Search

Genotype imputation using a reference panel that combines high-density array data and publicly available whole genome sequence consortium variant data is potentially a cost-effective method to increase the density of extant lower-density array datasets. In this study, three datasets (two Border Collie; one Italian Spinone) generated using a legacy array (Illumina CanineHD, 173 662 SNPs) were utilised to assess the feasibility and accuracy of this approach and to gather additional evidence for the efficacy of canine genotype imputation. The cosmopolitan reference panels used to impute genotypes comprised dogs of 158 breeds, mixed breed dogs, wolves and Chinese indigenous dogs, as well as breed-specific individuals genotyped using the Axiom Canine HD array. The two Border Collie reference panels comprised 808 individuals including 79 Border Collies and 426 326 or 426 332 SNPs; and the Italian Spinone reference panel comprised 807 individuals including 38 Italian Spinoni and 476 313 SNPs. A high accuracy for imputation was observed, with the lowest accuracy observed for one of the Border Collie datasets (mean R2  = 0.94) and the highest for the Italian Spinone dataset (mean R2  = 0.97). This study's findings demonstrate that imputation of a legacy array study set using a reference panel comprising both breed-specific array data and multi-breed variant data derived from whole genomes is effective and accurate. The process of canine genotype imputation, using the valuable growing resource of publicly available canine genome variant datasets alongside breed-specific data, is described in detail to facilitate and encourage use of this technique in canine genetics.

Case summary: A 4-year-old female spayed domestic shorthair cat was presented with facial swelling, ocular discharge and intermittent bilateral exophthalmos. Haematology revealed mild eosinophilia. Serum biochemistry showed a markedly elevated creatine kinase activity. MRI of the head revealed diffuse and severe changes of the masticatory muscles, including irregular areas compatible with fluid or necrosis within the abnormal muscle tissue. Cytological analysis of the left temporal muscle revealed eosinophilic and macrophagic inflammation. Bacterial and fungal cultures were negative. Serological titres against Toxoplasma gondii were compatible with previous exposure. A canine ELISA against masticatory muscle type IIM fibre proteins was positive at 1:4000 (reference interval <1:100). Histopathological examination of the left temporalis muscle revealed moderately severe and multifocal myositis. A diagnosis of immune-mediated masticatory myositis was made and immunosuppressive therapy was started. The cat initially responded to tapering doses of prednisolone, but subsequent relapses required therapy modulation. At the time of writing, 27 months after the initial diagnosis, the cat was in remission, but was diagnosed with diabetes mellitus, probably secondary to chronic glucocorticoid use. Relevance and novel information: To our knowledge, this is the first case report to describe the MRI appearance of masticatory myositis in a cat and the second to describe the clinical presentation, histopathology, response to treatment and outcome in a cat with this condition. [ABSTRACT FROM AUTHOR]

Abstract Background Chiari-like malformation (CM) and syringomyelia is a neurological disease complex with high prevalence in cavalier King Charles spaniels (CKCS). The natural progression of this disease with time has not been described. The objectives of this study were to i) determine if syringomyelia progresses with time ii) determine if features of craniocrebral morphology previously associated with CM are progressive (including caudal cranial fossa volume, caudal cranial fossa parenchymal volume, ventricular dimensions, height of the foramen magnum and degree of cerebellar herniation). A retrospective morphometric analysis was undertaken in 12 CKCS with CM for which repeat magnetic resonance images were available without surgical intervention. Results The maximal syrinx width, height of the foramen magnum, length of cerebellar herniation and caudal cranial fossa volume increased over time. Ventricular and caudal fossa parenchymal volumes were not significantly different between scans. Conclusions The results of this study suggest that syringomyelia progresses with time. Increased caudal cranial fossa volume may be associated with active resorption of the supraoccipital bone, which has previously been found in histology specimens from adult CKCS. We hypothesise that active resorption of the supraoccipital bone occurs due to pressure from the cerebellum. These findings have important implications for our understanding of the pathogenesis and variable natural clinical progression of CM and syringomyelia in CKCS.

Abstract Background Neonatal cerebellar cortical degeneration is a neurodegenerative disease described in several canine breeds including the Beagle. Affected Beagles are unable to ambulate normally from the onset of walking and the main pathological findings include Purkinje cell loss with swollen dendritic processes. Previous reports suggest an autosomal recessive mode of inheritance. The development of massively parallel sequencing techniques has presented the opportunity to investigate individual clinical cases using genome-wide sequencing approaches. We used genome-wide mRNA sequencing (mRNA-seq) of cerebellum tissue from a single Beagle with neonatal cerebellar cortical degeneration as a method of candidate gene sequencing, with the aim of identifying the causal mutation. Results A four-week old Beagle dog presented with progressive signs of cerebellar ataxia and the owner elected euthanasia. Histopathology revealed findings consistent with cerebellar cortical degeneration. Genome-wide mRNA sequencing (mRNA-seq) of RNA from cerebellum tissue was used as a method of candidate gene sequencing. After analysis of the canine orthologues of human spinocerebellar ataxia associated genes, we identified a homozygous 8 bp deletion in the β-III spectrin gene, SPTBN2, associated with spinocerebellar type 5 in humans. Genotype analysis of the sire, dam, ten clinically unaffected siblings, and an affected sibling from a previous litter, showed the mutation to fully segregate with the disorder. Previous studies have shown that β-III spectrin is critical for Purkinje cell development, and the absence of this protein can lead to cell damage through excitotoxicity, consistent with the observed Purkinje cell loss, degeneration of dendritic processes and associated neurological dysfunction in this Beagle. Conclusions An 8 bp deletion in the SPTBN2 gene encoding β-III spectrin is associated with neonatal cerebellar cortical degeneration in Beagle dogs. This study shows that mRNA-seq is a feasible method of screening candidate genes for mutations associated with rare diseases when a suitable tissue resource is available.

