To describe current clinical practices in the management of cervical Hansen type I intervertebral disc herniation among American College of Veterinary Internal Medicine/European College of Veterinary Neurology neurologists. An anonymous web-based survey was distributed via professional listservs between October and November 2025. Survey items addressed diagnostic imaging, indications and urgency for surgery, surgical technique and fenestration, foraminal injections, analgesia, medical management, activity restriction and perceived prognostic factors. Responses were summarised descriptively and compared between North American and European veterinary neurologists. Of 233 responses, 198 met inclusion criteria. Magnetic resonance imaging was the most commonly used diagnostic modality. Surgery was infrequently recommended for first-presentation cervical pain without neurological deficits, but was commonly recommended for recurrent or refractory pain, ambulatory tetraparesis and non-ambulatory tetraparesis or tetraplegia, with increasing urgency reported for more severe neurological dysfunction and the presence of hypoventilation. Ventral slot decompression was the predominant surgical approach. Fenestration practices varied, with prophylactic fenestration reported more frequently by American College of Veterinary Internal Medicine neurologists. Compared with European College of Veterinary Neurology neurologists, American College of Veterinary Internal Medicine neurologists reported more frequent use of corticosteroids and strict crate confinement, whereas European College of Veterinary Neurology neurologists more commonly reported use of non-steroidal anti-inflammatory drugs and opioid-based local or bolus analgesic techniques. Additionally, European College of Veterinary Neurology neurologists reported more frequent use of foraminal injections. Management of cervical Hansen type I intervertebral disc herniation shows strong agreement regarding diagnostic imaging and surgical decompression, but notable variation in analgesic strategies, medical management and activity restriction. These findings identify areas where further evidence and consensus guidelines may help standardise clinical decision-making.
Sleep medicine relies on patient-reported outcome measures (PROMs) to complement clinical interviews and objective sleep tests. Available sleep questionnaires focus on isolated symptoms or single disorders, limiting their ability to capture the complexity of sleep conditions. Also, many PROMs remain poorly validated. The European Sleep Questionnaire (ESQ) is being developed as a generic transdiagnostic sleep PROM designed to address these limitations. By integrating relevant interview components, it aims to streamline clinical assessment and better reflect real-world phenotypes across the full spectrum of sleep disorders. The ESQ has been initiated within the EU-funded Sleep Revolution project and is still being developed through an iterative process. Its design is informed by a comprehensive literature review as well as expert and patient input. The ESQ prototype contains 119 items organized into nine sections and uses Likert-type scales to assess symptom severity, frequency, and bothersomeness over the past month. It is equipped with an additional module for follow-up assessment. It is translated into 17 languages and is digitally implemented to support multicenter studies. Initial validation includes cognitive interviews and evaluation of psychometric properties in patients with various sleep disorders. Item refinement and scoring key creation will guide the further development of the ESQ, after which it will be made available for public use. The ESQ aims to support personalized clinical diagnosis and appraisal of treatment results. Future research will extend into other sleep disorders and specific populations, strengthening the ESQ as a comprehensive tool for clinical practice, research, and preventive strategies.
The 'European Prospective Investigation into Cancer and Nutrition' cohort (EPIC) is a prospective study including ~ 520,000 participants recruited across Europe (1991-2000) with in-depth baseline data on nutritional, lifestyle, medical, and anthropometric variables, and baseline blood samples. Here we introduce EPIC4ND, a case-cohort study within EPIC designed to identify biomarkers predicting a future onset of dementia, Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). EPIC4ND comprises 6415 initially non-diseased participants (aged 35-80 years, mean age at baseline: 54 ± 9, 64% women) including 1899 incident cases with up to 30 years of follow-up and data on at least one omics domain available from pre-disease blood samples. EPIC4ND includes 4604 subcohort members (4441 non-cases and 163 incident cases) and 1811 additional incident cases ascertained from the broader EPIC cohort. Among the incident cases, there are 1190 dementia cases (818 AD), 610 PD cases, and 199 ALS cases. Additionally, 72 prevalent PD cases and 118 incident Parkinsonism cases are available for comparison. Molecular data generated encompass proteomics, genome-wide DNA methylation, and SNP genotyping with 4127 EPIC4ND participants (including 1635 incident cases) having data on all three domains. Smaller studies include data on metals, metabolites, and environmental chemicals, while ongoing efforts focus on ultrasensitive targeted biomarker measurements and small RNA sequencing. Genome-wide association studies and analyses of epidemiological risk factors validate the dataset by confirming many known risk factors. Leveraging these extensive pre-disease multi-layered omics data offers a unique opportunity to identify biomarker signatures predicting neurodegenerative diseases and to explore their interplay with epidemiological risk factors.
