Invasive nasal histiocytic sarcoma as a cause of temporal lobe epilepsy in a cat

Case summary A 10-year-old neutered female domestic shorthair cat was presented with an acute onset of neurological signs suggestive of a right-sided forebrain lesion, temporal lobe epilepsy and generalised seizure activity. MRI of the head revealed an expansile soft tissue mass in the caudal nasal passages (both sides but predominantly right-sided) involving the ethmoid bone and extending through the cribriform plate into the cranial vault affecting predominantly the right frontal lobe and temporal lobe. Histopathological examination of the tumour revealed a histiocytic sarcoma. Relevance and novel information This is the first report of a cat with clinical signs of temporal lobe epilepsy due to an invasive, histiocytic sarcoma. Histiocytic sarcoma, although rare, should be included in the list of differential diagnoses for soft tissue masses extending through the cribriform plate. Other differential diagnoses are primary nasal neoplasia (eg, adenocarcinoma, squamous cell carcinoma, chondrosarcoma and other types of sarcomas), lymphoma and olfactory neuroblastoma. Temporal lobe epilepsy in cats can be the consequence of primary pathology of temporal lobe structures, or it can be a consequence of pathology with an effect on these structures (eg, mass effect or disruption of interconnecting neuronal pathways)

Challenges of transsphenoidal pituitary surgery in severe brachycephalic dogs

INTRODUCTION: Transsphenoidal hypophysectomy is the standard surgical technique for the excision of pituitary neoplasms. Anatomy may be more obscured in brachycephalic skull types due to the crowding of soft tissue and osseous structures. We describe the unique challenges to approach the sphenoid bone and localize the correct burr hole site in severe brachycephalic dogs. MATERIALS AND METHODS: A single institution retrospective case series of brachycephalic dogs with pituitary-dependent hypercortisolism (PDH). Preoperative computed tomography enabled 3D-, and cross-sectional reconstruction to plan and dry-practice the position of the ideal burr hole in relation to the sella turcica, pterygoid hamular processes, and hard palate. Rostral burring of the caudal hard palate obscuring the direct sphenoid approach necessitated adaptations to the original transsphenoidal hypophysectomy procedure. Postoperative outcomes and complications with respect to those seen in mesocephalic dogs are described. RESULTS: Ten brachycephalic dogs including French Bulldogs ( n = 9) and a single Dogue de Bordeaux were included. All dogs were diagnosed with PDH and had preoperative advanced imaging performed on the skull. All but one dog had an enlarged pituitary gland, with a median pituitary/brain value of 0.5 (range 0.21-0.9). A total of 11 transsphenoidal hypophysectomy procedures were performed in these 10 dogs. Rostral extension of the soft palate incision into the hard palate was performed to access the burr hole site on the sphenoid bone. Major complications included aspiration pneumonia ( n = 1), severe gastroesophageal reflux ( n = 1), and central nervous signs (=1). All dogs survived until discharge, with a median time to follow-up of 618 days (range 79-1,669 days). Seven dogs experienced long-term remission of PDH. CONCLUSION: Brachycephalic dogs undergoing transsphenoid al hypophysectomy benefit from meticulous presurgical planning and extension of the approach into the caudal hard palate. Advanced surgical skills can render a good outcome in a technically challenging environment

Challenges of transsphenoidal pituitary surgery in severe brachycephalic dogs

IntroductionTranssphenoidal hypophysectomy is the standard surgical technique for the excision of pituitary neoplasms. Anatomy may be more obscured in brachycephalic skull types due to the crowding of soft tissue and osseous structures. We describe the unique challenges to approach the sphenoid bone and localize the correct burr hole site in severe brachycephalic dogs.Materials and methodsA single institution retrospective case series of brachycephalic dogs with pituitary-dependent hypercortisolism (PDH). Preoperative computed tomography enabled 3D-, and cross-sectional reconstruction to plan and dry-practice the position of the ideal burr hole in relation to the sella turcica, pterygoid hamular processes, and hard palate. Rostral burring of the caudal hard palate obscuring the direct sphenoid approach necessitated adaptations to the original transsphenoidal hypophysectomy procedure. Postoperative outcomes and complications with respect to those seen in mesocephalic dogs are described.ResultsTen brachycephalic dogs including French Bulldogs (n = 9) and a single Dogue de Bordeaux were included. All dogs were diagnosed with PDH and had preoperative advanced imaging performed on the skull. All but one dog had an enlarged pituitary gland, with a median pituitary/brain value of 0.5 (range 0.21–0.9). A total of 11 transsphenoidal hypophysectomy procedures were performed in these 10 dogs. Rostral extension of the soft palate incision into the hard palate was performed to access the burr hole site on the sphenoid bone. Major complications included aspiration pneumonia (n = 1), severe gastroesophageal reflux (n = 1), and central nervous signs (=1). All dogs survived until discharge, with a median time to follow-up of 618 days (range 79–1,669 days). Seven dogs experienced long-term remission of PDH.ConclusionBrachycephalic dogs undergoing transsphenoid al hypophysectomy benefit from meticulous presurgical planning and extension of the approach into the caudal hard palate. Advanced surgical skills can render a good outcome in a technically challenging environment

