while interobserver agreement was fair to moderate with significant differences in evaluation. Comparison of imaging methods showed a fair to moderate agreement without statistically significant differences in evaluation.
Conclusions
DEBIT-nomenclature cannot be recommended for veterinary clinical usage yet. The largest variability was found in the evaluation of the bulged canine intervertebral disk. The observers’ experience and the imaging method influenced DEBIT- evaluation only slightly, while training and working at different institutions influenced DEBIT-evaluation strongly.
doi:10.1186/s12917-015-0421-x
PMCID: PMC4436149  PMID: 25972009
8.  Transcranial magnetic motor evoked potentials in Great Danes with and without clinical signs of cervical spondylomyelopathy: Association with neurological findings and magnetic resonance imaging 
Transcranial magnetic motor evoked potentials (TMMEPs) assess the functional integrity of the descending motor pathways, which are typically compromised in canine cervical spondylomyelopathy (CSM). The objective of this prospective study was to establish the reference ranges of TMMEPs latency and amplitude in clinically normal (control) Great Danes (GDs), compare TMMEPs obtained in GDs with and without CSM, and determine whether there is any association between TMMEP data and severity of neurological signs or magnetic resonance imaging (MRI) findings. Twenty-nine client-owned GDs were enrolled (15 controls, 14 CSM-affected). All dogs underwent TMMEPs under sedation, and latencies and amplitudes were recorded from the extensor carpi radialis (ECR) and cranial tibial (CT) muscles. MRI of the cervical vertebral column was performed to evaluate the presence and severity of spinal cord (SC) compression, and the presence of SC signal changes.
Extensor carpi radialis and CT latencies were significantly longer in CSM-affected than control GDs. No significant differences between groups were found for amplitudes or neuronal path lengths. For the CT TMMEPs, CSM-affected GDs with moderate and severe clinical signs had significantly longer latencies that those with mild clinical signs. Significantly longer CT latencies were found in dogs with moderate and severe SC compression compared to dogs with mild compression. CT TMMEPs could not be recorded in 8/9 CSM-affected GDs with SC signal changes. These results provide a reference range for TMMEPs of clinically normal GDs. The use of TMMEPs is a valid ancillary test to assess the integrity of motor pathways in GDs with CSM.
doi:10.1016/j.tvjl.2014.05.035
PMCID: PMC4160397  PMID: 24929532
Cervical spine; Dog; Magnetic stimulation; MRI; Wobbler syndrome
9.  A Review of Fibrocartilaginous Embolic Myelopathy and Different Types of Peracute Non-Compressive Intervertebral Disk Extrusions in Dogs and Cats 
This review discusses terminology, pathological, clinical, and magnetic resonance imaging (MRI) findings, treatment, outcome, and prognostic factors of fibrocartilaginous embolic myelopathy (FCEM), acute non-compressive nucleus pulposus extrusion (ANNPE), and intradural/intramedullary intervertebral disk extrusion (IIVDE). FCEM, ANNPE, and IIVDE have a similar clinical presentation characterized by peracute onset of neurological dysfunction that is generally non-progressive after the initial 24–48 h. Differentiating between these conditions can be challenging, however, certain clinical and imaging findings can help. FCEM can occur in both adult and immature animals, whereas ANNPE or IIVDE have been reported only in animals older than 1 year. In dogs, ANNPE and IIVDE most commonly occur in the intervertebral disk spaces between T12 and L2, whereas FCEM has not such site predilection. In cats, FCEM occurs more frequently in the cervical spinal cord than in other locations. Data on cats with ANNPE and IIVDE are limited. Optimal MRI definition and experience in neuroimaging can help identify the findings that allow differentiation between FCEM, ANNPE, and IIVDE. In animals with ANNPE and IIVDE, the affected intervertebral disk space is often narrowed and the focal area of intramedullary hyperintensity on T2-weighted images is located above the affected intervertebral disk space. In dogs with ANNPE signal changes associated with the extruded nucleus pulposus and epidural fat disruption can be identified in the epidural space dorsal to the affected intervertebral disk. Identification of a linear tract (predominantly hyperintense on T2-weighted images, iso to hypointense on T1-weighted images and hypointense on T2*-weighted gradient recall echo images) extending from the intervertebral disk into the spinal cord parenchyma is highly suggestive of IIVDE. Treatment of FCEM and ANNPE is conservative. Dogs reported with IIVDE have been managed either conservatively or surgically. Prognostic factors include degree of neurological dysfunction (particularly loss of nociception) and disease-specific MRI variables.
