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Meningoencephalitis of unknown origin (MUO) represents an umbrella term for inflammatory, non-infectious central nervous system (CNS) diseases in dogs. Current therapeutic approaches, involving long-term glucocorticosteroid use, often fail to provide adequate relief or cure, and the effectiveness of additional immunosuppressive medications remains uncertain. Future advancements in MUO treatment may benefit from patient-specific therapies, potentially enhancing treatment precision, efficacy, and minimizing side effects. However, significant challenges impede this progress, including ambiguity in MUO subtype classification, uncertainties regarding the autoimmune nature vs. infectious triggers, and the lack of reliable diagnostic biomarkers. Clinical heterogeneity and overlapping signs with other encephalopathies further complicate diagnosis and treatment. This review gives an overview about diagnostic findings and immunological features of MUO. It advocates for a more overall characterization of MUO by using a polythetic system to better characterize MUO subtypes, identify immunological treatment targets, and establish a conceptual foundation for future therapeutic trials. Addressing these themes may lead to more effective and less burdensome treatments, improving the quality of life for dogs afflicted with MUO and their owners.

Idiopathic generalized tremor syndrome is a disorder characterized by an acute onset of full-body tremors, sometimes accompanied by vestibulo-cerebellar signs, that is responsive to treatment with corticosteroids. Although considered to have an overall good outcome, relapsing and persistent mild clinical signs have been described. So far, little is known about the etiopathology of this syndrome, but it is believed to have an immune-mediated origin. In human medicine, description of numerous autoantibodies involved in certain non-infectious neurologic disorders has revolutionized understanding of their pathophysiology, diagnosis and treatment. In this multicenter retrospective study, we aimed to describe the clinical signs, course, and outcome of dogs with idiopathic generalized tremor syndrome and correlate potential findings with the presence or absence of autoantibodies associated with autoimmune cerebellar syndromes in humans. Information regarding signalment, history, clinical signs, laboratory findings, diagnostic imaging and testing for regional infectious diseases was gathered and the remaining serum and CSF samples were then analyzed for neural antibodies against targets associated with autoimmune encephalitic diseases of humans. Thirty-three dogs were included, and screening for neural antibodies was performed in 30 of those dogs. The analysis showed an increased titer of mGluR1 antibodies in two dogs, GFAP and later in the course of disease mGluR1 antibodies in one dog and an increase in unspecific autoantibodies which could not be further classified in two dogs. Dogs with detectable neural autoantibodies always had cerebrospinal fluid abnormalities in the form of a pleocytosis, with or without increased protein concentration, and tended to present with hyperthermia, potentially indicating a more severe clinical form of idiopathic generalized tremor syndrome in these cases. In conclusion, idiopathic generalized tremor syndrome is proposed to be an immune-mediated disorder potentially mediated by neural autoantibodies in a subgroup of dogs.

IntroductionThis study investigates the relationship between approaches to learning, self-perceived study burnout, and the level of knowledge among veterinary students. Veterinary educational programs are under regular development and would benefit greatly from detailed feedback on students' knowledge, proficiency, influencing factors, and coping mechanisms.MethodsThe VetRepos consortium developed and calibrated an item repository testing knowledge across the entire veterinary curriculum. Two hundred forty-eight students from seven European veterinary institutions took the VetRepos test, comprising a subset of the repository. They also responded to a questionnaire assessing deep and unreflective learning approaches and self-perceived study burnout, represented by exhaustion and cynicism. Structural equation modeling analyzed the relationship between these latent traits and the VetRepos test score.ResultsThe model failed the exact-fit test but was retained based on global fit indices, inter-item residual correlations, and standardized residual covariances. Root Mean Square Error of Approximation with robust standard errors and scaled test statistic was 0.049 (95% confidence interval 0.033–0.071), scaled and robust Comparative Fit Index 0.95 (0.90–0.98), and scaled Standardized Root Mean Square Residual 0.056 (0.049–0.071). Measurement invariance across study years was not violated (ΔCFI = 0.00, χ2 = 3.78, Δdf = 4, p = 0.44), but it could not be confirmed between genders or universities. The VetRepos test score regressed on the study year [standardized regression coefficient = 0.68 (0.62–0.73)], showed a negative regression on the unreflective learning approach [−0.25 (−0.47 to −0.03)], and a positive regression on the deep approach [0.16 (0.03–0.28)]. No direct association with perceived burnout was observed; however, a significant, medium-sized association was found between the unreflective approach and self-perceived study burnout. No significant differences in learning approaches or perceived burnout were found between study years.DiscussionThe most important source of variance in VetRepos test scores, unrelated to the study year, was the learning approach. The association between the VetRepos test score and self-perceived burnout was indirect. Future research should complement this cross-sectional approach with longitudinal and person-oriented studies, further investigating the relationship between study burnout and learning approaches.

The digitalization of university teaching has been taking place for many years and, in addition to traditional teaching formats such as practicals and face-to-face lectures, more and more e-learning courses have been used in veterinary education for several years. In the context of the COVID-19 pandemic, universities across Germany had to switch to an ad-hoc, purely digital summer semester. This study evaluated the experiences and implementation of the digital summer semester 2020 at the University of Veterinary Medicine Hannover (TiHo) Foundation from the perspective of the teaching staff. In addition to the technical equipment used by lecturers, this survey also focused on the effects of the digital semester on teaching and the future practicality of digital teaching formats and strategies in veterinary education. Therefore, a questionnaire was designed and distributed among lecturers involved in the digital summer semester 2020. One hundred and three completed questionnaires were evaluated. The results of the evaluation show that teachers see huge potential in blended learning as a teaching method in veterinary education. In addition, teachers were able to digitize teaching well with the available hardware and software. The teaching staff saw difficulties above all in the loss of practical training and in the digitalization of practical exercises. Teachers also needed significantly more time to plan and implement digital teaching compared to pure face-to-face teaching. In summary blended learning offers many advantages, such as increased flexibility for students and teaching staff. In order to be able to use digital teaching methods and strategies profitably in veterinary education in the future, well thought-out didactic concepts and further technical expansion of the universities are required. In addition, the digital skills of teaching staff should be further trained and promoted.