Complete androgen insensitivity syndrome (CAIS) is a rare condition affecting sex development. Due to limited literature, especially for providing care in adulthood, clinical management remains challenging, and several issues remain inadequately addressed. We conducted an international survey to examine current clinical practices in the management of CAIS across the Referral Centres (RC) of Main Thematic Group 7 (MTG7) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN), with the aim of identifying needs for standardization and potential gaps in care. We collected responses from 24 RC in 11 countries for a total of 256 individuals with CAIS. The majority of respondents were paediatric centres (62.5%), highlighting the challenges in obtaining comprehensive data on adults with CAIS. The survey addressed various aspects of care, including diagnosis, genetic testing, gonadectomy, hormone replacement therapy (HRT), bone health, management of vaginal hypoplasia, and sexual outcomes. Key findings highlight significant variability in HRT protocols across centres, especially in adulthood, and reveal a lack of standardization in assessing potential long-term outcomes such as bone and sexual health. Given the complexity and rarity of CAIS, a centralized approach referring patients to centres with expertise in the management of the condition and the development of a clinical practice expert opinion for the management of CAIS beyond the paediatric age could help address current gaps, particularly in the transition from paediatric to adult care. All participating experts emphasized the need to develop such document to optimize CAIS care.
Carotid artery intima-media thickness (cIMT) is a highly heritable measure of subclinical atherosclerosis and a predictor of cardiovascular diseases. However, knowledge about its shared genetic basis remains limited. The majority of genome-wide association studies have been conducted in individuals of European ancestry, leaving the genetic determinants of cIMT in non-European ancestry populations largely understudied. A single-trait genome-wide association study was performed in 22 370 participants from the China Kadoorie Biobank to identify new genetic variants associated with cIMT. We then leveraged cIMT and cardiometabolic disease and trait data from populations of European and East Asian ancestries, to conduct linkage disequilibrium score regression and genome-wide cross-trait analysis, followed by gene-based analysis and Mendelian randomization. We identified 2 genome-wide significant loci for cIMT in the overall China Kadoorie Biobank analysis, including the known APOE locus and a novel locus at GGT5. In addition, a female-specific analysis identified a further novel locus at LINC02732. cIMT showed significant positive genetic correlations with coronary artery disease, type 2 diabetes, body mass index, and systolic blood pressure in both European and East Asian populations. Pleiotropic analysis found 110 and 699 significant pleiotropic variants in 4 trait pairs for East Asian and European populations, respectively, with 27 and 186 colocalized loci detected. Gene-based analysis highlighted important biological pathways involving lipid metabolism and carbohydrate metabolism. Mendelian randomization estimates indicated that higher systolic blood pressure and body mass index, and coronary artery disease and type 2 diabetes, were causal for cIMT, and a reverse effect was observed between cIMT and systolic blood pressure. Our large-scale genome-wide association study of cIMT identified novel loci in the Chinese population and shared genetic underpinnings and causal relationships with cardiometabolic diseases and traits. These findings potentially provide targets for intervention that may allow the development of new strategies targeting this aspect of atherosclerosis.
