Nele Ondreka

Volume reduction of the jugular foramina in Cavalier King Charles Spaniels with syringomyelia

BackgroundUnderstanding the pathogenesis of the chiari-like malformation in the Cavalier King Charles Spaniel (CKCS) is incomplete, and current hypotheses do not fully explain the development of syringomyelia (SM) in the spinal cords of affected dogs. This study investigates an unconventional pathogenetic theory for the development of cerebrospinal fluid (CSF) pressure waves in the subarachnoid space in CKCS with SM, by analogy with human diseases. In children with achondroplasia the shortening of the skull base can lead to a narrowing of the jugular foramina (JF) between the cranial base synchondroses. This in turn has been reported to cause a congestion of the major venous outflow tracts of the skull and consequently to an increase in the intracranial pressure (ICP). Amongst brachycephalic dog breeds the CKCS has been identified as having an extremely short and wide braincase. A stenosis of the JF and a consequential vascular compromise in this opening could contribute to venous hypertension, raising ICP and causing CSF jets in the spinal subarachnoid space of the CKCS. In this study, JF volumes in CKCSs with and without SM were compared to assess a possible role of this pathologic mechanism in the development of SM in this breed.ResultsComputed tomography (CT) scans of 40 CKCSs > 4 years of age were used to create three-dimensional (3D) models of the skull and the JF. Weight matched groups (7–10 kg) of 20 CKCSs with SM and 20 CKCSs without SM were compared. CKCSs without SM presented significantly larger JF -volumes (median left JF: 0.0633 cm3; median right JF: 0.0703 cm3; p < 0.0001) when compared with CKCSs with SM (median left JF: 0.0382 cm3; median right JF: 0.0434 cm3; p < 0.0001). There was no significant difference between the left and right JF within each group. Bland-Altman analysis revealed excellent reproducibility of all volume measurements.ConclusionA stenosis of the JF and consecutive venous congestion may explain the aetiology of CSF pressure waves in the subarachnoid space, independent of cerebellar herniation, as an additional pathogenetic factor for the development of SM in this breed.

Comparison of closure times for cranial base synchondroses in mesaticephalic, brachycephalic, and Cavalier King Charles Spaniel dogs.

Premature closure of cranial base synchondroses has been proposed as the mechanism for brachycephaly in dogs and caudal occipital malformation syndrome (COMS) in Cavalier King Charles Spaniels. The purpose of this retrospective study was to compare times of closure for cranial base synchondroses in mesaticephalic, brachycephalic, and Cavalier King Charles Spaniel dogs. Cranial magnetic resonance imaging studies were retrieved for client-owned dogs less than 18 months of age. Breed, age, skull conformation, and the open or closed state of cranial base synchondroses were independently recorded by two observers. For dogs with a unanimous observer agreement, regression analysis was used to test effects of age and gender on the open or closed status of synchondroses and differences between groups. A total of 174 dogs were included in MRI interpretations and 165 dogs were included in the regression analysis. Statistically significant differences in closure time of the spheno-occipital synchondrosis were identified between brachycephalic and mesaticephalic dogs (P = 0.016), Cavalier King Charles Spaniels and mesaticephalic dogs (P < 0.0001), and Cavalier King Charles Spaniels and brachycephalic dogs (P = 0.014). Findings from the current study supported the theory that morphological changes leading to the skull phenotype of the Cavalier King Charles Spaniels could be due to an earlier closure of the spheno-occipital synchondrosis.

Comparison of the endocranial- and brain volumes in brachycephalic dogs, mesaticephalic dogs and Cavalier King Charles spaniels in relation to their body weight

BackgroundA number of studies have attempted to quantify the relative volumes of the endocranial volume and brain parenchyma in association with the pathogenesis of the Chiari-like malformation (CLM) in the Cavalier King Charles spaniel (CKCS). In our study we examine the influence of allometric scaling of the brain and cranial cavity volume on morphological parameters in different dog breeds. MRI scans of 110 dogs (35 mesaticephalic dogs, 35 brachycephalic dogs, 20 CKCSs with SM, and 20 CKCSs without SM) have been used to create 3-dimensional volumetric models of skull and brain parts. Volumes were related to body weight calculating the adjusted means for different breeds.ResultsThere was a strong global dependency of all volumes to body weight (P < 0.0001). The adjusted means of the absolute and relative volumes of brain parenchyma and cranial compartments are not significantly larger in CKCSs in comparison to brachycephalic and mesaticephalic dogs. A difference in absolute or relative volumes between CKCSs with and without SM after relating these values to body weight could not be identified. The relative volume of the hindbrain parenchyma (caudal fossa parenchyma percentage) was larger in brachycephalic dogs than in CKCSs, without causing herniation or SM.ConclusionAn influence of body weight exist in dogs, which can be sufficiently large to render conclusions on the difference in volumes of the brain and skull unsafe unless some account of the body weight is taken in the analysis. The results of this study challenge the role of overcrowding for the development of SM in dogs.