IntroductionThis study investigates the log data and response behavior from invigilated in-person electronic timed exams at the University of Veterinary Medicine Hannover, Foundation, Germany. The primary focus is on understanding how various factors influence the time needed per exam item, including item format, item difficulty, item discrimination and character count. The aim was to use these results to derive recommendations for designing timed online distance examinations, an examination format that has become increasingly important in recent years.MethodsData from 216,625 log entries of five electronic exams, taken by a total of 1,241 veterinary medicine students in 2021 and 2022, were analyzed. Various statistical methods were employed to assess the correlations between the recorded parameters.ResultsThe analysis revealed that different item formats require varying amounts of time. For instance, image-based question formats and Kprim necessitated more than 60 s per item, whereas one-best-answer multiple-choice questions (MCQs) and individual Key Feature items were effectively completed in less than 60 s. Furthermore, there was a positive correlation between character count and response time, suggesting that longer items require more time. A negative correlation could be verified for the parameters “difficulty” and “discrimination index” towards response time, indicating that more challenging items and those that are less able to differentiate between high- and low-performing students take longer to answer.ConclusionThe findings highlight the need for careful consideration of the ratio of item formats when defining time limits for exams. Regarding exam design, the literature mentions that time pressure is a critical factor, since it can negatively impact students’ exam performance and some students, such as those with disabilities, are particularly disadvantaged. Therefore, this study emphasizes finding the right time limits to provide sufficient time for answering questions and reducing time pressure. In the context of unsupervised online exams, the findings of this study support previous recommendations that implementation of a stringent time limit might be a useful strategy to reduce cheating.

The OSCE is a proven instrument for testing practical skills of students, not only in the (veterinary) medical field. At the University of Veterinary Medicine Hannover, Foundation (TiHo), students must complete a 10-week rotation in one of the university’s own clinics during the practical year in the 9th and 10th semesters in addition to other practical training. Within this framework, the first training for acquiring clinical practical skills with a formative examination (OSCE; Objective Structured Clinical Examination) was developed in the Clinical Skills Lab (CSL) in 2014. Since 2018, the TiHo has been the first veterinary medical training institution in Germany to conduct electronic OSCEs (eOSCEs). In the future, eOSCEs will also be introduced as a summative examination at the TiHo. For this reason, students in the practical year of the winter semester 2021/2022 and summer semester 2022 as well as former and current examiners were surveyed regarding their satisfaction with the eOSCE examination format as part of this study. The 175 analyzed questionnaires from students and 27 analyzed questionnaires from examiners showed a high level of satisfaction with the eOSCE overall, but at the same time indicated problems that should be ironed out before it is introduced as a summative examination in the state examination. In addition to its standardization and objectivity, the examination format also convinced with its quality-assurance review procedure and the direct feedback possibility with regard to the students’ performance.

Meningoencephalitis of unknown origin (MUO) represents an umbrella term for inflammatory, non-infectious central nervous system (CNS) diseases in dogs. Current therapeutic approaches, involving long-term glucocorticosteroid use, often fail to provide adequate relief or cure, and the effectiveness of additional immunosuppressive medications remains uncertain. Future advancements in MUO treatment may benefit from patient-specific therapies, potentially enhancing treatment precision, efficacy, and minimizing side effects. However, significant challenges impede this progress, including ambiguity in MUO subtype classification, uncertainties regarding the autoimmune nature vs. infectious triggers, and the lack of reliable diagnostic biomarkers. Clinical heterogeneity and overlapping signs with other encephalopathies further complicate diagnosis and treatment. This review gives an overview about diagnostic findings and immunological features of MUO. It advocates for a more overall characterization of MUO by using a polythetic system to better characterize MUO subtypes, identify immunological treatment targets, and establish a conceptual foundation for future therapeutic trials. Addressing these themes may lead to more effective and less burdensome treatments, improving the quality of life for dogs afflicted with MUO and their owners. [ABSTRACT FROM AUTHOR]

Idiopathic generalized tremor syndrome is a disorder characterized by an acute onset of full-body tremors, sometimes accompanied by vestibulo-cerebellar signs, that is responsive to treatment with corticosteroids. Although considered to have an overall good outcome, relapsing and persistent mild clinical signs have been described. So far, little is known about the etiopathology of this syndrome, but it is believed to have an immune-mediated origin. In human medicine, description of numerous autoantibodies involved in certain noninfectious neurologic disorders has revolutionized understanding of their pathophysiology, diagnosis and treatment. In this multicenter retrospective study, we aimed to describe the clinical signs, course, and outcome of dogs with idiopathic generalized tremor syndrome and correlate potential findings with the presence or absence of autoantibodies associated with autoimmune cerebellar syndromes in humans. Information regarding signalment, history, clinical signs, laboratory findings, diagnostic imaging and testing for regional infectious diseases was gathered and the remaining serum and CSF samples were then analyzed for neural antibodies against targets associated with autoimmune encephalitic diseases of humans. Thirty-three dogs were included, and screening for neural antibodies was performed in 30 of those dogs. The analysis showed an increased titer of mGluR1 antibodies in two dogs, GFAP and later in the course of disease mGluR1 antibodies in one dog and an increase in unspecific autoantibodies which could not be further classified in two dogs. Dogs with detectable neural autoantibodies always had cerebrospinal fluid abnormalities in the form of a pleocytosis, with or without increased protein concentration, and tended to present with hyperthermia, potentially indicating a more severe clinical form of idiopathic generalized tremor syndrome in these cases. In conclusion, idiopathic generalized tremor syndrome is proposed to be an immune-mediated disorder potentially mediated by neural autoantibodies in a subgroup of dogs. [ABSTRACT FROM AUTHOR]