The burden of ischaemic stroke in Europe has evolved over recent decades, shaped by changes in prevention, acute care and population ageing. Understanding long-term trends in mortality and disability is essential for guiding policy and service planning. Using Global Burden of Disease (GBD) 2023 estimates, we analysed age-standardised disability-adjusted life years (DALYs), years of life lost (YLLs) and years lived with disability (YLDs) for ischaemic stroke across all European countries from 1990 to 2023. We estimated country-specific annual percentage changes (EAPCs), assessed non-linear trajectories, examined shifts in the fatal vs non-fatal composition of DALYs and synthesised trends using mixed-effects models and descriptive meta-analytic pooling. Disability-adjusted life year rates declined in every European country, with the steepest reductions in Central and Western Europe and more modest improvements in parts of Eastern and Southeastern Europe. Years of life lost declines closely paralleled DALY trends, indicating that falling premature mortality was the main driver of the overall reduction. Years lived with disability trends were smaller and more heterogeneous across countries. Mixed-effects modelling indicated average European EAPCs of -3.40% (95% CI, -3.74 to -3.05) for DALYs, -1.26% (-1.43 to -1.09) for YLLs and -3.86% (-4.26 to -3.46) for YLDs. Meta-analytic pooling of national patterns showed large declines in YLLs (random-effects EAPC -3.81%) relative to YLDs (-0.86%). Ischaemic stroke burden has fallen substantially across Europe, driven primarily by reductions in premature mortality. Slower progress in disability outcomes and persistent regional disparities highlight the need to strengthen long-term rehabilitation and address uneven improvements across the continent.
Since genome-wide association studies (GWAS) of sleep phenotypes have been conducted in differing populations and definitions of sleep phenotypes vary across studies, we investigated associations between several polygenic risk scores (PRSs) and potential sleep definitions among multiethnic cohorts. Using data from four cohorts (HCHS/SOL, ARIC, MESA, BHS, N = 16 895), we considered multiple definitions of short and long sleep, insomnia, and excessive daytime sleepiness (EDS). PRSs were developed based on summary statistics from GWAS in European ancestry individuals from the UK Biobank (UKB) and from GWAS conducted in a multiethnic population from the Million Veteran Program (MVP). Study-specific analyses estimated associations between sleep PRSs and corresponding sleep measures per 1 standard deviation increase in the PRS. Models were adjusted for age, sex, ancestral principal components, and center and race as appropriate. Results were meta-analyzed across studies. PRSs based on European ancestry UKB GWAS had statistically significant associations with multiple definitions of the corresponding sleep phenotypes. Associations that were most consistent across studies included: short sleep PRS with ≤6 hours (OR = 1.23,p = 1.80x10-7,phet = 0.97); long sleep PRS with ≥9 hours (OR = 1.09,p = 6.76x10-4,phet = 0.77); insomnia PRS with the Women's Health Initiative Insomnia Rating Scale (WHIIRS) ≥10 or a subset of three questions ≥6 in ARIC (OR = 1.17,p = 5.51x10-10,phet = 0.69); and EDS PRS with Epworth Sleepiness Scale (ESS) ≥11 (OR = 1.23,p = 1.83x10-13,phet = 0.83). PRSs based on multi-ancestry MVP GWAS had weaker associations compared to those based on European ancestry only. By evaluating several types of sleep PRSs and sleep phenotypes, we were able to highlight which sleep PRS performed well across diverse populations and which sleep definitions better captured genetic underpinnings.