doi:10.3389/fvets.2015.00024
PMCID: PMC4672181  PMID: 26664953
dog; cat; fibrocartilaginous embolic myelopathy; non-compressive nucleus pulposus extrusion; intramedullary intervertebral disk extrusion
10.  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.
doi:10.1111/vru.12159
PMCID: PMC4163098  PMID: 24698393
cervical spine; dog; radiography; vertebra; wobbler syndrome
11.  Clinical and magnetic resonance imaging (MRI) findings in 26 dogs with canine osseous-associated cervical spondylomyelopathy 
The Canadian Veterinary Journal  2014;55(2):169-174.
The potential link between degenerative changes seen on magnetic resonance imaging (MRI) in osseous-associated cervical spondylomyelopathy (OA-CSM) and clinical signs has not been explored. Our goal was to retrospectively evaluate MRI findings, while investigating potential correlations between these changes, signalment, and clinical signs. Twenty-six dogs diagnosed with OA-CSM were included in the study. Clinical signs were converted into a Modified Frankel Score (MFS) and MRI findings were assessed and graded. Giant breeds had multiple compressed sites and presented at a younger age than large breeds, suggesting a different underlying pathophysiology. Spinal cord compression, most commonly bilateral, was present in 36.8% of intervertebral spaces. Synovial fluid loss and articular process sclerosis were the most common degenerative changes. Most dogs showed identical MFS scores, and no significant correlations were found between MFS and MRI changes. More detailed functional scales should be used to investigate this in the future.
PMCID: PMC3894878  PMID: 24489397
12.  Direct repair of defects in lumbar spondylolysis with a new pedicle screw hook fixation: clinical, functional and Ct-assessed study 
European Spine Journal  2007;16(10):1650-1658.
Spondylolysis is a common entity, a minority of people affected by this disease need medical care, and only a few require surgery. Reconstruction of the pars interarticularis is an interesting alternative to segmental fusion; this technique has the advantage of preserving segmental motion. Most authors report good results for young patients without intervertebral disk or facet degenerative changes. Moreover Louis also showed good to excellent results with his technique carried out among people who presented a satisfactory disk height (equal to two thirds of normal height). This could extend the number of patients for whom pars interarticularis repair could be proposed. In this study, the limit of reconstruction was set at grade 3of the Pfirrmann’s classification. The fixation of the isthmus was done with a new kind of pedicle screw hook system. This stable and strong device is easy to use, allows an anatomic pars interarticularis reconstruction of spondylolysis and avoids a postoperative bracing. Twenty-three patients were assessed in this study, the mean age at operation was 34 (range 16–52 years) and the average follow-up was for 59 months (range 6–113 months). Eight patients showed moderate degenerative disk disease before the surgery and 12 patients had a grade 1 spondylolisthesis. The visual analogical scale, the Oswestry disability index (ODI) and the modified Prolo score were used for assessment of pain and clinical outcome before and after surgery. The results were from “excellent” to “good” for twenty patients (87%) and “fair” for three of them (13%). The consolidation of the isthmus was assessed at the end of the study (CT-scan); the fusion rate was observed in 91%. Among patients aged less than 30 years results are from “good”, to “excellent” in all cases and consolidation was always observed. All of them showed normal disc signal before the surgery. In the group aged more than 30 years, the results varied from “good” to “excellent’ in 73% and fusion of the defect was discovered in 82% of cases. Eight of them (73%) had moderate disk signal modification before the surgery. All people with fair results displayed moderate disk degeneration signs at MRI before surgery; but two of those three patients had a failure of defect consolidation too and it is also associated with poor results by several authors. No complication was found in this series. According to the good results reported by Louis and upto the current finding, the authors believe that pars interarticularis repair can be carried out on patients with moderate degenerative disk disease; the stage 3 of Pfirrmann’s classification seems a good limit. The Bone and joint research (B.J.R. system) is readily usable by any surgeon using pedicle screw systems and having a short learning curve. No device failure has been observed in this series.