Magnetic resonance imaging signs of high intraventricular pressure - comparison of findings in dogs with clinically relevant internal hydrocephalus and asymptomatic dogs with ventriculomegaly

BackgroundMagnetic resonance imaging (MRI) findings of canine brains with enlarged ventricles in asymptomatic dogs were compared to those in dogs with clinically relevant internal hydrocephalus, in order to determine the imaging findings indicative of a relevant increase in intraventricular pressure. Discrimination between clinically relevant hydrocephalus and ventriculomegaly based on MRI findings has not been established yet and is anything but trivial because of the wide variation in ventricular size in different dog breeds and individuals. The MRI scans of the brains of 67 dogs of various breeds, skull conformation and weight were reviewed retrospectively. Based on clinical and imaging findings, the dogs were divided into three groups: a normal group (n = 20), a group with clinically silent ventriculomegaly (n = 25) and a group with severe clinically relevant internal hydrocephalus (n = 22). In addition to the ventricle/brain-index, a number of potential subjective signs of increased intraventricular pressure were recorded and compared between the groups.ResultsThe ventricle/brain-index was significantly higher in dogs with relevant hydrocephalus (p < 0.001) and a threshold value of 0.6 was specified as a discriminator between internal hydrocephalus and ventriculomegaly. Other MR imaging findings associated with clinically relevant hydrocephalus were an elevation of the corpus callosum (p < 0.01), dorsoventral flattening of the interthalamic adhesion (p < 0.0001), periventricular edema (p < 0.0001), dilation of the olfactory recesses (p < 0.0001), thinning of the cortical sulci (p < 0.0001) and/or the subarachnoid space (p < 0.0027) and disruption of the internal capsule adjacent to the caudate nucleus (p < 0.0001).ConclusionA combination of the abovementioned criteria may support a diagnosis of hydrocephalus that requires treatment.

A potential role for substance P and interleukin-6 in the cerebrospinal fluid of Cavalier King Charles Spaniels with neuropathic pain.

BACKGROUND Neuropathic pain can be a clinical sign in Cavalier King Charles Spaniels (CKCS) with syringomyelia. The pathophysiology of this pain is not fully understood. HYPOTHESIS Neuropathic pain in CKCS is a result of a neuroinflammatory process. ANIMALS Twenty-six client-owned dogs: 15 dogs with clinical signs of cervical hyperesthesia (group 1), and 11 dogs without of clinical signs (group 2). METHODS Dogs were examined by magnetic resonance imaging (MRI). Interleukin-6, tumor necrosis factor alpha, and substance P were measured in CSF and compared with morphological findings on MRI and clinical pain scores. RESULTS All dogs without clinical signs had symmetrical syringomyelia, whereas in the group with pain, 6 dogs had symmetrical and 9 dogs had asymmetrical syringomyelia. Pain and syringomyelia asymmetry were correlated, and a strong association between pain and dorsal horn involvement of syringomyelia was observed. There was no significant difference between the mean width of the syringomyelia in dogs with or without pain. The concentrations of interleukin-6 and substance P were significantly higher in dogs with neuropathic pain. Tumor necrosis factor alpha was not detected in either group. Concentrations of substance P were significantly higher in dogs with asymmetrical syringomyelia or dorsal horn involvement, whereas interleukin-6 concentrations were not significantly different between groups. CONCLUSION Release of interleukin-6 and substance P may initiate proinflammatory effects leading to development of persistent pain in CKCSs with syringomyelia.

