Preliminary assessment of cognitive impairments in canine idiopathic epilepsy

In humans, epilepsy can induce or accelerate cognitive impairment (CI). There is emerging evidence of CI in dogs with idiopathic epilepsy (IE) from recent epidemiological studies. The aim of our study was to assess CI in dogs with IE using two tests of cognitive dysfunction designed for use in a clinical setting. Dogs with IE (n=17) were compared against controls (n=18) in their performance in two tasks; a spatial working memory task and a problem-solving task. In addition, owners completed the Canine Cognitive Dysfunction Rating (CCDR) scale for their dog. The groups did not differ statistically with respect to age and breed. Dogs with IE performed significantly worse than controls on the spatial working memory task (P=0.016), but not on the problem solving task (P=0.683). CCDR scores were significantly higher in the IE group (P=0.016); however, no dogs reach the recommended threshold score for CCD diagnosis. Our preliminary data suggest that dogs with IE exhibit impairments in a spatial working memory task. Further research is required to explore the effect of IE on other cognitive abilities in dogs with a larger sample, characterising the age of onset, nature and progression of any impairments and the impact of anti-epileptic drugs

Epilepsy beyond seizures: a review of the impact of epilepsy and its comorbidities on health-related quality of life in dogs

Epilepsy is one of the most common chronic neurological conditions in the dog, estimated to affect 0.6 to 0.75 per cent of dogs. Owners of dogs with epilepsy have previously indicated that their dog's quality of life (QoL) is of greatest importance to them above seizure frequency; however, much of the research into canine epilepsy to date has focussed on seizure frequency, and how to reduce it via antiepileptic drug treatment. In people, the impact of epilepsy upon QoL has been widely studied, exploring not only its impact on physical health, but also the psychological health and cognitive capabilities of affected individuals. This paper reviews the existing literature on canine epilepsy, identifies potential threats to QoL, and draws parallels from human epilepsy research. We suggest that canine epilepsy poses threats to both quality and quantity of life, with treatment interventions posing a fine balance of potential benefits and harms to the patient. At present, little is known about the neurobehavioural, emotional and cognitive effects of epilepsy upon affected dogs. Further studies are needed to establish the extent to which unknown QoL-inhibiting comorbidities exist in the dog, in order to avoid their undertreatment, and to objectively quantify the effects of epilepsy on canine QoL

Physiological reactivity to spontaneously occurring seizure activity in dogs with epilepsy and their carers

There is a complex bidirectional relationship between stress and epilepsy. Stressful stimuli and subsequent cortisol release act as a trigger for seizure activity in some individuals with epilepsy, and seizure activity itself may act as a stressor to the affected individual. Epilepsy is the most common chronic neurological condition in domestic dogs and requires chronic management by their human carers, impacting upon the quality of life of both dog and carer. Seizures occur unpredictably and may be stressful for carers to witness and manage. In the present study we investigated the role of seizure activity as a stressor, measuring the effect of spontaneously occurring seizure activity in dogs with epilepsy upon their own cortisol levels and that of their carers. Furthermore, we tested whether individual differences in HPA reactivity were associated with owner personality characteristics and the quality of the dog carer relationship. Saliva samples were obtained from sixteen dog carer dyads in the home setting 20 and 40 minute post-seizure, and at time-matched points on the following (non-seizure) day. Significant differences in cortisol levels were found in dogs at 40 minute post-seizure (265.1% increase), and at 20 minute post-seizure in their carers (40.5% increase). No associations were found between cortisol reactivity and the strength of the dog-carer bond. Carers with higher neuroticism scores exhibited higher cortisol levels at both post-seizure sampling points. As there was a gender bias in the carer sample (15/16 were female), and there are known sex differences in cortisol reactivity in response to psychological stress, the conclusions of this study may be limited to female carers. These findings are the first to objectively demonstrate the acutely stressful effects of seizures in dogs with epilepsy and their carers

Clinical reasoning in feline epilepsy: Which combination of clinical information is useful?

