New insights into neuropathology and pathogenesis of autoimmune glial fibrillary acidic protein meningoencephalomyelitis.

Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease diagnosable by the presence of anti-GFAP autoantibodies in the cerebrospinal fluid and presents as meningoencephalomyelitis in the majority of patients. Only few neuropathological reports are available and little is known about the pathogenic mechanisms. We performed a histopathological study of two autopsies and nine CNS biopsies of patients with anti-GFAP autoantibodies and found predominantly a lymphocytic and in one autopsy case a granulomatous inflammatory phenotype. Inflammatory infiltrates were composed of B and T cells, including tissue-resident memory T cells. Although obvious astrocytic damage was absent in the GFAP-staining, we found cytotoxic T cell-mediated reactions reflected by the presence of CD8+/perforin+/granzyme A/B+ cells, polarized towards astrocytes. MHC-class-I was upregulated in reactive astrocytes of all biopsies and two autopsies but not in healthy controls. Importantly, we observed a prominent immunoreactivity of astrocytes with the complement factor C4d. Finally, we provided insight into an early phase of GFAP autoimmunity in an autopsy of a pug dog encephalitis that was characterized by marked meningoencephalitis with selective astrocytic damage with loss of GFAP and AQP4 in the lesions.Our histopathological findings indicate that a cytotoxic T cell-mediated immune reaction is present in GFAP autoimmunity. Complement C4d deposition on astrocytes could either represent the cause or consequence of astrocytic reactivity. Selective astrocytic damage is prominent in the early phase of GFAP autoimmunity in a canine autopsy case, but mild or absent in subacute and chronic stages in human disease, probably due to the high regeneration potential of astrocytes. The lymphocytic and granulomatous phenotypes might reflect different stages of lesion development or patient-specific modifications of the immune response. Future studies will be necessary to investigate possible implications of pathological subtypes for clinical disease course and therapeutic strategies.

A retrospective evaluation of phenobarbital-induced hematologic changes in 69 cats.

BACKGROUND: Phenobarbital (PB) is used as a first-line treatment for recurrent epileptic seizures in cats. While hematologic abnormalities are well-known side effects of antiepileptic therapy with PB in humans and dogs, little is known about such alterations in cats. OBJECTIVES: The aim of this retrospective study was to investigate the prevalence and clinical relevance of cytopenia during PB treatment in cats. METHODS: In this single-center, retrospective clinical study, 69 cats-with suspected idiopathic epilepsy admitted to the Small Animal Clinic of the University of Veterinary Medicine in Vienna (VMU)-were included. A complete blood count for each patient was performed, and changes in hematocrit, leukocytes, neutrophils, and thrombocytes were documented and graded. RESULTS: Fifty-three out of 69 cats (76.8%) showed cytopenias with a reduction of at least one cell fraction during PB treatment. The most frequent change was neutropenia (60%), followed by leukopenia (49.3%), thrombocytopenia (24.1%), and anemia (20.3%). Most of the changes were mild or moderate; only one patient (1.5%) showed severe leukopenia and neutropenia, and one was a life-threatening neutropenia (1.5%) with a serum PB concentration within or even below the therapeutic range. These patients did not present with clinical symptoms other than those related to epileptic episodes. Cats who received combination therapy showed lower hematocrits than those who received monotherapy. A tendency for leukocytes and neutrophils to decrease during PB treatment was also seen. CONCLUSIONS: Blood cytopenias may frequently occur in cats on chronic PB therapy, even when serum drug levels are within the therapeutic range. However, clinical signs are typically mild to moderate and rarely severe.

Diagnostic value of cerebrospinal fluid analysis in epileptic cats with unremarkable brain MRI or hippocampal signal changes only.

