A Review of Fibrocartilaginous Embolic Myelopathy and Different Types of Peracute Non-Compressive Intervertebral Disk Extrusions in Dogs and Cats

This review discusses terminology, pathologic, clinical and magnetic resonance imaging findings, treatment, outcome and prognostic factors of fibrocartilaginous embolic myelopathy (FCEM), acute non-compressive nucleus pulposus extrusion (ANNPE) and intradural/ intramedullary intervertebral disc extrusion (IIVDE). FCEM, ANNPE, and IIVDE have a similar clinical presentation characterised by peracute onset of neurologic dysfunction that is generally non progressive after the initial 24-48 hours. Differentiating between these conditions can be challenging, however certain clinical and imaging findings can help. FCEM can occur in both adult and immature animals, whereas ANNPE or IIVDE have been reported only in animals older than 1 year. In dogs, ANNPE and IIVDE most commonly occur in the intervertebral disc spaces between T12 and L2, whereas FCEM has not such site predilection. In cats, FCEM occurs more frequently in the cervical spinal cord than in other locations. Data on cats with ANNPE and IIVDE is limited. Optimal magnetic resonance imaging (MRI) definition and experience in neuroimaging can help identify the findings that allow differentiation between FCEM, ANNPE, and IIVDE. In animals with ANNPE and IIVDE the affected intervertebral disc space is often narrowed and the focal area of intramedullary hyperintensity on T2-weighted images is located above the affected intervertebral dis

Prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats

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

Substance Related Exogenous Psychosis: a post-modern syndrome

© 2020 Cambridge University Press. This paper has been accepted for publication and will appear in a revised form, subsequent to peer-review and/or editorial input by Cambridge University Press. This manuscript is made available under the terms of the Creative Commons Non-Commercial No-Derivatives License (CC-BY-NC-ND). For further information please see: https://creativecommons.org/licenses/by-nc-nd/4.0/.The past two decades have been marked by dramatic social changes, widely characterized by the term “postmodern”. These major transformations have had profound and complex implications for psychiatry, influencing mental health risk factors, dynamics in clinical encounters, styles of help-seeking behavior and clinical outcomes. Underlying themes of postmodern thought that are particularly relevant to psychiatry include: individualization and social roles; the nature of self-identity and intimacy; future orientation (Whitley r. 2008).Peer reviewe

Gambling disorder and bilateral transcranial direct current stimulation: A case report

Introduction Gambling disorder (GD) is a major public health concern with currently no validated and efficacious treatments approved. In this single case study, we report the short- and long-term effect of bilateral transcranial direct current stimulation (tDCS) of dorsolateral prefrontal cortex (DLPFC) on craving and impulse control in a subject with GD. Methods The patient is a 26-year-old Caucasian male with an 8-year history of GD as well as alcohol and cocaine misuse. Treatment consisted of twice-a-day stimulation for 10 days. According to the literature, both the left (to control craving) and the right (to control emotional impulses) DLPFC were stimulated. Patients subsequently received tDCS once a week for 3 months and then once every 2 weeks for another 3 months. Results After 10 days of treatment, the subject reported improved psychiatric symptoms (depression, anxiety, and impulsivity), as well as reduced gambling craving symptom severity. After 3 and 6 months of treatment, the clinical picture further improved. Discussion This is the first report of tDCS effectiveness in a single case study of GD. Therapeutic effects, both on the addictive behavior and on psychiatric comorbid symptomatology, were lasting and continued over 6 months of tDCS maintenance treatment. Future case–control studies are required to test the efficacy of this tool in patients with GD

Characterisation of canine KCNIP4: A novel gene for cerebellar ataxia identified by whole-genome sequencing two affected Norwegian Buhund dogs

Author summary Hereditary ataxias, which are a group of disorders characterised by incoordination of movement, are typically incurable and there are often no disease-modifying treatments available. Canine hereditary ataxias are a notable group of movement disorders in dogs, and represent well characterised naturally occurring disease models of ataxia that can help improve our understanding of the underlying biology of the disorder in both dogs and humans. We used the whole genome sequences of two affected siblings to investigate the genetic cause of a slowly progressive form of hereditary ataxia in the Norwegian Buhund dog breed, and identified a single base change within the KCNIP4 gene. We have characterised the expression of KCNIP4 in the dog, and investigated the effect of the identified mutation. This gene has not previously been implicated in inherited ataxia in any species, and our findings suggest that this and related genes represent potential candidates for ataxia in future studies in other species. Our findings will allow dog breeders to avoid producing affected dogs, reduce the disease allele frequency, and eventually eliminate the disease from the breed, through the use of a DNA test. A form of hereditary cerebellar ataxia has recently been described in the Norwegian Buhund dog breed. This study aimed to identify the genetic cause of the disease. Whole-genome sequencing of two Norwegian Buhund siblings diagnosed with progressive cerebellar ataxia was carried out, and sequences compared with 405 whole genome sequences of dogs of other breeds to filter benign common variants. Nine variants predicted to be deleterious segregated among the genomes in concordance with an autosomal recessive mode of inheritance, only one of which segregated within the breed when genotyped in additional Norwegian Buhunds. In total this variant was assessed in 802 whole genome sequences, and genotyped in an additional 505 unaffected dogs (including 146 Buhunds), and only four affected Norwegian Buhunds were homozygous for the variant. The variant identified, a T to C single nucleotide polymorphism (SNP) (NC_006585.3:g.88890674T>C), is predicted to cause a tryptophan to arginine substitution in a highly conserved region of the potassium voltage-gated channel interacting protein KCNIP4. This gene has not been implicated previously in hereditary ataxia in any species. Evaluation of KCNIP4 protein expression through western blot and immunohistochemical analysis using cerebellum tissue of affected and control dogs demonstrated that the mutation causes a dramatic reduction of KCNIP4 protein expression. The expression of alternative KCNIP4 transcripts within the canine cerebellum, and regional differences in KCNIP4 protein expression, were characterised through RT-PCR and immunohistochemistry respectively. The voltage-gated potassium channel protein KCND3 has previously been implicated in spinocerebellar ataxia, and our findings suggest that the Kv4 channel complex KCNIP accessory subunits also have an essential role in voltage-gated potassium channel function in the cerebellum and should be investigated as potential candidate genes for cerebellar ataxia in future studies in other species.Peer reviewe

