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Background Syringomyelia (SM) and myxomatous mitral valve disease (MMVD) are highly prevalent in Cavalier King Charles spaniels (CKCS). Cardiac status in CKCS with and without SM is currently unknown. Objectives To investigate the association between SM and MMVD severity in CKCS and CKCS with SM with and without clinical signs of SM. Animals Fifty-five CKCS: 40 with SM (22 symptomatic and 18 asymptomatic) and 15 without SM. Methods A combined retrospective and prospective study. MRI and echocardiography were used to diagnose SM and MMVD, respectively. The association between SM and MMVD severity (left ventricle internal diameter in diastole normalized to bodyweight [LVIDDN] and left atrium to aortic ratio [LA/Ao]) were tested using multivariable linear regression analysis adjusting for sex and age. Results Overall, no significant difference in LVIDDN and LA/Ao was found between CKCS with or without SM. However, CKCS with symptomatic SM had significantly smaller LVIDDN (1.45 [1.30-1.50]) (median [IQR]) and LA/Ao (1.20 [1.10-1.28]) compared to CKCS with asymptomatic SM (1.60 [1.50-1.90] and 1.40 [1.20-1.75]) as well as CKCS without SM (0.24 [0.03-0.45] and 0.30 [0.05-0.56]) (all P values <.03). Conclusions and Clinical Importance An association between MMVD and SM was not confirmed in this cohort of CKCS, indicating that MMVD and SM do not co-segregate. However, CKCS with symptomatic SM had smaller left ventricle and atrial size compared to CKCS with asymptomatic SM and CKCS without SM., BACKGROUND: Syringomyelia (SM) and myxomatous mitral valve disease (MMVD) are highly prevalent in Cavalier King Charles spaniels (CKCS). Cardiac status in CKCS with and without SM is currently unknown.OBJECTIVES: To investigate the association between SM and MMVD severity in CKCS and CKCS with SM with and without clinical signs of SM.ANIMALS: Fifty-five CKCS: 40 with SM (22 symptomatic and 18 asymptomatic) and 15 without SM.METHODS: A combined retrospective and prospective study. MRI and echocardiography were used to diagnose SM and MMVD, respectively. The association between SM and MMVD severity (left ventricle internal diameter in diastole normalized to bodyweight [LVIDDN] and left atrium to aortic ratio [LA/Ao]) were tested using multivariable linear regression analysis adjusting for sex and age.RESULTS: Overall, no significant difference in LVIDDN and LA/Ao was found between CKCS with or without SM. However, CKCS with symptomatic SM had significantly smaller LVIDDN (1.45 [1.30-1.50]) (median [IQR]) and LA/Ao (1.20 [1.10-1.28]) compared to CKCS with asymptomatic SM (1.60 [1.50-1.90] and 1.40 [1.20-1.75]) as well as CKCS without SM (0.24 [0.03-0.45] and 0.30 [0.05-0.56]) (all P values <.03).CONCLUSIONS AND CLINICAL IMPORTANCE: An association between MMVD and SM was not confirmed in this cohort of CKCS, indicating that MMVD and SM do not co-segregate. However, CKCS with symptomatic SM had smaller left ventricle and atrial size compared to CKCS with asymptomatic SM and CKCS without SM.

Objectives: Intervertebral disc disease (IVDD) is a common neurological condition in dogs. Information of prognosis and quality of life (QOL) is however limited. We aimed to investigate the outcome and QOL of dogs treated for IVDD. Methods: Retrospective case study of dogs with clinical signs of IVDD alongside a pre-planned structured QOL telephone follow-up owner interview, using closed- and open-ended questions. A modified Frankel score was used to compare disease severity between surgically and conservatively treated dogs. Data from follow-up interviews were analysed using Excel. Response categories were made to analyse open-ended questions. Results: 129 dogs were included in the study. Forty-two owners participated in follow-up interviews. Surgically treated dogs had significantly worse modified Frankel scores at initial presentation compared to conservatively treated dogs (p < 0.003). In both treatment groups, 50% of dogs experienced long-term deficiencies after IVDD treatment e.g difficulty jumping or reduced stamina. Twice as many dogs in the surgical group received physiotherapy as part of treatment. Almost all owners believed their dogs QOL was the same as before the disease. A majority of owners however, reported that IVDD in their dog caused them emotional distress, thus influencing their life negatively. Impact: Our results suggest that the prognosis of dogs treated for IVDD is good; however, owners should be informed that long-term sequelae are not uncommon. There is a need for more focus on how dogs’ IVDD affect their owners and guidelines on how to provide the most optimal owner support.