OBJECTIVES: Cerebrospinal fluid (CSF) analysis is used in the diagnostic investigation of cats with epileptic seizures. The aim of this retrospective study was to evaluate the diagnostic value of CSF analysis in cats with epileptic seizures that have unremarkable brain MRI or only hippocampal signal changes. METHODS: Unremarkable brain MRI or MRI studies with signal alterations in the hippocampus only in cats with suspected epilepsy and CFS analysis performed at the Small Animal Internal Department or Diagnostic Imaging Department at Vetmeduni Vienna, Austria, between 2011 and 2017 were reviewed. Total nucleated cell count, total protein, blood contamination and cytology data from CSF analysis were evaluated. RESULTS: In total, 87 cats were included. Seventy cats (80.5%) had unremarkable MRI, five (5.7%) had hippocampal signal changes with contrast enhancement and 12 (13.8%) had hippocampal signal changes without contrast enhancement. Overall, four cats (4.6%) had abnormalities on CSF analysis; all (100%) had an increased total nucleated cell count (22 cells/µl, 7 cells/µl, 6 cells/µl and 6 cells/µl, respectively), and no cat had increased total protein (100%), although in one cat total protein was not evaluated. Three of these cats had unremarkable MRI and one had hippocampal signal changes without contrast enhancement. The median duration of epileptic signs prior to the MRI study was 2 days. CONCLUSIONS AND RELEVANCE: Our results show that, in our cohort of epileptic cats with unremarkable brain MRI or with hippocampal signal changes, CSF analysis was usually normal. This should be considered before performing a CSF tap.

Temporal lobe epilepsy in cats.

In recent years there has been increased attention to the proposed entity of feline temporal lobe epilepsy (TLE). Epileptic discharges in certain parts of the temporal lobe elicit very similar semiology, which justifies grouping these epilepsies under one name. Furthermore, feline TLE patients tend to have histopathological changes within the temporal lobe, usually in the hippocampus. The initial aetiology is likely to be different but may result in hippocampal necrosis and later hippocampal sclerosis. The aim of this article was not only to summarise the clinical features and the possible aetiology, but also being work to place TLE within the veterinary epilepsy classification. Epilepsies in cats, similar to dogs, are classified based on the aetiology into idiopathic epilepsy, structural epilepsy and unknown cause. TLE seems to be outside of this classification, as it is not an aetiologic category, but a syndrome, associated with a topographic affiliation to a certain anatomical brain structure. Magnetic resonance imaging, histopathologic aspects and current medical therapeutic considerations will be summarised, and emerging surgical options are discussed.

Parallel roles of neuroinflammation in feline and human epilepsies.

Autoimmune encephalitis refers to a group of disorders characterised by a non-infectious encephalitis, often with prominent seizures and surface neuronal autoantibodies. AE is an important cause of new-onset refractory status epilepticus in humans and is frequently responsive to immunotherapies including corticosteroids, plasma exchange, intravenous immunoglobulin G and rituximab. Recent research suggests that parallel autoantibodies can be detected in non-human mammalian species. The best documented example is leucine-rich glioma-inactivated 1 (LGI1)-antibodies in domestic cats with limbic encephalitis (LE). In this review, we discuss the role of neuroinflammation and autoantibodies in human and feline epilepsy and LE.

[Magnetic resonance imaging findings in 143 epileptic cats]. / Magnetresonanztomographische Befunde bei 143 Katzen mit Epilepsie.

OBJECTIVE: Epilepsy is one of the more common chronic neurological diseases in cats in which MRI plays a key role in the diagnostic work-up. Hippocampal MRI changes are common in cats, however it is unclear whether these changes represent the reason or the consequence of the disease.The goal of the present study was the retrospective analysis of the MRI findings in a large cohort of epileptic cats. MATERIAL AND METHODS: In total, 143 cats of 3 age groups (< 1 year, 1-6 years, and > 6 years) were included in the study. MRI findings were divided into 4 categories: normal, with extrahippocampal lesions, and hippocampal signal alterations with or without contrast enhancement. The prevalence and frequency of these MRI findings in the age groups were examined using chi-quadrat test and nominal regression model. RESULTS: In approximately one half of the cats (49 %), MRI displayed normal findings. Extrahippocampal changes occurred in 18 % of the animals. Hippocampal alterations were present in 33 % of the cats. Hippocampal sclerosis was found histopathologically in all four MRI categories. CONCLUSION AND CLINICAL RELEVANCE: Brain MRI was normal in approximately 50 % of the epileptic cats. Extrahippocampal changes are expected mostly in cats older than 6 years. The etiology of the hippocampal alterations is unclear in most cases. Further investigations are needed for a better understanding of the hippocampal signal alterations.