We sought to identify the association between clinical risk factors and the diagnosis of idiopathic epilepsy (IE) or structural epilepsy (SE) in cats, using statistical models to identify combinations of discrete parameters from the patient signalment, history and neurological examination findings that could suggest the most likely diagnosis. Data for 138 cats with recurrent seizures were reviewed, of which 110 were valid for inclusion. Seizure aetiology was classified as IE in 57% and SE in 43% of cats. Binomial logistic regression analyses demonstrated that pedigree status, older age at seizure onset (particularly >7 years old), abnormal neurological examinations, and ictal vocalisation were associated with a diagnosis of SE compared to IE, and that ictal salivation was more likely to be associated with a diagnosis of IE than SE. These findings support the importance of considering inter-ictal neurological deficits and seizure history in clinical reasoning

Proportionate and Disproportionate Functional Mitral Regurgitation: A New Conceptual Framework That Reconciles the Results of the MITRA-FR and COAPT Trials

Traditional approaches to the characterization of secondary or functional mitral regurgitation (MR) have largely ignored the critical importance of the left ventricle (LV). We propose that patients with secondary MR represent a heterogenous group, which can be usefully subdivided based on understanding that the effective regurgitant orifice area (EROA) is dependent on left ventricular end-diastolic volume (LVEDV). According to the Gorlin hydraulic orifice equation, patients with heart failure, an LV ejection fraction of 30%, an LVEDV of 220 to 250 ml, and a regurgitant fraction of 50% would be expected to have an EROA of ≈0.3 cm2 independent of specific tethering abnormalities of the mitral valve leaflets. The MR in these patients is proportionate to the degree of LV dilatation and can respond to drugs and devices that reduce LVEDV. In contrast, patients with EROA of 0.3 to 0.4 cm2 but with LVEDV of only 160 to 200 ml exhibit degrees of MR that are disproportionately higher than predicted by LVEDV. These patients appear to preferentially benefit from interventions directed at the mitral valve. Our proposed conceptual framework explains the apparently discordant results from 2 recent randomized controlled trials of mitral valve repair. The MITRA-FR (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) trial enrolled patients who had MR that was proportionate to the degree of LV dilatation, and during long-term follow-up, the LVEDV and clinical outcomes of these patients did not differ from medically-treated control subjects. In comparison, the patients enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial had an EROA ≈30% higher but LV volumes that were ≈30% smaller, indicative of disproportionate MR. In these patients, transcatheter mitral valve repair reduced the risk of death and hospitalization for heart failure, and these benefits were paralleled by a meaningful decrease in LVEDV. Thus, characterization of MR as proportionate or disproportionate to LVEDV appears to be critical to the selection of an optimal treatment for patients with chronic heart failure and systolic dysfunction

Clinical and magnetic resonance imaging characteristics of thoracolumbar intervertenral disk extrusions and protrusions in large breed dogs

It has recently been shown that the fat-derived hormone adiponectin has the ability to decrease hyperglycemia and to reverse insulin resistance. However, bacterially produced full-length adiponectin is functionally inactive. Here, we show that endogenous adiponectin secreted by adipocytes is post-translationally modified into eight different isoforms, as shown by two-dimensional gel electrophoresis. Carbohydrate detection revealed that six of the adiponectin isoforms are glycosylated. The glycosylation sites were mapped to several lysines (residues 68, 71, 80, and 104) located in the collagenous domain of adiponectin, each having the surrounding motif of GXKGE(D). These four lysines were found to be hydroxylated and subsequently glycosylated. The glycosides attached to each of these four hydroxylated lysines are possibly glucosylgalactosyl groups. Functional analysis revealed that full-length adiponectin produced by mammalian cells is much more potent than bacterially generated adiponectin in enhancing the ability of subphysiological concentrations of insulin to inhibit gluconeogenesis in primary rat hepatocytes, whereas this insulin-sensitizing ability was significantly attenuated when the four glycosylated lysines were substituted with arginines. These results indicate that full-length adiponectin produced by mammalian cells is functionally active as an insulin sensitizer and that hydroxylation and glycosylation of the four lysines in the collagenous domain might contribute to this activity.link_to_subscribed_fulltex

Transmission dynamics and prospects for the elimination of canine rabies

Rabies has been eliminated from domestic dog populations in Western Europe and North America, but continues to kill many thousands of people throughout Africa and Asia every year. A quantitative understanding of transmission dynamics in domestic dog populations provides critical information to assess whether global elimination of canine rabies is possible. We report extensive observations of individual rabid animals in Tanzania and generate a uniquely detailed analysis of transmission biology, which explains important epidemiological features, including the level of variation in epidemic trajectories. We found that the basic reproductive number for rabies, R<sub>0</sub>, is very low in our study area in rural Africa (∼1.2) and throughout its historic global range (<2). This finding provides strong support for the feasibility of controlling endemic canine rabies by vaccination, even near wildlife areas with large wild carnivore populations. However, we show that rapid turnover of domestic dog populations has been a major obstacle to successful control in developing countries, thus regular pulse vaccinations will be required to maintain population-level immunity between campaigns. Nonetheless our analyses suggest that with sustained, international commitment, global elimination of rabies from domestic dog populations, the most dangerous vector to humans, is a realistic goal