Thoracic to lumbar vertebral column length and length ratios in miniature dachshunds with and without thoracolumbar intervertebral disc extrusion.

BACKGROUND: The chondrodystrophic body type predisposes miniature dachshunds to thoracolumbar intervertebral disc extrusion (IVDE). However, the relationship between thoracolumbar IVDE and the relative lengths of the thoracic and lumbar vertebral columns has not yet been evaluated. METHODS: This prospective multicentre study included 151 miniature dachshunds with (n = 47) and without (n = 104) thoracolumbar IVDE. All dogs had their thoracic and lumbar vertebral columns measured with a tape measure. Detailed descriptions were provided to facilitate consistent measurement. A thoracic to lumbar vertebral column ratio was calculated. Thoracolumbar IVDE was confirmed by magnetic resonance imaging or computed tomography. RESULTS: The thoracic to lumbar vertebral column length ratio and absolute thoracic vertebral column length were significantly smaller in miniature dachshunds with IVDE than in those without IVDE (p < 0.0001 for both). There were no significant differences in lumbar vertebral column length, age, sex or neuter status between the two groups. LIMITATIONS: The dogs without IVDE did not undergo a neurological examination and the thoracic and lumbar vertebral column measurements were not validated. CONCLUSIONS: The relative lengths of the thoracic and lumbar vertebral column segments could contribute to the development of thoracolumbar IVDE in miniature dachshunds. Further studies are needed to evaluate ideal thoracic to lumbar vertebral column length ratios in miniature dachshunds.

Metabolic fingerprinting of dogs with idiopathic epilepsy receiving a ketogenic medium-chain triglyceride (MCT) oil.

Consumption of medium-chain triglycerides (MCT) has been shown to improve seizure control, reduce behavioural comorbidities and improve cognitive function in epileptic dogs. However, the exact metabolic pathways affected by dietary MCT remain poorly understood. In this study, we aimed to identify changes in the metabolome and neurotransmitters levels relevant to epilepsy and behavioural comorbidities associated with the consuming of an MCT supplement (MCT-DS) in dogs with idiopathic epilepsy (IE). Metabolic alterations induced by a commercial MCT-DS in a population of 28 dogs with IE were evaluated in a 6-month multi-centre, prospective, randomised, double-blinded, controlled cross-over trial design. A metabolic energy requirement-based amount of 9% MCT or control oil was supplemented to the dogs' stable base diet for 3 months, followed by the alternative oil for another 3 months. A validated, quantitative nuclear magnetic resonance (NMR) spectroscopy platform was applied to pre- and postprandially collected serum samples to compare the metabolic profile between both DS and baseline. Furthermore, alterations in urinary neurotransmitter levels were explored. Five dogs (30%) had an overall reduction in seizure frequency of ≥50%, and were classified as MCT-responders, while 23 dogs showed a ≤50% reduction, and were defined as MCT non-responders. Amino-acid metabolism was significantly influenced by MCT consumption compared to the control oil. While the serum concentrations of total fatty acids appeared similar during both supplements, the relative concentrations of individual fatty acids differed. During MCT supplementation, the concentrations of polyunsaturated fatty acids and arachidonic acid were significantly higher than under the control oil. ß-Hydroxybutyric acid levels were significantly higher under MCT supplementation. In total, four out of nine neurotransmitters were significantly altered: a significantly increased γ-aminobutyric acid (GABA) concentration was detected during the MCT-phase accompanied by a significant shift of the GABA-glutamate balance. MCT-Responders had significantly lowered urinary concentrations of histamine, glutamate, and serotonin under MCT consumption. In conclusion, these novel data highlight metabolic changes in lipid, amino-acid and ketone metabolism due to MCT supplementation. Understanding the metabolic response to MCT provides new avenues to develop better nutritional management with improved anti-seizure and neuroprotective effects for dogs with epilepsy, and other behavioural disorders.

Cholesterol granuloma in the choroid plexus of a cat.

BACKGROUND: This case report describes the clinical presentation, magnetic resonance imaging (MRI) as well as the histopathological findings in an elderly cat with an intracranial cholesterol granuloma. CASE PRESENTATION: An 11.5-year-old, male neutered cat was presented at the emergency service with deteriorating behavioral changes including aggression, and progressive generalized ataxia. Magnetic resonance imaging (MRI) of the brain revealed a large, well demarcated, inhomogeneous and contrast enhancing mass in the lateral ventricles with marked mass effect. Due to a poor clinical prognosis, the cat was euthanized. Histological examination identified the mass as a bilateral cholesterol granuloma in the choroid plexus of the lateral ventricles. CONCLUSIONS: Although plexus cholesterol granulomas are rarely seen in cats, they should be considered as a differential diagnosis in elderly patients with neurological signs such as behavioral changes.

