Rapid hearing threshold assessment with modified auditory brainstem response protocols in dogs.

Introduction: Auditory brainstem response (ABR) is the gold standard for hearing testing in dogs. ABR is commonly used in puppies to diagnose congenital sensorineural deafness. Long test times limit the use for a more comprehensive hearing screening in veterinary practice. This study aimed to establish a super-fast hearing screening protocol in dogs. Methods: Hearing thresholds were routinely measured with a mobile device designed for newborn hearing screening in 90 dogs. We introduced modifications of the ABR protocol, e. g., a binaural test mode, higher stimulus rates, a broadband chirp stimulus, and an algorithm for automatic peak V detection in a stepwise fashion. Hearing thresholds were then measured with fast protocols utilizing either 30 Hz click or 90 Hz broadband chirp stimuli with 80, 60, 40, 30, 20, 10, 0 and -10 dBnHL stimulation intensities. Interrater reliability, agreement between click and chirp hearing thresholds and correlations with clinical characteristics of the dogs were assessed. Results: Using all innovations, the test time for hearing threshold assessment in both ears was reduced to 1.11 min (mean). The chirp stimulus accentuated both, peak V and the subsequent trough, which are essential features for judgement of the hearing threshold, but preceding peaks were less conspicuous. Interrater reliability and agreement between click and chirp hearing threshold was excellent. Dogs >10 years of age and dogs with abnormal hearing score or otitis score had significantly higher hearing thresholds than younger dogs (p ≤ 0.001) or dogs without abnormalities (p < 0.001). Conclusion: The results demonstrate that modifications in ABR protocols speed-up test times significantly while the quality of the recordings for hearing threshold assessment is maintained. Modified ABR protocols enable super-fast hearing threshold assessment in veterinary practice.

Gene-edited pigs: a translational model for human food allergy against alpha-Gal and anaphylaxis.

The prevalence of food allergy is rising and is estimated to approach 10%. Red meat allergy is the first known food allergy elicited by immunoglobulin E (IgE) antibodies recognizing a carbohydrate. Due to the loss of function of the alpha-1,3-galactosyltransferase (GGTA1) gene in humans, the disaccharide galactose-α-1,3-galactose (α-Gal) cannot be synthesized and therefore became immunogenic. IgE sensitization is elicited through the skin by repetitive tick bites transmitting α-Gal. The underlying mechanisms regarding innate and adaptive immune cell activation, including the B-cell isotype switch to IgE, are poorly understood, requiring further research and physiologically relevant animal models. Here, we describe a new animal model of red meat allergy using percutaneous α-Gal sensitization of gene-edited GGTA1-deficient pigs. Total and α-Gal-specific IgG, IgG1, IgG2, IgG4, and IgE levels were tracked. Further key factors associated with allergic skin inflammation, type 2 immunity, and allergy development were measured in PBMCs and skin samples. Significant increases in α-Gal-specific IgG1 and IgE levels indicated successful sensitization to the allergen α-Gal. Intracutaneous sensitizations with α-Gal recruited lymphocytes to the skin, including elevated numbers of T helper 2 (Th2) cells. Finally, α-Gal-sensitized pigs not only recognized α-Gal as non-self-antigen following α-Gal exposure through the skin but also developed anaphylaxis upon antigen challenge. Based on the similarities between the porcine and human skin, this new large animal model for α-Gal allergy should help to unveil the consecutive steps of cutaneous sensitization and aid the development of prophylactic and treatment interventions.

Neutrophil extracellular traps in CSF and serum of dogs with steroid-responsive meningitis-arteritis.