Diffuse gliomas are biologically heterogeneous primary brain tumors with variable clinical behavior, and age is a well-recognized prognostic factor; however, integrated real-world data from Eastern European populations remain limited. The aim of this study was to describe how clinical, imaging, molecular, treatment, and survival data co-vary across age groups in a Romanian tertiary neuro-oncology cohort, rather than to identify new biological associations. We conducted a single-center retrospective cohort study of 283 consecutive adult patients with histologically confirmed diffuse gliomas diagnosed between 2021 and 2024, classified according to the WHO 2021 framework. Patients were stratified into three predefined age groups (<40, 40-60, and >60 years), and clinical, histopathological, molecular, preoperative imaging, and treatment variables were compared using Pearson chi-square or Fisher exact tests; recurrence-free survival (RFS) was estimated using the Kaplan-Meier method with log-rank tests. Molecular testing availability varied across the cohort, reflecting progressive adoption of integrated molecular diagnostics. Older patients more frequently harbored IDH-wildtype glioblastoma, more aggressive imaging features, lower Karnofsky Performance Status, and received less intensive multimodal therapy. Unadjusted RFS decreased with advancing age (log-rank P < 0.001); without multivariable adjustment, this reflects the combined effects of age-correlated covariates rather than an independent age effect. This study contributes region-specific real-world evidence from an underrepresented Eastern European setting, where integrated molecular diagnostics were being progressively implemented during the study period.
To investigate the potential causal relationship between inflammatory cytokines and type 2 diabetes (T2D) using two-sample Mendelian randomization (MR) and to explore the transferability of inflammatory genetic susceptibility in a Mongolian population through polygenic score (PGS) analysis. A two-sample MR analysis was conducted using genome-wide association study (GWAS) summary statistics. Inflammatory cytokine data were obtained from protein quantitative trait locus GWAS datasets (GCST90274758-GCST90274848), and T2D summary statistics were derived from the IEU Open GWAS database (ebi-a-GCST006867). The inverse variance weighted method was used as the primary MR approach, complemented by sensitivity analyses. In an independent Mongolian cohort (N = 351), a PGS was constructed from directly genotyped cytokine-associated SNPs. We assessed PGS-T2D associations using logistic regression adjusted for age, sex, and principal components (PCs), with sensitivity analyses to determine the optimal PC number. In the European population, genetically predicted higher FGF-21 levels were associated with an increased risk of T2D (OR = 1.141, 95% CI: 1.032-1.261, P = 0.010), and IL-5 also showed a positive association with T2D risk (OR = 1.114, 95% CI: 1.004-1.237, P = 0.042). In contrast, ARTN, CD5, CSF-1, CXCL10, CXCL9, FGF-19, and SLAMF1 were associated with lower T2D risk. In the Mongolian population, the PGS for inflammation-related cytokine levels demonstrated a significant association with T2D status across models adjusting for 0 to 6 principal components (all P< 0.05). In the full model (adjusted for age, sex, and the first 4 PCs), each 1-SD increase in the PGS corresponded to a 25.4% increase in the odds of T2D (OR = 1.254, 95% CI: 1.005-1.575, P = 0.048; AUC = 0.625). These findings are suggestive and exploratory, necessitating further validation in independent cohorts. This study identified nine inflammatory cytokines with potential causal associations with T2D in European populations. Notably, in a Mongolian cohort, a PGS for genetically predicted cytokine levels showed a modest yet independent association with T2D risk after controlling for population stratification. These cross-population findings warrant replication in larger-scale studies.
The ataxias are rare complex neurological disorders challenging for clinicians to manage. The costs of ataxia care and differences in healthcare use and treatment outcomes between specialised ataxia centres (SAC) and standard neurology services have not been investigated. This study explored patient pathways, healthcare use and costs, comparing SAC with non-specialist settings in Italy. A patient survey was distributed in Italy (May-September 2021) to collect information about the diagnosis and management of ataxias in SAC and non-specialist settings, healthcare service visits, and patients' satisfaction. We compared per-patient mean resource use for each contact type and health service cost, stratifying patients by SAC attendance. Among 174 participants, 44% saw a neurologist within 6 months of seeking medical advice, and 56% went to a SAC directly. Travelling was a top reason why people stopped going to a SAC and a barrier preventing patients from accessing it. SACs delivered better service to patients in various aspects of care. The differences in the number of contacts for various health services between the SAC and non-SAC groups were mostly non-significant. The mean total cost per patient over a one-year period was €1952 for non-SAC and €1666 for SAC. There was a trend towards patients' appreciation for SAC services compared with non-SAC services, without significant change in costs. We identified difficulties in attendance and adherence despite the significant number of SACs in Italy. We believe that the combination of face-to-face and telemedicine could improve patients' attendance at SACs.