doi:10.1007/s00586-007-0392-0
PMCID: PMC2078304  PMID: 17520298
Pars interarticularis repair; Lumbar spondylolysis; Functional outcome; Surgery; Pedicular screw hook fixation
13.  Polymorphisms within the canine MLPH gene are associated with dilute coat color in dogs 
BMC Genetics  2005;6:34.
Background
Pinschers and other dogs with coat color dilution show a characteristic pigmentation phenotype. The fur colors are a lighter shade, e.g. silvery grey (blue) instead of black and a sandy color (Isabella fawn) instead of red or brown. In some dogs the coat color dilution is sometimes accompanied by hair loss and recurrent skin inflammation, the so called color dilution alopecia (CDA) or black hair follicular dysplasia (BHFD). In humans and mice a comparable pigmentation phenotype without any documented hair loss is caused by mutations within the melanophilin gene (MLPH).
Results
We sequenced the canine MLPH gene and performed a mutation analysis of the MLPH exons in 6 Doberman Pinschers and 5 German Pinschers. A total of 48 sequence variations was identified within and between the breeds. Three families of dogs showed co-segregation for at least one polymorphism in an MLPH exon and the dilute phenotype. No single polymorphism was identified in the coding sequences or at splice sites that is likely to be causative for the dilute phenotype of all dogs examined. In 18 German Pinschers a mutation in exon 7 (R199H) was consistently associated with the dilute phenotype. However, as this mutation was present in homozygous state in four dogs of other breeds with wildtype pigmentation, it seems unlikely that this mutation is truly causative for coat color dilution. In Doberman Pinschers as well as in Large Munsterlanders with BHFD, a set of single nucleotide polymorphisms (SNPs) around exon 2 was identified that show a highly significant association to the dilute phenotype.
Conclusion
This study provides evidence that coat color dilution is caused by one or more mutations within or near the MLPH gene in several dog breeds. The data on polymorphisms that are strongly associated with the dilute phenotype will allow the genetic testing of Pinschers to facilitate the breeding of dogs with defined coat colors and to select against Large Munsterlanders carrying BHFD.
doi:10.1186/1471-2156-6-34
PMCID: PMC1183202  PMID: 15960853
14.  Quantitative evaluation of an automatic segmentation method for 3D reconstruction of intervertebral scoliotic disks from MR images 
BMC Medical Imaging  2012;12:26.
Background
For some scoliotic patients the spinal instrumentation is inevitable. Among these patients, those with stiff curvature will need thoracoscopic disk resection. The removal of the intervertebral disk with only thoracoscopic images is a tedious and challenging task for the surgeon. With computer aided surgery and 3D visualisation of the interverterbral disk during surgery, surgeons will have access to additional information such as the remaining disk tissue or the distance of surgical tools from critical anatomical structures like the aorta or spinal canal. We hypothesized that automatically extracting 3D information of the intervertebral disk from MR images would aid the surgeons to evaluate the remaining disk and would add a security factor to the patient during thoracoscopic disk resection.