Evaluation of the effect of phenobarbital administration on the biochemistry profile, with a focus on serum liver values, in epileptic cats.

OBJECTIVES: Phenobarbital (PB) is the most common antiseizure drug (ASD) used for the management of feline epilepsy. In dogs, PB is known to cause serum liver enzyme induction and hepatotoxicity, especially after administration long term or in high concentrations. In cats, insufficient evidence is available to draw similar conclusions. The aim of this study was to evaluate the effect of PB administration on the serum biochemistry profile of epileptic cats. As an additional objective, other adverse effects arising, related to PB treatment, were recorded. METHODS: Medical records of four veterinary centres were retrospectively reviewed for epileptic cats receiving PB treatment. Cats were included if they had a diagnosis of idiopathic epilepsy or structural epilepsy; a normal baseline serum biochemistry profile; at least one follow-up serum biochemistry profile; no concurrent disease or had not received medication that could possibly influence liver function or lead to serum liver enzyme induction. Alkaline phosphatase, alanine aminotransferase (ALT), aspartate transaminase and gamma-glutamyl transferase activities, and total bilirubin, bile acids, glucose, albumin, total protein, urea and creatinine concentrations before and during PB administration were recorded. PB serum concentration was also recorded, when available. RESULTS: Thirty-three cats (24 males, nine females) with a median age of 3 years (range 2 months to 12 years) met the inclusion criteria. Idiopathic or structural epilepsy was diagnosed in 25 (76%) and eight (24%) cats, respectively. The follow-up period ranged from 9 to 62 months. This study found an increase in ALT in three cats, possibly related to a PB serum concentration >30 µg/ml. No statistically significant increase in serum liver enzymes or other evaluated biochemistry parameters was found by comparing pre- and post-treatment parameters. CONCLUSIONS AND RELEVANCE: PB administration did not result in hepatic enzyme induction or other biochemical abnormalities in cats. This strengthens the safety profile of PB as an ASD in cats.

A retrospective case series of clinical signs in 28 Beagles with Lafora disease.

BACKGROUND: Clinical signs and their progression in Beagles with Lafora disease are poorly described. OBJECTIVES: To describe clinical signs in Beagles with Lafora disease. ANIMALS: Twenty-eight Beagles with Lafora disease confirmed by genetic testing or histopathology. METHODS: Retrospective multicenter case series. Data regarding signalment, clinical signs, diagnostic tests and treatment were retrieved from hospital data files. A questionnaire was sent to owners asking about neurological deficits, changes in cognitive functions, behavioral changes, response to treatment and survival time. RESULTS: Onset of clinical signs was 8.3 years (mean; range, 6.3-13.3). All dogs had myoclonic episodes as an initial clinical sign with tonic-clonic seizures in n = 11/28 (39%) and n = 12/28 (43%) later developing tonic-clonic seizures. Deficits of coordination (n = 21/25; 84%), impaired vision (n = 15/26; 58%), and impaired hearing (n = 13/26; 50%) developed later. Mental decline was observed as loss of house training (urination; n = 8/25; 32%), difficulties performing learned tasks (n = 9/25; 36%), and difficulties learning new tasks (n = 7/23; 30%). Common behavioral changes were: increased photosensitivity (n = 20/26; 77%), staring into space (n = 16/25; 64%), reduced stress resistance (n = 15/26; 58%), increased noise sensitivity (n = 14/26; 54%), and separation anxiety (n = 11/25; 44%). Twenty-one dogs were alive (median age 11.9 years; range, 9.8-18.6), and 7 dogs were dead (mean age 12.1 years; SD: 1.3; range, 10.5-12.6) at time of writing. CONCLUSIONS AND CLINICAL IMPORTANCE: Lafora disease in Beagles causes significant behavioral changes, and mental decline as well as neurological deficits in addition to myoclonic episodes and generalized tonic-clonic seizures. Nevertheless, a relatively normal life span can be expected.

