Niklas Bergknut

Degenerative lumbosacral stenosis in dogs

Degenerative lumbosacral stenosis (DLSS) is the most common disorder of the caudal lumbar spine in dogs. This article reviews the management of this disorder and highlights the most important new findings of the last decade. Dogs with DLSS are typically neuro-orthopedic patients and can be presented with varying clinical signs, of which the most consistent is lumbosacral pain. Due to the availability of advanced imaging techniques such as computed tomography and magnetic resonance imaging that allow visualization of intervertebral disc degeneration, cauda equina compression, and nerve root entrapment, tailor-made treatments can be adopted for the individual patient. Current therapies include conservative treatment, decompressive surgery, and fixation-fusion of the L7-S1 junction. New insight into the biomechanics and pathobiology of DLSS and developments in minimally invasive surgical techniques will influence treatment options in the near future.

The Dog as an Animal Model for Intervertebral Disc Degeneration

Study Design. Prospective observational and analytic study. Objective. To investigate whether spontaneous intervertebral disc degeneration (IVDD) occurring in both chondrodystrophic (CD) and nonchondrodystrophic dogs (NCD) can be used as a valid translational model for human IVDD research. Summary of Background Data. Different animal models are used in IVDD research, but in most of these models IVDD is induced manually or chemically rather than occurring spontaneously. Methods. A total of 184 intervertebral discs (IVDs) from 19 dogs of different breeds were used. The extent of IVDD was evaluated by macroscopic grading, histopathology, glycosaminoglycan content, and matrix metalloproteinase 2 activity. Canine data were compared with human IVD data acquired in this study or from the literature. Results. Gross pathology of IVDD in both dog types (CD and NCD) and humans showed many similarities, but the cartilaginous endplates were significantly thicker and the subchondral cortices significantly thinner in humans than in dogs. Notochordal cells were still present in the IVDs of adult NCD but were not seen in the CD breeds or in humans. Signs of degeneration were seen in young dogs of CD breeds (<1 year of age), whereas this was only seen in older dogs of NCD breeds (5–7 years of age). The relative glycosaminoglycan content and metalloproteinase 2 activity in canine IVDD were similar to those in humans: metalloproteinase 2 activity increased and glycosaminoglycan content decreased with increasing severity of IVDD. Conclusion. IVDD is similar in humans and dogs. Both CD and NCD breeds may therefore serve as models of spontaneous IVDD for human research. However, as with all animal models, it is important to recognize interspecies differences and, indeed, the intraspecies differences between CD and NCD breeds (early vs. late onset of IVDD, respectively) to develop an optimal canine model of human IVDD.

Intervertebral disc degeneration in the dog. Part 2: Chondrodystrophic and non-chondrodystrophic breeds

Dogs can be grouped into two distinct types of breed based on the predisposition to chondrodystrophy, namely, non-chondrodystrophic (NCD) and chondrodystrophic (CD). In addition to a different process of endochondral ossification, NCD and CD breeds have different characteristics of intravertebral disc (IVD) degeneration and IVD degenerative diseases. The anatomy, physiology, histopathology, and biochemical and biomechanical characteristics of the healthy and degenerated IVD are discussed in the first part of this two-part review. This second part describes the similarities and differences in the histopathological and biochemical characteristics of IVD degeneration in CD and NCD canine breeds and discusses relevant aetiological factors of IVD degeneration.

Intervertebral disc degeneration in the dog. Part 1: Anatomy and physiology of the intervertebral disc and characteristics of intervertebral disc degeneration

Intervertebral disc (IVD) degeneration is common in dogs and can give rise to a number of diseases, such as IVD herniation, cervical spondylomyelopathy, and degenerative lumbosacral stenosis. Although there have been many reports and reviews on the clinical aspects of canine IVD disease, few reports have discussed and reviewed the process of IVD degeneration. In this first part of a two-part review, the anatomy, physiology, histopathology, and biochemical and biomechanical characteristics of the healthy and degenerated IVD are described. In Part 2, the aspects of IVD degeneration in chondrodystrophic and non-chondrodystrophic dog breeds are discussed in depth.

