The science behind One Health: at the interface of humans, animals, and the environment.

Humans face a grand quality-of-life challenge as growing demands for resources for an ever-expanding population threaten the existence of wildlife populations, degrade land, and pollute air and water. Public investment and policy decisions that will shape future interactions of humans, animals, and the environment need scientific input to help find common ground for durable and sustainable success. The Second International Conference on One Medicine One Science brought together a broad range of scientists, trainees, regulatory authorities, and health experts from 34 countries to inform and discuss the human impacts of air quality; the complexities of water quality, access, and conflicts; the opportunities and uncertainties in precision medicine; and the role of science communication in health policy formulation. Workshops focused on the roles and development of physician-scientists and multidisciplinary teams in complex problem solving, Big Data tools for analysis and visualization, international policy development processes, and health models that benefit animals and humans. Key realizations were that local and regional health challenges at the interface of humans, animals, and the environment are variations of the same overarching conflicts and that international gatherings provide new opportunities for investigation and policy development that are broadly applicable.

Temporal behavior of seizures and interictal bursts in prolonged intracranial recordings from epileptic canines.

OBJECTIVE: Epilepsy is a chronic disorder, but seizure recordings are usually obtained in the acute setting. The chronic behavior of seizures and the interictal bursts that sometimes initiate them is unknown. We investigate the variability of these electrographic patterns over an extended period of time using chronic intracranial recordings in canine epilepsy. METHODS: Continuous, yearlong intracranial electroencephalography (iEEG) recordings from four dogs with naturally occurring epilepsy were analyzed for seizures and interictal bursts. Following automated detection and clinician verification of interictal bursts and seizures, temporal trends of seizures, burst count, and burst-burst similarities were determined. One dog developed status epilepticus, the recordings of which were also investigated. RESULTS: Multiple seizure types, determined by onset channels, were observed in each dog, with significant temporal variation between types. The first 14 days of invasive recording, analogous to the average duration of clinical invasive recordings in humans, did not capture the entirety of seizure types. Seizures typically occurred in clusters, and isolated seizures were rare. The count and dynamics of interictal bursts form distinct groups and do not stabilize until several weeks after implantation. SIGNIFICANCE: There is significant temporal variability in seizures and interictal bursts after electrode implantation that requires several weeks to reach steady state. These findings, comparable to those reported in humans implanted with the NeuroPace Responsive Neurostimulator System (RNS) device, suggest that transient network changes following electrode implantation may need to be taken into account when interpreting or analyzing iEEG during evaluation for epilepsy surgery. Chronic, ambulatory iEEG may be better suited to accurately map epileptic networks in appropriate individuals.

Mining continuous intracranial EEG in focal canine epilepsy: Relating interictal bursts to seizure onsets.

OBJECTIVE: Brain regions are localized for resection during epilepsy surgery based on rare seizures observed during a short period of intracranial electroencephalography (iEEG) monitoring. Interictal epileptiform bursts, which are more prevalent than seizures, may provide complementary information to aid in epilepsy evaluation. In this study, we leverage a long-term iEEG dataset from canines with naturally occurring epilepsy to investigate interictal bursts and their electrographic relationship to seizures. METHODS: Four dogs were included in this study, each monitored previously with continuous iEEG for periods of 475.7, 329.9, 45.8, and 451.8 days, respectively, for a total of >11,000 h. Seizures and bursts were detected and validated by two board-certified epileptologists. A published Bayesian model was applied to analyze the dynamics of interictal epileptic bursts on EEG and compare them to seizures. RESULTS: In three dogs, bursts were stereotyped and found to be statistically similar to periods before or near seizure onsets. Seizures from one dog during status epilepticus were markedly different from other seizures in terms of burst similarity. SIGNIFICANCE: Shorter epileptic bursts explored in this work have the potential to yield significant information about the distribution of epileptic events. In our data, bursts are at least an order of magnitude more prevalent than seizures and occur much more regularly. Our finding that bursts often display pronounced similarity to seizure onsets suggests that they contain relevant information about the epileptic networks from which they arise and may aide in the clinical evaluation of epilepsy in patients.

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.

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 months or >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.This consensus article represents the basis for a more standardised diagnostic approach to the seizure patient. These recommendations will evolve over time with advances in neuroimaging, electroencephalography, and molecular genetics of canine epilepsy.