IntroductionInformation on the use of telemedical approaches in the context of veterinary medicine is evolving. As in human medicine, veterinary medicine is subject to an increasing digitalization effort. The aim of the current study was to investigate the perspective of German veterinarians regarding their awareness and usage of telemedical approaches. Furthermore, the degree of implementation of different digital approaches in the context of German veterinary medicine was elaborated.MethodsA literature review, that also aimed to address the necessary framework or standardization of these digitalization efforts and potential barriers such as legal or infrastructural aspects, provided information for the empirical research. Using a quantitative research approach, the perspective of German veterinarians was surveyed.ResultsIn total, responses from 169 veterinarians were analyzed. The results show that digital approaches were used by veterinarians and the usage was enhanced by the COVID-19 crisis.DiscussionHowever, the lack of a clear legal framework may be a significant barrier for further implementation. This survey provides a basis for a critical discussion on the use of veterinary telemedicine in Germany. The results may contribute to future strategies for the implementation and development of necessary policies, training, and service applications within Germany, which may be transferable for the profession in other countries.

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. β-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.

The term “meningoencephalitis of unknown origin” (MUO) describes a group of different encephalitides in dogs in which no infectious agent can be identified and a multifactorial etiology is suspected. Among others, genetic factors and unknown triggers seem to be involved. Included are necrotizing leukoencephalitis (NLE), necrotizing meningoencephalitis (NME), and granulomatous meningoencephalitis (GME). In this case series, we describe the histopathological findings of four toy breed dogs with focal or multifocal necrotizing encephalitis and mainly lymphocytic perivascular infiltrates on histopathological examination. At the same time, however, in all dogs, focal or multifocal high-grade angiocentric granulomatous inflammatory lesions were evident with focal histiocytic perivascular infiltrates in the brain. The former changes are typical for NLE and NME. In contrast, the latter changes are indicative of GME. This case series shows that the boundaries between the necrotizing and granulomatous variants of MUO might be smooth and suggests that NLE, NME, and GME are not as distinct as previously described. This finding could be a crucial piece of the puzzle in the study of the pathogenesis of MUO as individual susceptibility and specific triggers could be responsible for the manifestation of the different MUO subtypes.

Introduction: This study investigates the relationship between approaches to learning, self-perceived study burnout, and the level of knowledge among veterinary students. Veterinary educational programs are under regular development and would benefit greatly from detailed feedback on students' knowledge, proficiency, influencing factors, and coping mechanisms. Methods: The VetRepos consortium developed and calibrated an item repository testing knowledge across the entire veterinary curriculum. Two hundred forty-eight students from seven European veterinary institutions took the VetRepos test, comprising a subset of the repository. They also responded to a questionnaire assessing deep and unreflective learning approaches and self-perceived study burnout, represented by exhaustion and cynicism. Structural equation modeling analyzed the relationship between these latent traits and the VetRepos test score. Results: The model failed the exact-fit test but was retained based on global fit indices, inter-item residual correlations, and standardized residual covariances. Root Mean Square Error of Approximation with robust standard errors and scaled test statistic was 0.049 (95% confidence interval 0.033-0.071), scaled and robust Comparative Fit Index 0.95 (0.90-0.98), and scaled Standardized Root Mean Square Residual 0.056 (0.049-0.071). Measurement invariance across study years was not violated (ΔCFI = 0.00, χ² = 3.78, Δdf = 4, p = 0.44), but it could not be confirmed between genders or universities. The VetRepos test score regressed on the study year [standardized regression coefficient = 0.68 (0.62-0.73)], showed a negative regression on the unreflective learning approach [-0.25 (-0.47 to -0.03)], and a positive regression on the deep approach [0.16 (0.03-0.28)]. No direct association with perceived burnout was observed; however, a significant, medium-sized association was found between the unreflective approach and self-perceived study burnout. No significant differences in learning approaches or perceived burnout were found between study years. Discussion: The most important source of variance in VetRepos test scores, unrelated to the study year, was the learning approach. The association between the VetRepos test score and self-perceived burnout was indirect. Future research should complement this cross-sectional approach with longitudinal and person-oriented studies, further investigating the relationship between study burnout and learning approaches. [ABSTRACT FROM AUTHOR]

The digitalization of university teaching has been taking place for many years and, in addition to traditional teaching formats such as practicals and face-to-face lectures, more and more e-learning courses have been used in veterinary education for several years. In the context of the COVID-19 pandemic, universities across Germany had to switch to an ad-hoc, purely digital summer semester. This study evaluated the experiences and implementation of the digital summer semester 2020 at the University of Veterinary Medicine Hannover (TiHo) Foundation from the perspective of the teaching staff. In addition to the technical equipment used by lecturers, this survey also focused on the effects of the digital semester on teaching and the future practicality of digital teaching formats and strategies in veterinary education. Therefore, a questionnaire was designed and distributed among lecturers involved in the digital summer semester 2020. One hundred and three completed questionnaires were evaluated. The results of the evaluation show that teachers see huge potential in blended learning as a teaching method in veterinary education. In addition, teachers were able to digitize teaching well with the available hardware and software. The teaching staff saw difficulties above all in the loss of practical training and in the digitalization of practical exercises. Teachers also needed significantly more time to plan and implement digital teaching compared to pure face-to-face teaching. In summary blended learning offers many advantages, such as increased flexibility for students and teaching staff. In order to be able to use digital teaching methods and strategies profitably in veterinary education in the future, well thought-out didactic concepts and further technical expansion of the universities are required. In addition, the digital skills of teaching staff should be further trained and promoted. [ABSTRACT FROM AUTHOR]