In steroid-responsive meningitis-arteritis (SRMA), inflammatory dysregulation is driven by neutrophilic granulocytes resulting in purulent leptomeningitis. Neutrophils can generate neutrophil extracellular traps (NET). Uncontrolled NET-formation or impaired NET-clearance evidently cause tissue and organ damage resulting in immune-mediated diseases. The aim of the study was to verify that NET-formation is detectable in ex vivo samples of acute diseased dogs with SRMA by visualizing and measuring NET-markers in serum and cerebrospinal fluid (CSF) samples. CSF-samples of dogs with acute SRMA (n = 5) and in remission (n = 4) were examined using immunofluorescence (IF)-staining of DNA-histone-1-complexes, myeloperoxidase and citrullinated Histone H3 (H3Cit). Immunogold-labeling of H3Cit and neutrophil elastase followed by transmission electron microscopy (TEM) were used to determine ultrastructural NET-formation in the CSF of one exemplary dog. H3Cit-levels and DNase-activity were measured in CSF and serum samples using an H3Cit-ELISA and a DNase-activity-assay, respectively in patients with the following diseases: acute SRMA (n = 34), SRMA in remission (n = 4), bacterial encephalitis (n = 3), meningioma with neutrophilic inflammation (n = 4), healthy dogs (n = 6). NET-formation was detectable with IF-staining in n = 3/5 CSF samples of dogs with acute SRMA but were not detectable during remission. Vesicular NET-formation was detectable in one exemplary dog using TEM. DNase-activity was significantly reduced in dogs suffering from acute SRMA compared to healthy control group (p < 0.0001). There were no statistical differences of H3Cit levels in CSF or serum samples of acute diseased dogs compared to dogs under treatment, dogs suffering from meningioma or bacterial encephalitis or the healthy control group. Our findings demonstrate that NET-formation and insufficient NET-clearance possibly drive the immunologic dysregulation and complement the pathogenesis of SRMA. The detection of NETs in SRMA offers many possibilities to explore the aetiopathogenetic influence of this defence mechanism of the innate immune system in infectious and non-infectious canine neuropathies.

Retrospective study of tetanus in 18 dogs-Causes, management, complications, and immunological status.

Objective: Tetanus is a severe neurologic disease caused by Clostridium tetani, resulting in spastic paralysis. Canine tetanus is associated with serious complications such as aspiration and a high mortality rate of up to 50%. Materials and methods: Medical records of all dogs diagnosed with tetanus over 8 years (2014-2022) were analyzed for severity grade, treatment protocols, nutritional management, and complications, as well as outcome, vaccination, and antibody production in some dogs. No medical records were excluded. Normality was analyzed by the D'Agostino-Pearson test. Parametric, normally distributed data were presented as mean ± standard deviation. Non-parametric, non-normally distributed data were presented as median (m) and range (minimum-maximum). The association between tetanus grade, progression of diseases, and duration of hospitalization was analyzed using the t-test, Mann-Whitney U test, and Kruskal-Wallis test. A P ≤ 0.05 was considered significant. Results: Eighteen dogs were identified. Most affected dogs were classified into severity grade II (66.7%, 12 of 18). Clinical signs deteriorated in 55.6% of dogs (10 of 18). A source was identified in 88.9% of dogs (16 of 18). Nine dogs required surgical wound revision. A percutaneous endoscopic gastropexy tube was placed in 83.3% of dogs (15 of 18) for nutritional support. Medical treatment included metronidazole, methocarbamol, and combinations of different sedatives adapted to the patient's requirements. Tetanus antitoxin was used in 72.2% of dogs (13 of 18) without reported adverse events. The survival rate was 88.9% (16 of 18). Complications, such as hypertension, aspiration pneumonia, and laryngeal spasm occurred in 12 of 18 dogs. Median hospitalization time (8 days; range 0-16 days) was associated with the maximum tetanus severity grade (p = 0.022). Rapid eye movement behavior disorder was observed in 72.2% of dogs (13 of 18). In 5 dogs, antibodies were measured after recovery, and in 4 of 5 dogs, no antibodies were detectable despite generalized tetanus disease. Vaccination with tetanus toxoid was performed in five dogs following the disease. Conclusion: In the present study, the mortality rate was lower than previously reported. Tetanus is still a life-threatening disease, but the prognosis may be good if adequate management and monitoring can be ensured.