Higher prevalence of seizure activity in a small population of atopic dogs: a retrospective breed- and age-matched study.

BACKGROUND: Atopic dermatitis (AD) is considered to be a systemic disease in people shown to have an association with epilepsy. However, so far, no data about the association of epilepsy and atopy have been reported in dogs. OBJECTIVES: Given the homology between human and canine AD, and the increased incidence of epilepsy in atopic people, we investigated the association between AD and seizure-associated activity in a small canine population. ANIMALS: We included 34 atopic dogs and 34 breed- and age range-matched nonatopic dogs. METHODS AND MATERIALS: We investigated the association between canine AD and signs of seizures in a retrospective, breed- and age range-matched, case-controlled study. Dog owners were interviewed using a standardized questionnaire. The presence or absence of signs of seizure activity and possible comorbidities were questioned. RESULTS: Seven of the 34 atopic dogs also suffered from seizure activity. By contrast, only one dog affected with seizure signs could be identified among the 34 nonatopic dogs. Atopic dermatitis was associated with a higher frequency of seizure activity (McNemar test, P = 0.035; one-sided) and atopic dogs had a higher odds ratio to develop seizures [(95% CI) 7 (0.9-56.9)] compared to the age- and breed-matched nonatopic control group. No other comorbidities were detected. CONCLUSION AND CLINICAL IMPORTANCE: In our small retrospective study, we observed an increased prevalence of seizure activity in the atopic dog population. Further larger and prospective studies are needed to confirm these results.

Delineation of the Feline Hippocampal Formation: A Comparison of Magnetic Resonance Images With Anatomic Slices.

The hippocampal formation (HF) is a relevant brain structure that is involved in several neurological and psychiatric diseases. In cats, structural changes of the HF are associated with epilepsy. The knowledge of a detailed anatomy of this brain region may lead to the accurate diagnosis and development of better therapies. There are, however, discrepancies among the research findings, which may be due to different definitions being used, according to anatomical guidelines and boundaries, as well as different magnetic resonance (MR) protocols. The aim of this study is to evaluate the anatomical borders of the HF on transverse MR images and the correlated anatomic sections in three cats. The boundaries of the HF were mostly visible in the formalin fixed anatomic sections, except in the areas where the hippocampus proper exchanges into the subicular complex. Also, the delineation of the anteroventral part and the latero-caudal borders of the HF were not clearly defined. Based on our preliminary results these problems are reinforced on MR images, and further histological and anatomical research must be done to find a way to delineate these neurological structures accurately.

Hippocampal necrosis and sclerosis in cats: A retrospective study of 35 cases.

Hippocampal necrosis and hippocampal sclerosis in cats is a neuropathological entity which is a major concern in feline epilepsy. The aim of our study was to identify associated pathologic brain lesions possibly serving as aetiological triggers in this condition. Therefore, the formalin-fixed and paraffin waxembedded brain tissue of 35 cats diagnosed with hippocampal necrosis or sclerosis was examined retrospectively. In 26 cats inflammatory infiltrates could be found in the hippocampus or adjacent brain regions. Fifteen out of these animals demonstrated mild to moderate infiltrations by lymphocytes and complement deposition in the hippocampus similar to human limbic encephalitis, seven showed unspecific, predominantly non-suppurative inflammation, and two demonstrated suppurative inflammation of the hippocampus or adjacent brain regions. Additionally, one cat was diagnosed with central nervous manifestation of feline infectious peritonitis virus and another one with cerebral Toxoplasma gondii infection. Intracranial neoplasia was present in five cases altogether. Three of them comprised meningioma which was present additionally to lesions resembling limbic encephalitis in two cases, and a dentate gyrus alteration in one case. The other two tumour-associated cases comprised oligodendroglioma. Structural alterations of the dentate gyrus together with hippocampal sclerosis were encountered in three cases in total. Besides the case associated with a meningioma, one case demonstrated lesions resembling limbic encephalitis. A vascular infarct in the temporal lobe was encountered in one cat. In four cases no lesions other than hippocampal necrosis or sclerosis were found. The involvement of feline immunodeficiency virus infections, which may be able to produce hippocampal lesions, was not encountered in the cats examined.