Robot-assisted nephrectomy with renal vein or inferior vena cava (IVC) tumor thrombectomy is a technically demanding procedure used in selected patients with renal cell carcinoma (RCC) and venous tumor thrombus. The research map of this field has not been clearly described, and recent technical, comparative, and systemic-therapy developments make an updated focused analysis timely. We searched the Science Citation Index Expanded of the Web of Science Core Collection from database inception to 4 May 2026. English articles and reviews about robot-assisted nephrectomy or radical nephrectomy with renal vein or IVC tumor thrombectomy for RCC were included. Titles, abstracts, keywords, authors, affiliations, journals, citations, and cited references were extracted. Python 3.11 was used for descriptive analysis, keyword analysis, co-citation analysis, visualization, and clinical theme coding. We included 51 SCIE publications from 2011 to 2026, including 40 articles and 11 reviews. The papers received 1229 citations, with a mean of 24.10 citations per paper and a median of 12. Annual publications peaked in 2020 with 7 papers. The United States published 24 papers, China published 21, and Italy published 8 when all author affiliations were counted. The Chinese People's Liberation Army General Hospital published 14 papers, and the University of Southern California published 7. Ma X, Zhang X, and Wang BJ were the most productive authors. European Urology, Journal of Urology, and Journal of Endourology were the leading journals. After term cleaning, the most frequent keywords were renal cell carcinoma, tumor thrombus, robotic surgery, experience, inferior vena cava, and thrombectomy. This field has moved from early technical exploration to early evidence building. Future work should use multicenter prospective designs and should study high-level IVC thrombus, long-term oncologic outcomes, perioperative safety after neoadjuvant therapy, robotic training, and multidisciplinary care pathways.
This study aimed to investigate the frequency of primary sarcopenia in individuals with and without restless legs syndrome (RLS). In this cross-sectional study, 114 patients who presented to our outpatient clinic for the first time and were diagnosed with RLS and 147 patients without RLS were consecutively included. Patients with malignancy, uncontrolled diabetes mellitus, or diseases that may cause secondary sarcopenia or neuropathy were excluded from the study. The European Working Group on Sarcopenia in Older People 2 criteria for the diagnosis of sarcopenia and the International RLS Study Group criteria for the diagnosis of RLS were applied. The association between RLS and sarcopenia was analyzed using a logistic regression analysis. There were no significant differences in terms of chronic diseases. While there was no significant difference between the groups with and without RLS (70.11 ± 9.56 vs 71.76 ± 9.61) in terms of age (P = .170), females were significantly higher in the RLS group (P = .001). The rate of sarcopenia was significantly higher in patients with RLS (54% vs 37%, P = .005). In the multivariate logistic regression analysis of sarcopenia and sex (female), it was determined that both were associated with RLS [odds ratio 1.941 (95%) confidence interval 1.107-3.402, P = .021; odds ratio 2.733, (95%) confidence interval 1.442-5.177, P = .002], respectively). Primary sarcopenia is more common in patients with RLS than in those without RLS. Screening for sarcopenia should be considered in patients with restless leg syndrome.
