bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histological features of liver disease development in the Atp7b−/−mouse: a model of Wilson’s disease
Authors: Lavrut Pierre-Marie , Guillaud Olivier , Dumortier Jérôme , Mintz Elisabeth , Brun Virginie , Heissat Sophie , Couchonnal Bedoya Eduardo , Lachaux Alain , Bost Muriel , Hervieu Valerie 
Published: November 2023

AimsWilson’s disease (WD) is caused by mutations in the ATP7B gene, resulting in copper accumulation and toxicity in liver and brain tissues. Due to the initial asymptomatic liver involvement, the progression of liver injuries in WD stays primarily unknown. Atp7b−/− knockout mice have been shown to be an appropriate model of WD for liver involvement.MethodsA total of 138 Atp7b−/− mice were included and separated into five groups according to age as follows: 6, 20, 39 and 50 weeks without treatment, and 50 weeks with copper chelator treatment from 39 to 50 weeks of age and compared with 101 wild-type (WT) mice at the same stages. The evolution of histological liver lesions was analysed and compared between groups.ResultsSignificant changes were observed in Atp7b−/− mice compared with WT. Copper deposits in hepatocytes appeared as early as 6 weeks but no significant increase over time was observed. Inflammation appeared as early as 6 weeks and progressed henceforth. Lobular and periportal acidophilic bodies appeared after 20 weeks. Significant atypia was also observed at 20 weeks and increased over time to reach a severe stage at 39 weeks. Fibrosis also became apparent at 20 weeks, progressing subsequently to precirrhotic stages at 50 weeks. Copper content, inflammation and fibrosis scores were significantly reduced in the treated group. No bile duct lesions or dysplastic changes were noted.ConclusionsCopper accumulation leads to progressive changes in Atp7b−/− mice regarding inflammation, fibrosis and atypia. The severity of liver damage is lessened by chelation therapy.
Language as a biomarker in dementia
Authors: Garrard Peter 
Published: November 2023

Professor Peter Garrard is an expert consultant neurologist and active clinician scientist in London, with a focus on linguistic profiles of disorders of the nervous system. He has more than 25 years of clinical experience, including 15 years as an accredited specialist in neurology. His specialist interests include neurological disorders, cognitive disorders, progressive language disorders, frontotemporal dementia, and early-onset dementia.In 1990, Professor Garrard received his primary medical qualification from the University of Bristol and subsequently undertook his higher medical training in Edinburgh for surgery and Yeovil for medicine. Once in London, he completed his general medical training before taking on specialist training in neurology in 2000. During this time, Professor Garrard completed his PhD at Cambridge University on language abnormalities in Alzheimer’s and other dementias as a Medical Research Council clinical training fellow.Professor Garrard has completed extensive neuroscience research, and currently holds the position of Professor of Neurology at St George’s University of London, where his primary research interest is in the early language changes associated with neurodegenerative dementians, such as Alzheimer’s. He is deputy director of the Molecular and Clinical Sciences Research Institute at St George’s, and also leads an active dementia research laboratory. Additionally, Professor Garrard has continuously taken on educational roles in his field since becoming a member of the General Medical Council.AbstractIn this talk I will briefly review the origins and development of the idea that the neurodegenerative dementias may have a presymptomatic signature detectable in spontaneous speech, and the implications of the diagnostic potential that this idea may hold. I will move on to discussing the special case of neurodegenerative syndromes that selectively impair language (the primary progressive aphasias), and describe the principles by which clinical information relevant to these conditions can be obtained using the newly developed mini linguistic state examination (MLSE). Finally, the diagnostic properties of the MLSE and its further development will be discussed.
Placebo, suggestion and FND – interactions and clues to pathophysiology
Authors: Terhune Devin , Edwards Mark 
Published: November 2023