Metastatic Canine Phaeochromocytoma with Unusual Manifestation.

We report the clinical, pathological and immunohistochemical characteristics of a phaeochromocytoma (PCC) in a 9-year-old male neutered Golden Retriever dog. The dog presented with acute onset of deteriorating cervical pain but was otherwise normal on general physical and neurological examinations. Magnetic resonance imaging of the cervical spine revealed a focal, extramedullary, infiltrative, poorly demarcated, heterogeneous mass with moderate contrast enhancement at the left cranial articular process of C2, associated with osteolysis and pathological fractures of C2, and marked soft tissue trauma. Due to the severe lesions and grave prognosis, the dog was euthanized. Post-mortem examination revealed severe enlargement of the right adrenal gland due to a neoplasm of the adrenal medulla. C2 was lytic and there was a white, well-demarcated, firm neoplastic mass in the surrounding musculature. Neoplasms were also present in, and adjacent to, the prostate gland and in pulmonary lymph nodes. Histologically, the neoplasms were composed of dense sheets and nests of small, round to polyhedral cells with frequent palisading along fine connective tissue septa, karyomegaly, multinucleated cells and frequent mitotic figures. Immunohistochemically, neoplastic cells expressed chromogranin A and synaptophysin. Gross, microscopic and immunohistochemical findings support the diagnosis of PCC, originating from the right adrenal gland, with multiple metastases in the cervical spine, prostate gland and pulmonary lymph nodes. This case highlights the difficulty of intra-vitam diagnosis of PCC as its manifestation can be highly variable. PCC should be considered as a rare but possible differential diagnosis for painful vertebral masses in elderly dogs.

Th17 cell-mediated immune response in a subpopulation of dogs with idiopathic epilepsy.

BACKGROUND: Canine idiopathic epilepsy (IE) is a common neurological disease with severe impact on the owner´s and the dog's quality of life. A subpopulation of dogs with IE does not respond to antiseizure drugs (non-responder). Th17 cells (T helper cells) and their proinflammatory Interleukin-17 (IL-17) are part of the immune system and previous studies showed their involvement in the pathogenesis of several autoimmune diseases. Non-responder might have an abnormal immune response against structures of the central nervous system. To discover a new aetiology of canine IE and thereby optimising the therapy of intractable IE, this prospective study aimed to investigate Th17 cells and IL-17 in dogs with IE. The underlying hypothesis was that in some dogs with IE a Th17 cell-mediated immune response could be detectable. METHODS: 57 dogs with IE and 10 healthy dogs (control group, C) were enrolled in the study. EDTA blood was taken to measure Th17 cells by flow cytometry. IL-17 was measured in 35 cerebrospinal fluid (CSF) and 33 serum samples using an enzyme-linked immunosorbent assay (ELISA). It was investigated whether there was a significant increase of stimulated Th17 cells in blood samples or of IL-17 in serum and CSF samples of dogs with IE in comparison to C. Correlations between the amount of Th17 cells/µL or IL-17 and different clinical parameters e.g. seizure frequency, seizure type, seizure severity or treatment response were evaluated. Additionally, Th17 cells/µL were randomly controlled of 17 dogs with IE and were examined for changes over time and in relation to treatment response. RESULTS: Ten dogs with IE had strongly elevated stimulated Th17 cells/µL within the blood (>100 Th17 cells/µL). A slight positive correlation between stimulated Th17 cells/µL and seizure severity (p = 0.046; rSpear = 0.27) was proven in these dogs. In addition, 4/10 dogs with elevated Th17 levels experienced cluster seizures and status epilepticus in comparison to 9% of the dogs with non-elevated Th17 levels (<100 Th17 cells/µL). Dogs with IE had significantly higher IL-17 values in CSF and serum samples compared to C (p<0.001; p<0.002; respectively). CONCLUSION: In single dogs with IE, strongly increased amounts of Th17 cells were detectable and dogs with elevated Th17 cells seemed to have a greater risk for experiencing a combination of cluster seizures and status epilepticus. Therefore, an underlying Th17-cell mediated immune response was suspected and hence anti-inflammatory drugs could be indicated in these single cases with intractable epilepsy.

LTBP3 Frameshift Variant in British Shorthair Cats with Complex Skeletal Dysplasia.