Biomechanical assessment of the effects of decompressive surgery in non-chondrodystrophic and chondrodystrophic canine multisegmented lumbar spines

Purpose Dogs are often used as an animal model in spinal research, but consideration should be given to the breed used as chondrodystrophic (CD) dog breeds always develop IVD degeneration at an early age, whereas nonchondrodystrophic (NCD) dog breeds may develop IVD degeneration, but only later in life. The aim of this study was to provide a mechanical characterization of the NCD [non-degenerated intervertebral discs (IVDs), rich in notochordal cells] and CD (degenerated IVDs, rich in chondrocyte-like cells) canine spine before and after decompressive surgery (nucleotomy). Methods The biomechanical properties of multisegmented lumbar spine specimens (T13-L5 and L5-Cd1) from 2-year-old NCD dogs (healthy) and CD dogs (early degeneration) were investigated in flexion/extension (FE), lateral bending (LB), and axial rotation (AR), in the native state and after nucleotomy of L2-L3 or dorsal laminectomy and nucleotomy of L7-S1. The range of motion (ROM), neutral zone (NZ), and NZ stiffness (NZS) of L1-L2, L2- L3, L6-L7, and L7-S1 were calculated. Results In native spines in both dog groups, the greatest mobility in FE was found at L7-S1, and the greatest mobility in LB at L2-L3. Surgery significantly increased the ROM and NZ, and significantly decreased the NZS in FE, LB, and AR in both breed groups. However, surgery at L2-L3 resulted in a significantly larger increase in NZ and decrease in NZS in the CD spines compared with the NCD spines, whereas surgery at L7-S1 induced a significantly larger increase in ROM and decrease in NZS in the NCD spines compared with the CD spines. Conclusions Spinal biomechanics significantly differ between NCD and CD dogs and researchers should consider this aspect when using the dog as a model for spinal research. © Springer-Verlag 2012

Mechanical characterization of a novel biomimetic artificial disc for the cervical spine

A novel biomimetic artificial intervertebral disc (bioAID) replacement implant has been developed containing a swelling hydrogel representing the nucleus pulposus, a tensile strong fiber jacket as annulus fibrosus and titanium endplates with pins to primarily secure the device between the vertebral bodies. In this study, the design safety of this novel implant was evaluated based on several biomechanical parameters, namely compressive strength, shear-compressive strength, risk of subsidence and device expulsion as well as identifying the diurnal creep-recovery characteristics of the device. The bioAID remained intact up to 1 kN under static axial compression and only 0.4 mm of translation was observed under a compressive shear load of 20 N. No subsidence was observed after 0.5 million cycles of sinusoidal compressive loading between 50 and 225 N. After applying 400 N in antero-posterior direction under 100 N axial compressive preload, approximately 2 mm displacement was found, being within the range of displacements reported for other commercially available cervical disc replacement devices. The diurnal creep recovery behavior of the bioAID closely resembled what has been reported for natural intervertebral discs in literature. Overall, these results indicate that the current design can withstand (shear-compression loads and is able to remain fixed in a mechanical design resembling the vertebral bodies. Moreover, it is one of the first implants that can closely mimic the poroelastic and viscoelastic behavior of natural disc under a diurnal loading pattern

Gene expression profiling of early intervertebral disc degeneration reveals a down-regulation of canonical Wnt signaling and caveolin-1 expression: implications for development of regenerative strategies

