Single-Voxel Proton Magnetic Resonance Spectroscopy of the Thalamus in Idiopathic Epileptic Dogs and in Healthy Control Dogs.

The role of magnetic resonance spectroscopy (MRS) in the investigation of brain metabolites in epileptic syndromes in dogs has not been explored systematically to date. The aim of this study was to investigate metabolites in the thalamus in dogs affected by idiopathic epilepsy (IE) with and without antiepileptic drug treatment (AEDT) and to compare them to unaffected controls. Our hypothesis is that similar to humans with generalized epilepsy and loss of consciousness, N-acetyl aspartate (NAA) would be reduced, and glutamate-glutamine (Glx) would be increased in treated and untreated IE in comparison with the control group. In this prospective case-control study, Border Collie (BC) and Greater Swiss Mountain dog (GSMD) were divided into three groups: (1) healthy controls, IE with generalized tonic-clonic seizures with (2) and without (3) AEDT. A total of 41 BC and GSMD were included using 3 Tesla single-voxel proton MRS of the thalamus (PRESS localization, shortest TE, TR = 2000 ms, NSA = 240). After exclusion of 11 dogs, 30 dogs (18 IE and 12 healthy controls) remained available for analysis. Metabolite concentrations were estimated with LCModel using creatine as reference and compared using Kruskal-Wallis and Wilcoxon rank-sum tests. The Kruskal-Wallis test revealed significant differences in the NAA-to-creatine (p = 0.04) and Glx-to-creatine (p = 0.03) ratios between the three groups. The Wilcoxon rank-sum test further showed significant reduction in the NAA/creatine ratio in idiopathic epileptic dogs under AEDT compared to epileptic dogs without AEDT (p = 0.03) and compared to healthy controls (p = 0.03). In opposite to humans, Glx/creatine ratio was significantly reduced in dogs with IE under AEDT compared to epileptic dogs without AEDT (p = 0.03) and controls (p = 0.02). IE without AEDT and healthy controls did not show significant difference, neither in NAA/creatine (p = 0.60), nor in Glx-to-creatine (p = 0.55) ratio. In conclusion, MRS showed changes in dogs with IE and generalized seizures under AEDT, but not in those without AEDT. Based upon these results, MRS can be considered a useful advanced imaging technique for the evaluation of dogs with IE in the clinical and research settings.

Ketamine administration in idiopathic epileptic and healthy control dogs: Can we detect differences in brain metabolite response with spectroscopy?

Introduction: In recent years ketamine has increasingly become the focus of multimodal emergency management for epileptic seizures. However, little is known about the effect of ketamine on brain metabolites in epileptic patients. Magnetic resonance spectroscopy (MRS) is a non-invasive technique to estimate brain metabolites in vivo. Our aim was to measure the effect of ketamine on thalamic metabolites in idiopathic epileptic (IE) dogs using 3 Tesla MRS. We hypothesized that ketamine would increase the glutamine-glutamate (GLX)/creatine ratio in epileptic dogs with and without antiseizure drug treatment, but not in control dogs. Furthermore, we hypothesized that no different responses after ketamine administration in other measured brain metabolite ratios between the different groups would be detected. Methods: In this controlled prospective experimental trial IE dogs with or without antiseizure drug treatment and healthy client-owned relatives of the breeds Border Collie and Greater Swiss Mountain Dog, were included. After sedation with butorphanol, induction with propofol and maintenance with sevoflurane in oxygen and air, a single voxel MRS at the level of the thalamus was performed before and 2 min after intravenous administration of 1 mg/kg ketamine. An automated data processing spectral fitting linear combination model algorithm was used to estimate all commonly measured metabolite ratios. A mixed ANOVA with the independent variables ketamine administration and group allocation was performed for all measured metabolites. A p < 0.05 was considered statistically significant. Results: Twelve healthy control dogs, 10 untreated IE and 12 treated IE dogs were included. No significant effects for GLX/creatine were found. However, increased glucose/creatine ratios were found (p < 0.001) with no effect of group allocation. Furthermore, increases in the GABA/creatine ratio were found in IEU dogs. Discussion: MRS was able to detect changes in metabolite/creatine ratios after intravenous administration of 1 mg/kg ketamine in dogs and no evidence was found that excitatory effects are induced in the thalamus. Although it is beyond the scope of this study to investigate the antiseizure potential of ketamine in dogs, results of this research suggest that the effect of ketamine on the brain metabolites could be dependent on the concentrations of brain metabolites before administration.