A questionnaire-based investigation of the swimming puppy syndrome: 115 dogs.

Swimming Puppy Syndrome (SPS) is a benign reversible condition of unknown etiology in multiple dog breeds. Affected dogs show laterally abducted limbs and are unable to stand and walk on their own. The current knowledge of this condition derives from few case reports or small case series. Therefore, the aim of this study was to collect data on the clinical course from a large cohort of dogs with SPS with an online questionnaire supported by video footage. Potential risk factors were compared between 110 litters with SPS and 103 unaffected litters. SPS was reported in 115 dogs from 48 different breeds comprising a wide range of small, middle, and large breeds. Litters with SPS were significantly smaller than unaffected litters. Cesarean sections were reported more frequently in affected litters, but the overall rate of reported birth complications did not differ significantly from unaffected litters. Most puppies were able to stand and walk at a median age of 4.5 weeks (up to 12 weeks) and clinical signs resolved at a median age of six weeks (up to 12 weeks). Puppies from large breeds showed faster recovery than puppies from medium and small breeds. Occasionally, residual deficits were reported and only three dogs failed to recover. A clustering of SPS occurred in closely related litters in four kennels of four different dog breeds (Greater Swiss Mountain Dog, Golden Retriever, Miniature Bull Terrier, Norwich Terrier). The study shows the benign clinical course of SPS in a large cohort of puppies from multiple dog breeds. Potential risk factors including reports on birth complications, size and muscle mass compared to littermates and diet of the dam during pregnany were evaluated and no influence on the occurrence of SPS was identified.

Threads of memory: Reviving the ornament of a dead child at the Neolithic village of Ba`ja (Jordan).

In 2018, a well-constructed cist-type grave was discovered at Ba`ja, a Neolithic village (7,400-6,800 BCE) in Southern Jordan. Underneath multiple grave layers, an 8-year-old child was buried in a fetal position. Over 2,500 beads were found on the chest and neck, along with a double perforated stone pendant and a delicately engraved mother-of-pearl ring discovered among the concentration of beads. The first was found behind the neck, and the second on the chest. The meticulous documentation of the bead distribution indicated that the assemblage was a composite ornament that had gradually collapsed, partly due to the burying position. Our aim was to challenge time degradation and to reimagine the initial composition in order to best explore the significance of this symbolic category of material culture, not as mere group of beads, but as an ornamental creation with further aesthetic, artisanal and socioeconomic implications. The reconstruction results exceeded our expectations as it revealed an imposing multi-row necklace of complex structure and attractive design. Through multiple lines of evidence, we suggest that the necklace was created at Ba`ja, although significant parts of beads were made from exotic shells and stones, including fossil amber, an unprecedented material never attested before for this period. The retrieval of such an ornament from life and its attribution to a young dead child highlights the significant social status of this individual. Beyond the symbolic functions related to identity, the necklace is believed to have played a key role in performing the inhumation rituals, understood as a public event gathering families, relatives, and people from other villages. In this sense, the necklace is not seen as belonging completely to the realm of death but rather to the world of the living, materializing a collective memory and shared moments of emotions and social cohesion.

Long-term follow-up of cats in complete remission after treatment of feline infectious peritonitis with oral GS-441524.