INTRODUCTION: Early degeneration of the intervertebral disc (IVD) involves a change in cellular differentiation from notochordal cells (NCs) in the nucleus pulposus (NP) to chondrocyte-like cells (CLCs). The purpose of this study was to investigate the gene expression profiles involved in this process using NP tissue from non-chondrodystrophic and chondrodystrophic dogs, a species with naturally occurring IVD degeneration. METHODS: Dual channel DNA microarrays were used to compare 1) healthy NP tissue containing only NCs (NC-rich), 2) NP tissue with a mixed population of NCs and CLCs (Mixed), and 3) NP tissue containing solely CLCs (CLC-rich) in both non-chondrodystrophic and chondrodystrophic dogs. Based on previous reports and the findings of the microarray analyses, canonical Wnt signaling was further evaluated using qPCR of relevant Wnt target genes. We hypothesized that caveolin-1, a regulator of Wnt signaling that showed significant changes in gene expression in the microarray analyses, played a significant role in early IVD degeneration. Caveolin-1 expression was investigated in IVD tissue sections and in cultured NCs. To investigate the significance of Caveolin-1 in IVD health and degeneration, the NP of 3-month-old Caveolin-1 knock-out mice was histopathologically evaluated and compared with the NP of wild-type mice of the same age. RESULTS: Early IVD degeneration involved significant changes in numerous pathways, including Wnt/β-catenin signaling. With regard to Wnt/β-catenin signaling, axin2 gene expression was significantly higher in chondrodystrophic dogs compared with non-chondrodystrophic dogs. IVD degeneration involved significant down-regulation of axin2 gene expression. IVD degeneration involved significant down-regulation in Caveolin-1 gene and protein expression. NCs showed abundant caveolin-1 expression in vivo and in vitro, whereas CLCs did not. The NP of wild-type mice was rich in viable NCs, whereas the NP of Caveolin-1 knock-out mice contained chondroid-like matrix with mainly apoptotic, small, rounded cells. CONCLUSIONS: Early IVD degeneration involves down-regulation of canonical Wnt signaling and Caveolin-1 expression, which appears to be essential to the physiology and preservation of NCs. Therefore, Caveolin-1 may be regarded an exciting target for developing strategies for IVD regeneration

Biomechanical evaluation of a novel biomimetic artificial intervertebral disc in canine cervical cadaveric spines

Background Context Cervical disc replacement (CDR) aims to restore motion of the treated level to reduce the risk of adjacent segment disease (ASD) compared with spinal fusion. However, first-generation articulating devices are unable to mimic the complex deformation kinematics of a natural disc. Thus, a biomimetic artificial intervertebral CDR (bioAID), containing a hydroxyethylmethacrylate (HEMA)—sodium methacrylate (NaMA) hydrogel core representing the nucleus pulposus, an ultra-high-molecular-weight-polyethylene fiber jacket as annulus fibrosus, and titanium endplates with pins for primary mechanical fixation, was developed. Purpose To assess the initial biomechanical effect of the bioAID on the kinematic behavior of the canine spine, an ex vivo biomechanical study in 6-degrees-of-freedom was performed. Study Design A canine cadaveric biomechanical study. Methods Six cadaveric canine specimens (C3-C6) were tested in flexion-extension (FE), lateral bending (LB) axial rotation (AR) using a spine tester in three conditions: intact, after C4-C5 disc replacement with bioAID, and after C4-C5 interbody fusion. A hybrid protocol was used where first the intact spines were subjected to a pure moment of ±1 Nm, whereafter the treated spines were subjected to the full range of motion (ROM) of the intact condition. 3D segmental motions at all levels were measured while recording the reaction torsion. Biomechanical parameters studied included ROM, neutral zone (NZ), and intradiscal pressure (IDP) at the adjacent cranial level (C3-C4). Results The bioAID retained the sigmoid shape of the moment-rotation curves with a NZ similar to the intact condition in LB and FE. Additionally, the normalized ROMs at the bioAID-treated level were statistically equivalent to intact during FE and AR while slightly decreased in LB. At the two adjacent levels, ROMs showed similar values for the intact compared to the bioAID for FE and AR and an increase in LB. In contrast, levels adjacent to the fused segment showed an increased motion in FE and LB as compensation for the loss of motion at the treated level. The IDP at the adjacent C3-C4 level after implantation of bioAID was close to intact values. After fusion, increased IDP was found compared with intact but did not reach statistical significance. Conclusion This study indicates that the bioAID can mimic the kinematic behavior of the replaced intervertebral disc and preserves that for the adjacent levels better than fusion. As a result, CDR using the novel bioAID is a promising alternative treatment for replacing severely degenerated intervertebral discs

Spinal fixation after laminectomy in pigs prevents postoperative spinal cord injury