Duration of carriage of multidrug-resistant bacteria in dogs and cats in veterinary care and co-carriage with their owners.

BACKGROUND: The emergence and spread of multidrug-resistant organisms (MDROs) represent a threat to human and animal health. OBJECTIVES: To assess duration of carriage of MDROs in dogs and cats presented to veterinary clinics/hospitals in Switzerland. To estimate prevalence, duration of and risk factors for MDRO carriage in their owners and the occurrence of co-carriage in owner-pet pairs. METHODS: Prospective, longitudinal, observational study. Nasal swabs and fecal samples were collected from 50 owners of dogs and cats presented to 3 large veterinary hospitals, 1 medium-sized clinic and 1 practice. If pet or owner tested positive for a MDRO, follow-up samples were collected for up to 8 months. Methicillin-resistant (MR) Staphylococcus aureus, MR S. pseudintermedius, MR coagulase-negative staphylococci (MRCoNS), MR Macrococcus spp., cephalosporinase- and carbapenemase-producing (CP) Enterobacterales were isolated and further characterized by MALDI-TOF MS, microdilution, ß-lactam resistance gene detection, REP/ERIC-PCR, multilocus sequence typing or whole-genome sequencing. Risk factors for MDRO carriage in owners were explored based on questionnaire-derived data. RESULTS: Five out of 50 owners carried 3rd generation cephalosporin-resistant Enterobacterales (3GC-R-Ent.), and 5/50 MRCoNS. In 3 dogs and 4 cats carriage of 3GC-R-Ent. persisted for up to 136 days after discharge (median 99 days, IQR 83 days, range 36-136 days), in two cats isolates were carbapenem-resistant. Owner-pet co-carriage was not observed. No specific risk factors for MDRO carriage in owners were identified. CONCLUSIONS: After discharge from veterinary care, dogs and cats may carry 3GC-R-Ent. for prolonged time periods. Carriage of MDROs was common in owners, but pet-owner co-carriage of the same MDRO was not observed.

Acquisition and carriage of multidrug-resistant organisms in dogs and cats presented to small animal practices and clinics in Switzerland.

BACKGROUND: The emergence and spread of multidrug-resistant organisms (MDRO) present a threat to human and animal health. OBJECTIVES: To assess acquisition, prevalence of and risk factors for MDRO carriage in dogs and cats presented to veterinary clinics or practices in Switzerland. ANIMALS: Privately owned dogs (n = 183) and cats (n = 88) presented to 4 veterinary hospitals and 1 practice. METHODS: Prospective, longitudinal, observational study. Oronasal and rectal swabs were collected at presentation and 69% of animals were sampled again at discharge. Methicillin-resistant (MR) staphylococci and macrococci, cephalosporinase-, and carbapenemase-producing (CP) Enterobacterales were isolated. Genetic relatedness of isolates was assessed by repetitive sequence-based polymerase chain reaction and multilocus sequence typing. Risk factors for MDRO acquisition and carriage were analyzed based on questionnaire-derived and hospitalization data. RESULTS: Admission prevalence of MDRO carriage in pets was 15.5% (95% confidence interval [CI], 11.4-20.4). The discharge prevalence and acquisition rates were 32.1% (95% CI, 25.5-39.3) and 28.3% (95% CI, 22-35.4), respectively. Predominant hospital-acquired isolates were extended spectrum ß-lactamase-producing Escherichia coli (ESBL-E coli; 17.3%) and ß-lactamase-producing Klebsiella pneumoniae (13.7%). At 1 institution, a cluster of 24 highly genetically related CP (blaoxa181 and blaoxa48 ) was identified. Multivariate analysis identified hospitalization at clinic 1 (odds ratio [OR], 5.1; 95% CI, 1.6-16.8) and days of hospitalization (OR 3-5 days, 4.4; 95% CI, 1.8-10.9; OR > 5 days, 6.2; 95% CI, 1.3-28.8) as risk factors for MDRO acquisition in dogs. CONCLUSIONS: Veterinary hospitals play an important role in the selection and transmission of MDRO among veterinary patients.