The global burden of age-associated diseases continues to grow. In particular, the accelerating impact of neurodegenerative diseases on individuals, communities and societies necessitates more effective approaches to diagnosis, prognosis and treatment of such disorders. Hence, the establishment of imaging biomarkers for early detection of disease, progression monitoring, and therapeutic evaluation is of utmost importance. Yet, despite the scientific consensus on the benefits of scientific collaboration and consequently medical innovation including biomarker development, substantial barriers for sharing neuroimaging data remain, demanding a transformation in how scientific data are generated, made accessible, re-used and valued. These barriers range from technical and infrastructural limitations to legal and motivational challenges that hinder widespread adoption of open science practices. Here, we present a comprehensive overview of the current landscape of brain imaging data sharing in neurodegenerative disease research. We explore the status of preregistration, data harmonization and storage standardization, legal compliance, and researcher incentives. We highlight best practices before, during and after data generation and the pressing need for a coordinated strategy regarding simplified and unified legal frameworks compliant with the General Data Protection Regulation of the European Union. Finally, we advocate for the establishment of an academic credit system designed to reward data stewardship. Only with a combined effort from researchers, stakeholders and funding agencies including a sustained infrastructure investment and community education, the field can fully overcome inertia and move towards much-desired open science, thereby fully leveraging shared data to improve patient outcomes and scientific discovery.
As longevity increases and the population over age 65 expands, advancing age remains the most reliable predictor of cognitive decline, highlighting the need to identify biological mechanisms that support exceptional cognitive aging. We tested whether lower inherited risk of Alzheimer's disease (AD) dementia predicts SuperAger status (adults ≥ 80 years with episodic memory at least as good as middle-age adults) using prospectively enrolled SuperAgers and Cognitively Average Controls (Controls) from the multisite SuperAging Research Initiative. We studied 231 participants (SuperAgers n = 142; Controls n = 89). We confirmed that the genetic ancestry structure across groups was comparable. We evaluated whether APOE status (ε2, ε3, ε4) and three AD polygenic risk scores (PRS) derived from large contemporary Genome-Wide Association Studies (GWAS) (PRSLambert, PRSWightman, PRSBellenguez) predicted SuperAging status using logistic regression models adjusted for age, sex, and education, considering ancestry interactions. APOE allele and genotype distributions did not differ between groups, and neither APOE nor any of the three PRS predicted SuperAger status. Results were unchanged when accounting for global non-European or African ancestry or principal components. In this well-characterized cohort, neither APOE nor contemporary PRS explained SuperAger status. These findings suggest that the exceptional late-life memory phenotype that is characteristic of SuperAging is not explained by common-variant AD genetic risk captured by APOE or contemporary AD PRS, motivating a deeper investigation of potential rare genetic variations and experiential factors contributing to exceptional cognitive aging.
This multinational survey explored caregivers' preferences and training needs regarding the administration of rescue medication for prolonged convulsive seizures in children and adolescents with epilepsy across 7 European countries. A total of 68 caregivers of children with epilepsy (aged 6 months to 18 years) who had experienced a prolonged convulsive seizure in the past 12 months completed an anonymous survey in 2024. The survey assessed caregiver preferences and satisfaction with buccal, nasal, or rectal rescue medication, quality of life (QoL), valued medication attributes, and training experience. Intranasal formulations were not consistently available across countries during the study period. Most caregivers (80.9%) preferred buccal over rectal or nasal administration, and satisfaction was higher among users of buccal midazolam compared with rectal diazepam. This preference aligned with a positive impact on patients' and caregivers' QoL. Caregivers rated ease of administration as the most important attribute of rescue medication (mean: 4.8/5), followed by effectiveness in stopping seizures (mean: 4.1/5). Despite their critical role, 44.1% had received no specific training; among those trained, 62.2% preferred face-to-face sessions. Training satisfaction was higher among caregivers who administered buccal midazolam (mean: 8.3/10; standard deviation [SD]: 2.4) compared with those using rectal diazepam (mean: 5.3/10; SD: 3.3). This survey underscores a strong caregiver preference for buccal midazolam in pediatric out-of-hospital settings. However, caregiver training remains a substantial unmet need, and standardized programs could improve preparedness for managing prolonged seizures. These findings reinforce the importance of integrating caregiver perspectives to optimize emergency pediatric epilepsy care.