Methods
This paper presents a quantitative evaluation of an automatic segmentation method for 3D reconstruction of intervertebral scoliotic disks from MR images. The automatic segmentation method is based on the watershed technique and morphological operators. The 3D Dice Similarity Coefficient (DSC) is the main statistical metric used to validate the automatically detected preoperative disk volumes. The automatic detections of intervertebral disks of real clinical MR images are compared to manual segmentation done by clinicians.
Results
Results show that depending on the type of MR acquisition sequence, the 3D DSC can be as high as 0.79 (±0.04). These 3D results are also supported by a 2D quantitative evaluation as well as by robustness and variability evaluations. The mean discrepancy (in 2D) between the manual and automatic segmentations for regions around the spinal canal is of 1.8 (±0.8) mm. The robustness study shows that among the five factors evaluated, only the type of MRI acquisition sequence can affect the segmentation results. Finally, the variability of the automatic segmentation method is lower than the variability associated with manual segmentation performed by different physicians.
Conclusions
This comprehensive evaluation of the automatic segmentation and 3D reconstruction of intervertebral disks shows that the proposed technique used with specific MRI acquisition protocol can detect intervertebral disk of scoliotic patient. The newly developed technique is promising for clinical context and can eventually help surgeons during thoracoscopic intervertebral disk resection.
doi:10.1186/1471-2342-12-26
PMCID: PMC3443448  PMID: 22856667
15.  Proteomic Analysis of Cerebrospinal Fluid in Canine Cervical Spondylomyelopathy 
Spine  2015;40(9):601-612.
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 two-dimensional electrophoresis. A Student’s 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 one of the three comparisons. Compared to the CSF of control dogs, CSM-affected dogs demonstrated increased CSF expression of eight proteins including vitamin D-binding protein, gelsolin, creatine kinase B-type, angiotensinogen, alpha-2-HS-glycoprotein, SPARC, 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, alpha-2-HS-glycoprotein, and gelsolin.
Conclusions
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.
doi:10.1097/BRS.0000000000000831
PMCID: PMC4451599  PMID: 26030213
biomarker; cervical spine; DIGE; dog; electrophoresis; Great Dane; mass spectrometry; myelopathy; osseous-associated cervical spondylomyelopathy; proteomics; spinal cord; stenosis; wobbler syndrome
16.  Sphericity Index and E‐Point‐to‐Septal‐Separation (EPSS) to Diagnose Dilated Cardiomyopathy in Doberman Pinschers 
Background
E‐point‐to‐septal‐separation (EPSS) and the sphericity index (SI) are echocardiographic parameters that are recommended in the ESVC‐DCM guidelines. However, SI cutoff values to diagnose dilated cardiomyopathy (DCM) have never been evaluated.
Objectives
To establish reference ranges, calculate cutoff values, and assess the clinical value of SI and EPSS to diagnose DCM in Doberman Pinschers.
Animals
One hundred seventy‐nine client‐owned Doberman Pinschers.
Methods
Three groups were formed in this prospective longitudinal study according to established Holter and echocardiographic criteria using the Simpson method of disk (SMOD): control group (97 dogs), DCM with echocardiographic changes (75 dogs) and “last normal” group (n = 7), which included dogs that developed DCM within 1.5 years, but were still normal at this time point. In a substudy, dogs with early DCM based upon SMOD values above the reference range but still normal M‐Mode measurements were selected, to evaluate if EPSS or SI were abnormal using the established cutoff values.
Results
ROC‐curve analysis determined <1.65 for the SI (sensitivity 86.8%; specificity 87.6%) and >6.5 mm for EPSS (sensitivity 100%; specificity 99.0%) as optimal cutoff values to diagnose DCM. Both parameters were significantly different between the control group and the DCM group (P < 0.001), but were not abnormal in the “last normal” group. In the substudy, EPSS was abnormal in 13/13 dogs and SI in 2/13 dogs.