OBJECTIVES: Feline infectious peritonitis (FIP), a common disease in cats caused by feline coronavirus (FCoV), is usually fatal once clinical signs appear. Successful treatment of FIP with oral GS-441524 for 84 days was demonstrated recently by this research group. The aim of this study was to evaluate the long-term outcome in these cats. METHODS: A total of 18 successfully treated cats were followed for up to 1 year after treatment initiation (9 months after completion of the antiviral treatment). Follow-up examinations were performed at 12-week intervals, including physical examination, haematology, serum biochemistry, abdominal and thoracic ultrasound, FCoV ribonucleic acid (RNA) loads in blood and faeces by reverse transciptase-quantitative PCR and anti-FCoV antibody titres by indirect immunofluorescence assay. RESULTS: Follow-up data were available from 18 cats in week 24, from 15 cats in week 36 and from 14 cats in week 48 (after the start of treatment), respectively. Laboratory parameters remained stable after the end of the treatment, with undetectable blood viral loads (in all but one cat on one occasion). Recurrence of faecal FCoV shedding was detected in five cats. In four cats, an intermediate short-term rise in anti-FCoV antibody titres was detected. In total, 12 cats showed abdominal lymphadenomegaly during the follow-up period; four of them continuously during the treatment and follow-up period. Two cats developed mild neurological signs, compatible with feline hyperaesthesia syndrome, in weeks 36 and 48, respectively; however, FCoV RNA remained undetectable in blood and faeces, and no increase in anti-FCoV antibody titres was observed in these two cats, and the signs resolved. CONCLUSIONS AND RELEVANCE: Treatment with GS-441524 proved to be effective against FIP in both the short term as well as the long term, with no confirmed relapse during the 1-year follow-up period. Whether delayed neurological signs could be a long-term adverse effect of the treatment or associated with a 'long FIP syndrome' needs to be further evaluated.

CBCT-based deformable dose accumulation of external beam radiotherapy in cervical cancer.

Background: Delivered radiotherapy doses do not exactly match those planned for a course of treatment, largely due to inter-fraction changes in anatomy. In this study, accumulated delivered dose was calculated for a sample of cervical cancer patients, by deformably registering daily cone beam computed tomography (CBCT) images to the planning computed tomography (CT) scan. Planned and accumulated doses were compared for the clinical target volume (CTV), bladder, and rectum.Material and Methods: For 10 patients receiving 45 Gy in 25 fractions of external beam radiotherapy, daily dose distributions were calculated on CBCT. These images were deformed onto the planning CT and the dose was accumulated using Velocity 4.1 (Varian Medical Systems, Palo Alto, USA). The quality of deformable image registration was evaluated visually and by calculating Dice similarity coefficients and mean distance to agreement.Results: V95%>99% was achieved for the primary CTV in 9/10 patients for the planned dose distribution and 7/10 patients for the accumulated dose distribution. Primary CTV coverage by 95% of the prescription dose was reduced in one patient, due to an increase in anterior-posterior separation. Comparison of planned and accumulated dose volume histograms (DVHs) for the bladder and rectum found agreement within 5% at low and intermediate doses, but differences exceeded 20% at higher doses. Direct addition of CBCT DVHs was seen to be a poor estimate for the accumulated DVH at higher doses.Conclusion: Computation of delivered radiotherapy dose that accounts for inter-fraction anatomical changes is important for establishing dose-effect relationships. Updating delivered dose distributions after each fraction would support informed clinical decision making on any potential treatment interventions.

Pathophysiology of drug-resistant canine epilepsy.

Drug resistance continues to be a major clinical problem in the therapeutic management of canine epilepsies with substantial implications for quality of life and survival times. Experimental and clinical data from human medicine provided evidence for relevant contributions of intrinsic severity of the disease as well as alterations in pharmacokinetics and -dynamics to failure to respond to antiseizure medications. In addition, several modulatory factors have been identified that can be associated with the level of therapeutic responses. Among others, the list of potential modulatory factors comprises genetic and epigenetic factors, inflammatory mediators, and metabolites. Regarding data from dogs, there are obvious gaps in knowledge when it comes to our understanding of the clinical patterns and the mechanisms of drug-resistant canine epilepsy. So far, seizure density and the occurrence of cluster seizures have been linked with a poor response to antiseizure medications. Moreover, evidence exists that the genetic background and alterations in epigenetic mechanisms might influence the efficacy of antiseizure medications in dogs with epilepsy. Further molecular, cellular, and network alterations that may affect intrinsic severity, pharmacokinetics, and -dynamics have been reported. However, the association with drug responsiveness has not yet been studied in detail. In summary, there is an urgent need to strengthen clinical and experimental research efforts exploring the mechanisms of resistance as well as their association with different etiologies, epilepsy types, and clinical courses.