Stem cell-based therapies for movement disorders show inconsistent translation due to variations in product characterisation, delivery, endpoints, safety, and follow-up. Regulatory guidance provides principles but lacks a unified trial framework. The objective was to create a practical framework that translates scientific, regulatory, manufacturing, ethical, and clinical expectations into an auditable pre-First Patient In (FPI) checklist for stem cell trials. A structured review of the literature, clinical trials, and guidance documents was conducted. Searches were performed in PubMed/MEDLINE, Embase, Google Scholar, and clinical trial registries, including ClinicalTrials.gov, Japan Registry, European Union Register, and Clinical Trials Registry-India, until January 2026. Key guidance documents from the FDA, EMA, ICH, ISSCR, and selected PMDA sources were reviewed. Recurring requirements related to nonclinical evidence, manufacturing quality, ethics, trial design, safety, and follow-up were identified and translated into auditable pre-FPI checklist items. A framework was developed, structured as a universal Core Gate plus three risk-proportionate modules: Module A for pluripotent-derived neural grafts, Module B for somatic neural grafts, and Module C for mesenchymal stromal cell/secretome approaches. The Core Gate outlines the minimum pre-FPI requirements across preclinical justification, GMP release documentation, regulatory and ethics readiness, patient selection, trial design, safety oversight, trial conduct, long-term follow-up, and transparency. The modules add platform-specific requirements according to biological and procedural risks, including tumourigenicity and genomic stability assessment, immunologic monitoring, and route-appropriate biodistribution and persistence expectations. Movement disorder-specific operational elements not defined in general guidance were also incorporated, including harmonised baseline phenotyping, disease-specific endpoint menus, practical imaging and biomarker options. This framework turns fragmented guidance into a practical, auditable pre-FPI roadmap for stem cell trials in movement disorders. By combining a universal Core Gate with risk-proportionate modules, it aims to reduce protocol heterogeneity, improve cross-trial comparability, strengthen regulatory planning, and support safer, interpretable clinical translation.
Borderline personality disorder (BPD) is a severe mental health condition influenced by environmental risk factors (for example, interpersonal trauma) and genetic factors. We conducted the largest genome-wide association study (GWAS) meta-analysis of BPD so far, with a discovery sample of 12,339 cases and 1,041,717 controls, and a replication study of 685 cases and 107,750 controls (all participants of European ancestry). We identified 11 independent associated genomic loci and 9 risk genes in gene-based analyses. We observed a single-nucleotide polymorphism heritability of 17.3% and derived polygenic scores (PGS) that predicted 4.6% of the phenotypic variance in BPD on the liability scale. BPD showed the strongest positive genetic correlations with GWAS of post-traumatic stress disorder, depression, attention deficit hyperactivity disorder, antisocial behavior, and measures of suicide and self-harm. Phenome-wide analyses in Vanderbilt University Medical Center Biobank and UK Biobank using BPD-PGS confirmed these associations and also identified associations with other medical conditions, including obstructive pulmonary disease and diabetes. These analyses highlight BPD as a polygenic disorder, with the genetic risk showing substantial overlap with psychiatric and physical health conditions.
The treatment of tic disorders in children and adolescents poses significant challenges, especially when comorbid conditions such as obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) are present. Pharmacological treatments are often guided by clinical judgment, prescriber preferences, and medication availability. This study describes pharmacological treatment use in a large cohort of children and adolescents with chronic tic disorders (CTDs). We analyzed baseline data from the European Multicenter Tics in Children Study (EMTICS) to examine associations between medication use, tic severity, and psychiatric comorbidities, using parent-reported questionnaires and clinical interviews to assess tics, obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and children's self-rated premonitory urges. Among 709 children aged 3-16 years with CTDs, 230 (32%) received any pharmacological treatment, 22% received antipsychotics and 10% received ADHD medications, with limited use of alpha-2 agonists (3%). Medication use was more common among individuals with comorbid ADHD (54%) than those with CTD only (23%) or comorbid OCD only (26%). Those on tic-suppressing medications had significantly greater severity of tics, tic-related impairment, and comorbid ADHD, ODD, and obsessive symptom severity compared to those with non-tic-suppressing medications. There was no relationship with the severity of compulsions or premonitory urges. While largely consistent with published guidelines, these findings indicate limited utilization of recommended agents, such as alpha-2 agonists, alongside higher reported symptom severity among those receiving tic-suppressing medications. Further studies should explore the integration of pharmacological, behavioral, and psychoeducational approaches tailored to comorbidity profiles and symptom severity.
