International Veterinary Epilepsy Task Force consensus report on epilepsy definition, classification and terminology in companion animals

Dogs with epilepsy are among the commonest neurological patients in veterinary practice and therefore have historically attracted much attention with regard to definitions, clinical approach and management. A number of classification proposals for canine epilepsy have been published during the years reflecting always in parts the current proposals coming from the human epilepsy organisation the International League Against Epilepsy (ILAE). It has however not been possible to gain agreed consensus, “a common language”, for the classification and terminology used between veterinary and human neurologists and neuroscientists, practitioners, neuropharmacologists and neuropathologists. This has led to an unfortunate situation where different veterinary publications and textbook chapters on epilepsy merely reflect individual author preferences with respect to terminology, which can be confusing to the readers and influence the definition and diagnosis of epilepsy in first line practice and research studies. In this document the International Veterinary Epilepsy Task Force (IVETF) discusses current understanding of canine epilepsy and presents our 2015 proposal for terminology and classification of epilepsy and epileptic seizures. We propose a classification system which reflects new thoughts from the human ILAE but also roots in former well accepted terminology. We think that this classification system can be used by all stakeholders

Hydrophobically Modified Sulfobetaine Copolymers with Tunable Aqueous UCST through Postpolymerization Modification of Poly(pentafluorophenyl acrylate)

Polysulfobetaines, polymers carrying highly polar zwitterionic side chains, present a promising research field by virtue of their antifouling properties, hemocompatibility, and stimulus-responsive behavior. However, limited synthetic approaches exist to produce sulfobetaine copolymers comprising hydrophobic components. Postpolymerization modification of an activated ester precursor, poly(pentafluorophenyl acrylate), employing a zwitterionic amine, 3-((3-aminopropyl)dimethylammonio)propane-1-sulfonate, ADPS, is presented as a novel, one-step synthetic concept toward sulfobetaine (co)polymers. Modifications were performed in homogeneous solution using propylene carbonate as solvent with mixtures of ADPS and pentylamine, benzylamine, and dodecylamine producing a series of well-defined statistical acrylamido sulfobetaine copolymers containing hydrophobic pentyl, benzyl, or dodecylacrylamide comonomers with well-controllable molar composition as evidenced by NMR and FT-IR spectroscopy and size exclusion chromatography.This synthetic strategy was exploited to investigate, for the first time, the influence of hydrophobic modification on the upper critical solution temperature (UCST) of sulfobetaine copolymers in aqueous solution. Surprisingly, incorporation of pentyl groups was found to increase solubility over a wide composition range, whereas benzyl groups decreased solubility—an effect attributed to different entropic and enthalpic contributions of both functional groups. While UCST transitions of polysulfobetaines are typically limited to higher molar mass samples, incorporation of 0–65 mol % of benzyl groups into copolymers with molar masses of 25.5–34.5 kg/mol enabled sharp, reversible transitions from 6 to 82 °C in solutions containing up to 76 mM NaCl, as observed by optical transmittance and dynamic light scattering. Both synthesis and systematic UCST increase of sulfobetaine copolymers presented here are expected to expand the scope and applicability of these smart materials

The effects of Δ9-tetrahydrocannabinol on the dopamine system

Δ(9)-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, is a pressing concern to global mental health. Patterns of use are changing drastically due to legalisation, availability of synthetic analogues (‘spice’), cannavaping and aggrandizements in the purported therapeutic effects of cannabis. Many of THC’s reinforcing effects are mediated by the dopamine system. Due to complex cannabinoid-dopamine interactions there is conflicting evidence from human and animal research fields. Acute THC causes increased dopamine release and neuron activity, whilst long-term use is associated with blunting of the dopamine system. Future research must examine the long-term and developmental dopaminergic effects of the drug

Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker

The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T-1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status

Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders: findings from the ENIGMA ADHD, ASD, and OCD Working Groups

Objective Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders. Methods Structural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures). Results We found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed. Conclusion Our findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders