Permanent Iatrogenic Fibular Nerve Injury following Tibial Plateau Levelling Osteotomy.

The aim of this study was to describe three dogs with permanent fibular nerve injury following tibial plateau levelling osteotomy (TPLO). Fibular nerve injury following TPLO led to atrophy of the cranial tibial muscle, absent hock flexion and a mild lameness. Fibular nerve injury was confirmed in one case with electrodiagnostics. All three cases had a drill tract in the same location, on the caudal aspect of the tibia, immediately distal to the tibial osteotomy. Permanent fibular nerve injury following TPLO occurred with a more caudally positioned plate and care should be taken when drilling the tibia from medial to lateral in the region described. Careful gait assessment at routine follow-up was required to identify this complication.

Medial versus lateral transcondylar screw placement for canine humeral intracondylar fissures: A randomized clinical trial.

OBJECTIVE: To determine the influence of screw direction on complications following transcondylar screw placement for the treatment of canine humeral intracondylar fissures (HIFs). STUDY DESIGN: Equivalence, parallel group, randomized clinical trial. SAMPLE POPULATION: Fifty-two client owned dogs (73 elbows). METHODS: Transcondylar screw placement was randomized to either a medial or lateral approach. The primary outcome was the incidence of postoperative complications. RESULTS: There were 37 cases in the lateral approach group and 36 cases in the medial approach group. There was a significantly greater proportion of postoperative complications following placement of transcondylar screws from a lateral to medial direction (p = .001). There were seven cases with complications (19%) in the medial approach group versus 23 cases with complications (62%) in the lateral approach group. The majority of complications were seromas (n = 13) and surgical site infections (n = 16) with 4 complications requiring further surgery. Implant area moment of inertia (AMI), normalized to bodyweight, was lower in dogs with a major complication (p = .037). CONCLUSION: Transcondylar screws placed from lateral to medial for canine HIFs had a greater proportion of postoperative complications in this randomized clinical trial design. Implants with a lower AMI, relative to bodyweight, were more likely to lead to major complications. CLINICAL SIGNIFICANCE: We recommend placing transcondylar screws from medial to lateral for canine HIFs to reduce the risk of postoperative complications. Relatively small diameter implants had an increased risk of major complications.

Delivery of chondroitinase by canine mucosal olfactory ensheathing cells alongside rehabilitation enhances recovery after spinal cord injury.

Spinal cord injury (SCI) can cause chronic paralysis and incontinence and remains a major worldwide healthcare burden, with no regenerative treatment clinically available. Intraspinal transplantation of olfactory ensheathing cells (OECs) and injection of chondroitinase ABC (chABC) are both promising therapies but limited and unpredictable responses are seen, particularly in canine clinical trials. Sustained delivery of chABC presents a challenge due to its thermal instability; we hypothesised that transplantation of canine olfactory mucosal OECs genetically modified ex vivo by lentiviral transduction to express chABC (cOEC-chABC) would provide novel delivery of chABC and synergistic therapy. Rats were randomly divided into cOEC-chABC, cOEC, or vehicle transplanted groups and received transplant immediately after dorsal column crush corticospinal tract (CST) injury. Rehabilitation for forepaw reaching and blinded behavioural testing was conducted for 8 weeks. We show that cOEC-chABC transplanted animals recover greater forepaw reaching accuracy on Whishaw testing and more normal gait than cOEC transplanted or vehicle control rats. Increased CST axon sprouting cranial to the injury and serotonergic fibres caudal to the injury suggest a mechanism for recovery. We therefore demonstrate that cOECs can deliver sufficient chABC to drive modest functional improvement, and that this genetically engineered cellular and molecular approach is a feasible combination therapy for SCI.

Influence of muscle-sparing lateral thoracotomy on postoperative pain and lameness: A randomized clinical trial.