We investigated a highly inbred family of British Shorthair cats in which two offspring were affected by deteriorating paraparesis due to complex skeletal malformations. Radiographs of both affected kittens revealed vertebral deformations with marked stenosis of the vertebral canal from T11 to L3. Additionally, compression of the spinal cord, cerebellar herniation, coprostasis and hypogangliosis were found. The pedigree suggested monogenic autosomal recessive inheritance of the trait. We sequenced the genome of an affected kitten and compared the data to 62 control genomes. This search yielded 55 private protein-changing variants of which only one was located in a likely functional candidate gene, LTBP3, encoding latent transforming growth factor ß binding protein 3. This variant, c.158delG or p.(Gly53Alafs*16), represents a 1 bp frameshift deletion predicted to truncate 95% of the open reading frame. LTBP3 is a known key regulator of transforming growth factor ß (TGF-ß) and is involved in bone morphogenesis and remodeling. Genotypes at the LTBP3:c.158delG variant perfectly co-segregated with the phenotype in the investigated family. The available experimental data together with current knowledge on LTBP3 variants and their functional impact in human patients and mice suggest LTBP3:c.158delG as a candidate causative variant for the observed skeletal malformations in British Shorthair cats. To the best of our knowledge, this study represents the first report of LTBP3-related complex skeletal dysplasia in domestic animals.

Evaluation of the involvement of Th17-cells in the pathogenesis of canine spinal cord injury.

Intervertebral disc herniation (IVDH) is a frequently occurring neurological disease of dogs and the most common reason for spinal cord injury (SCI). Clinical signs are variable thus a reliable prognosis is crucial for further treatment decisions. Currently, the prognosis of IVDH primarily depends on presence or absence of deep pain perception. The purpose of this study was to investigate if Th17-cells could serve as a potential, prognostic biomarker for IVDH. We investigated a possible role of the adaptive immune system in the pathophysiology of IVDH in dogs. The investigation was performed by analyzing the influence of Th17-cells in blood and cerebrospinal fluid (CSF) of sixty-two dogs suffering from IVDH. In addition, we examined if Th17-cells might influence the course of this disease. As controls, paired blood and CSF samples of ten healthy clinic-owned dogs were examined and the values were compared to those of the IVDH group. Isolated lymphocytes were analyzed after stimulation by using multicolour flow cytometry to measure the number of Th17-cells. IL-17 levels were measured in paired serum and CSF samples by Enzyme-linked Immunosorbent Assays (ELISA). Highly significant differences of stimulated Th17-cells in EDTA-blood samples could be determined between Th17-cell levels of dogs suffering from IVDH and the healthy control group and also between three sampling time points: preoperative, after clinical improvement and after six months. Preoperatively, Th17-cell levels were strongly decreased in contrast to the healthy controls. The decreased amount of Th17-cell levels recovered postoperatively so that Th17-cell levels of the last follow-up examinations were comparable to the control group after six months. At the same time IL-17 measured in serum preoperatively was significantly higher in dogs with IVDH than in healthy controls. However, there was no considerable difference of IL-17 measured in CSF between the groups. In conclusion, a high activity and consequent consumption of IL-17-producing Th17-cells is suspected in acute IVDH. These findings may indicate an involvement of Th17-cells in the pathogenesis of IVDH and emphasize that these cells might be involved in the interaction of pain, stress and immune reaction. However, based on the findings of this study the development of Th17-cells as a biomarker cannot be recommended, yet.

Medium-chain triglycerides dietary supplement improves cognitive abilities in canine epilepsy.

OBJECTIVE: Cognitive impairments (CI) have recently been identified in canine epilepsy patients. A medium-chain triglyceride (MCT) enriched diet has been demonstrated to improve cognition in aged dogs and seizure control in canine epilepsy. This study evaluates the short-term effects of MCT-oil consumption on cognitive abilities in dogs with epilepsy, a naturally occurring animal model. METHODS: A 6-month multicenter, prospective, randomized, double-blinded, controlled cross-over diet trial was conducted comparing dietary supplementation (DS) of MCT oil to a control oil. Allocation to dietary oil supplements, consisting of 9% total caloric intake, was block-randomized and supplemented into each dogs' diet for 3 months followed by a respective switch of DS-oil for a further 3 months. Noninvasive cognitive tests and a validated psychometric tool were utilized to evaluate cognitive function and perturbations associated with dietary intervention. RESULTS: Twenty-nine dogs completed the trial, of which 18 completed noninvasive cognitive testing. Spatial-working memory (P = 0.008), problem-solving ability (P = 0.048), and owner-reported trainability (P = 0.041) were significantly improved during MCT-oil supplementation compared to control-DS. SIGNIFICANCE: MCT-oil DS improves cognition in dogs with epilepsy when compared to a control-DS. MCT supplementation may represent a promising option to address CI associated with epilepsy.