Introduction: This study investigates the log data and response behavior from invigilated in-person electronic timed exams at the University of Veterinary Medicine Hannover, Foundation, Germany. The primary focus is on understanding how various factors influence the time needed per exam item, including item format, item difficulty, item discrimination and character count. The aim was to use these results to derive recommendations for designing timed online distance examinations, an examination format that has become increasingly important in recent years. Methods: Data from 216,625 log entries of five electronic exams, taken by a total of 1,241 veterinary medicine students in 2021 and 2022, were analyzed. Various statistical methods were employed to assess the correlations between the recorded parameters. Results: The analysis revealed that different item formats require varying amounts of time. For instance, image-based question formats and Kprim necessitated more than 60 s per item, whereas one-best-answer multiple-choice questions (MCQs) and individual Key Feature items were effectively completed in less than 60 s. Furthermore, there was a positive correlation between character count and response time, suggesting that longer items require more time. A negative correlation could be verified for the parameters "difficulty" and "discrimination index" towards response time, indicating that more challenging items and those that are less able to differentiate between high- and low-performing students take longer to answer. Conclusion: The findings highlight the need for careful consideration of the ratio of item formats when defining time limits for exams. Regarding exam design, the literature mentions that time pressure is a critical factor, since it can negatively impact students' exam performance and some students, such as those with disabilities, are particularly disadvantaged. Therefore, this study emphasizes finding the right time limits to provide sufficient time for answering questions and reducing time pressure. In the context of unsupervised online exams, the findings of this study support previous recommendations that implementation of a stringent time limit might be a useful strategy to reduce cheating. [ABSTRACT FROM AUTHOR]

Drug-resistant epilepsy is a common complaint in dogs and affects up to 30% of dogs with idiopathic epilepsy. Experimental data suggest that targeting cyclooxygenase-2 (COX-2) mediated signaling might limit excessive excitability and prevent ictogenesis. Moreover, the role of COX-2 signaling in the seizure-associated induction of P-glycoprotein has been described. Thus, targeting this pathway may improve seizure control based on disease-modifying effects as well as enhancement of brain access and efficacy of the co-administered antiseizure medication. The present open-label non-controlled pilot study investigated the efficacy and tolerability of a COX-2 inhibitor (firocoxib) add-on therapy in a translational natural occurring chronic epilepsy animal model (client-owned dogs with phenobarbital-resistant idiopathic epilepsy). The study cohort was characterized by frequent tonic–clonic seizures and cluster seizures despite adequate phenobarbital treatment. Enrolled dogs (n = 17) received a firocoxib add-on therapy for 6 months. Tonic–clonic seizure and cluster seizure frequencies were analyzed at baseline (6 months) months during the study (6 months). The responders were defined by a substantial reduction of tonic–clonic seizure and cluster seizure frequency (≥50%). In total, eleven dogs completed the study and were considered for the statistical analysis. Two dogs (18%, 2/11) were classified as responders based on their change in seizure frequency. Interestingly, those two dogs had the highest baseline seizure frequency. The overall tolerability was good. However, given the low percentage of responders, the present data do not support an overall considerable efficacy of COX-2 inhibitor add-on therapy to overcome naturally occurring phenobarbital-resistant epilepsy in dogs. Further translational evaluation should only be considered in the canine patients with a very high baseline seizure density.

Progress testing is an assessment tool for longitudinal measurement of increase in knowledge of a specific group, e.g., students, which is well-known in medical education. This article gives an overview of progress testing in veterinary education with a focus on the progress test of the German-speaking countries. The “progress test veterinary medicine” (PTT) was developed in 2013 as part of a project by the Competence Centre for E-Learning, Didactics and Educational Research in Veterinary Medicine—a project cooperation of all German-speaking institutes for veterinary medicine in Germany, Austria, and Switzerland. After the end of the project, the PTT was still continued at six locations, at each of the five German schools for veterinary medicine and additionally in Austria. Further changes to the PTT platform and the analysis were carried out to optimize the PTT for continuing to offer the test from 2017 to 2019. The PTT is an interdisciplinary, formative electronic online test. It is taken annually and is composed of 136 multiple-choice single best answer questions. In addition, a “don't know” option is given. The content of the PTT refers to the day 1 competencies described by the European Association of Establishments for Veterinary Education. The platform Q-Exam® Institutions (IQuL GmbH, Bergisch Gladbach, Germany) is used for creating and administrating the PTT questions, the review processes and organizing of the online question database. After compiling the test by means of a blueprint, the PTT file is made available at every location. After the last PTT in 2018, the link to an evaluation was sent to the students from four out of these six partner Universities. The 450 analyzed questionnaires showed that the students mainly use the PTT to compare their individual results with those of fellow students in the respective semester. To conclude our study, a checklist with our main findings for implementing progress testing was created.

Meningoencephalomyelitis of unknown origin (MUO) is an umbrella term describing inflammatory changes of the central nervous system (CNS) with suspected non-infectious etiology. Diagnosis of MUO mostly remains presumed in a clinical setting. Histopathological and immunohistochemical examination of CNS tissue represent additional tools for detection of inflammation and the exclusion of specific infectious agents. While MUO is well-described in canine patients, only little is known about MUO in cats. Previous reports of feline MUO involve either clinical findings or histopathological examination but not both. The present case series is the first report describing both clinical and histopathological findings of feline MUO: Four cats (age: 1.7–17.8 years) showed acute to chronic progressive neurological signs of encephalopathy or myelopathy. Three cats had extraneural signs (hyperthermia, weight loss, hyporexia, leukocytosis). Magnetic resonance imaging (MRI) showed multifocal intraparenchymal lesions in forebrain, brainstem or spinal cord with homogenous contrast enhancement (2/2). Cerebrospinal fluid (CSF) examination was normal or displayed albuminocytologic dissociation. Histopathology revealed a multifocal, lympho-histiocytic meningoencephalitis in three cases and a lympho-histiocytic myelitis in one case. Immunohistochemistry for feline parvovirus, feline coronavirus, feline herpesvirus, tick borne encephalitis virus, Borna disease virus, morbillivirus, rabies virus, suid herpesvirus-1, and Toxoplasma gondii were negative in all cases.One Sentence SummaryThis case series is the first one reporting both clinical and histopathological findings in cats with MUO. Feline MUO incorporates heterogeneous subtypes of sterile CNS inflammation.