Objectives: The study objective was to investigate the prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats. Methods: The medical records of two veterinary referral clinics from 2007 to 2017 were searched for cats fulfilling the inclusion criteria of a diagnosis of epilepsy, treatment with phenobarbitone and available follow-up information on the occurrence of adverse effects. Follow-up information was obtained from the medical records of the primary veterinarian and referral institutions and a questionnaire completed by the cats' owners. Results: Seventy-seven cats met the inclusion criteria. Fifty-eight were affected by idiopathic epilepsy and 19 by structural epilepsy. One or more of the following adverse effects were reported in 47% of the cats: sedation (89%); ataxia (53%); polyphagia (22%); polydipsia (6%); polyuria (6%); and anorexia (6%). Logistic regression analyses revealed significant associations between adverse effect occurrence and both phenobarbitone starting dosage and administration of a second antiepileptic drug (AED). For each 1 mg/kg q12h increment of phenobarbitone, the likelihood of adverse effects increased 3.1 times. When a second AED was used, the likelihood of adverse effects increased 3.2 times. No association was identified between epilepsy aetiology and adverse effect occurrence. An idiosyncratic adverse effect, characterised by severe neutropenia and granulocytic hypoplasia, was diagnosed in one cat. This resolved following phenobarbitone discontinuation. Conclusions and relevance: The prevalence of phenobarbitone-associated adverse effects was 47%. Sedation and ataxia were most common. These are type A adverse effects and are predictable from phenobarbitone's known pharmacological properties. In the majority of cases, adverse effects occurred within the first month of treatment and were transient. Idiosyncratic (type B) adverse effects, which were not anticipated given the known properties of the drug, occurred in one cat. Increased phenobarbitone starting dosage and the addition of a second AED were significantly associated with the occurrence of adverse effects. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the MRI findings in cats following traumatic brain injury (TBI), and establish which features identified might correlate with prognosis. Methods: The magnetic resonance images of 30 cats with clinical signs attributed to the brain following TBI were retrospectively reviewed to assess the imaging features seen and their correlation with outcome. Results: Twenty-one of 30 cats had a good outcome (full recovery or minor ongoing neurological deficits); the other nine either died or had ongoing neurological deficits that significantly affected quality of life. There was evidence of parenchymal injury in only 20/30 cats, including 8/9 that had a poor outcome. The frequency of bilateral or multifocal parenchymal lesions on T2-weighted imaging, and mass effect, particularly caudal transtentorial herniation, was statistically significantly higher in patients with a poorer outcome. Extra-axial haemorrhage was not identified. Concurrent soft tissue injury was noted in all cats, with a poorer prognosis statistically associated with a peripharyngeal pattern of injury and orbital trauma. Conclusions and relevance: The number of cases with MRI-identified brain pathology, the patterns of injuries identified and the specific imaging features that appear to have effects on prognosis differ in this series of cats from those published in similar case series of dogs. Further work is needed to establish if cat-specific guidelines are needed to assess brain MRI following trauma. [ABSTRACT FROM AUTHOR]

Introduction: Cocaine use disorder (CUD) currently represents a notable public health concern, linked with significant disability, high chances of chronicity, and lack of effective pharmacological or psychological treatments. Repetitive transcranial magnetic stimulation (rTMS) is supposed to be a potential therapeutic option for addictive disorders. Aim of this study was to evaluate the feasibility of rTMS on (1) cocaine craving and consumption and (2) other comorbid psychiatric symptoms. Methods: Twenty treatment seeking CUD subjects underwent 2 weeks of intensive rTMS treatment (15Hz; 5 days/week, twice a day for a total of 20 stimulation sessions) of the left dorsolateral prefrontal cortex, followed by 2 weeks of maintenance treatment (15Hz, 1 day/week, twice a day). Sixteen patients completed the study. Patients were evaluated at baseline (T0), after 2 weeks of treatment (T1), and at the end of the study (T2; 4 weeks), with the following scales: Cocaine Selective Severity Assessment (CSSA), Zung Self-Rating Anxiety Scale, Beck Depression Inventory (BDI), Symptom Checklist-90 (SCL-90), and the Insomnia Severity Index. Results: After four weeks of rTMS treatment, 9 out of 16 subjects (56.25%) had a negative urinalysis test, with a significant conversion rate with respect to baseline (Z = −3.00; p = 0.003). Craving scores significantly improved only at T2 (p = 0.020). The overall psychopathological burden, as measured by the SCL-90 Global Severity Index (GSI), significantly decreased during the study period (Z = −2.689; p = 0.007), with a relevant improvement with regards to depressive symptoms, anhedonia, and anxiety. Subjects exhibiting lower baseline scores on the SCL-90 were more likely to be in the positive outcome group at the end of the study (Z = −3.334; p = 0.001). Discussion: Findings from this study are consistent with previous contributions on rTMS use in subjects with cocaine use disorder. We evidenced a specific action on some psychopathological areas and a consequent indirect effect in terms of relapse prevention and craving reduction. A double-blind, sham-controlled, neuro-navigated rTMS study design is needed, in order to confirm the potential benefits of this technique, opening new scenarios in substance use disorders treatment. [ABSTRACT FROM AUTHOR]