Devin Terhune. I joined the Department of Psychology at KCL in 2022 as a Reader in Experimental Psychology. I completed my BA in Philosophy and Psychology at Concordia University (Canada), my MSc in Psychology (with distinction) at the University of Liverpool, and my PhD in Psychology at Lund University (Sweden). After completing my PhD, I was a Postdoctoral Research Fellow in the Department of Experimental Psychology at the University of Oxford. More recently, before joining KCL, I lectured in statistics and coding in the Department of Psychology at Goldsmiths, University of London.Mark Edwards is a Professor of Neurology and Interface Disorders at the Institute of Psychiatry, Psychology and Neuroscience at King’s College London and works clinically at the Maudsley Hospital and Kings College Hospital. He has a specialist clinical and research interest in Movement Disorders and Functional Neurological Disorder (FND). He did his PhD with Professor John Rothwell and Professor Kailash Bhatia at the UCL Institute of Neurology, studying the pathophysiology of genetic dystonia. Following completion of neurology training he became a Senior Lecturer and Honorary Consultant Neurologist at UCL and the National Hospital for Neurology. Here he developed an NIHR funded research program and specialist diagnostic and treatment service for patients with FND. He is President of the Association of British Neurology Movement Disorders Group, International Executive Committee member of the International Parkinson’s and Movement Disorders Society, Board Member of the Functional Neurological Disorder Society, Associate Editor of the European Journal of Neurology, and medical advisor for FNDHope, the UK Dystonia Society and the British Association of Performing Arts Medicine.AbstractBoth abnormal beliefs (predictions) and attention are proposed as key pathophysiological processes in Functional Neurological Disorder. These processes are also central to our current understanding of the effects of suggestion (for example in the context of hypnosis) and placebo and nocebo phenomena and thereby suggest mechanistic overlap across these domains. In this talk we will discuss the mechanisms of suggestion, placebo/nocebo and FND. We will then consider ways in which these phenomena might overlap, including whether dissociation and predictive processing may be useful unifying themes here, the relevance of placebo and suggestion as methods for modelling FND and their potential therapeutic role.
Psychiatry in humanitarian emergencies
Authors: Hughes Peter 
Published: November 2023

Dr Peter Hughes is a UK based Consultant Psychiatrist. He has been working globally for over 15 years in Humanitarian and development settings. He has worked with UN and non UN organisations. He founded the RCPsych Volunteering Special Interest group. He has written extensively on the topic and launches his book on Global Mental Health volunteering this year. He has been Chair of the London Division of RCPsych. He has most recently been working in Afghanistan. His main professional interest is in integrated mental health in Primary Care and Humanitarian emergencies.AbstractThis is an overview of humanitarian emergencies. There will be a description of background context of global mental health and in particular complex humanitarian emergencies. The basic principles of emergency response through the Global Interagency Standing Committee, ‘building back better’ and the mental health effects will be outlined. The message of hope comes through the building back better narrative. Effects on front line workers are discussed along with the importance of self care. There is a discussion around how high income countries need to have some accountability for emergencies in other parts of the world. There is guidance on how Psychiatrists can become involved in these emergencies worldwide.
01 Functional seizures and their misdiagnosis and mimics: a review of video-telemetry referrals and case outcomes in a tertiary epilepsy centre
Authors: Dudley Peter , Marquez Jan-Paul , O’Sullivan Suzanne , Walker Matthew , Farrell Fiona , Benson Jennifer , Yogarajah Mahinda 
Published: November 2023

ObjectivesTo identify, describe, and characterize functional seizure mimics by analyzing patients referred with a putative functional seizure diagnosis that following video telemetry EEG (VT-EEG), received an alternate diagnosis. In addition, identify the proportion of patients who had habitual events captured that had this revision.BackgroundMaking a diagnosis of functional seizures from description alone can prove challenging as they share several features with epileptic seizures. The misdiagnosis of functional seizures as epileptic has previously been described in the literature.1However, little is known on the reverse.MethodsThe reports of VT-EEGs performed on patients admitted to the Chalfont Centre for Epilepsy between 2019 and 2022 were reviewed. Recordings that did not capture habitual events were excluded. The VT-EEG report, referral letters, and pre-admission clinic letters were reviewed to identify the pre-VT-EEG impression. These were categorised as epileptic, functional, unclear, or both. Subsequently, the VT-EEG reports were categorised based on the VT-EEG findings of the habitual event as epileptic, functional, or an alternative diagnosis. Those seizures that had a pre-VTEEG impression of functional and a post-VT-EEG diagnosis of epileptic, or other miscellaneous conditions, were analysed to identify clinically relevant features that favour an alternate diagnosis. In some cases, these features were used to localize seizure fociResultsThere were 444 VT-EEG reports where habitual events were recorded. Approximately 5% of these were of those with functional seizures who had their diagnosis revised. Several groups could be identified in those whose diagnoses were amended. The largest group were of frontal lobe seizures with bizarre semiology. In another group, no ictal abnormalities were present but stereotyped seizures arose during EEG defined sleep. Others included: patients with insular epilepsy and predominant autonomic features; patients with absence seizures; patients with brief epileptic seizures followed by functional overlay or elaboration; and patients with a dual diagnosis whose epileptic seizures were revealed on drug reduction.ConclusionIn patients referred to a tertiary epilepsy unit, the majority of patients retained their diagnosis or changed from epileptic to functional. However, in a small minority of cases, seizures previously diagnosed as functional were reclassified as epileptic or an alternative diagnosis. It is clinically important to be aware of these mimics.ReferenceLanzillotti AI, Sarudiansky M, Lombardi NR, Korman GP, D Alessio L. Updated review on the diagnosis and primary management of psychogenic nonepileptic seizure disorders.Neuropsychiatr Dis Treat. 2021;17:1825–1838. Published 2021 Jun 4. doi:10.2147/NDT.S286710
02 Predicting the cause of TLOC using an automated analysis of interactions with a virtual agent
Authors: Pevy Nathan , Christensen Heidi , Walker Traci , Reuber Markus 
Published: November 2023