Meningoencephalitis of unknown origin (MUO) is an umbrella term for a variety of subtypes of meningoencephalitis of dogs and cats with no identifiable infectious agent. In dogs, granulomatous meningoencephalitis (GME), necrotizing meningoencephalitis (NME), and necrotizing leukoencephalitis (NLE) are the most commonly reported subtypes. However, sporadically there are reports about other subtypes such as greyhound encephalitis or eosinophilic meningoencephalitis. The following case series presents three dogs with peracute to acute progressive signs of encephalopathy. The magnetic resonance imaging (MRI) of two dogs (post mortem n = 1/2) showed severe, diffuse swelling of the cortical gray matter with increased signal intensity in T2weighted (w) and fluid-attenuated inversion recovery (FLAIR) and decreased signal intensity in T1w. Additionally, focal to multifocal areas with signal void in both dogs and caudal transforaminal herniation of the cerebellum in one dog was observed. Post mortem histopathological examination revealed lympho-histiocytic encephalitis and central nervous system (CNS) vasculitis in all dogs. No infectious agents were detectable by histopathology (hematoxylin and eosin stain), periodic acid-Schiff reaction (PAS), Ziehl-Neelsen stain and immunohistochemistry for Canine adenovirus-1, Parvovirus, Listeria monocytogenes, Parainfluenzavirus, Toxoplasma gondii, Herpes-suis virus, Pan-Morbillivirus, Tick born encephalitis virus, Severe acute respiratory syndrome coronavirus (SARS-CoV) 2. Furthermore, two dogs were tested negative for rabies virus. To the best of the authors' knowledge, this is the first report of a lympho-histiocytic encephalitis with CNS vasculitis with no identifiable infectious agent. It is suggested to consider this as an additional subtype of MUO with severe clinical signs.

To provide students of veterinary medicine with the necessary day 1 competences, e-learning offerings are increasingly used in addition to classical teaching formats such as lectures. For example, virtual patients offer the possibility of case-based, computer-assisted learning. A concept to teach and test clinical decision-making is the key feature (KF) approach. KF questions consist of three to five critical points that are crucial for the case resolution. In the current study usage, learning success, usability and acceptance of KF cases as neurological virtual patients should be determined in comparison to the long cases format. Elective courses were offered in winter term 2019/20 and summer term 2020 and a total of 38 virtual patients with neurological diseases were presented in the KF format. Eight cases were provided with a new clinical decision-making application (Clinical Reasoning Tool) and contrasted with eight other cases without the tool. In addition to the evaluation of the learning analytics (e.g., processing times, success rates), an evaluation took place after course completion. After 229 course participations (168 individual students and additional 61 with repeated participation), 199 evaluation sheets were completed. The average processing time of a long case was 53 min, while that of a KF case 17 min. 78% of the long cases and 73% of KF cases were successfully completed. The average processing time of cases with Clinical Reasoning Tool was 19 min. The success rate was 58.3 vs. 60.3% for cases without the tool. In the survey, the long cases received a ranking (1 = very good, 6 = poor) of 2.4, while KF cases received a grade of 1.6, 134 of the respondents confirmed that the casework made them feel better prepared to secure a diagnosis in a real patient. Flexibility in learning (n = 93) and practical relevance (n = 65) were the most frequently listed positive aspects. Since KF cases are short and highlight only the most important features of a patient, 30% (n = 70) of respondents expressed the desire for more specialist information. KF cases are suitable for presenting a wide range of diseases and for training students' clinical decision-making skills. The Clinical Reasoning Tool can be used for better structuring and visualizing the reasoning process.

A male 10-year-old captive red kangaroo (Macropus rufus) was presented with a chronic progressive pelvic limb lameness and reluctance to jump. The general examination revealed a palpable induration of the lumbar epaxial muscles. Magnetic resonance imaging performed under general anesthesia revealed bilateral almost symmetric, well-circumscribed mass lesions in superficial erector spinae muscles. The lesions had irregular to multilobulated appearance with hyper-, hypo-, and isointense areas in T2- and T1-weighted (w) sequences without contrast enhancement. On computed tomography, a peripheral rim of mineralization was apparent. Histopathological analysis of a muscle biopsy showed osseous trabeculae with rare clusters of chondrocytes indicating metaplasia of muscle tissue to bone. No indications of inflammation or malignancy were visible. The clinical, histopathological, and imaging workup of this case was consistent with myositis ossificans circumscripta. This disorder is particularly well-known among human professional athletes such as basketball players, where excessive, chronic-repetitive force or blunt trauma causes microtrauma to the musculature. Metaplasia of muscle tissue due to abnormal regeneration processes causes heterotopic ossification. The kangaroo's clinical signs improved with cyto-reductive surgery, cage rest, weight reduction, and meloxicam without further relapse.

Genetic predisposition of idiopathic epilepsy (IE) has been demonstrated in individual breeds. According to the responsible breeding association in Germany, the average incidence of registered Great Swiss Mountain Dogs (GSMDs) with seizures between the years 1999 and 2019 is 2.56%, a genetic predisposition in this breed is suspected. To describe the seizure phenotype and to examine seizure causes, a retrospective, questionnaire-based study was performed. In cooperation with the Swiss Mountain Dog Association of Germany e.V. (SSV e.V.), 114 questionnaires filled in by owners of GSMD displaying seizures and filled in by their respective veterinarians between the years 2005–2021 were evaluated. Seizure characteristics, clinical and further examinations, treatment, treatment responses, and pedigree information were collected. In this study, 94 (83.06%) dogs had IE (suspected genetic epilepsy) confirmed with confidence level TIER 1, 2, or 3. The remaining 20 dogs showed the signs of structural epilepsy, reactive seizures, or epilepsy of unknown cause and were therefore excluded from further analysis. The average age at seizure onset was 28.83 months. Male GSMDs were significantly more often affected by IE than females. The most common seizure type was focal evolving into generalized seizures (64.5%). Seizures often began with vomiting, retching, or salivation. Cluster seizures (CS) (48.9%) and status epilepticus (SE) (37.2%) were observed in a large proportion of dogs. During the observation time, a total of 49 animals (52.13%) died. Out of those, 19 dogs (20.21%) were euthanized in SE or during CS and 14 dogs (14.9%) died spontaneously during CS or SE. The median age at death was 4 years, and the median survival time for the time, when the dog was suffering from seizures, was found to be 18 months. Both occurrence of CS (p = 0.0076) and occurrence of SE (p = 0.0859) had an impact on survival time. In GSMD, idiopathic epilepsy presents with a severe phenotype with frequently occurring CS and SE. This study could serve as basis for further genetic evaluations as well as to provide individual treatment recommendations.