Incidence of intervertebral disk degeneration–related diseases and associated mortality rates in dogs

OBJECTIVE To determine the incidence and distribution of intervertebral disk (IVD) degeneration-related diseases in a large population of dogs of various breeds, ages, and sexes and to determine mortality rates among dogs with these diseases. DESIGN Epidemiological study. SAMPLE Insurance data for dogs with veterinary health-care and life insurance coverage (n = 665,249 and 552,120, respectively). PROCEDURES Insurance claim records of 1 company in Sweden were searched to identify dogs with IVD degeneration-related diseases; incidence and mortality rates were determined for affected dogs < 12 years old and < 10 years old, respectively. Only the first paid IVD degeneration-related claim for a dog was included in incidence rate calculations. RESULTS The incidence rate of IVD degeneration-related diseases was 27.8 (95% confidence interval [CI], 27.2 to 28.4) occurrences/10,000 dog-years at risk (DYAR), indicating that approximately 0.3% of dogs/y in this population were affected. Miniature Dachshund was the most highly represented breed, followed by Standard Dachshund and Doberman Pinscher (237.1 [95% CI, 212.9 to 261.4], 141.5 [95% CI, 135.5 to 147.4], and 88.6 [95% CI, 72.1 to 105.2] occurrences/10,000 DYAR, respectively). The incidence rate of IVD degeneration-related disease was greater in male than in female dogs and increased with age. Overall mortality rate attributed to IVD degeneration-related diseases was 9.4 (95% CI, 8.9 to 9.8) deaths/10,000 DYAR and was greater in males than in females. CONCLUSIONS AND CLINICAL RELEVANCE Differences in incidence rates among various breeds suggested a genetic involvement. Knowledge of the distribution of IVD degeneration-related diseases among dogs of various breeds and ages may facilitate early diagnosis and preemptive treatments in patients at risk for developing these diseases.

Evaluation of intervertebral disk degeneration in chondrodystrophic and nonchondrodystrophic dogs by use of Pfirrmann grading of images obtained with low-field magnetic resonance imaging

OBJECTIVE To assess whether the Pfirrmann system for grading lumbar intervertebral disk (IVD) degeneration in humans can also be used in dogs. ANIMALS 202 dogs. PROCEDURES Magnetic resonance imaging was used to obtain images of vertebral segments from dogs, which were reviewed separately by 3 observers who graded the extent of degeneration in each visible IVD by use of the Pfirrmann classification system used for grading lumbar IVD degeneration in humans. Grading was validated against 2 factors associated with the extent of disk degeneration: type of dog (chondrodystrophic or nonchondrodystrophic breeds) and age. RESULTS Interobserver and intraobserver agreement for Pfirrmann grading of IVD degeneration were good (κ scores, 0.81 to 0.93). An increase in the extent of disk degeneration was positively correlated with increases in age and with chondrodystrophic breed. CONCLUSIONS AND CLINICAL RELEVANCE The Pfirrmann system was reliably used to grade IVD degeneration in dogs of various breeds and ages. An increase in the extent of IVD degeneration was positively correlated with increases in age and with chondrodystrophic-type dogs.

Intervertebral disc disease in dogs – Part 2: Comparison of clinical, magnetic resonance imaging, and histological findings in 74 surgically treated dogs

The relationship between intervertebral disc (IVD) disease and IVD degeneration remains unclear. The aim of the present study was to compare the clinical severity of IVD herniation (IVDH), determined with a neurological grading system, with findings of magnetic resonance imaging (MRI) and histology using grading systems for IVD degeneration in chondrodystrophic (CD; n=37) and non-chondrodystrophic (NCD; n=37) dogs. This study is the second part of a two-part investigation, where the first part involved the development and validation of a histological grading scheme for classification of canine IVD degeneration. IVD degeneration graded on MRI correlated significantly with IVD degeneration graded on histology, but not with pre-operative clinical signs. Hansen type 1 hernias were more common in the cervical and thoracolumbar segments and Hansen type 2 hernias were more common in the lumbosacral segment. Type 1 hernias occurred more often in CD dogs than in NCD dogs, and CD dogs were clinically more severely affected than NCD dogs. The grade of IVD degeneration on MRI was higher in CD dogs than in NCD dogs, but there was no difference between dogs with type 1 and type 2 hernias. No significant differences in histological grade were found between CD and NCD dogs or between type 1 and type 2 hernias. It was possible to conclude that IVD degeneration did not correlate with the neurological severity of IVDH. The extent of degeneration identified on MRI correlated with degeneration seen histologically. Although the MRI grading system reflected the severity of IVD degenerative changes as confirmed by histopathology, it appeared less useful in predicting the clinical implications.

