International Veterinary Epilepsy Task Force Consensus Proposal: Diagnostic approach to epilepsy in dogs

This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset 6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered

Using Narrative Therapy to Treat Eating Disorder Not Otherwise Specified

Eating disorders have proved resistant to therapy with high relapse rates. Enhanced cognitive behavior therapy (CBT-E) is the favored treatment of choice but has been criticized for placing a similar emphasis on controlling eating behavior as the psychopathology it seeks to counter. In contrast, narrative therapy focuses on the development of an anti-eating disorder lifestyle and values. Evidence for this approach primarily consists of informal case study material. This case study describes a 28-year-old woman with a recurring history of anorexia nervosa, who self-referred to a university psychology clinic, due to fears of imminent relapse. The client received 10 sessions of narrative therapy and made significant progress in externalizing her eating disorder, in lessening her adherence to the ascetic values underpinning it, and in developing/expressing her non-eating disorder character and values. This case study provides evidence of the potential effectiveness of narrative therapy and contains valuable learning for clinicians regarding its implementation

PATHOS: a phase II/III trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for Human papillomavirus (HPV) positive oropharyngeal cancer

Background Human papillomavirus-positive oropharyngeal squamous cell carcinoma is increasing in incidence worldwide. Current treatments are associated with high survival rates but often result in significant long-term toxicities. In particular, long-term dysphagia has a negative impact on patient quality of life and health. The aim of PATHOS is to determine whether reducing the intensity of adjuvant treatment after minimally invasive transoral surgery in this favourable prognosis disease will result in better long-term swallowing function whilst maintaining excellent disease-specific survival outcomes. Methods/Design The study is a multicentre phase II/III randomised controlled trial for patients with biopsy-proven Human papillomavirus-positive oropharyngeal squamous cell cancer staged T1-T3 N0-N2b with a primary tumour that is resectable via a transoral approach. Following transoral surgery and neck dissection, patients are allocated into three groups based on pathological risk factors for recurrence. Patients in the low-risk pathology group will receive no adjuvant treatment, as in standard practice. Patients in the intermediate-risk pathology group will be randomised to receive either standard dose post-operative radiotherapy (control) or reduced dose radiotherapy. Patients in the high-risk pathology group will be randomised to receive either post-operative chemoradiotherapy (control) or radiotherapy alone. The primary outcome of the phase II study is patient reported swallowing function measured using the MD Anderson Dysphagia Inventory score at 12 months post-treatment. If the phase II study is successful, PATHOS will proceed to a phase III non-inferiority trial with overall survival as the primary endpoint. Discussion PATHOS is a prospective, randomised trial for Human papillomavirus-positive oropharyngeal cancer, which represents a different disease entity compared with other head and neck cancers. The trial aims to demonstrate that long-term dysphagia can be lessened by reducing the intensity of adjuvant treatment without having a negative impact on clinical outcome. The study will standardise transoral surgery and post-operative intensity-modulated radiotherapy protocols in the UK and develop a gold-standard swallowing assessment panel. An associated planned translational research programme, underpinned by tumour specimens and sequential blood collected as part of PATHOS, will facilitate further empirical understanding of this new disease and its response to treatment

Intravenous Topiramate: Pharmacokinetics in Dogs with Naturally-Occurring Epilepsy

Barriers to developing treatments for human status epilepticus (SE) include the inadequacy of experimental animal models. In contrast, naturally-occurring canine epilepsy is similar to the human condition and can serve as a platform to translate research from rodents to humans. The objectives of this study were to characterize the pharmacokinetics (PK) of an intravenous (IV) dose of topiramate (TPM) in dogs with epilepsy, and evaluate its effect on intracranial electroencephalographic (iEEG) features. Five dogs with naturally occurring epilepsy were used for this study. Three were getting at least one antiseizure drug as maintenance therapy including phenobarbital (PB). Four (ID 1-4) were used for the 10 mg/kg IV TPM + PO TPM study, and three (ID 3-5) were used for the 20 mg/kg IV TPM study. IV TPM was infused over 5 minutes at both doses. The animals were observed for vomiting, diarrhea, ataxia, and lethargy. Blood samples were collected at scheduled pre- and post-dose times. Plasma concentrations were measured using a validated HPLC-MS method. Non-compartmental and population compartmental modeling were performed (Phoenix WinNonLin and NLME) using plasma concentrations from all dogs in the study. Intracranial EEG (iEEG) was acquired in one dog. The difference between averaged iEEG energy levels at 15 minutes pre- and post-dose was assessed using a Kruskal-Wallis test. No adverse events were noted. Topiramate concentration-time profiles were best fit by a two-compartment model. PB co-administration was associated with a 5.6 fold greater clearance and a ~4 fold shorter elimination half-life. iEEG data showed that TPM produced a significant energy increase at frequencies >4 Hz across all 16 electrodes within 15 minutes of dosing. Simulations suggested that dogs on an enzyme inducer would require 25 mg/kg, while dogs on non-inducing drugs would need 20 mg/kg to attain the target concentration (20-30 µg/mL) at 30-minutes post-dose.This study shows that IV TPM has a relatively rapid onset of action, loading doses appear safe, and the presence of PB necessitates a higher dose to attain targeted concentrations. Consequently, it is a good candidate for further evaluation for treatment of seizure emergencies in dogs and people

Epilepsie aktuell - Zusammenfassung der IVETF-Empfehlungen zum "Therapeutischen Management der kaninen Epilepsie in Europa"

Das therapeutische Management der kaninen Epilepsie muss an die individuellen Bedürfnisse des Hundes und seines Besitzers angepasst werden. 2015 hat die International Veterinary Epilepsy Task Force (IVETF) die Konsensempfehlungen „Therapeutisches Management der kaninen Epilepsie in Europa“ veröffentlicht. In diesen Empfehlungen wird eine systematische therapeutische Vorgehensweise bei Hunden mit idiopathischer oder struktureller Epilepsie vorgeschlagen. Das Konsenspapier gibt außerdem einen Überblick über die in Europa zur Anwendung beim Hund zugelassenen Antiepileptika (AE) und empfiehlt Protokolle für die Arzneimitteltherapie. Der Konsensvorschlag basiert auf der aktuellen evidenzbasierten Literatur, berücksichtigt die aktuellen gesetzlichen Rahmenbedingungen in Europa und gibt die Erfahrungen der Autoren wieder. Im vorliegenden Artikel wird der Inhalt der Konsensusempfehlungen in deutscher Sprache zusammengefasst

Epilepsie aktuell - Zusammenfassung des Konsens papiers des IVETF "Vorschlag fur die diagnostische Herangehensweise bei Hunden mit Epilepsie"

In 2015, the International Veterinary Epilepsy Task Force (IVETF) published the “Consensus Proposal: Diagnostic Approach to Epilepsy in Dogs“, proposing the basis for a standardized method of diagnostic procedures in patients suffering from seizures. The recommended modus operandi comprises two fundamental steps to clarify if the patient is truly suffering from epilepsy and to determine its underlying cause. The authors suggest a tier system of three confidence levels describing the reliability of the diagnosis “idiopathic epilepsy”. The authors of the consensus proposal emphasize that these recommendations will evolve over time with advances in neuroimaging, electroencephalography, and molecular genetics of canine epilepsy. In this article, the contents of the consensus proposal are summarized in German language