Conclusions and Clinical Importance
E‐point‐to‐septal‐separation is a valuable additional parameter for the diagnosis of DCM, which can enhance diagnostic capabilities of M‐Mode and which performs similar as well as SMOD.
doi:10.1111/jvim.12242
PMCID: PMC4895524  PMID: 24428318
Canine; Cardiology; DCM; Diagnostic tools; Dogs; Echocardiography; Heart; Occult cardiomyopathy; Ultrasound
17.  Cervical Vertebral Trabecular Bone Mineral Density in Great Danes With and Without Osseous-Associated Cervical Spondylomyelopathy 
Background
Great Danes (GDs) with osseous-associated cervical spondylomyelopathy (CSM) have osteoarthritis (OA) of the cervical vertebrae. OA is often associated with increases in bone mineral density (BMD) in people and dogs.
Hypothesis/Objectives
To compare the trabecular BMD of the cervical vertebrae between clinically normal (control) GDs and GDs with osseous-associated CSM by using computed tomography (CT). We hypothesized that the vertebral trabecular BMD of CSM-affected GDs would be higher than that of control GDs.
Animals
Client-owned GDs: 12 controls, 10 CSM affected.
Methods
Prospective study. CT of the cervical vertebral column was obtained alongside a calibration phantom. By placing a circular region of interest at the articular process joints, vertebral body, pedicles, and within each rod of the calibration phantom, trabecular BMD was measured in Hounsfield units, which were converted to diphosphate equivalent densities. Trabecular BMD measurements were compared between CSM-affected and control dogs, and between males and females within the control group.
Results
Differences between CSM-affected and control dogs were not significant for the articular processes (mean = −39; P = .37; 95% CI: −102 to 24), vertebral bodies (mean = −62; P = .08; 95% CI: −129 to 6), or pedicles (mean = −36; P = .51; 95% CI: −105 to 33). Differences between female and male were not significant.
Conclusions and Clinical Importance
This study revealed no difference in BMD between control and CSM-affected GDs. Based on our findings no association was detected between cervical OA and BMD in GDs with CSM.
doi:10.1111/jvim.12444
PMCID: PMC4330089  PMID: 25312453
Cervical spine; Computed tomography; Dog; Osteoarthritis; Wobbler syndrome
18.  Cervical Vertebral Trabecular Bone Mineral Density in Great Danes With and Without Osseous‐Associated Cervical Spondylomyelopathy 
Background
Great Danes (GDs) with osseous‐associated cervical spondylomyelopathy (CSM) have osteoarthritis (OA) of the cervical vertebrae. OA is often associated with increases in bone mineral density (BMD) in people and dogs.
Hypothesis/Objectives
To compare the trabecular BMD of the cervical vertebrae between clinically normal (control) GDs and GDs with osseous‐associated CSM by using computed tomography (CT). We hypothesized that the vertebral trabecular BMD of CSM‐affected GDs would be higher than that of control GDs.
Animals
Client‐owned GDs: 12 controls, 10 CSM affected.
Methods
Prospective study. CT of the cervical vertebral column was obtained alongside a calibration phantom. By placing a circular region of interest at the articular process joints, vertebral body, pedicles, and within each rod of the calibration phantom, trabecular BMD was measured in Hounsfield units, which were converted to diphosphate equivalent densities. Trabecular BMD measurements were compared between CSM‐affected and control dogs, and between males and females within the control group.
Results
Differences between CSM‐affected and control dogs were not significant for the articular processes (mean = −39; P = .37; 95% CI: −102 to 24), vertebral bodies (mean = −62; P = .08; 95% CI: −129 to 6), or pedicles (mean = −36; P = .51; 95% CI: −105 to 33). Differences between female and male were not significant.
Conclusions and Clinical Importance
This study revealed no difference in BMD between control and CSM‐affected GDs. Based on our findings no association was detected between cervical OA and BMD in GDs with CSM.
doi:10.1111/jvim.12444
PMCID: PMC4330089  PMID: 25312453
Cervical spine; Computed tomography; Dog; Osteoarthritis; Wobbler syndrome
19.  Are magnetic resonance imaging or radiographic findings correlated with clinical prognosis in spinal cord neuropathy? 