Inflammatory polyradiculoneuropathy (IMPN) is one of the causes of sudden onset of neuromuscular signs such as para-/tetraparesis in young cats. Even though most cases have a favorable outcome, persistent deficits, relapses, and progressive courses are occasionally seen. As clinical presentation does not always appear to predict outcome and risk of recurrence, this study was initiated to screen for prognostic biopsy findings in a large cohort of histologically confirmed IMPN cases with clinical follow-up. In total, nerve and muscle specimens of 107 cats with biopsy diagnosis of presumed autoreactive inflammatory polyneuropathy and 22 control cases were reviewed by two blinded raters for a set of 36 histological parameters. To identify patterns and subtypes of IMPN, hierarchical k-means clustering of 33 histologic variables was performed. Then, the impact of histological parameters on IMPN outcome was evaluated via an univariate analysis to identify variables for the final multivariate model. The data on immediate outcome and follow-up were collected from submitting neurologists using a purpose-designed questionnaire. Hierarchical k-means clustering sorted the tissues into 4 main categories: cluster 1 (44/129) represents a purely inflammatory IMPN picture, whereas cluster 2 (47/129) was accompanied by demyelinating features and cluster 3 (16/129) by Wallerian degeneration. Cluster 4 (22/129) reflects normal tissues from non-neuropathic control cats. Returned questionnaires provided detailed information on outcome in 63 animals. They were categorized into recovered and non-recovered. Thereby, fiber-invasive infiltrates by mononuclear cells and mild fiber loss in intramuscular nerve branches correlated with higher probabilities of recovery. Remyelination in semithin sections, on the other hand, is correlated with a less favorable outcome. Animals grouping in cluster 1 had a tendency to a higher probability of recovery compared to other clusters. In conclusion, diagnosis of feline IMPN from nerve and muscle biopsies allowed for the identification of histologic features that were positively or negatively correlated with outcome.

Extracellular traps (ETs) are DNA networks formed by immune cells to fight infectious diseases by catching and attacking pathogenic microorganisms. Uncontrolled ET formation or impaired ET clearance can cause tissue and organ damage. Steroid-responsive meningitis-arteritis (SRMA) represents an immune-mediated, presumably non-infectious, purulent leptomeningitis and fibrinoid-necrotizing arteritis and periarteritis of young-adult dogs. Chronic and recurrent cases of SRMA are characterized by lymphohistiocytic inflammatory cell infiltration in the meninges and perivascular tissue. This study aimed to identify extracellular traps in dogs with SRMA, a model for immune-mediated diseases in the central nervous system (CNS). Hematoxylin and eosin-stained samples of two young dogs with chronic, recurrent SRMA were examined by light microscopy for characteristic lesions and consecutive slices of affected tissues were stained for detection of ETs by immunofluorescence microscopy using antibodies against DNA–histone-1 complexes, myeloperoxidase, and citrullinated histone H3. Histology revealed purulent and lymphohistiocytic leptomeningitis (n = 2/2) with meningeal periarteritis (n = 2/2) and periadrenal located lymphohistiocytic periarteritis (n = 1). Extracellular DNA networks and inflammatory cell infiltrates of macrophages, neutrophil granulocytes, and lymphocytes were detected in the subarachnoid space of the leptomeninx (n = 2/2) and perivascularly in meningeal (n = 2/2) as well as periadrenal vessels (n = 1/1). In summary, extracellular DNA fibers and attached ET markers are detectable in affected perivascular and meningeal tissues of dogs suffering from SRMA. The proof of principle could be confirmed that ETs are present in canine, inflammatory, and non-infectious CNS diseases and possibly play a role in the pathogenesis of SRMA.

There is a paucity of information on the clinical course and outcome of young cats with polyneuropathy. The aim of the study was to describe the clinical features, diagnostic investigations, and outcome of a large cohort of cats with inflammatory polyneuropathy from several European countries. Seventy cats with inflammatory infiltrates in intramuscular nerves and/or peripheral nerve biopsies were retrospectively included. Information from medical records and follow up were acquired via questionnaires filled by veterinary neurologists who had submitted muscle and nerve biopsies (2011–2019). Median age at onset was 10 months (range: 4–120 months). The most common breed was British short hair (25.7%), followed by Domestic short hair (24.3%), Bengal cat (11.4%), Maine Coon (8.6%) and Persian cat (5.7%), and 14 other breeds. Male cats were predominantly affected (64.3%). Clinical signs were weakness (98.6%) and tetraparesis (75.7%) in association with decreased withdrawal reflexes (83.6%) and, less commonly, cranial nerve signs (17.1%), spinal pain/hyperesthesia (12.9%), and micturition/defecation problems (14.3%). Onset was sudden (30.1%) or insidious (69.1%), and an initial progressive phase was reported in 74.3%. Characteristic findings on electrodiagnostic examination were presence of generalized spontaneous electric muscle activity (89.6%), decreased motor nerve conduction velocity (52.3%), abnormal F-wave studies (72.4%), pattern of temporal dispersion (26.1%) and unremarkable sensory tests. The clinical course was mainly described as remittent (49.2%) or remittent-relapsing (34.9%), while stagnation, progressive course or waxing and waning were less frequently reported. Relapses were common and occurred in 35.7% of the cats' population. An overall favorable outcome was reported in 79.4% of patients. In conclusion, young age at the time of diagnosis and sudden onset of clinical signs were significantly associated with recovery (p < 0.05). Clinical and electrodiagnostic features and the remittent-relapsing clinical course resembles juvenile chronic inflammatory demyelinating polyneuropathy (CIDP), as seen in human (children/adolescents), in many aspects.