Objectives/AimsA clinical decision tool for Transient Loss of Consciousness (TLOC) could reduce misdiagnosis rates and waiting times. Most clinical decision tools fail to stratify between the three most common causes of TLOC (epilepsy, functional (dissociative) seizures, and syncope) or are hindered by the challenging differentiation between epilepsy and FDS. Based on previous research describing differences in spoken accounts of epileptic and nonepileptic seizures, this study explored the feasibility of predicting the cause of TLOC by combining the automated analysis of patient-reported symptoms and spoken TLOC descriptions.MethodParticipants completed an online web application that consisted of a 34-item medical history and symptom questionnaire (iPEP) and interaction with a virtual agent (VA) that asked eight questions about the most recent experience of TLOC. Support Vector Machines (SVM) were trained using different combinations of features and nested leave-one-out cross validation. The iPEP provided a baseline performance. Three language-based feature sets were created: features designed to measure formulation effort, features that measured the proportion of words from different semantic categories, and features based on verb, adverb, and adjective usage. Two methods of integrating the iPEP and language features were compared. Method one involved training a single SVM model using all features and all diagnoses. Method two used a ‘model stacking’ approach whereby predictions of epilepsy or FDS from the iPEP model were passed into a second stage language analysis to improve this differential diagnosis.Results76 participants completed the application (Epilepsy = 24, FDS = 36, syncope = 16). Only 61 participants also completed the VA interaction (Epilepsy = 20, FDS = 29, syncope = 12). The iPEP model accurately predicted 65.8% of diagnoses. For the binary classification between epilepsy and FDS, the three language feature sets predicted the diagnosis with an accuracy between 75.5–85.7%. Combining the iPEP and language features resulted in an overall accuracy of 59% for the first integration method and 85.5% for method two (model stacking).ConclusionThese findings suggest that an automated analysis of TLOC descriptions collected using an online web application and VA could improve the accuracy of current clinical decisions tools for TLOC and facilitate clinical stratification processes (such as the appropriate referral to cardiological versus neurological investigation and management pathways). Future research should aim to improve the baseline performance of the iPEP and explore methods for analysing TLOC descriptions from patients with syncope that can improve the identification of this diagnostic group.
03 Development of a screening checklist to diagnose functional memory symptoms: a Delphi study
Authors: Cabreira Verónica , McWhirter Laura , Frostholm Lisbeth , Stone Jon , Carson Alan 
Published: November 2023

IntroductionCurrently there is no standardized way to diagnose functional cognitive disorder (FCD) in clinical practice. We aimed to develop a bedside screening tool to differentiate between FCD and neurodegenerative causes of memory complaints.MethodsA Delphi methodology was used to obtain consensus based on expert opinion through a series of three consecutive rounds. International experts with an interest and experience in cognitive disorders and functional neurological disorders were selected. The first and second rounds included both clinical vignettes and a list of diagnostic clinical signs favoring a FCD diagnosis (obtained from a systematic review of the literature), to be ranked using a 7-point Likert scale. Qualitative and quantitative analysis were undertaken. Finally, experts reviewed the component items for which consensus had been achieved and provided recommendations for modifications to better discriminate between FCD and dementia.Results45 experts, from 12 different countries, participated in the first round. A retention rate of at least 80% was obtained in subsequent rounds. 47% of the participants diagnosed between 10 and 50 patients with FCD over the last year. 69% reported that FCD comprises between 5 and 30% of the patients with memory complaints seen in the clinic. 91.4% would be interested in using a newly developed resource of this kind with the patients. A checklist was built and adapted into a scale, based on 11 statements for which strong (discrepancy between the level of symptoms reported and observed everyday functioning; patient’s ability to detail memory complaints with specific examples; and variable and/or fluctuating cognitive symptoms; 2 points each), moderate (ability to detail the list of drugs and/or previous interactions with other doctors; history of a non-cognitive functional neurological disorder or somatic symptoms; 1 point each) or low consensus (patient more aware of the cognitive changes than others; normal/incongruent cognitive performance; absence of symptom progression; dating symptom onset with precision; presence of psychological stressors; and ability to answer compound questions; 1 point each) was achieved. There was poor inter-rater agreement (Fleiss’ kappa=.035, p<.000). Regarding the vignettes, there was a major consensus gap in diagnosing FCD (<50% agreement) and neurodegenerative syndromes including Alzheimer’s disease (60–95% agreement).ConclusionsThis 11-item checklist is a simple complementary clinical tool aiming to improve diagnostic accuracy and direct patients to early post-diagnostic treatment. Further retrospective and prospective validation will be needed before it can be used clinically. This study is part of a wider project trying to improve the diagnosis of FCD.
07 Identifying ADHD in adult patients with dissociative seizures using the ASRS v1.1 questionnaire
Authors: Singhal Sumeet 
Published: November 2023