A multicenter randomized controlled trial of medium-chain triglyceride dietary supplementation on epilepsy in dogs.

BACKGROUND: Medium-chain triglyceride (MCT) enriched diet has a positive effect on seizure control and behavior in some dogs with idiopathic epilepsy (IE). OBJECTIVE: To evaluate the short-term efficacy of MCTs administered as an add-on dietary supplement (DS) to a variable base diet to assess seizure control and antiseizure drug's (ASD) adverse effect profiles. ANIMALS: Twenty-eight dogs with International Veterinary Epilepsy Task Force Tier II (IVETF) level diagnosis of treated IE with 3 or more seizures in the last 3 months were used. METHODS: A 6-month multicenter, prospective, randomized, double-blinded, placebo-controlled crossover trial was completed, comparing an MCT-DS with a control-DS. A 9% metabolic energy-based amount of MCT or control oil was supplemented to the dogs' diet for 3 months, followed by a control oil or MCT for another 3 months, respectively. Dogs enrolled in this study satisfied most requirements of IE diagnosis stated by the IVETF II level. If they received an oil DS or drugs that could influence the metabolism of the investigated DS or chronic ASD, the chronic ASD medication was adjusted, or other causes of epilepsy were found, the dogs were excluded from the study. RESULTS: Seizure frequency (median 2.51/month [0-6.67] versus 2.67/month [0-10.45]; P = .02) and seizure-day frequency were significantly (1.68/month [0-5.60] versus 1.99/month [0-7.42], P = .01) lower when dogs were fed MCT-DS in comparison with the control-DS. Two dogs were free of seizures, 3 had ≥50% and 12 had <50% reductions in seizure frequency, and 11 dogs showed no change or an increase in seizure frequency. CONCLUSIONS AND CLINICAL IMPORTANCE: These data show antiseizure properties of an MCT-DS compared to a control oil and support former evidence for the efficacy of MCTs as a nutritive, management option for a subpopulation of drug-resistant dogs with epilepsy.

A double-blinded randomised dietary supplement crossover trial design to investigate the short-term influence of medium chain fatty acid (MCT) supplement on canine idiopathic epilepsy: study protocol.

BACKGROUND: Epilepsy is the most common brain disease in dogs. Recently, diets have been reported to have a positive impact on seizure activity and behaviour in various species including dogs with idiopathic epilepsy (IE). Historically, classic high fat ketogenic diets (KD) and medium chain triglycerides (MCT) KD have been successfully used to manage drug-resistant epilepsy. Similarly, an MCT enriched diet has been shown to improve seizure control and behavioural comorbidities in some dogs with IE. However, it is unknown whether an MCT dietary supplement (DS) may provide similar positive effects. METHODS: A 6-month prospective, randomised, double-blinded, placebo-controlled, crossover, multicentre dietary trial is designed comparing a 9% metabolic energy based calculated medium-chain triglyceride (MCT) oil supplement to a conventional 'control' DS. Only dogs which will have an International Veterinary Epilepsy Task Force Tier II level like diagnosis of IE which satisfied the following inclusion criteria are included: age between 6 months and ≤ 12 years; weighing between 4 and ≤ 65 kg; unremarkable interictal neurological examinations; no clinically significant findings on routine laboratory diagnostics; unremarkable brain MRI scan; have had at least 3 seizures in the previous 3 months prior to enrolment; treated with at least one ASD and being classified as resistant. All dogs are fed initially for 90 ± 2 days with either the control oil or the MCT oil alongside their normal diet, followed by 97 ± 2 days with the other supplement including a 7-day washout period. Overall, the aim is to recruit thirty-six patients at five different centres and to investigate the effect of MCTs as DS on seizure activity, tolerability, behavioural comorbidities and quality of life (QoL). DISCUSSION: Dietary interventions are rarely studied in a standardised form in veterinary medicine. The background diet, the cohort of animals and ASD received is standardised in this prospective diet trial to ensure representative data about the potential effect of MCT DS. If the study data confirms former findings, this would provide further evidence for the efficacy of MCTs as a management option for canine epilepsy. This publication should offer a repository of trial conditions and variable description with forecasted statistical analysis.