Investigation of the presence of specific neural antibodies in dogs with epilepsy or dyskinesia using murine and human assays.

BACKGROUND: Autoimmune mechanisms represent a novel category for causes of seizures and epilepsies in humans, and LGI1-antibody associated limbic encephalitis occurs in cats. HYPOTHESIS/OBJECTIVES: To investigate the presence of neural antibodies in dogs with epilepsy or dyskinesia of unknown cause using human and murine assays modified for use in dogs. ANIMALS: Fifty-eight dogs with epilepsy of unknown cause or suspected dyskinesia and 57 control dogs. METHODS: Serum and CSF samples were collected prospectively as part of the diagnostic work-up. Clinical data including onset and seizure/episode type were retrieved from the medical records. Screening for neural antibodies was done with cell-based assays transfected with human genes for typical autoimmune encephalitis antigens and tissue-based immunofluorescence assays on mouse hippocampus slices in serum and CSF samples from affected dogs and controls. The commercial human und murine assays were modified with canine-specific secondary antibody. Positive controls were from human samples. RESULTS: The commercial assays used in this study did not provide unequivocal evidence for presence of neural antibodies in dogs including one dog with histopathologically proven limbic encephalitis. Low titer IgLON5 antibodies were present in serum from one dog from the epilepsy/dyskinesia group and in one dog from the control group. CONCLUSION AND CLINICAL IMPORTANCE: Specific neural antibodies were not detected using mouse and human target antigens in dogs with epilepsy and dyskinesia of unknown origin. These findings emphasize the need for canine-specific assays and the importance of control groups.

A loss-of-function variant in canine GLRA1 associates with a neurological disorder resembling human hyperekplexia.

Hereditary hyperekplexia is a rare neuronal disorder characterized by an exaggerated startle response to sudden tactile or acoustic stimuli. In this study, we present a Miniature Australian Shepherd family showing clinical signs, which have genetic and phenotypic similarities with human hereditary hyperekplexia: episodes of muscle stiffness that could occasionally be triggered by acoustic stimuli. Whole genome sequence data analysis of two affected dogs revealed a 36-bp deletion spanning the exon-intron boundary in the glycine receptor alpha 1 (GLRA1) gene. Further validation in pedigree samples and an additional cohort of 127 Miniature Australian Shepherds, 45 Miniature American Shepherds and 74 Australian Shepherds demonstrated complete segregation of the variant with the disease, according to an autosomal recessive inheritance pattern. The protein encoded by GLRA1 is a subunit of the glycine receptor, which mediates postsynaptic inhibition in the brain stem and spinal cord. The canine GLRA1 deletion is located in the signal peptide and is predicted to cause exon skipping and subsequent premature stop codon resulting in a significant defect in glycine signaling. Variants in GLRA1 are known to cause hereditary hyperekplexia in humans; however, this is the first study to associate a variant in canine GLRA1 with the disorder, establishing a spontaneous large animal disease model for the human condition.

Translational veterinary epilepsy: A win-win situation for human and veterinary neurology.

Epilepsy is a challenging multifactorial disorder with a complex genetic background. Our current understanding of the pathophysiology and treatment of epilepsy has substantially increased due to animal model studies, including canine studies, but additional basic and clinical research is required. Drug-resistant epilepsy is an important problem in both dogs and humans, since seizure freedom is not achieved with the available antiseizure medications. The evaluation and exploration of pharmacological and particularly non-pharmacological therapeutic options need to remain a priority in epilepsy research. Combined efforts and sharing knowledge and expertise between human medical and veterinary neurologists are important for improving the treatment outcomes or even curing epilepsy in dogs. Such interactions could offer an exciting approach to translate the knowledge gained from people and rodents to dogs and vice versa. In this article, a panel of experts discusses the similarities and knowledge gaps in human and animal epileptology, with the aim of establishing a common framework and the basis for future translational epilepsy research.