Sudden unexpected death in human epileptic patients (SUDEP) is defined as death related to recurrent unprovoked seizures, death occurring unexpectedly, and suddenly in a patient with reasonable state of health, without an obvious medical cause of death, trauma, asphyxia, or intractable status epilepticus, and in post mortem examination no obvious reason for death can be found. “Probable SUDEP” (pSUDEP) is defined as SUDEP not confirmed pathologically. The adapted abbreviation for dogs is used in the following: “pSUDED” (probable sudden unexpected death in dogs with epilepsy). The aim of the present monocentric retrospective study using an online questionnaire was to evaluate the occurrence of pSUDED. Data of canine patients presented with seizures between 01/1998 and 05/2018 were retrospectively analyzed and classified according to their etiology (n = 1,503). Owners were contacted by telephone to participate in answering a validated questionnaire. A total of 509 owners were reached, and 373 owners completed the questionnaire. In addition to signalement (e.g., breed), special attention was paid to the frequency and presentation of seizures and seizures in the context of death. Fifty-one percent (191/373) of the dogs were dead at the endpoint of the study. A large proportion of the dogs was euthanized (149/191) because of seizure severity or health problems unrelated to seizures. Idiopathic epilepsy (IE) was diagnosed in 19/34 dogs which died unexpectedly. Of these seven animals had to be excluded for further investigation of pSUDED because of status epilepticus or aspiration pneumonia as a result of the seizures. In 12 dogs with IE the last seizure event occurred between 6 h and ~3 months before death. pSUDED was suspected in these dogs and an occurrence rate of 4.5–10% was calculated. pSUDED appears in a similar occurrence rate as human SUDEP and should be considered as a possible complication in epileptic dogs. The results of this study suggest that dogs with IE but especially those with brachycephalic syndrome and cluster seizures have an increased risk to die of pSUDED. Owners of dogs with seizures should be educated about the risk of sudden death in dogs with epilepsy.

Spinal cord injury (SCI) in dogs is commonly attributed to intervertebral disc extrusion (IVDE). Over the last years substantial progress was made in the elucidation of factors contributing to the pathogenesis of this common canine disease. A detailed understanding of the underlying histopathological and molecular alterations in the lesioned spinal cord represents a prerequisite to translate knowledge on the time course of secondary injury processes into the clinical setting. This review summarizes the current state of knowledge of the underlying pathology of canine IVDE-related SCI. Pathological alterations in the spinal cord of dogs affected by IVDE-related SCI include early and persisting axonal damage and glial responses, dominated by phagocytic microglia/macrophages. These processes are paralleled by a pro-inflammatory microenvironment with dysregulation of cytokines and matrix metalloproteinases within the spinal cord. These data mirror findings from a clinical and therapeutic perspective and can be used to identify biomarkers that are able to more precisely predict the clinical outcome. The pathogenesis of progressive myelomalacia, a devastating complication of SCI in dogs, is not understood in detail so far; however, a fulminant and exaggerating secondary injury response with massive reactive oxygen species formation seems to be involved in this unique neuropathological entity. There are substantial gaps in the knowledge of pathological changes in IVDE with respect to more advanced and chronic lesions and the potential involvement of demyelination. Moreover, the role of microglia/macrophage polarization in IVDE-related SCI still remains to be investigated. A close collaboration of clinical neurologists and veterinary pathologists will help to facilitate an integrative approach to a more detailed understanding of the molecular pathogenesis of canine IVDE and thus to identify therapeutic targets.

Intervertebral disc disease (IVDD) has been recognized in dogs since the 1800s, when the first descriptions of extruded disc material within the vertebral canal were published. In the intervening time our understanding of intervertebral disc pathology in dogs and cats has increased dramatically, with many variations of IVDD described. Whilst the volume of literature and collective understanding of IVDD has expanded, there has also been scope for confusion as the definition of intervertebral disc disease, with its myriad different manifestations, becomes more complicated. A large volume of literature has aimed to combine the use of histopathology, diagnostic imaging and clinical findings to better understand the various ways in which IVDD can be classified. Much of this research has focused on the classification of mechanisms of intervertebral disc degeneration, centering around the differences between, and overlaps in, IVDD in chondrodystrophic and non-chondrodystrophic dog breeds. However, with the increasing availability of advanced imaging modalities allowing more accurate antemortem diagnosis, the concept of IVDD has expanded to include other clinical presentations that may not fit into traditional models of classification of IVDD. This review aims to provide an up to date overview of both historical and current systems of IVDD classification, highlighting the important findings and controversies underpinning them.

Some dogs do not make a full recovery following medical or surgical management of acute canine intervertebral disc herniation (IVDH), highlighting the limits of currently available treatment options. The multitude of difficulties in treating severe spinal cord injury are well-recognized, and they have spurred intense laboratory research, resulting in a broad range of strategies that might have value in treating spinal cord-injured dogs. These include interventions that aim to directly repair the spinal cord lesion, promote axonal sparing or regeneration, mitigate secondary injury through neuroprotective mechanisms, or facilitate functional compensation. Despite initial promise in experimental models, many of these techniques have failed or shown mild efficacy in clinical trials in humans and dogs, although high quality evidence is lacking for many of these interventions. However, the continued introduction of new options to the veterinary clinic remains important for expanding our understanding of the mechanisms of injury and repair and for development of novel and combined strategies for severely affected dogs. This review outlines adjunctive or emerging therapies that have been proposed as treatment options for dogs with acute IVDH, including discussion of local or lesion-based approaches as well as systemically applied treatments in both acute and subacute-to-chronic settings. These interventions include low-level laser therapy, electromagnetic fields or oscillating electrical fields, adjunctive surgical techniques (myelotomy or durotomy), systemically or locally-applied hypothermia, neuroprotective chemicals, physical rehabilitation, hyperbaric oxygen therapy, electroacupuncture, electrical stimulation of the spinal cord or specific peripheral nerves, nerve grafting strategies, 4-aminopyridine, chondroitinase ABC, and cell transplantation.

