Björn P. Meij

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.

Cross-sectional study of the prevalence and clinical features of osteoarthritis in 100 cats

To assess clinical signs and relevance of osteoarthritis (OA) in cats, the radiographic prevalence of OA in the appendicular skeleton of 100 client-owned cats (≥ 6 years old) was assessed. Possible associations between radiographic OA, clinical locomotor system examination, and owner-perceived behavioural changes were evaluated. OA was most prevalent in the shoulders, elbows, hips and tarsal joints with 61% of cats having OA in at least one joint and 48% in more than one joint. Overall, clinical examination of the larger peripheral joints had the highest sensitivity and specificity for radiographic OA. Regression analysis showed age to be related to OA (P = 0.002), as were decreased mobility and grooming (P = 0.008), although there was a correlation with age. Finally, increased inappropriate elimination was associated with OA (P = 0.046). It was concluded that the prevalence of OA in cats is strikingly high and increases with age. OA in cats seems to be associated with behavioural changes.

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.

The selector gene Pax7 dictates alternate pituitary cell fates through its pioneer action on chromatin remodeling

The anterior and intermediate lobes of the pituitary gland derive from the surface ectoderm. They provide a simple system to assess mechanisms of developmental identity established by tissue determinants. Each lobe contains a lineage expressing the hormone precursor pro-opiomelanocortin (POMC): the corticotropes and melanotropes. The T-box transcription factor Tpit controls terminal differentiation of both lineages. We now report on the unique role of Pax7 as a selector of intermediate lobe and melanotrope identity. Inactivation of the Pax7 gene results in loss of melanotrope gene expression and derepression of corticotrope genes. Pax7 acts by remodeling chromatin and allowing Tpit binding to a new subset of enhancers for activation of melanotrope-specific genes. Thus, the selector function of Pax7 is exerted through pioneer transcription factor activity. Genome-wide, the Pax7 pioneer activity is preferentially associated with composite binding sites that include paired and homeodomain motifs. Pax7 expression is conserved in human and dog melanotropes and defines two subtypes of pituitary adenomas causing Cushings disease. In summary, expression of Pax7 provides a unique tissue identity to the pituitary intermediate lobe that alters Tpit-driven differentiation through pioneer and classical transcription factor activities.

Progress in transsphenoidal hypophysectomy for treatment of pituitary-dependent hyperadrenocorticism in dogs and cats

Cushings disease or pituitary-dependent hyperadrenocorticism (PDH) is common in dogs and rare in cats. PDH is caused by a pituitary tumor producing adrenocorticotropin (ACTH). Pituitary imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is required to assess the size and location of the pituitary adenoma in relation to the surgical landmarks. In a specialized veterinary institution, microsurgical transsphenoidal hypophysectomy has proven to be a safe and effective treatment for dogs (n=84) and cats (n=7) with Cushings disease. Pituitary surgery requires a team approach and the neurosurgeon performing hypophysectomies must master a learning curve. The surgical results compared favorably with those for dogs with PDH treated medically with mitotane at the same institution. The recurrence rate after initially successful surgery increases with longer follow up-times. Pituitary function testing in 39 dogs with PDH treated with hypophysectomy revealed that, much more so than the other adenohypophyseal cell types, residual corticotropes present in the sella turcica after surgery are functional. Such normal ACTH secreting cells may maintain normocorticism whereas residual adenoma cells may lead to mild recurrence after relatively long periods of remission. Microsurgical transsphenoidal hypophysectomy is an effective treatment for canine and feline Cushings disease.

Prognostic factors for outcome after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism

OBJECT The aim of this study was to determine prognostic factors for outcome after transsphenoidal hypophysectomy in dogs with pituitary-dependent hyperadrenocorticism (PDH). METHODS One veterinary neurosurgeon performed transsphenoidal hypophysectomies in 181 dogs with PDH over a 12-year period. Survival analysis was performed with the Kaplan-Meier method. Prognostic factors were analyzed with the univariate Cox proportional hazard analysis followed by stepwise multivariate analysis. The log-rank test was used to assess disease-free fractions in three groups categorized according to early postoperative urinary corticoid/creatinine (C/C) ratios. RESULTS Multivariate analysis revealed that old age, large pituitary size, and high preoperative concentrations of plasma adrenocorticotropic hormone were associated with an increased risk of PDH-related death. In addition, large pituitary size, thick sphenoid bone, high C/C ratio, and high concentration of plasma alpha-melanocyte-stimulating hormone (alpha-MSH) before surgery were associated with an increased risk of disease recurrence in the dogs that went into remission after hypophysectomy. Disease-free fractions were significantly higher in dogs with postoperative urinary C/C ratios in the lower normal range (< 5 x 10(-6)) than in dogs with postoperative C/C ratios in the upper normal range (5-10 x 10(-6)). CONCLUSIONS The results of this study indicate that pituitary size, sphenoid bone thickness, plasma alpha-MSH concentration, and preoperative level of urinary cortisol excretion are predictors of long-term remission after transsphenoidal hypophysectomy for PDH in dogs. Urinary C/C ratios measured 6 to 10 weeks after surgery can be used as a guide for predicting the risk of tumor recurrence.

Imaging of the pituitary gland in dogs with pituitary-dependent hyperadrenocorticism.

Detailed imaging of the pituitary gland is a prerequisite for a successful outcome of transsphenoidal hypophysectomy in dogs because it allows for accurate preoperative localization and assessment of the size of the pituitary gland. Cisternography allows assessment of even small increases in the height of the pituitary gland, but the magnitude of suprasellar expansion of pituitary tumors cannot be assessed with this technique. Large pituitary tumors with suprasellar expansion can readily be detected with conventional contrast-enhanced computed tomography (CT), while pituitary microadenomas can be localized with dynamic contrast-enhanced CT. Dynamic examination of the entire pituitary may be possible with spiral dynamic CT. Magnetic resonance imaging (MRI) of the canine pituitary gland provides a clear differentiation between the pituitary gland and the surrounding structures, but it remains to be investigated whether in dogs MRI can replace dynamic CT for the detection of microadenomas and whether it allows accurate localization of the pituitary gland relative to the surgical landmarks.

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.