OBJECTIVE: To assess and compare the magnitude of lameness and level of pain after muscle-sparing lateral thoracotomy (MSLT) and standard lateral thoracotomy (SLT) in dogs. STUDY DESIGN: Randomized, blinded, prospective clinical study. ANIMALS: Twenty-eight client-owned dogs. METHODS: The latissimus dorsi muscle was retracted in the MSLT group and was transected in the SLT group. Gait was analyzed with a force plate, and the peak vertical force symmetry index (SI) was calculated within 24 hours before surgery, 3 days postoperatively, and 8 to 12 weeks postoperatively. Symmetry index and pain scores as measured by the Glasgow Composite Measure Pain Scale - Short Form were assessed as primary outcome measures. RESULTS: The SI 3 days postoperatively was lower compared with the preoperative SI value in all dogs, consistent with lameness of the ipsilateral thoracic limb (P < .001). The absolute differences in preoperative and 3-day-postoperative SI provided evidence that this change was 3.1-fold greater after SLT compared with after MSLT (P = .009). Pain scores 1 day after surgery were lower after MSLT (1) compared with after SLT (2.5, P < .001). CONCLUSION: Lateral thoracotomies caused postoperative pain and ipsilateral forelimb lameness, and both were reduced by sparing the latissimus dorsi. CLINICAL SIGNIFICANCE: Sparing the latissimus dorsi should be considered to decrease immediate postoperative morbidity in dogs undergoing lateral thoracotomy.

Establishment of Normal Mechanical Tibial Joint Angles in Dachshunds.

OBJECTIVE: The aim of this study was to establish breed-standard mechanical tibial joint reference angles in the frontal plane in Dachshunds. STUDY DESIGN: Craniocaudal (n = 38) and mediolateral (n = 32) radiographs of normal tibiae from Dachshunds were retrospectively reviewed. The mechanical medial proximal, mechanical medial distal, mechanical caudal proximal and mechanical cranial distal tibial angles were measured on three occasions by two separate observers using previously established methodology. Interclass correlation coefficient was used to assess the reliability of radiographic measurements. RESULTS: The mean and standard deviation for mechanical medial proximal, mechanical medial distal, mechanical caudal proximal and mechanical cranial distal were 93.1 degrees ± 4.2, 97.5 degrees ± 3.9, 75.3 degrees ± 3.7 and 85.0 degrees ± 5.3 respectively. Intra-observer reliability was good to excellent for all measures, while inter-observer reliability was moderate to excellent in the frontal plane and poor to good in the sagittal plane. Dachshund-specific joint reference angles were similar to a range of previously reported non-chondrodystrophic breeds in the frontal plane but differed to most in the sagittal plane. CONCLUSION: Dachshund tibial joint reference angles are reported which can be used in surgical planning for correction of bilateral pes varus.

Three-Dimensional-Printed Patient-Specific Osteotomy Guides, Repositioning Guides and Titanium Plates for Acute Correction of Antebrachial Limb Deformities in Dogs.

OBJECTIVE: The aim of this study was to describe the use of patient-specific three-dimensional (3D)-printed osteotomy guides, repositioning guides and custom-printed titanium plates for acute correction of antebrachial limb deformities in four dogs. METHODS: Retrospective review of antebrachial limb deformities in small breed chondrodystrophic dogs that were surgically corrected using a closing wedge ostectomy of the radius at a predetermined site using patient-specific osteotomy guides. Reduction was achieved without the need for intraoperative measurements using patient-specific 3D-printed repositioning guides secured and manipulated using temporary Kirschner wire fixation. The ostectomy of the radius was stabilized with a patient-specific 3D-printed titanium plate. RESULTS: All limbs were corrected to within 3.5 degrees (standard deviation [SD]: 1 degree) and 7.5 degrees (SD: 3 degrees) of the pre-planned deformity correction in the frontal and sagittal planes, respectively. No complications were encountered. Owners completed a canine orthopaedic index survey at a median postoperative follow-up time of 19 months. Surgery eliminated the main presenting complaint of buckling over of the manus in all cases. CLINICAL SIGNIFICANCE: The 3D-printed osteotomy repositioning guides and titanium plates facilitated accurate acute correction of antebrachial deformities in this case series. The methodology described simplifies intraoperative surgical decision-making on limb position with good clinical outcomes seen in a small number of clinical cases.

Methods of olfactory ensheathing cell harvesting from the olfactory mucosa in dogs.