MR‐IMAGING OF LUMBOSACRAL INTERVERTEBRAL DISC DEGENERATION IN CLINICALLY SOUND GERMAN SHEPHERD DOGS COMPARED TO OTHER BREEDS

German shepherd dogs are overrepresented in the group of dogs with cauda equina compression syndrome due to degenerative lumbosacral stenosis. A congenital predisposition for early degeneration of the lumbosacral intervertebral disc has been suspected. Our aims were to assess the morphologic appearance of the lumbosacral intervertebral disc and the lumbosacral junction in healthy German shepherd dogs compared to other breeds and to evaluate for an early onset of degenerative changes. The lumbosacral spine of 110 clinically sound German shepherd dogs and 47 healthy dogs of other large breeds was examined using magnetic resonance (MR) imaging. The degeneration of every intervertebral disc was graded using an established classification system. Signal intensity of the entire lumbosacral disc and the nucleus pulposus was determined independently. Lumbosacral malalignment was assessed according to a previously described method. The findings for the German shepherd dogs were compared to those of the other breeds. Although most dogs were younger than 18 months at the date of examination, significantly higher grades of degeneration were detected for the lumbosacral intervertebral disc of German shepherd dogs (P < 0.003). Degeneration of the lumbosacral intervertebral disc was independent from findings in the other lumbar discs. We conclude that the German shepherd dog has a predisposition for degenerative changes in the lumbosacral intervertebral disc.

Skeletal morphology and morphometry of the lumbosacral junction in German shepherd dogs and an evaluation of the possible genetic basis for radiographic findings

The aim of this study was to identify skeletal variations in the lumbosacral junction (LSJ) of the German shepherd dog (GSD) compared with other large breeds. The radiographic traits of the LSJ were investigated in a group of 733 GSDs and a control group of 334 dogs of other breeds that were matched in terms of size. Nine morphological and 17 morphometric traits were recorded and analysed. Furthermore, the possibility of a genetic basis for these radiographic features was evaluated by calculation of genetic variance components. Five of the morphological and 14 of the morphometric traits varied significantly between the GSD group and the control group (P<0.05). Osteochondrosis of the sacral endplate (SOC) had a higher prevalence in the GSDs (10.1%) compared with controls (5.7%). The majority of LSJ degenerative changes recorded from the radiographs occurred in the GSDs. The extent and relative proportion of lumbosacral step formations were greater in the GSD group compared with controls (P<0.001). The lumbosacral vertebral canal height was reduced in the GSD compared with the control dogs (P<0.001) suggesting a primary stenosis. This was accentuated by an abrupt tapering of the vertebral canal at the level of the LSJ indicated by a lumbosacral ratio of 1.51 in the GSD. The skeletal morphology and morphometry of the LSJ in the GSD seem to be different from that found in other large dogs. For multiple traits frequently observed in GSD such as SOC, step formations, and LSJ stenosis, moderate to high non-zero heritabilities were noted. As these features are also assumed to promote lumbosacral disease, selection against these traits is suggested.