Background: Microglia contribute to Alzheimer's disease (AD) pathogenesis by clearing amyloid-β (Aβ) and driving neuroinflammation. Domestic dogs with age-related dementia (canine cognitive dysfunction (CCD)) develop cerebral amyloidosis like humans developing AD, and studying such dogs can provide novel information about microglial response in prodromal AD. Objective: The aim was to investigate the microglial response in the cortical grey and the subcortical white matter in dogs with CCD versus age-matched cognitively normal dogs. Methods: Brains from aged dogs with CCD and age-matched controls without dementia were studied. Cases were defined by dementia rating score. Brain sections were stained for Aβ, thioflavin S, hyperphosphorylated tau, and the microglial-macrophage ionized calcium binding adaptor molecule 1 (Iba1). Results were correlated to dementia rating score and tissue levels of Aβ. Results: Microglial numbers were higher in the Aβ plaque-loaded deep cortical layers in CCD versus control dogs, while the coverage by microglial processes were comparable. Aβ plaques were of the diffuse type and without microglial aggregation. However, a correlation was found between the %Iba1 area and insoluble Aβ 42 and N-terminal pyroglutamate modified Aβ(N3pE)-42. The %Iba1 area was higher in white matter, showing phosphorylation of S396 tau, versus grey matter. Perivascular macrophage infiltrates were abundant in the white matter particularly in CDD dogs. Conclusion: The results from this study of the microglial-macrophage response in dogs with CCD are suggestive of relatively mild microglial responses in the Aβ plaque-loaded deep cortical layers and perivascular macrophage infiltrates in the subcortical white matter, in prodromal AD.

Steroid responsive meningitis-arteritis (SRMA) in dogs causes severe inflammation of meningeal arteries leading to generalized meningitis with possible neurological signs, as well as a systemic inflammatory response. The etiology and exact pathogenesis are unknown, but an immune-mediated origin has been suggested and is supported by a positive response to immunosuppressive treatment with corticosteroids. A collection of clinical and paraclinical characteristics may be highly indicative of SRMA, but a single and conclusive diagnostic test or biomarker is currently not available. The aim of this review is to provide an overview of the current understanding and knowledge on SRMA, with special emphasis on potential biomarkers and their applicability in the diagnostic work-up. Though no specific markers for SRMA currently exist, clinically useful markers include IgA and several acute phase proteins e.g. C-reactive protein. A frequent problem of both acknowledged and proposed biomarkers, is, however, their inability to effectively differentiate SRMA from other systemic inflammatory conditions. Other proposed diagnostic markers include genetic markers, acute phase proteins such as serum amyloid A, cytokines such as interleukin-17 and CC-motif ligand 19, endocannabinoid receptors and heat shock protein 70; these suggestions however either lack specificity or need further investigation.

Domestic dogs are superior models for translational medicine due to greater anatomical and physiological similarities with humans than rodents, including hereditary diseases with human equivalents. Particularly with respect to neurodegenerative medicine, dogs can serve as a natural, more relevant model of human disease compared to transgenic rodents. Herein we report attempts to develop a canine-derived in vitro model for neurodegenerative diseases through the generation of induced pluripotent stem cells from a 14-year, 9-month-old female West Highland white terrier with mild cognitive impairment (MCI). Canine induced pluripotent stem cells-like cells (ciPSCLC) were generated using human OSKM and characterized by positive expression of pluripotency markers. Due to inefficient viral vector silencing we refer to them as ciPSCLCs. Subsequently, the ciPSCLC were subjected to neural induction according to two protocols both yielding canine neural progenitor cells (cNPCs), which expressed typical NPC markers. The cNPCs were cultured in neuron differentiation media for 3 weeks, resulting in the derivation of morphologically impaired neurons as compared to iPSC-derived human counterparts generated in parallel. The apparent differences encountered in this study regarding the neural differentiation potential of ciPSCLC reveals challenges and new perspectives to consider before using the canine model in translational neurological studies.