There is a clear need for new methods of treatment of acute disc herniation in dogs, most obviously to address the permanent loss of function that can arise because of the associated spinal cord injury. Clinical trials form the optimal method to introduce new therapies into everyday clinical practice because they are a reliable source of unbiased evidence of effectiveness. Although many designs are available, parallel cohort trials are most widely applicable to acute disc herniation in dogs. In this review another key trial design decision—that between pragmatic and explanatory approaches—is highlighted and used as a theme to illustrate the close relationship between trial objective and design. Acute disc herniation, and acute spinal cord injury, is common in dogs and there is a multitude of candidate interventions that could be trialed. Most current obstacles to large-scale clinical trials in dogs can be overcome by collaboration and cooperation amongst interested veterinarians.

Acute thoracolumbar spinal cord injury (SCI) is common in dogs frequently secondary to intervertebral disc herniation. Following severe injury, some dogs never regain sensory function to the pelvic limbs or tail and are designated chronically “deep pain negative.” Despite this, a subset of these dogs develop spontaneous motor recovery over time including some that recover sufficient function in their pelvic limbs to walk independently without assistance or weight support. This type of ambulation is commonly known as “spinal walking” and can take up to a year or more to develop. This review provides a comparative overview of locomotion and explores the physiology of locomotor recovery after severe SCI in dogs. We discuss the mechanisms by which post-injury plasticity and coordination between circuitry contained within the spinal cord, peripheral sensory feedback, and residual or recovered supraspinal connections might combine to underpin spinal walking. The clinical characteristics of spinal walking are outlined including what is known about the role of patient or injury features such as lesion location, timeframe post-injury, body size, and spasticity. The relationship between the emergence of spinal walking and electrodiagnostic and magnetic resonance imaging findings are also discussed. Finally, we review possible ways to predict or facilitate recovery of walking in chronically deep pain negative dogs. Improved understanding of the mechanisms of gait generation and plasticity of the surviving tissue after injury might pave the way for further treatment options and enhanced outcomes in severely injured dogs.

In veterinary medicine levetiracetam (LEV) is a well-tolerated antiepileptic drug (AED) with only mild to moderate side effects. Behavioral changes are rarely reported in animals. In contrast, in human medicine the impact of LEV on behavior has frequently been described. Since in the Clinic for Small Animals at the University of Veterinary Medicine Hannover single canine patients were observed with behavioral abnormalities after LEV treatment, it was hypothesized that levetiracetam induces behavioral changes or causes an intensifying of pre-existing behavioral abnormalities in dogs with epileptic seizures. This monocentric retrospective study evaluated the incidence of behavioral changes in epileptic dogs treated with the antiepileptic drug LEV based on information obtained in a questionnaire completed by dog owners. Eighty-four client-owned dogs with recurrent seizures receiving LEV as monotherapy, add on treatment or pulse therapy met inclusion criteria. Approximately half of the dogs in the study population were reported to have preexisting behavioral changes before treatment with LEV, and some of these dogs were reported to experience a worsening of behavioral changes (14/44) or the emergence of new behaviors after initiation of LEV therapy (4/44). One quarter of the dogs without pre-existing behavioral abnormalities developed behavioral changes associated with the administration of LEV (10/40). Based on these results, the authors conclude that behavioral changes can occur in dogs being administered LEV, and this should be taken into consideration when discussing treatment options with owners.

In the current study the hypothesis should be proven that T1 weighted Fast Field Echo (FFE) sequence is a useful method to visualize intervertebral disc degeneration, respectively changes of the expected disc appearance. Medical records of 208 dogs were reviewed and images of 781 intervertebral discs were evaluated by two blinded examiners using a modified Pfirrmann classification system in two MRI sequences: FFE and Turbo-Spin-Echo T2-weighted sequence (T2W). The patients were allocated to three categories based on body conformation: (1) brachycephalic and chondrodystrophic breeds, (2) non-chondrodystrophic and non-brachycephalic breeds with a body weight of < 25 kg, and (3) non-chondrodystrophic and non-brachycephalic breeds with a body weight greater or equal 25 kg. In brachycephalic and chondrodystrophic dogs 340 intervertebral discs were evaluated, the majority of them presented a mild change of the normal disc structure, 53% in the FFE sequence and 41% in T2W images. High discrepancies were observed between mild and moderate degeneration: in the FFE-sequence 15% (n = 50) of the discs had signs of mild degeneration, whereas in T2W the same discs were graded as moderately degenerated. In non-chondrodystrophic and non-brachycephalic breeds under 25 kg body weight 320 intervertebral discs were assessed. In the FFE-sequence 52% (n = 166) of the intervertebral discs were judged as having a mild degeneration. In contrast, these same discs were graded as healthy discs (22%), mildly degenerated (33%), moderately degenerated (37%), and severely degenerated (8%) in T2W. In non-chondrodystrophic and non-brachycephalic breeds greater or equal 25 kg 121 intervertebral discs were assessed. The grading was equal in 43%, but differed in one grade (47%) and in two grades (10%) between the two sequences. In both sequences intervertebral disc herniations were equally well-diagnosed. The Kappa coefficient revealed a high discrepancy between the two MRI-sequences. In conclusion, FFE cannot replace the well-established T2W sequence for grading disc degeneration.

A 9-month-old female Weimaraner was presented to the emergency service due to episodes of fever and neck pain. Physical examination revealed a stiff neck posture and elevated body temperature. Shortly after clinical examination was performed, the dog developed peracute onset of non-ambulatory tetraparesis compatible with a C1–C5 spinal cord (SC) lesion. Immediately thereafter (