Veterinary Research Forum  2016;7(3):261-266.
Dogs presented to the Small Animal Hospital of Veterinary Medicine, University of Tehran were included in the present study if spinal or intervertebral disc involvement was suspected. Clinical signs were recorded as well as general information of the patient such as age, breed and sex. Sixty dogs were examined radiographically and two standard orthogonal lateral and ventrodorsal projections were taken from the suspected region. Then magnetic resonance imaging (MRI) was performed for all patients. Agreement between MRI and radiographic findings, comparison of sex and breed with diagnostic imaging grades, comparison between diagnostic imaging grades and mean age, recovery rate after surgery or medical treatment, effects of diagnostic imaging severity grades on surgical or medical referrals were evaluated statistically. There were no significant association between age, sex and breed and frequency of the intervertebral disk disease. Intervertebral disc involvements between L2-L3 and T13-L1 were estimated as the most frequent sites of involvements. Sensitivity and specificity of radiography were evaluated 90.0% and 46.0%, respectively, by considering the MRI as a gold standard modality. There was a significant association between severity of disease in the MRI with referral to surgery and medical treatment. The recovery rate after surgery was significantly higher than medical treatment. These results can be used as a foundation for other studies with more focuses on details of injury and larger group of patients.
PMCID: PMC5094159  PMID: 27872724
Dog; Intervertebral disk disease; Magnetic resonance imaging; Treatment
20.  Risk Prediction for Development of Traumatic Cervical Spinal Cord Injury without Spinal Instability 
Global Spine Journal  2015;5(4):315-321.
Study Design Retrospective comparative study.
Objective A narrow spinal canal is an important risk factor for predicting a spinal cord injury (SCI); however, the radiologic parameters have not been fully established. The authors conducted a comparative study to forecast SCI risk by determining a predictive spinal canal diameter (SCD) cutoff value from magnetic resonance image (MRI) in the Korean population.
Methods On T2-weighted MRI of the cervical spine, the SCD at the pedicle (SCDpedicle) and the intervertebral disk level (SCDdisk) were measured in patients with SCI without spinal instability and in healthy subjects. Additionally, the vertebral body diameter (Dvertebral body) and intervertebral disk diameter (Dintervertebral disk) were measured, and the two ratios (SCDpedicle to Dvertebral body and SCDdisk to Dintervertebral disk) were calculated. In the SCI group, the extent of high signal intensity on the T2-weighted midsagittal MRI was determined.
Results The data obtained from 20 patients in the SCI group (18 men, mean age 61.35 years) and 65 individuals in the control group (47 men, mean age 57.05 years) was compared. All the parameters including the SCD and the calculated ratios were significantly smaller in the SCI group than in the control group. Among them, the area under the receiver operating curve (AUC) value for the SCDdisk-to-Dintervertebral disk ratio at C2–C3, with a cutoff ratio value of 0.59, provided the greatest positive predictive value. A low SCDdisk-to-Dintervertebral disk ratio at C4–C5 and the presence of >40 mm of high signal intensity on the MRI were related with the presence of complete SCI.