The collection of cerebrospinal fluid (CSF) plays a pivotal role in the diagnosis of central nervous system diseases. Prior training in this invasive procedure is essential to minimize the risk of harming animals. Because of this risk, stress and anxiety can influence the learning process. Simulators can be used to teach and learn invasive procedures.The aim of this mixed-methods study was to validate a CSF collection simulator and investigate students' perceptions of the simulator as an educational tool.The quantitative approach validated the simulator for face and content validity, and students provided a general evaluation of the simulator using surveys.The simulator's construct validity was measured by means of a global rating scale. Students' perceptions were investigated qualitatively using semi-structured interviews. Experts (n = 13) confirmed the simulator's face and content validity. Students (n = 16) evaluated the simulator as supportive of their learning. Results for construct validity demonstrated higher global rating scores from experts than from students. The scores for procedural performance and procedural knowledge and flow showed significant differences (p ≤.05).Analysis of interviews with students (n = 10) revealed four main themes: emotions, learning process, evaluation of the model, and CSF collection procedure. In conclusion, this study validated the use of the CSF simulator as an educational tool that can help students overcome some of their anxiety in relation to performing an invasive procedure.

Objective: We aimed to assess the efficacy and benefit-risk profile of pregabalin (PGN) to reduce the clinical signs of central neuropathic pain (CNeP) as reflected by scratching episodes in dogs with symptomatic syringomyelia (SM). Study design: Randomized, double-blind, placebo-controlled crossover study. Animals: A total of 12 client-owned Cavalier King Charles Spaniels (age, 1.1–7.4 years, bodyweight, 8.2–10.8 kg) with magnetic resonance imaging-confirmed SM and clinical signs of CNeP. Methods: Dogs were randomized to either PGN 150 mg or placebo for 25 days, followed by 48 hour washout period before crossover to the alternate phase of 25 days. The primary outcome was defined as number of scratching events during 10 minutes of video-recorded physical activity. Treatment effect was estimated using a generalized estimation equation model. Benefit-risk and quality of life assessments were obtained through owner interviews focusing on potential adverse events. Results: The treatment effect estimate was an 84% (95% confidence interval = 75–89%) reduction in mean number of scratching events relative to baseline compared with placebo (p < 0.0001). Owner-assessed satisfactory quality of life was status quo and rated as ‘good’ or ‘could not be better’ in six/11 dogs and improved in four/11 dogs. The most prevalent adverse events were increased appetite in nine/12 dogs and transient ataxia in nine/12 dogs. There was one dog withdrawn by the owner 7 days after crossover to PGN owing to persistent ataxia. No dogs needed rescue analgesia during the trial. Conclusions and clinical relevance: PGN is superior to placebo in the reduction of clinical signs of SM-related CNeP in dogs. At a dose range of 13–19 mg kg–1 orally twice daily, the encountered adverse events were acceptable to all but one owner.

Canine cognitive dysfunction (CCD) is a potential natural model for human Alzheimer’s disease (AD). In this chapter we are addressing the current procedures of how to obtain canine induced pluripotent stem cells (ciPSCs) from geriatric dogs and the available protocols for differentiation of ciPSC into neurons. Moreover, we present how these neurons derived from ciPSC can be compared to human iPSC (hiPSC)-derived neurons in order to validate dogs with CCD as natural models for AD. This practical example presents the importance to generate species-specific iPSC to broaden our knowledge of cell type-specific disease models and to investigate, compare, and evaluate the different animal models as appropriate disease models for human diseases.