Systematic review of antiepileptic drugs' safety and effectiveness in feline epilepsy.

BACKGROUND: Understanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease. However, there is a lack of information about the treatment of feline epilepsy and therefore a systematic review was constructed to assess current evidence for the AEDs' efficacy and tolerability in cats. The methods and materials of our former systematic reviews in canine epilepsy were mostly mirrored for the current systematic review in cats. Databases of PubMed, CAB Direct and Google scholar were searched to detect peer-reviewed studies reporting efficacy and/or adverse effects of AEDs in cats. The studies were assessed with regards to their quality of evidence, i.e. study design, study population, diagnostic criteria and overall risk of bias and the outcome measures reported, i.e. prevalence and 95% confidence interval of the successful and affected population in each study and in total. RESULTS: Forty studies describing clinical outcomes of AEDs' efficacy and safety were included. Only two studies were classified as "blinded randomised controlled trials". The majority of the studies offered high overall risk of bias and described low feline populations with unclear diagnostic criteria and short treatment or follow-up periods. Individual AED assessments of efficacy and safety profile showed that phenobarbital might currently be considered as the first choice AED followed by levetiracetam and imepitoin. Only imepitoin's safety profile was supported by strong level of evidence. Imepitoin's efficacy as well as remaining AEDs' efficacy and safety profile were supported by weak level of evidence. CONCLUSIONS: This systematic review reflects an evidence-based assessment of the published data on the AEDs' efficacy and safety for feline epilepsy. Currently, phenobarbital is likely to be the first-line for feline epileptic patients followed by levetiracetam and imepitoin. It is essential that clinicians evaluate both AEDs' effectiveness and tolerability before tailoring AED to the individual patient. Further studies in feline epilepsy treatment are by far crucial in order to establish definite guidelines for AEDs' efficacy and safety.

Selective Limbic Blood-Brain Barrier Breakdown in a Feline Model of Limbic Encephalitis with LGI1 Antibodies.

Human leucine-rich glioma-inactivated protein 1 encephalitis (LGI1) is an autoimmune limbic encephalitis in which serum and cerebrospinal fluid contain antibodies targeting LGI1, a protein of the voltage gated potassium channel (VGKC) complex. Recently, we showed that a feline model of limbic encephalitis with LGI1 antibodies, called feline complex partial seizures with orofacial involvement (FEPSO), is highly comparable to human LGI1 encephalitis. In human LGI1 encephalitis, neuropathological investigations are difficult because very little material is available. Taking advantage of this natural animal model to study pathological mechanisms will, therefore, contribute to a better understanding of its human counterpart. Here, we present a brain-wide histopathological analysis of FEPSO. We discovered that blood-brain barrier (BBB) leakage was present not only in all regions of the hippocampus but also in other limbic structures such as the subiculum, amygdale, and piriform lobe. However, in other regions, such as the cerebellum, no leakage was observed. In addition, this brain-region-specific immunoglobulin leakage was associated with the breakdown of endothelial tight junctions. Brain areas affected by BBB dysfunction also revealed immunoglobulin and complement deposition as well as neuronal cell death. These neuropathological findings were supported by magnetic resonance imaging showing signal and volume increase in the amygdala and the piriform lobe. Importantly, we could show that BBB disturbance in LGI1 encephalitis does not depend on T cell infiltrates, which were present brain-wide. This finding points toward another, so far unknown, mechanism of opening the BBB. The limbic predilection sites of immunoglobulin antibody leakage into the brain may explain why most patients with LGI1 antibodies have a limbic phenotype even though LGI1, the target protein, is ubiquitously distributed across the central nervous system.