A SINE Insertion in ATP1B2 in Belgian Shepherd Dogs Affected by Spongy Degeneration with Cerebellar Ataxia (SDCA2).

Spongy degeneration with cerebellar ataxia (SDCA) is a genetically heterogeneous neurodegenerative disorder with autosomal recessive inheritance in Malinois dogs, one of the four varieties of the Belgian Shepherd breed. Using a combined linkage and homozygosity mapping approach we identified an ∼10.6 Mb critical interval on chromosome 5 in a Malinois family with four puppies affected by cerebellar dysfunction. Visual inspection of the 10.6 Mb interval in whole-genome sequencing data from one affected puppy revealed a 227 bp SINE insertion into the ATP1B2 gene encoding the ß2 subunit of the Na+/K+-ATPase holoenzyme (ATP1B2:c.130_131insLT796559.1:g.50_276). The SINE insertion caused aberrant RNA splicing. Immunohistochemistry suggested a reduction of ATP1B2 protein expression in the central nervous system of affected puppies. Atp1b2 knockout mice had previously been reported to show clinical and neurohistopathological findings similar to the affected Malinois puppies. Therefore, we consider ATP1B2:c.130_131ins227 the most likely candidate causative variant for a second subtype of SDCA in Malinois dogs, which we propose to term spongy degeneration with cerebellar ataxia subtype 2 (SDCA2). Our study further elucidates the genetic and phenotypic complexity underlying cerebellar dysfunction in Malinois dogs and provides the basis for a genetic test to eradicate one specific neurodegenerative disease from the breeding population in Malinois and the other varieties of the Belgian Shepherd breed. ATP1B2 thus represents another candidate gene for human inherited cerebellar ataxias, and SDCA2-affected Malinois puppies may serve as a naturally occurring animal model for this disorder.

A Missense Variant in KCNJ10 in Belgian Shepherd Dogs Affected by Spongy Degeneration with Cerebellar Ataxia (SDCA1).

Spongy degeneration with cerebellar ataxia (SDCA) is a severe neurodegenerative disease with monogenic autosomal recessive inheritance in Malinois dogs, one of the four varieties of the Belgian Shepherd breed. We performed a genetic investigation in six families and seven isolated cases of Malinois dogs with signs of cerebellar dysfunction. Linkage analysis revealed an unexpected genetic heterogeneity within the studied cases. The affected dogs from four families and one isolated case shared a ∼1.4 Mb common homozygous haplotype segment on chromosome 38. Whole genome sequence analysis of three affected and 140 control dogs revealed a missense variant in the KCNJ10 gene encoding a potassium channel (c.986T>C; p.Leu329Pro). Pathogenic variants in KCNJ10 were reported previously in humans, mice, and dogs with neurological phenotypes. Therefore, we consider KCNJ10:c.986T>C the most likely candidate causative variant for one subtype of SDCA in Malinois dogs, which we propose to term spongy degeneration with cerebellar ataxia 1 (SDCA1). However, our study also comprised samples from 12 Malinois dogs with cerebellar dysfunction which were not homozygous for this variant, suggesting a different genetic basis in these dogs. A retrospective detailed clinical and histopathological analysis revealed subtle neuropathological differences with respect to SDCA1-affected dogs. Thus, our study highlights the genetic and phenotypic complexity underlying cerebellar dysfunction in Malinois dogs and provides the basis for a genetic test to eradicate one specific neurodegenerative disease from the breeding population. These dogs represent an animal model for the human EAST syndrome.