With the aim of improving students' ability to handle the complexity of surgery, we introduced a creative assignment in a veterinary surgical course. We hypothesized that by using this active, inductive educational method, reflection, creativity and self-efficacy in student novice surgeons could be improved. During a companion animal surgical course an intervention group was investigated against a control group. Twenty-nine fourth-year students were instructed in ovariohysterectomy by classical lectures, while 23 fourth-year students were provided with creative materials and assigned to consider and illustrate how to perform the procedure themselves. Surgical performance was assessed for both groups using a modified Objective Structured Assessment of Technical Skills (OSATS) while performing a simulated ovariohysterectomy. Furthermore, both groups were investigated with respect to how they would handle a specific hypothetical surgical complication. Semi-structured interviews were conducted with 17 intervention-group students and were analyzed using thematic analysis. The intervention group showed a significantly better performance and needed significantly less help with the surgical complication than the control group students. Data from interviews furthermore demonstrated that students believed the creative intervention produced increased reflection, more creative initiatives, and a feeling of security before surgery. Our study results thus indicate that an educational tool which stimulates creative thinking can promote reflection, creativity, and self-efficacy in novice surgeons without compromising surgical performance.

Ischemic stroke is a condition increasingly recognized in dogs; however, the number of publications on dogs with ischemic stroke is still limited and hemostatic parameters are infrequently reported. D-dimer levels have been shown to be elevated in people with acute ischemic stroke compared to a healthy control population and it has been proposed that a normal D-dimer can be used to exclude thromboembolism in dogs. In this case series, we report hemostatic parameters, including D-dimer and thromboelastography (TEG) along with clinical and imaging findings for five dogs diagnosed with ischemic stroke. All dogs had a normal D-dimer concentration on presentation. A hypercoagulable state was identified in two dogs based on the results of the TEG, and was suspected in the remaining three cases based on a shortened TEG clot reaction time. Based on the findings in the present cases, a D-dimer within the normal reference range does not seem an appropriate negative predictor for canine ischemic stroke. The demonstration of a possible hypercoagulable state, as identified by the TEG, is an interesting finding which should be explored further to help reveal predisposing hypercoagulable conditions in dogs with ischemic stroke.

Volume measurements of the brain are of interest in the diagnosis of brain pathology. This is particularly so in the investigation hydrocephalus and canine cognitive dysfunction (CCD), both of which result in thinning of the cerebral cortex and enlarged ventricles. Volume assessment can be made using computed tomography or more usually magnetic resonance imaging (MRI). There is, however, some uncertainty in the interpretation of such volume data due to the great variation in skull size and shape seen in dog. In this retrospective study, we examined normal MRI images from 63 dogs < 6 years of age. We used a continuous variable, the cranial index (CrI) to indicate skull shape and compared it with MRI volume measurements derived using Cavalieri's principle. We found a negative correlation between CrI and the ratio of cortical to ventricular volume. Breeds with a high CrI (large laterolateral compared to rostrocaudal cranial cavity dimension) had a smaller ratio of cortical to ventricular volume (low C:V ratio) than breeds with lower CrI skull types. It is important to consider this effect of skull shape on the relative volume estimates of the cerebral cortex and ventricles when trying to establish if pathology is present.

Background Dogs develop spontaneous ischaemic stroke with a clinical picture closely resembling human ischaemic stroke patients. Animal stroke models have been developed, but it has proved difficult to translate results obtained from such models into successful therapeutic strategies in human stroke patients. In order to face this apparent translational gap within stroke research, dogs with ischaemic stroke constitute an opportunity to study the neuropathology of ischaemic stroke in an animal species. Case presentation A 7 years and 8 months old female neutered Rottweiler dog suffered a middle cerebral artery infarct and was euthanized 3 days after onset of neurological signs. The brain was subjected to histopathology and immunohistochemistry. Neuropathological changes were characterised by a pan-necrotic infarct surrounded by peri-infarct injured neurons and reactive microglia/macrophages and astrocytes. Conclusions The neuropathological changes reported in the present study were similar to findings in human patients with ischaemic stroke. The dog with spontaneous ischaemic stroke is of interest as a complementary spontaneous animal model for further neuropathological studies.