BACKGROUND: A safe, effective, and ethically sound animal model is essential for preclinical research to investigate spinal medical devices. We report the initial failure of a porcine spinal survival model and a potential solution by fixating the spine. METHODS: Eleven female Dutch Landrace pigs underwent a spinal lumbar interlaminar decompression with durotomy and were randomized for implantation of a medical device or control group. Magnetic resonance imaging (MRI) was performed before termination. RESULTS: Neurological deficits were observed in 6 out of the first 8 animals. Three of these animals were terminated prematurely because they reached the predefined humane endpoint. Spinal cord compression and myelopathy was observed on postoperative MRI imaging. We hypothesized postoperative spinal instability with epidural hematoma, inherent to the biology of the model, and subsequent spinal cord injury as a potential cause. In the subsequent 3 animals, we fixated the spine with Lubra plates. All these animals recovered without neurological deficits. The extent of spinal cord compression on MRI was variable across animals and did not seem to correspond well with neurological outcome. CONCLUSION: This study shows that in a porcine in vivo model of interlaminar decompression and durotomy, fixation of the spine after lumbar interlaminar decompression is feasible and may improve neurological outcomes. Additional research is necessary to evaluate this hypothesis

Intradiscal injection of human recombinant BMP-4 does not reverse intervertebral disc degeneration induced by nuclectomy in sheep

Background: Intervertebral disc (IVD) degeneration is suggested as a major cause of chronic low back pain (LBP). Intradiscal delivery of growth factors has been proposed as a promising strategy for IVD repair and regeneration. Previously, BMP-4 was shown to be more potent in promoting extracellular matrix (ECM) production than other BMPs and TGF-β in human nucleus pulposus (NP) cells, suggesting its applicability for disc regeneration. Methods: The effects of BMP-4 on ECM deposition and cell proliferation were assessed in sheep NP and annulus fibrosus (AF) cells in a pellet culture model. Further, a nuclectomy induced sheep lumbar IVD degeneration model was used to evaluate the safety and effects of intradiscal BMP-4 injection on IVD regeneration. Outcomes were assessed by magnetic resonance imaging, micro-computed tomography, histological and biochemical measurements. Results: In vitro, BMP-4 significantly increased the production of proteoglycan and deposition of collagen type II and proliferation of NP and AF cells. Collagen type I deposition was not affected in NP cells, while in AF cells it was high at low BMP-4 concentrations, and decreased with increasing concentration of BMP-4. Intradiscal injection of BMP-4 induced extradiscal new bone formation and Schmorl's node-like changes in vivo. No regeneration in the NP nor AF was observed. Conclusion: Our study demonstrated that although BMP-4 showed promising regenerative effects in vitro, similar effects were not observed in a large IVD degeneration animal model. The Translational Potential of This Article: The contradictory results of using BMP-4 on IVD regeneration between in vitro and in vivo demonstrate that direct BMP-4 injection for disc degeneration-associated human chronic low back pain should not be undertaken. In addition, our results may also shed light on the mechanisms behind pathological endplate changes in human patients as a possible target for therapy

Acetabular rim extension using a personalized titanium implant for treatment of hip dysplasia in dogs: short-term results

Hip dysplasia (HD) is a common orthopedic problem in young dogs. To decrease the laxity of the hip joint related to HD, the surgical treatments are recommended to increase femoral head coverage. ACEtabular rim eXtension (ACE-X) using a personalized 3-dimensional printed titanium shelf implant is a new surgical treatment to increase femoral head coverage and decrease laxity of the dysplastic hip joint, however, the efficacy is less know. Client-owned dogs older than 6 months with clinical signs of coxofemoral joint subluxation and radiographic evidence of HD with no or mild osteoarthritis (OA) were included. The Norberg angle (NA), linear percentage of femoral head overlap (LFO), and percentage of femoral head coverage (PC) were investigated radiographically and with computed tomography (CT) before and after surgery. OA was graded (scores 0–3) according to the maximum osteophyte size measured on CT. In addition, joint laxity (Ortolani) test results, gait analysis, and the Helsinki chronic pain index (HCPI) questionnaire were obtained at preoperative, immediately postoperative and at 1.5- and 3-month evaluations. Acetabular rim extension was performed in 61 hips of 34 dogs; NA, LFO, and PC were significantly higher immediately postoperatively and at the 1.5- and 3-month follow-up examinations compared with preoperative values (p < 0.05). Osteophyte size gradually increased over time (p < 0.05). The OA score significantly increased between preoperatively and directly postoperatively, and between preoperatively and at 3-month follow-up (p < 0.05). The laxity test normalized in 59 out of 61 hips after surgery, and the HCPI questionnaire showed that the pain score decreased significantly at 1.5 and 3 months, postoperatively. The force plate showed no significant improvement during the 3 months follow-up. Although pain reduction by the implant was unclear in short-term results, a personalized shelf implant significantly increased femoral head coverage and eliminated subluxation of the dysplastic hip joint. Further studies are required to study the long-term efficacy of gait, chronic pain, and progression of osteoarthritis