Laboratory indicators of hypothyroidism and TgAA-positivity in the Eurasian dog breed.

BACKGROUND: Hereditary hypothyroidism represents a concern for dog breeders; thus, surveillance programs have been established for several dog breeds. METHODS: Thyroid profiles (total thyroxine (TT4), thyrotropin (thyroid stimulating hormone (TSH)), and thyroglobulin autoantibodies (TgAA)) collected as part of a breed surveillance program in Eurasians (2009-2017) were retrospectively analyzed. The study included data from 1,501 Eurasians from a German breeding club. Classification was exclusively based on laboratory data. Hypothyroidism was defined as a combined decrease in TT4 and increase in TSH in serum and was classified as TgAA-positive and TgAA-negative hypothyroidism. Thyroglobulin autoantibodies (TgAA) independent of the concentrations of TT4 and TSH were determined. The overall prevalence of hypothyroidism, TgAA-positive hypothyroidism, TgAA-negative hypothyroidism and TgAA-positivity was assessed when the dogs entered the program. Follow-up laboratory data was available for 324 dogs without hypothyroidism on initial examination. RESULTS: The initial screening was performed at a median age of 18 months (interquartile range (IQR): 15-29). The overall prevalence of hypothyroidism was 3.9% (n = 58; 95% CI: 2.9-4.8%) and the prevalence of a positive TgAA status was 7.9% (n = 118; 95% CI: 6.6-9.3%). The prevalence of TgAA-positive and TgAA-negative hypothyroidism was 1.7% (n = 26; 95% CI: 1.1-2.4%) and 2.1% (n = 32; 95% CI: 1.4-2.9%), respectively. 22.0% of dogs with positive TgAA status (26/118) were already hypothyroid on initial examination. Overall, 42.5% (17/40) of TgAA-positive dogs on initial examination developed hypothyroidism on follow-up. CONCLUSION: The results of this study demonstrate that the Eurasian dog breed exhibits a relevant risk for hypothyroidism and presence of TgAA. The predictive value of TgAA for hypothyroidism or developing hypothyroidism was high in this breed. Further investigations with longitudinal studies in individual dogs are warranted.

Successful Emergency Management of a Dog with Ventilator-Dependent Acquired Myasthenia Gravis with Immunoadsorption.

A one-year-old, female intact Samoyed, 12.5 kg, was presented with coughing for 2 weeks, progressive appendicular and axial muscle weakness, megaesophagus and labored breathing for 5 days. There was no improvement with standard treatment. Acquired myasthenia gravis was suspected and the dog was referred with increasing dyspnea. At presentation, the dog showed a severely reduced general condition, was non-ambulatory and showed abdominal and severely labored breathing. A marked hypercapnia (PvCO2 = 90.1 mmHg) was present in venous blood gas analysis. The serum anti-acetylcholine receptor antibody test was consistent with acquired myasthenia gravis (2.1 nmol/L). The dog was anesthetized with propofol and mechanically ventilated with a Hamilton C1 ventilator. Immunoadsorption was performed with the COM.TEC® and ADAsorb® platforms and a LIGASORB® adsorber to eliminate anti-acetylcholine receptor antibodies. Local anticoagulation was performed with citrate. Treatment time for immunoadsorption was 1.5 h with a blood flow of 50 mL/min. A total plasma volume of 1.2 L was processed. Further medical treatment included intravenous fluid therapy, maropitant, esomeprazole, antibiotic therapy for aspiration pneumonia and neostigmine 0.04 mg/kg intramuscularly every 6 h for treatment of acquired myasthenia gravis. Mechanical ventilation was stopped after 12 h. A percutaneous gastric feeding tube was inserted under endoscopic control on day 2 for further medical treatment and nutrition. A second treatment with immunoadsorption was performed on day 3. Again, a total plasma volume of 1.2 L was processed. Immediately after this procedure, the dog regained muscle strength and was able to stand and to walk. After 6 days, the dog was discharged from the hospital. This is the first report of immunoadsorption for emergency management of a dog with acute-fulminant acquired myasthenia gravis. Immunoadsorption may be an additional option for emergency treatment in dogs with severe signs of acquired myasthenia gravis.