Conclusion Because the C2–C3 level is relatively wide compared with the subaxial cervical spine, a small ratio at C2–C3 provided the greatest positive predictive value in SCI. Complete SCI is associated with a small SCDdisk-to-Dintervertebral disk ratio at C4–C5 and with extensive high signal intensity on MRI.
doi:10.1055/s-0035-1547526
PMCID: PMC4516744  PMID: 26225281
spinal cord injury; spinal instability; Torg-Pavlov ratio; cervical spine
21.  Perineural Injection for Treatment of Root-Signature Signs Associated with Lateralized Disk Material in Five Dogs (2009–2013) 
Intervertebral disk disease (IVDD) is common in dogs; cervical IVDD accounts for 13–25% of all cases. Ventral slot decompression provides access to ventral and centrally extruded or protruded disk material. However, procedures to remove dorsally or laterally displaced material are more difficult. This case series describes the use of perineural injection as a potential treatment option for dogs experiencing root-signature signs associated with lateralized disk material in the cervical spine. Five dogs underwent fluoroscopically guided perineural injection of methylprednisolone ± bupivacaine. Most patients experienced improvement in root-signature signs and remained pain free without the assistance of oral pain medication. These findings suggest the perineural injection of methylprednisolone ± bupivacaine represents a viable option for dogs with cervical lateralized disk material causing root-signature signs.
doi:10.3389/fvets.2016.00001
PMCID: PMC4728328  PMID: 26858952
perineural; root-signature; intervertebral disk disease; lateralized disk; fluoroscopy
22.  Cytokine Concentrations in the Cerebrospinal Fluid of Great Danes with Cervical Spondylomyelopathy 
Background
Chronic inflammation is involved in the pathogenesis of human cervical spondylotic myelopathy and could also play a role in cervical spondylomyelopathy (CSM) in dogs.
Hypothesis/Objectives
That cerebrospinal fluid (CSF) cytokine concentrations would differ between clinically normal (control) and CSM-affected Great Danes (GDs), with affected GDs showing higher levels of inflammatory cytokines, such as interleukin (IL)-6 and monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2).
Animals
Client-owned GDs: 15 control, 15 CSM-affected.
Methods
Prospective study. Dogs underwent cervical vertebral column magnetic resonance imaging and collection of CSF from the cerebellomedullary cistern. Cytokine concentrations were measured using a commercially available canine multiplex immunoassay. Cytokine concentrations were compared between groups. Associations with the administration of anti-inflammatory medications, disease duration and severity, severity of spinal cord (SC) compression, and SC signal changes were investigated in affected GDs.
Results
Affected GDs had significantly lower MCP-1/CCL2 (mean 138.03 pg/mL, 95% confidence interval [CI] = 114.85–161.20) than control GDs (212.89 pg/mL, 95% CI = 165.68–260.11, P = .028). In affected GDs, MCP-1/CCL2 concentrations correlated inversely with the severity of SC compression. There were no associations with administration of anti-inflammatory medications, disease duration, or disease severity. IL-6 concentrations were significantly higher (2.20 pg/mL, 95% CI = 1.92–2.47, P < .001) in GDs with SC signal changes.
Conclusions and Clinical Importance
Lower MCP-1/CCL2 in CSM-affected GDs might compromise clearance of axonal and myelin debris, delay axon regeneration, and affect recovery. Higher IL-6 in CSM-affected GDs with SC signal changes suggests more severe inflammation in this group.
doi:10.1111/jvim.12388
PMCID: PMC4169188  PMID: 24965833
Biomarker; Dog; Spinal cord disease; Wobbler syndrome
23.  Cytokine Concentrations in the Cerebrospinal Fluid of Great Danes with Cervical Spondylomyelopathy 
Background
Chronic inflammation is involved in the pathogenesis of human cervical spondylotic myelopathy and could also play a role in cervical spondylomyelopathy (CSM) in dogs.
Hypothesis/Objectives
That cerebrospinal fluid (CSF) cytokine concentrations would differ between clinically normal (control) and CSM‐affected Great Danes (GDs), with affected GDs showing higher levels of inflammatory cytokines, such as interleukin (IL)‐6 and monocyte chemoattractant protein‐1/chemokine ligand 2 (MCP‐1/CCL2).
Animals
Client‐owned GDs: 15 control, 15 CSM‐affected.