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

IntroductionEarly 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.MethodsDual 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.ResultsEarly 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.ConclusionsEarly 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.

Reliability of macroscopic grading of intervertebral disk degeneration in dogs by use of the Thompson system and comparison with low-field magnetic resonance imaging findings

OBJECTIVE To evaluate the reliability of the Thompson system for use in grading the gross pathological changes of intervertebral disk (IVD) degeneration in dogs and to investigate the agreement between gross pathological findings and low-field (0.2-T) magnetic resonance imaging (MRI) findings. SAMPLE Vertebral columns from cadavers of 19 dogs of various ages, breeds, and origins. PROCEDURES 182 intervertebral segments were collected from 19 canine cadavers. Sagittal T2-weighted MRI of the T11 through S1 portion of the vertebral column was performed within 24 hours after the dogs were euthanized. The vertebral columns were subsequently divided in the midsagittal plane, and high-resolution photographs were obtained of each intervertebral segment (end plate-disk-end plate). The MRI images and photographs were graded separately in a blinded manner by 4 observers who used both Pfirrmann and Thompson grading criteria. RESULTS The interobserver agreement for Thompson scores ranged from 0.76 to 0.88, and the intraobserver agreement ranged from 0.88 to 0.94 (Cohen weighted κ analysis). Agreement between scores for the Pfirrmann and Thompson grading criteria was κ = 0.70. CONCLUSIONS AND CLINICAL RELEVANCE Grading of IVD degeneration in dogs by use of the Thompson system resulted in high interobserver and intraobserver agreement, and scores for the Thompson system had substantial agreement with low-field MRI findings graded by use of the Pfirrmann system. This suggested that low-field MRI can be used to diagnose IVD degeneration in dogs.

Inflammatory profiles in canine intervertebral disc degeneration

BackgroundIntervertebral disc (IVD) disease is a common spinal disorder in dogs and degeneration and inflammation are significant components of the pathological cascade. Only limited studies have studied the cytokine and chemokine profiles in IVD degeneration in dogs, and mainly focused on gene expression. A better understanding is needed in order to develop biological therapies that address both pain and degeneration in IVD disease. Therefore, in this study, we determined the levels of prostaglandin E2 (PGE2), cytokines, chemokines, and matrix components in IVDs from chondrodystrophic (CD) and non-chondrodystrophic (NCD) dogs with and without clinical signs of IVD disease, and correlated these to degeneration grade (according to Pfirrmann), or herniation type (according to Hansen). In addition, we investigated cyclooxygenase 2 (COX-2) expression and signs of inflammation in histological IVD samples of CD and NCD dogs.ResultsPGE2 levels were significantly higher in the nucleus pulposus (NP) of degenerated IVDs compared with non-degenerated IVDs, and in herniated IVDs from NCD dogs compared with non-herniated IVDs of NCD dogs. COX-2 expression in the NP and annulus fibrosus (AF), and proliferation of fibroblasts and numbers of macrophages in the AF significantly increased with increased degeneration grade. GAG content did not significantly change with degeneration grade or herniation type. Cytokines interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, immune protein (IP)-10, tumor necrosis factor (TNF)-α, and granulocyte macrophage colony-stimulating factor (GM-CSF) were not detectable in the samples. Chemokine (C-C) motif ligand (CCL)2 levels in the NP from extruded samples were significantly higher compared with the AF of these samples and the NP from protrusion samples.ConclusionsPGE2 levels and CCL2 levels in degenerated and herniated IVDs were significantly higher compared with non-degenerated and non-herniated IVDs. COX-2 expression in the NP and AF and reactive changes in the AF increased with advancing degeneration stages. Although macrophages invaded the AF as degeneration progressed, the production of inflammatory mediators seemed most pronounced in degenerated NP tissue. Future studies are needed to investigate if inhibition of PGE2 levels in degenerated IVDs provides effective analgesia and exerts a protective role in the process of IVD degeneration and the development of IVD disease.