Pregabalin Add-On vs. Dose Increase in Levetiracetam Add-On Treatment: A Real-Life Trial in Dogs With Drug-Resistant Epilepsy.

Epilepsy is a common neurological disorder affecting 0.6-0.75% of dogs in veterinary practice. Treatment is frequently complicated by the occurrence of drug-resistant epilepsy and cluster seizures in dogs with idiopathic epilepsy. Only few studies are available to guide treatment choices beyond licensed veterinary drugs. The aim of the study was to compare antiseizure efficacy and tolerability of two add-on treatment strategies in dogs with drug-resistant idiopathic epilepsy. The study design was a prospective, open-label, non-blinded, comparative treatment trial. Treatment success was defined as a 3-fold extension of the longest baseline interseizure interval and to a minimum of 3 months. To avoid prolonged adherence to a presumably ineffective treatment strategy, dog owners could leave the study after the third day with generalized seizures if the interseizure interval failed to show a relevant increase. Twenty-six dogs (mean age 5.5 years, mean seizure frequency 4/month) with drug-resistant idiopathic epilepsy and a history of cluster seizures were included. Dogs received either add-on treatment with pregabalin (PGB) 4 mg/kg twice daily (14 dogs) or a dose increase in levetiracetam (LEV) add-on treatment (12 dogs). Thirteen dogs in the PGB group had drug levels within the therapeutic range for humans. Two dogs in the PGB group (14.3%; 2/14) and one dog in the LEV group (8.3%; 1/12) achieved treatment success with long seizure-free intervals from 122 to 219 days but then relapsed to their early seizure frequency 10 months after the study inclusion. The overall low success rates with both treatment strategies likely reflect a real-life situation in canine drug-resistant idiopathic epilepsy in everyday veterinary practice. These results delineate the need for research on better pharmacologic and non-pharmacologic treatment strategies in dogs with drug-resistant epilepsy.

Biopsy Characteristics, Subtypes, and Prognostic Features in 107 Cases of Feline Presumed Immune-Mediated Polyneuropathy.

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.

Clinical Course and Diagnostic Findings of Biopsy Controlled Presumed Immune-Mediated Polyneuropathy in 70 European Cats.

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.

Pharmacokinetics of Cannabidiol Following Intranasal, Intrarectal, and Oral Administration in Healthy Dogs.

The therapeutic potential of cannabidiol (CBD), a non-psychtropic component of the Cannabis sativa plant, is substantiated more and more. We aimed to determine the pharmacokinetic behavior of CBD after a single dose via intranasal (IN) and intrarectal (IR) administration in six healthy Beagle dogs age 3-8 years old, and compare to the oral administration route (PO). Standardized dosages applied for IN, IR and PO were 20, 100, and 100 mg, respectively. Each dog underwent the same protocol but received CBD through a different administration route. CBD plasma concentrations were determined by ultra-high performance liquid chromatography-tandem mass spectrometry before and at fixed time points after administration. Non-compartmental analysis was performed on the plasma concentration-time profiles. Plasma CBD concentrations after IR administration were below the limit of quantification. The mean area under the curve (AUC) after IN and PO CBD administration was 61 and 1,376 ng/mL*h, respectively. The maximal plasma CBD concentration (Cmax) after IN and PO CBD administration was 28 and 217 ng/mL reached after 0.5 and 3.5 h (Tmax), respectively. Significant differences between IN and PO administration were found in the Tmax (p = 0.04). Higher AUC and Cmax were achieved with 100 mg PO compared to 20 mg IN, but no significant differences were found when AUC (p = 0.09) and Cmax (p = 0.44) were normalized to 1 mg dosages. IN administration of CBD resulted in faster absorption when compared to PO administration. However, PO remains the most favorable route for CBD delivery due to its more feasible administration. The IR administration route is not advised for clinical application.