Intra‐abdominal Mycobacterium tuberculosis Infection in a Dog

A 4-year-old, 30.6-kg castrated male mixed-breed dog was referred for evaluation of acute diarrhea, inappetence, weight loss, and lethargy. The dog had otherwise been healthy since being adopted from a Greek animal shelter 18 months before presentation. The only other household pet was its clinically healthy littermate. On examination, the dog was lethargic, hyperthermic (102.4°F), had a body condition score of 3/9, and was moderately painful upon palpation of the cranial abdomen. Abnormal hematologic findings included a moderate leukocytosis (19.3 9 10/L; reference range [RR], 5.5– 13.7 9 10/L) with neutrophilia (15.6 9 10/L; RR, 2.8–8.7 9 10/L) and a mild microcytic nonregenerative anemia (PCV, 35%; RR, 39–56%). Serum biochemistry profile results disclosed moderate hyperglobulinemia (56.4 g/L; RR, 22.9–35.6 g/L), hypoalbuminemia (19.9 g/L; RR, 29.6–37.0 g/L), and moderately increased alkaline phosphatase activity (169 U/L; RR, 0–130 U/L). Urinalysis was unremarkable. Results of serologic assays for anti-Leishmania infantum antibody and Dirofilaria immitis antigen were negative. Fecal flotation was negative. Thoracic radiographs were within normal limits, but abdominal radiographs showed marked loss of detail in the cranial abdomen caudal to the stomach with a mass effect causing caudal intestinal displacement. Ultrasonographic examination of the abdomen (Fig 1) identified an elongated, well-defined, multilobular, mixed echoic mass 5 cm in length within the cranial to midabdomen caudal to the pyloric antrum and porta hepatis, surrounded by hyperechoic mesentery and including the portal vein as well as parts of the mesenteric vein. Multifocal hypoto anechoic areas and hyperechoic foci with acoustic shadowing were noted. The surrounding mesenteric fat had mildly increased echogenicity. The stomach and pancreas were normal. Multiple hypoechoic nodules of varying size were visible throughout the parenchyma of all liver lobes. Based on the ultrasonographic findings, the most likely origin of the abdominal mass was thought to be mesenteric and hepatic lymph nodes. A multicentric neoplastic process or granulomatous disease of the mesenteric and hepatic lymph nodes and liver was suspected. Ultrasound-guided fine needle aspirates of the abdominal mass were stained using May-Gr€ unwaldGiemsa stain and cytologic evaluation indicated mild cellular necrosis and moderate pyogranulomatous inflammation consisting of nondegenerate neutrophils, small mature lymphocytes, and activated macrophages containing nonstaining rods suspicious for acid-fast bacteria. Because these bacteria were positive on ZiehlNeelsen staining, infection with Mycobacterium spp. was suspected. After consulting with the National Reference Center for Mycobacteria and Supranational Reference Laboratory of the World Health Organization (WHO, Borstel, Germany), 2 weeks after the 1st presentation a laparotomy was performed to obtain multiple diagnostic biopsy specimen samples. To determine the organ of origin, the extent of the disease throughout the abdomen, and possible involvement of the lungs and hilar lymph nodes, which would have led to euthanasia because of public health safety issues, a computed tomographic (CT) examination was performed before laparotomy. Computed tomography examination (Fig 2) was performed using a 16-slice helical scanner with a slice

Increased CSF aquaporin-4, and interleukin-6 levels in dogs with idiopathic communicating internal hydrocephalus and a decrease after ventriculo-peritoneal shunting.

BackgroundStudies in animal models, in which internal hydrocephalus has been induced by obstructing the cerebrospinal fluid pathways, have documented an up-regulation of the concentrations of aquaporin-4 (AQP4) in the brain. In this study, the concentrations of aquaporin-1 (AQP1), AQP1, AQP4 and interleukin-6 (IL-6) were determined in the CSF of dogs with idiopathic communicating hydrocephalus before and after the reduction of intraventricular volume following ventriculo-peritoneal shunt (VP-shunt) treatment.ResultsThe concentrations of AQP4 and IL-6 were increased in the cerebrospinal fluid of dogs with hydrocephalus compared to controls. Both parameters significantly decreased after surgical treatment, accompanied by decrease of ventricular size and the clinical recovery of the dogs. AQP1 was not detectable in CSF.ConclusionsBrain AQP4 up-regulation might be a compensatory response in dogs with hydrocephalus. Future determination of AQP4 at the mRNA and protein level in brain tissue is warranted to substantiate this hypothesis.

Comparison of the relative occipital bone volume between Cavalier King Charles spaniels with and without syringohydromyelia and French bulldogs.

Our aim was to determine the relative volume of the occipital bone of Cavalier King Charles spaniels with and without syringohydromyelia and normal French bulldogs to reappraise the role of a possible insufficiency of the paraxial mesoderm in the pathogenesis of the caudal occipital malformation syndrome. Analysis of the occipital bone volume of 43 dogs based on computed tomography datasets was performed. Volume was determined by means of three-dimensional models. Using manual segmentation of the occipital bone in sagittal, transverse, and dorsal images, the volume of the occipital bone and the rest of the skull was calculated. The absolute occipital bone volume was put in relation to the total skull volume, the occipital bone index. For the Cavalier King Charles spaniels without syringomyelia, the median occipital bone index was 0.0681; for Cavalier King Charles spaniels with syringomyelia, it was 0.0646 and for French bulldogs, it was 0.0676. There was no global difference of the occipital bone index between examined groups (P = 0.4331). A reduced volume of the occipital bone was not found in Cavalier King Charles spaniels in general in comparison to French bulldogs, or in Cavalier King Charles spaniels with syringomyelia compared to Cavalier King Charles spaniels without syringomyelia. These results do not support occipital hypoplasia as a cause for syringomyelia development, challenging the paraxial mesoderm insufficiency theory. This also suggests that the term Chiari-like malformation, a term derived from human studies, is not appropriate in the Cavalier King Charles spaniel.