This survey aimed to investigate how physicians in Italy recognize, diagnose, and manage tardive dyskinesia (TD), as well as to assess and identify gaps in the current treatment approaches. A non-interventional cross-sectional online survey was conducted among Italian physicians who had managed patients with TD in the 1 year prior to the survey. The questionnaire explored physicians' demographics, clinical experience, diagnostic methods, treatment strategies, perceptions of TD impact, and health care resource utilization related to TD. Data were summarized descriptively. The survey included 70 psychiatrists and 30 movement disorder neurologists. Most patients presented with mild (49%) or moderate (35%) TD. Treatment strategies varied by TD severity; antipsychotic dose modification or switching was common, particularly to clozapine, quetiapine, and aripiprazole, whereas TD-specific add-on treatments such as tetrabenazine were rarely used (12% to 21% of physicians prescribed the treatment). Movement impairment was primarily assessed through patient or caregiver reports on quality-of-life impact, while standardized scales like the Abnormal Involuntary Movement Scale were underused, especially by psychiatrists. Physicians acknowledged significant challenges including a lack of highly effective treatments and an absence of specific Italian or European guidelines. TD was perceived as significantly affecting patients' physical and psychosocial functioning and increasing health care resource utilization. This study highlights variability and unmet needs in TD diagnosis and management among Italian specialists. Add-on treatments such as tetrabenazine are not considered standard of care in Italy due to lack of clinical practice guidelines, concerns around drug efficacy, adverse events, and overall treatment satisfaction.
Chronic idiopathic axonal polyneuropathy (CIAP) is a common type of chronic polyneuropathy that often affects health-related quality of life. Currently, no patient-reported disease-specific outcome measure is available to assess functional deficit in patients with CIAP. The aim of this study was to construct a patient-reported Rasch-built interval scale for patients with CIAP. A historic prospective cohort study was conducted to develop a CIAP-specific Rasch-built overall disability scale (CIAP-RODS). The preliminary scale (pre-CIAP-RODS) comprised 196 items, including 146 activity and participation items selected from the World Health Organization International Classification of Functioning, Disability and Health and 50 expert-derived items formulated in collaboration with a CIAP patients advocacy group. Participants were patients with CIAP who were requested to score their perceived difficulty to perform each item as (0) unable to perform; (1) able to perform, but with difficulty; or (2) easily performed, without difficulty. For test-retest reliability studies, 150 participants completed the pre-CIAP-RODS twice with an interval of 2-4 weeks. The pre-CIAP-RODS was subjected to Rasch analyses (RUMM2030+) to develop the final CIAP-RODS, and external validity was assessed by examining associations with the European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L). Of 551 eligible patients invited, 268 completed the pre-CIAP-RODS (mean age 72 years; 31% female; median disease duration 14 years). Patients with relevant comorbidities or newly identified risk factors of polyneuropathy were excluded. The pre-CIAP-RODS was subjected to Rasch analyses and did not meet the Rasch model expectations. In a systematic and stepwise manner, items were removed based on disordered thresholds, misfit statistics, local dependency, previously reported patient perceptions, and clinical applicability, resulting in a final 24-item CIAP-RODS that fulfilled Rasch model requirements. Test-retest reliability was good, internal validity was robust (person separation index 0.95), and significant associations between CIAP-RODS person location and EQ-5D-3L item scores indicated good discriminative external validity. The 24-item CIAP-RODS is a disease-specific interval measure developed for detection of activity and participation limitations in patients with CIAP. Use of the CIAP-RODS in future studies is recommended to evaluate longitudinal changes in the disease course. Further studies are needed to determine responsiveness and cross-cultural validity.