Objectives and AimsA service evaluation was performed in patients with dissociative seizures to check if a screening tool was proving useful in identifying adult ADHD in this highly specialised group. The idea of using such a tool came about after several dissociative seizure patients were coincidentally diagnosed with ADHD and appeared to show improvements in seizure control and fatigue with treatment.MethodsAll suitable dissociative seizure patients attending a seizure clinic between October 2019 and October 2022 underwent screening with the World Health Organisation (WHO) Adult ADHD ASRS v1.1 18-point questionnaire. Patients with co-existent epilepsy were excluded for the purposes of the service evaluation.ResultsNinety-three new and follow up patients agreed to complete the ASRS. Of these, only one felt unable to complete the screen. Of the remainder, 11/92 failed to meet the eligibility criteria for formal ADHD testing based on the 6 point ASRS mini-screen. The remaining 81 scored a mean of 80.7/90 on the ASRS, which compares with a mean score of 41/90 in the normal population and 63/90 in the adult ADHD population. Of these 81, only 13 (16%) have so far had a formal assessment for ADHD, of which 12 (92%) were confirmed to have adult ADHD. Of the remainder, two were referred for formal assessment but were refused, one because of a negative assessment in 2015, the other for unclear reasons. Another sixteen were referred over 2 years before the study ended and are either still awaiting an assessment or DNA’ed the assessment or the results are pending. The remainder (62) had been referred in the last two years and given current waiting times are not expected to have yet had a formal assessment.ConclusionsIt was possible to apply the ASRS v1.1 to almost everyone in this cohort, a few face to face or over the telephone in clinic, but most self-completed in their own time and returned by post or email. The vast majority who completed the ASRS scored well within the adult ADHD range. For those who did go on to have a formal assessment, almost all ended up with a confirmed diagnosis of ADHD. This service evaluation therefore also suggests that the prevalence of ADHD in adult patients with dissociative seizures is worthy of formal study, and there are theoretical and anecdotal reasons to believe this could benefit control of the seizures themselves.
08 The economic cost of functional neurological disorders: a systematic review introduction
Authors: O’Mahony Brian 
Published: November 2023

Functional Neurological Disorders (FND) represent genuine involuntary neurological symptoms and signs including seizures, weakness and sensory disturbance which have characteristic clinical features, and represent a problem of voluntary control and perception despite normal basic structure of the nervous system. The historical view of FND as a diagnosis of exclusion can lead to unnecessary healthcare resource utilisation, and high direct and indirect economic costs. A systematic review was performed using PRISMA guidelines in order to assess these economic costs, and to assess for any cost- effective treatments.MethodsWe searched electronic databases (Pubmed, PsycInfo, Medline, EMBASE, and the National Health Service Economic Evaluations Database of the University of York) for original, primary research publications between inception of the databases and 8thApril 2022. Key search terms included ‘functional neurological disorder’, ‘conversion disorder’ and ‘functional seizures’. Reviews, case reports, case series and qualitative studies were excluded. We performed a descriptive and qualitative thematic analysis of the resulting studies.ResultsThe search resulted in a total of 3,244 studies. A hand-search of conference abstracts was also conducted. 16 studies were included after screening, and exclusion of duplicates. These included: cost-of-illness (COI) studies which were conducted alongside cohort studies without intervention, which included a comparator group, e.g. another neurological disorder (n=4); COI studies which were conducted alongside cohort studies without intervention, which did not include a comparator group (n=4); economic Evaluations (EE) of interventions which were either pre-post cohort studies (n=6) or randomized controlled trials (n=2). Of these, five studies assessed active interventions, and three studies assessed costs before and after a definitive diagnosis of FND.Studies showed an excess cost associated with FND, which consisted of both direct, but also large indirect costs. Studies showed promise that interventions, including provision of a definitive diagnosis, could reduce this cost. No cost-effective treatments were identified. Study comparison was limited by study design and location heterogeneity.ConclusionFND is associated with significant use of healthcare resources, resulting in economic costs to both the patient and the tax-payer, as well as intangible losses. Interventions, including accurate diagnosis, appear to offer an avenue towards reducing these costs.