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 >7years 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.

Magnetic resonance features of the feline hippocampus in epileptic and non-epileptic cats: a blinded, retrospective, multi-observer study.

BACKGROUND: Hippocampal necrosis in cats has been reported to be associated with epileptic seizures. Magnetic resonance imaging (MRI) features of temporal lobe (TL) abnormalities in epileptic cats have been described but MR images from epileptic and non-epileptic individuals have not yet been systematically compared. TL abnormalities are highly variable in shape, size and signal, and therefore may lead to varying evaluations by different specialists. The aim of this study was to investigate whether there were differences in the appearance of the TL between epileptic and non-epileptic cats, and whether there were any relationships between TL abnormalities and seizure semiologies or other clinical findings. We also investigated interobserver agreement among three specialists. METHODS: The MR images of 46 cats were reviewed independently by three observers, who were blinded to patient data, examination findings and the review of the other observers. Images were evaluated using a multiparametric scoring system developed for this study. Mann-Whitney U-tests and chi-square were used to analyse the differences between observers' evaluations. The kappa coefficient (k) and Fleiss' kappa coefficient were used to quantify interobserver agreement. RESULTS: The overall interobserver agreement was moderate to good (k =0.405 to 0.615). The MR scores between epileptic and non-epileptic cats did not differ significantly. However, there was a significant difference between the MR scores of epileptic cats with and without orofacial involvement according to all three observers. Likewise, MR scores of cats with cluster seizures were higher than those of cats without clusters. CONCLUSION: Cats presenting with recurrent epileptic seizures with orofacial involvement are more likely to have hippocampal pathologies, which suggests that TL abnormalities are not merely unspecific epileptic findings, but are associated with a certain type of epilepsy. TL signal alterations are more likely to be detected on FLAIR sequences. In contrast to severe changes in the TL which were described similarly among specialists, mild TL abnormalities may be difficult to interpret, thus leading to different assessments among observers.

Retrospective multicenter evaluation of the "fly-catching syndrome" in 24 dogs: EEG, BAER, MRI, CSF findings and response to antiepileptic and antidepressant treatment.

The fly-catching syndrome (FCS) is a rare canine condition of sudden, occasional, or constant episodes of biting the air. It may be accompanied by jumping, licking, and swallowing. The etiology of FCS is unknown and controversial. Various explanations for its occurrence have included epileptoid disorders such as visual cortex epileptiform disturbances and simple and complex partial seizures as well as compulsive disorders, hallucinatory behavior, and stereotypy. A retrospective multicenter analysis of 24 dogs with clinical symptoms of FCS is presented. Clinical signs at the time of presentation, the mean age at onset of the disease, the response to treatment, and the clinical outcome were recorded and analyzed in all patients. All dogs underwent clinical, neurological, and otoscopic examinations. Complete blood cell counts (CBCs) and serum chemistry panels were obtained from each dog. Diagnostic testing included MRI and EEG examinations in 21 cases, BAER in 19 cases, and CSF analysis in 20 cases. The EEG revealed spike activity in 8 (38%) of the 21 cases, 7 of which had activity in the occipital lobes. The brainstem auditory evoked response (BAER) revealed three cases of bilateral deafness. The MRI revealed six cases of Chiari malformation (CM), one case of syringohydromyelia (SM), and one case of a falx cerebri meningioma. The dogs were divided into groups according to their treatment protocol. Group A included dogs treated with phenobarbital (PB), and group B consisted of dogs treated with fluoxetine (FLX). Thirty-six percent of the dogs in group A responded to PB, while 100% of the dogs in group B responded to FLX. The results suggest that FCS is more responsive to FLX than PB. However, the etiology of this behavior remains unclear in most cases.

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

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.

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.