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Behavioral Changes in Dogs With Idiopathic Epilepsy Compared to Other Medical Populations.

ABSTRACT: Anxiety related behaviors have been reported in humans diagnosed with idiopathic epilepsy (IE) and such traits may be altered depending on seizure phase. The purpose of this study was to determine the presence and severity of anxiety related behaviors in dogs with IE compared to other medical populations, and to determine if behavioral changes were associated with seizure control. In this retrospective cross-sectional study, the owners of 102 dogs presenting for wellness examination (37), epilepsy (38), and intervertebral disc disease (27) were surveyed utilizing a questionnaire developed based on the shortened Canine Behavioral Assessment and Research Questionnaire (mini-CBARQ), previously validated for its ability to analyze canine behavior. Veterinarians of participating dogs completed a questionnaire to verify diagnoses. Dogs with IE and IVDD had a higher likelihood of being fearful/anxious when approached by an unfamiliar dog compared to the wellness group. Dogs with IE receiving polytherapy had decreased excitement before a walk (P = 0.0007) or car trip (P = 0.027), increased fear/anxiety when groomed (P = 0.0197), and increased shaking, shivering, or trembling when left alone (P = 0.0004) compared to dogs receiving monotherapy. Polytherapy dogs had increased agitation when their owner/others showed affection toward other people/dogs during preictal (Pperson = 0.005, Panimal = 0.0083), postictal (Pperson = 0.001, Panimal = 0.0068), and interictal (Pperson = 0.0083, Panimal = 0.02) period compared to monotherapy dogs. Seizure frequency and severity was not correlated with anxiety related behavior in dogs with IE. While seizure phase was associated with behavior changes in 38% (14/37) of our epileptic population, one specific seizure phase was not more likely to produce behavior changes than another. Behavioral changes noted in dogs with IE raises further questions about how this disease affects QoL. Research was presented in abstract form at the ACVIM Forum, Denver, CO, USA, June 2016.

SUBMITTER: Levitin H

PROVIDER: S-EPMC6857470 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Behavioral Changes in Dogs With Idiopathic Epilepsy Compared to Other Medical Populations.

Levitin Hilary H Hague Devon Wallis DW Ballantyne Kelly C KC Selmic Laura E LE

Frontiers in veterinary science 20191108

Anxiety related behaviors have been reported in humans diagnosed with idiopathic epilepsy (IE) and such traits may be altered depending on seizure phase. The purpose of this study was to determine the presence and severity of anxiety related behaviors in dogs with IE compared to other medical populations, and to determine if behavioral changes were associated with seizure control. In this retrospective cross-sectional study, the owners of 102 dogs presenting for wellness examination (37), epilep ...[more]

PMID: 31781583

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Project description:Epilepsy is the most common neurological disorder in dogs, with an incidence ranging from 0.5% to up to 20% in particular breeds. Canine epilepsy can be etiologically defined as idiopathic or symptomatic. Epileptic seizures may be classified as focal with or without secondary generalization, or as primary generalized. Nine genes have been identified for symptomatic (storage diseases) and one for idiopathic epilepsy in different breeds. However, the genetic background of common canine epilepsies remains unknown. We have studied the clinical and genetic background of epilepsy in Belgian Shepherds. We collected 159 cases and 148 controls and confirmed the presence of epilepsy through epilepsy questionnaires and clinical examinations. The MRI was normal while interictal EEG revealed abnormalities and variable foci in the clinically examined affected dogs. A genome-wide association study using Affymetrix 50K SNP arrays in 40 cases and 44 controls mapped the epilepsy locus on CFA37, which was replicated in an independent cohort (81 cases and 88 controls; combined p?=?9.70×10?¹?, OR?=?3.3). Fine mapping study defined a ?1 Mb region including 12 genes of which none are known epilepsy genes or encode ion channels. Exonic sequencing was performed for two candidate genes, KLF7 and ADAM23. No variation was found in KLF7 but a highly-associated non-synonymous variant, G1203A (R387H) was present in the ADAM23 gene (p?=?3.7×10??, OR?=?3.9 for homozygosity). Homozygosity for a two-SNP haplotype within the ADAM23 gene conferred the highest risk for epilepsy (p?=?6.28×10?¹¹, OR?=?7.4). ADAM23 interacts with known epilepsy proteins LGI1 and LGI2. However, our data suggests that the ADAM23 variant is a polymorphism and we have initiated a targeted re-sequencing study across the locus to identify the causative mutation. It would establish the affected breed as a novel therapeutic model, help to develop a DNA test for breeding purposes and introduce a novel candidate gene for human idiopathic epilepsies.