Olfactory ensheathing cells are thought to support regeneration and remyelination of damaged axons when transplanted into spinal cord injuries. Following transplantation, improved locomotion has been detected in many laboratory models and in dogs with naturally-occurring spinal cord injury; safety trials in humans have also been completed. For widespread clinical implementation, it will be necessary to derive large numbers of these cells from an accessible and, preferably, autologous, source making olfactory mucosa a good candidate. Here, we compared the yield of olfactory ensheathing cells from the olfactory mucosa using 3 different techniques: rhinotomy, frontal sinus keyhole approach and rhinoscopy. From canine clinical cases with spinal cord injury, 27 biopsies were obtained by rhinotomy, 7 by a keyhole approach and 1 with rhinoscopy. Biopsy via rhinoscopy was also tested in 13 cadavers and 7 living normal dogs. After 21 days of cell culture, the proportions and populations of p75-positive (presumed to be olfactory ensheathing) cells obtained by the keyhole approach and rhinoscopy were similar (~4.5 x 106 p75-positive cells; ~70% of the total cell population), but fewer were obtained by frontal sinus rhinotomy. Cerebrospinal fluid rhinorrhea was observed in one dog and emphysema in 3 dogs following rhinotomy. Blepharitis occurred in one dog after the keyhole approach. All three biopsy methods appear to be safe for harvesting a suitable number of olfactory ensheathing cells from the olfactory mucosa for transplantation within the spinal cord but each technique has specific advantages and drawbacks.

Nanoparticle-Based Imaging of Clinical Transplant Populations Encapsulated in Protective Polymer Matrices.

A recent clinical trial proves that autologous olfactory mucosal cell (OMC) transplantation improves locomotion in dogs with naturally occurring spinal injuries comparable to human lesions. However, not all dogs respond to the treatment, likely due to the transplantation procedures involving injections of cell suspensions that are associated with cell death, uneven cell distribution, and cell washout. Encapsulating cells in protective hydrogel matrices offers a tissue engineering solution to safely achieve 3D growth of viable transplant cells for implantation into injury sites, to improve regenerative outcomes. It is shown for the first time that canine OMCs (cOMCs) can be propagated with high viability in 3D collagen matrices. Further, a method to incorporate cOMCs pre-labeled with clinical-grade iron oxide nanoparticles into the constructs is described. Intraconstruct labeled cells are visualized using magnetic resonance imaging, offering substantial promise for in vivo tracking of cOMCs delivered in protective matrices.

Student Perceptions of Sectional CT/MRI Use in Teaching Veterinary Anatomy and the Correlation with Visual Spatial Ability: A Student Survey and Mental Rotations Test.

Diagnostic imaging technology is becoming more advanced and widely available to veterinary patients with the growing popularity of veterinary-specific computed tomography (CT) and magnetic resonance imaging (MRI). Veterinary students must, therefore, be familiar with these technologies and understand the importance of sound anatomic knowledge for interpretation of the resultant images. Anatomy teaching relies heavily on visual perception of structures and their function. In addition, visual spatial ability (VSA) positively correlates with anatomy test scores. We sought to assess the impact of including more diagnostic imaging, particularly CT/MRI, in the teaching of veterinary anatomy on the students' perceived level of usefulness and ease of understanding content. Finally, we investigated survey answers' relationship to the students' inherent baseline VSA, measured by a standard Mental Rotations Test. Students viewed diagnostic imaging as a useful inclusion that provided clear links to clinical relevance, thus improving the students' perceived benefits in its use. Use of CT and MRI images was not viewed as more beneficial, more relevant, or more useful than the use of radiographs. Furthermore, students felt that the usefulness of CT/MRI inclusion was mitigated by the lack of prior formal instruction on the basics of CT/MRI image generation and interpretation. To be of significantly greater use, addition of learning resources labeling relevant anatomy in tomographical images would improve utility of this novel teaching resource. The present study failed to find any correlation between student perceptions of diagnostic imaging in anatomy teaching and their VSA.

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury.

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients.

A fusion of minicircle DNA and nanoparticle delivery technologies facilitates therapeutic genetic engineering of autologous canine olfactory mucosal cells.