Methods
Prospective study. Dogs underwent cervical vertebral column magnetic resonance imaging and collection of CSF from the cerebellomedullary cistern. Cytokine concentrations were measured using a commercially available canine multiplex immunoassay. Cytokine concentrations were compared between groups. Associations with the administration of anti‐inflammatory medications, disease duration and severity, severity of spinal cord (SC) compression, and SC signal changes were investigated in affected GDs.
Results
Affected GDs had significantly lower MCP‐1/CCL2 (mean 138.03 pg/mL, 95% confidence interval [CI] = 114.85–161.20) than control GDs (212.89 pg/mL, 95% CI = 165.68–260.11, P = .028). In affected GDs, MCP‐1/CCL2 concentrations correlated inversely with the severity of SC compression. There were no associations with administration of anti‐inflammatory medications, disease duration, or disease severity. IL‐6 concentrations were significantly higher (2.20 pg/mL, 95% CI = 1.92–2.47, P < .001) in GDs with SC signal changes.
Conclusions and Clinical Importance
Lower MCP‐1/CCL2 in CSM‐affected GDs might compromise clearance of axonal and myelin debris, delay axon regeneration, and affect recovery. Higher IL‐6 in CSM‐affected GDs with SC signal changes suggests more severe inflammation in this group.
doi:10.1111/jvim.12388
PMCID: PMC4169188  PMID: 24965833
Biomarker; Dog; Spinal cord disease; Wobbler syndrome
24.  Novel Imaging of the Intervertebral Disk and Pain 
Global Spine Journal  2013;3(3):127-132.
T-1-rho (T1ρ) magnetic resonance imaging (MRI) and disc height ratio (DHR) are potential biomarkers of degenerative disk disease (DDD) related to biochemical composition and morphology of the intervertebral disk (IVD), respectively. To objectively detect DDD at an early stage, the hypothesis was tested that the average T1ρ relaxation time of the nucleus pulposus (NP) correlates with the disk height of degenerate IVDs, measured by MRI. Studies were performed on a 3-T Siemens Tim Trio clinical MRI scanner (Siemens Healthcare, Malvern, Pennsylvania, United States) on patients being treated for low back pain whose disks were categorized into (1) painful and (2) nonpainful subgroups based on provocative diskography and (3) age-matched healthy controls. Painful disks presented both low DHR and T1ρ values, nonpainful disks measured the highest DHR and extended to a higher range of T1ρ, and control disks presented a midrange DHR with the highest T1ρ values. T1ρ MRI evaluated in the NP of IVDs may be useful to establish a threshold (120 milliseconds here) above which indicates a healthy disk, and disks measuring low NP T1ρ (50 to 120 milliseconds here) would require disk height analysis to further categorize the disk. Combining T1ρ MRI and disk height analysis may hold promise in predicting painful disks without provocative diskography, and predictive models should be developed.
doi:10.1055/s-0033-1347930
PMCID: PMC3854607  PMID: 24436863
T1rho; MRI; disk degeneration; disk pain; biomarker; disk height
25.  Body conformation in Great Danes with and without clinical signs of cervical spondylomyelopathy 
It has been suggested that a combination of large head and long neck cause abnormal forces on the cervical vertebral column and are involved in the pathogenesis of cervical spondylomyelopathy (CSM) in Great Danes. The aim of this study was to compare the body conformation of 15 clinically normal and 15 CSM-affected Great Danes. There were no statistically significant differences between clinically normal and CSM-affected Great Danes in any body measurements. There were no significant associations between body conformation and the severity of neurological signs or cervical vertebral body dimensions determined by magnetic resonance imaging in CSM-affected Great Danes. The results of this study do not support the hypothesis that differences in body conformation related to head size, neck length, and body height and length, play a role in the pathogenesis of CSM in Great Danes.
doi:10.1016/j.tvjl.2014.12.003
PMCID: PMC4492279  PMID: 25555338
Cervical spondylomyelopathy; Great Dane; Magnetic resonance imaging

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