Project description:Phenobarbital (PB) is one of the most important antiseizure drugs (ASDs) to treat canine idiopathic epilepsy (IE). The effect of PB on the taxonomic changes in gastrointestinal microbiota (GIM) and their functions is less known, which may explain parts of its pharmacokinetic and pharmacodynamic properties, especially its antiseizure effect and drug responsiveness or drug resistance as well as its effect on behavioral comorbidities. Fecal samples of 12 dogs with IE were collected prior to the initiation of PB treatment and 90 days after oral PB treatment. The fecal samples were analyzed using shallow DNA shotgun sequencing, real-time polymerase chain reaction (qPCR)-based dysbiosis index (DI), and quantification of short-chain fatty acids (SCFAs). Behavioral comorbidities were evaluated using standardized online questionnaires, namely, a canine behavioral assessment and research questionnaire (cBARQ), canine cognitive dysfunction rating scale (CCDR), and an attention deficit hyperactivity disorder (ADHD) questionnaire. The results revealed no significant changes in alpha and beta diversity or in the DI, whereas only the abundance of Clostridiales was significantly decreased after PB treatment. Fecal SCFA measurement showed a significant increase in total fecal SCFA concentration and the concentrations of propionate and butyrate, while acetate concentrations revealed an upward trend after 90 days of treatment. In addition, the PB-Responder (PB-R) group had significantly higher butyrate levels compared to the PB-Non-Responder (PB-NR) group. Metagenomics of functional pathway genes demonstrated a significant increase in genes in trehalose biosynthesis, ribosomal synthesis, and gluconeogenesis, but a decrease in V-ATPase-related oxidative phosphorylation. For behavioral assessment, cBARQ analysis showed improvement in stranger-directed fear, non-social fear, and trainability, while there were no differences in ADHD-like behavior and canine cognitive dysfunction (CCD) scores after 90 days of PB treatment. While only very minor shifts in bacterial taxonomy were detected, the higher SCFA concentrations after PB treatment could be one of the key differences between PB-R and PB-NR. These results suggest functional changes in GIM in canine IE treatment.

Project description:BackgroundCanine idiopathic epilepsy (IE) is a common neurological disease with severe impact on the owner´s and the dog's quality of life. A subpopulation of dogs with IE does not respond to antiseizure drugs (non-responder). Th17 cells (T helper cells) and their proinflammatory Interleukin-17 (IL-17) are part of the immune system and previous studies showed their involvement in the pathogenesis of several autoimmune diseases. Non-responder might have an abnormal immune response against structures of the central nervous system. To discover a new aetiology of canine IE and thereby optimising the therapy of intractable IE, this prospective study aimed to investigate Th17 cells and IL-17 in dogs with IE. The underlying hypothesis was that in some dogs with IE a Th17 cell-mediated immune response could be detectable.Methods57 dogs with IE and 10 healthy dogs (control group, C) were enrolled in the study. EDTA blood was taken to measure Th17 cells by flow cytometry. IL-17 was measured in 35 cerebrospinal fluid (CSF) and 33 serum samples using an enzyme-linked immunosorbent assay (ELISA). It was investigated whether there was a significant increase of stimulated Th17 cells in blood samples or of IL-17 in serum and CSF samples of dogs with IE in comparison to C. Correlations between the amount of Th17 cells/μL or IL-17 and different clinical parameters e.g. seizure frequency, seizure type, seizure severity or treatment response were evaluated. Additionally, Th17 cells/μL were randomly controlled of 17 dogs with IE and were examined for changes over time and in relation to treatment response.ResultsTen dogs with IE had strongly elevated stimulated Th17 cells/μL within the blood (>100 Th17 cells/μL). A slight positive correlation between stimulated Th17 cells/μL and seizure severity (p = 0.046; rSpear = 0.27) was proven in these dogs. In addition, 4/10 dogs with elevated Th17 levels experienced cluster seizures and status epilepticus in comparison to 9% of the dogs with non-elevated Th17 levels (<100 Th17 cells/μL). Dogs with IE had significantly higher IL-17 values in CSF and serum samples compared to C (p<0.001; p<0.002; respectively).ConclusionIn single dogs with IE, strongly increased amounts of Th17 cells were detectable and dogs with elevated Th17 cells seemed to have a greater risk for experiencing a combination of cluster seizures and status epilepticus. Therefore, an underlying Th17-cell mediated immune response was suspected and hence anti-inflammatory drugs could be indicated in these single cases with intractable epilepsy.

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Behavioral Changes in Dogs With Idiopathic Epilepsy Compared to Other Medical Populations.

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Behavioral Changes in Dogs With Idiopathic Epilepsy Compared to Other Medical Populations.

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