Olfactory ensheathing cells (OECs) promote axonal regeneration and improve locomotor function when transplanted into the injured spinal cord. A recent clinical trial demonstrated improved motor function in domestic dogs with spinal injury following autologous OEC transplantation. Their utility in canines offers promise for human translation, as dogs are comparable to humans in terms of clinical management and genetic/environmental variation. Moreover, the autologous, minimally invasive derivation of OECs makes them viable for human spinal injury investigation. Genetic engineering of transplant populations may augment their therapeutic potential, but relies heavily on viral methods which have several drawbacks for clinical translation. We present here the first proof that magnetic particles deployed with applied magnetic fields and advanced DNA minicircle vectors can safely bioengineer OECs to secrete a key neurotrophic factor, with an efficiency approaching that of viral vectors. We suggest that our alternative approach offers high translational potential for the delivery of augmented clinical cell therapies.

Effectiveness of manual bladder expression in paraplegic dogs.

OBJECTIVE To determine the effectiveness of manual bladder expression in paraplegic dogs by comparing urine volumes measured by use of intermittent catheterization and ultrasonography. ANIMALS 36 paraplegic dogs. PROCEDURES 93 measurements of bladder volume were collected for the 36 dogs. Residual urine volume was determined by use of intermittent urethral catheterization and estimated by use of ultrasonography. RESULTS Manual bladder expression voided a mean of 49% of urine from the bladder in this population of dogs. There was no correlation (R2, 0.06) between the effectiveness of manual bladder expression and body weight. Ultrasonographic estimation of bladder volume had good correlation (R2, 0.62) with bladder volume determined by use of intermittent bladder catheterization, but clinically unacceptable variation for predicting actual bladder volume (mean difference, 22 mL; 95% confidence interval, -96 to 139 mL). CONCLUSIONS AND CLINICAL RELEVANCE Manual bladder expression was ineffective at completely emptying urine from the bladder of paraplegic dogs, but the effectiveness of the procedure was not affected by body weight. Manual bladder expression would likely be a useful procedure to prevent increases in pressure within the bladder. Ultrasonographic estimation of bladder volume could be a useful predictor of actual bladder volume, but it was susceptible to wide variations among dogs, and results should therefore be interpreted with caution.

Canine olfactory ensheathing cells from the olfactory mucosa can be engineered to produce active chondroitinase ABC.

A multitude of factors must be overcome following spinal cord injury (SCI) in order to achieve clinical improvement in patients. It is thought that by combining promising therapies these diverse factors could be combatted with the aim of producing an overall improvement in function. Chondroitin sulphate proteoglycans (CSPGs) present in the glial scar that forms following SCI present a significant block to axon regeneration. Digestion of CSPGs by chondroitinase ABC (ChABC) leads to axon regeneration, neuronal plasticity and functional improvement in preclinical models of SCI. However, the enzyme activity decays at body temperature within 24-72h, limiting the translational potential of ChABC as a therapy. Olfactory ensheathing cells (OECs) have shown huge promise as a cell transplant therapy in SCI. Their beneficial effects have been demonstrated in multiple small animal SCI models as well as in naturally occurring SCI in canine patients. In the present study, we have genetically modified canine OECs from the mucosa to constitutively produce enzymatically active ChABC. We have developed a lentiviral vector that can deliver a mammalian modified version of the ChABC gene to mammalian cells, including OECs. Enzyme production was quantified using the Morgan-Elson assay that detects the breakdown products of CSPG digestion in cell supernatants. We confirmed our findings by immunolabelling cell supernatant samples using Western blotting. OECs normal cell function was unaffected by genetic modification as demonstrated by normal microscopic morphology and the presence of the low affinity neurotrophin receptor (p75(NGF)) following viral transduction. We have developed the means to allow production of active ChABC in combination with a promising cell transplant therapy for SCI repair.

Acute spinal cord injury: tetraplegia and paraplegia in small animals.

Spinal cord injury (SCI) is a common problem in animals for which definitive treatment is lacking, and information gained from its study has benefit for both companion animals and humans in developing new therapeutic approaches. This review provides an overview of the main concepts that are useful for clinicians in assessing companion animals with severe acute SCI. Current available advanced ancillary tests and those in development are reviewed. In addition, the current standard of care for companion animals following SCI and recent advances in the development of new therapies are presented, and new predictors of recovery discussed.