International veterinary epilepsy task force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Matiasek et al. BMC Veterinary Research (2015) 11:216 DOI 10.1186/s12917-015-0467-9 CORRESPONDENCE Open Access International veterinary epilepsy task force recommendations for systematic sampling and processing of brains from epileptic dogs and cats Kaspar Matiasek1*, Martí Pumarola i Batlle2, Marco Rosati1, Francisco Fernández-Flores2, Andrea Fischer3, Eva Wagner1, Mette Berendt3, Sofie F. M. Bhatti4, Luisa De Risio5, Robyn G. Farquhar6, Sam Long7, Karen Muñana8, Edward E. Patterson9, Akos Pakozdy10, Jacques Penderis11, Simon Platt12, Michael Podell13, Heidrun Potschka14, Clare Rusbridge15,16, Veronika M. Stein17, Andrea Tipold17 and Holger A. Volk18 Abstract Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations. Keywords: Canine, Feline, Seizures, Hippocampus, Ictogenic, Epileptogenic, Processing, Neuropathology Background Paroxysmal seizure-like events are one of the most common causes of admission to neurological services in small animal practice. With a prevalence ranging between 0.5 % and 5.0 % amongst a general non-referral population of dogs, with higher number of dogs being affected in specific breeds [1–4], epilepsy is a major health issue that severely affects the performance, cognition and behaviour of pets with recurrent seizures and thereby the quality of life of the animals and owners, the owners’ economy as well as their range of social activities [5–7]. * Correspondence: 1 Section of Clinical and Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-University, Veterinärstr. 13, 80539 Munich, Germany Full list of author information is available at the end of the article Hence, the clinical and socioeconomical impact of epilepsy, more than its semiological and pathomechanistic resemblance to human epilepsy has been a trigger of clinical research in that field ever since. However, the most recent advances of imaging, video electroencephalography and telemetry, pharmacotherapy and neurogenetics kickedoff a new wave of enthusiasm in epileptology amongst veterinary neurologists [1, 8–13]. With some exceptions [14, 15], the pace of clinical achievements in diagnostics, classification and management of epilepsy patients in veterinary practice has not been paralleled by comparable insights into epilepsy-associated tissue changes and, in particular, those underlying drug resistance. Brain tissue studies in clinically affected animals often are anecdotal and rarely comprise investigations for causative changes and biomarkers. If tissue studies represent the mainstay of rodent models of epilepsy, research in © 2015 Matiasek et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Level Experience Anatomical baseline skills Semiological baseline skills & clinical neurolocalisation Neuropathology baseline skills Achievement 0 None: none none none n.a. External: Recognition of cerebrum, cerebellum, brain stem and frontal/parietal/temporal/ occipital regions. Distinction of clinical forebrain, cerebellar and brainstem signs. Macro: Spotting malacia, gross malformations, mass lesions, haemorrhage. Easy, Single training, Within weeks st 1 year student (veterinary & human medicine, neurobiology) Untrained technician I Basic: 2 nd year student, Trained technician Internal: Distinction of white vs grey matter. Matiasek et al. BMC Veterinary Research (2015) 11:216 Table 1 Skill level thresholds in brain pathology with special reference to epilepsy pathology Micro: None to basic neurohistology. II Advanced: Pathology & neurology residents Recognition of brain lobes, major brain regions (e.g. hippocampus thalamus, basal nuclei), tracts and of regions containing expected nuclei. General: Specific neurolocalisation based on clinical signs. General: Recognition of basic malformations, mass effects, haemorrhage, infiltrative lesions and basic neurodegeneration. Epilepsy-specific: Distinction and localisation of seizure types. Epilepsy-specific: Histological recognition of stereotypic seizure-associated changes. Capable of subregional and nuclear neuro-localisation. Recognition and classification of the above named entities, plus of microanomalies, distinct cytopathologies, brain specific disease markers and neurodegenerative disorders. Demanding, Repeated training, Within months PhD students General pathologist III Expert: A. broad-based Neurology-trained pathologist Pathology-trained neurologist B. topic-based Neuroscientist Detailed knowledge of the species-specific topographic and functional anatomy of the brain including gyri and folia organisation, distinct nuclei, cortical areas and their patterning as well as fibre connections, neurotransmitter maps, cell markers and the vascularity. Demanding, Cont´ training, Within years Knowledge and experience in comparative neuropathology including human disorders. Page 2 of 28 Matiasek et al. BMC Veterinary Research (2015) 11:216 Table 2 Important epilepsy-related brain zones and definitions (adapted from [59]) Epileptogenic zone Region of cortex that can generate epileptic seizures and removal or disconnection of which should lead to seizure freedom Epileptogenic lesion Distinct brain lesion, capable of generating and sustaining epileptic se (...truncated)