Improving the resolution of canine genome-wide association studies using genotype imputation: A study of two breeds.

Funder: Italian Spinone Club of Great BritainFunder: Kennel Club Charitable TrustGenotype 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

Prospective trial of different antimicrobial treatment durations for presumptive canine urinary tract infections

Abstract: Background: Avoidance of unnecessary antimicrobial administration is a key tenet of antimicrobial stewardship; knowing the optimal duration of therapy obviates over-treatment. However, little research has been performed to establish course lengths for common canine infections. In clinical practice, antimicrobial therapy is frequently prescribed in dogs presenting lower urinary tract signs (haematuria, pollakiuria and dysuria/stranguria). The proposed length of treatment in International Consensus guidelines has decreased with each iteration, but these recommendations remain arbitrary and largely extrapolated from experience in people. Methods: The objective of this prospective, multi-centre study is to find the shortest course duration that is non-inferior to the standard duration of 7 days of amoxicillin/clavulanate in terms of clinical outcomes for female dogs with lower urinary tract signs consistent with a urinary tract infection. An electronic data capture platform will be used by participating veterinarians working in clinical practice in the United Kingdom. Eligible dogs must be female, aged between 6 months and 10 years and have lower urinary tract signs of up to seven days’ duration. Enrolment will be offered in cases where the case clinician intends to prescribe antimicrobial therapy. Automatic pseudo-randomisation to treatment group will be based on the day of presentation (Monday-Friday); all antimicrobial courses will be completed on the Sunday after presentation generating different treatment durations. Follow-up data will be collected 1, 8 and 22–26 days after completion of the antimicrobial course to ensure effective safety netting, and to monitor short-term outcome and recurrence rates. Informed owner consent will be obtained in all cases. The study is approved by the Ethical Review Board of the University of Nottingham and has an Animal Test Certificate from the Veterinary Medicine’s Directorate. Discussion: This study has been designed to mirror current standards of clinical management; conclusions should therefore, be widely applicable and guide practising veterinarians in their antimicrobial decision-making process. A duration-response curve will be created allowing determination of the optimal treatment duration for the management of female dogs with lower urinary tract signs. It is hoped that these results will contribute valuable information to improve future antimicrobial stewardship as part of a wider one-health perspective

Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs : a multi‐center randomized parallel group clinical study

Background: The intranasal (IN) route for rapid drug administration in patients with brain disorders, including status epilepticus, has been investigated. Status epilepticus is an emergency, and the IN route offers a valuable alternative to other routes, especially when these fail. Objectives: To compare IN versus IV midazolam (MDZ) at the same dosage (0.2 mg/kg) for controlling status epilepticus in dogs. Animals Client-owned dogs (n = 44) with idiopathic epilepsy, structural epilepsy, or epilepsy of unknown origin manifesting as status epilepticus. Methods: Randomized parallel group clinical trial. Patients were randomly allocated to the IN-MDZ (n = 21) or IV-MDZ (n = 23) group. Number of successfully treated cases (defined as seizure cessation within 5 minutes and lasting for >= 10 minutes), seizure cessation time, and adverse effects were recorded. Comparisons were performed using the Fisher's exact and Wilcoxon rank sum tests with statistical significance set at alpha < .05. Results: IN-MDZ and IV-MDZ successfully stopped status epilepticus in 76% and 61% of cases, respectively (P = .34). The median seizure cessation time was 33 and 64 seconds for IN-MDZ and IV-MDZ, respectively (P = .63). When the time to place an IV catheter was taken into account, IN-MDZ (100 seconds) was superior (P = .04) to IV-MDZ (270 seconds). Sedation and ataxia were seen in 88% and 79% of the dogs treated with IN-MDZ and IV-MDZ, respectively. Conclusions and Clinical Importance: Both routes are quick, safe, and effective for controlling status epilepticus. However, the IN route demonstrated superiority when the time needed to place an IV catheter was taken into account

Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog