Assessing the extent and determinants of socioeconomic inequalities in epilepsy in the UK: a systematic review and meta-analysis of evidence.

BACKGROUND: Socioeconomic inequalities in epilepsy incidence and its adverse outcomes are documented internationally, yet the extent of inequalities and factors influencing the association can differ between countries. A UK public health response to epilepsy, which prevents epilepsy without widening inequalities, is required. However, the data on UK epilepsy inequalities have not been synthesised in a review and the underlying determinants are unknown. METHODS: In this systematic review and meta-analysis, we searched six bibliographic databases (MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and Scopus) and grey literature published between Jan 1, 1980, and Feb 21, 2024, to identify UK studies reporting epilepsy incidence or epilepsy-related adverse outcomes by socioeconomic factors (individual level or area level). We included longitudinal cohort studies, studies using routinely collected health-care data, cross-sectional studies, and matched cohort studies and excluded conference abstracts and studies not reporting empirical results in the review and meta-analysis. Multiple reviewers (KJB, EC, SER, WOP, and RHT) independently screened studies, KJB extracted data from included studies and a second reviewer (SM or EC) checked data extraction. We used Critical Appraisal Skills Programme checklists to assess quality. We used random-effects meta-analysis to pool incident rate ratios (IRRs) and synthesised results on adverse outcomes narratively. This study was registered on PROPSPERO (CRD42023394143). FINDINGS: We identified 2471 unique studies from database searches. We included 26 studies, ten of which reported epilepsy incidence and 16 reported epilepsy-related adverse outcomes according to socioeconomic factors. Misclassification, participation, and interpretive biases were identified as study quality limitations. Meta-analyses showed an association between socioeconomic deprivation and epilepsy incidence, with greater risks of epilepsy incidence in groups of high-deprivation (IRR 1·34 [95% CI 1·16-1·56]; I2=85%) and medium-deprivation (IRR 1·23 [95% CI 1·08-1·39]; I2=63%) compared with low-deprivation groups. This association persisted in the studies that only included children (high vs low: IRR 1·36 [95% CI 1·19-1·57]; I2=0%). Only two studies examined factors influencing epilepsy incidence. There is limited evidence regarding UK inequalities in adverse outcomes. INTERPRETATION: Socioeconomic inequalities in epilepsy incidence are evident in the UK. To develop an evidence-based public health response to epilepsy, further research is needed to understand the populations affected, factors determining the association, and the extent of inequalities in adverse outcomes. FUNDING: Epilepsy Research Institute UK.

UK Reproducibility Network open and transparent research practices survey dataset.

Openness and transparency in the research process are a prerequisite to the production of high quality research outputs. Efforts to maximise these features have substantially accelerated in recent years, placing open and transparent research practices at the forefront of funding and related priorities, and encouraging investment in resources and infrastructure to enable such practices. Despite these efforts, there has been no systematic documentation of current practices, infrastructure, or training and resources that support open and transparent research in the UK. To address this gap, we developed and conducted the Open and Transparent Research Practices survey, a large-scale audit study completed by research-active staff in UK research institutions to better understand existing practices, needs, support, and barriers faced when implementing open and transparent research. The data presented here capture responses from over 2,500 research-active staff based at 15 institutions affiliated with the UK Reproducibility Network. The data provide a snapshot of open research practices that can be used to identify barriers, training needs, and areas that require greater investments.

More doctors, better health? A generalised synthetic control approach to estimating impacts of increasing doctors under Brazil's Mais Medicos programme.

Worldwide, there are an insufficient number of primary care physicians to provide accessible, high-quality primary care services. Better knowledge on the health impacts of policies aimed at improving access to primary care physicians is important for informing future policies. Using a generalised synthetic control estimator (GSC), we estimate the effect of the increase in primary care physicians from the Programa Mais Médicos in Brazil. The GSC allows us to estimates a continuous treatment effects which are heterogenous by region. We exploit the variation in physicians allocated to each Brazilian microregion to identify the impact of an increasing Mais Médicos primary care physicians. We explore hospitalisations and mortality rates (both total and from ambulatory care sensitive conditions) as outcomes. Our analysis differs from previous work by estimating the impact of the increase in physician numbers, as opposed to the overall impact of programme participation. We examine the impact on hospitalisations and mortality rates and employ a panel dataset with monthly observations of all Brazilian microregion over the period 2008-2017. We find limited effects of an increase in primary care physicians impacting health outcomes - with no significant impact of the Programa Mais Médicos on hospitalisations or mortality rates. Potential explanations include substitution of other health professionals, impacts materialising over the longer-term, and poor within-region allocation of Mais Médicos physicians.

Incomplete resection of the intracranial electroencephalographic seizure onset zone is not associated with postsurgical outcomes.

Delineation of seizure onset regions using intracranial electroencephalography (icEEG) is vital in the surgical workup of drug-resistant epilepsy cases. However, it is unknown whether the complete resection of these regions is necessary for seizure freedom, or whether postsurgical seizure recurrence can be attributed to the incomplete removal of seizure onset regions. To address this gap, we retrospectively analyzed icEEG recordings from 63 subjects, identifying seizure onset regions visually and algorithmically. We assessed onset region resection and correlated this with postsurgical seizure control. The majority of subjects had more than half of their onset regions resected (82.46% and 80.65% of subjects using visual and algorithmic methods, respectively). There was no association between the proportion of the seizure onset zone (SOZ) that was subsequently resected and better surgical outcomes (area under the receiver operating characteristic curve [AUC] < .7). Investigating the spatial extent of onset regions, we found no substantial evidence of an association with postsurgical seizure control (all AUC < .7). Although seizure onset regions are typically resected completely or in large part, incomplete resection is not associated with worse postsurgical outcomes. We conclude that postsurgical seizure recurrence cannot be attributed to an incomplete resection of the icEEG SOZ alone. Other network mechanisms beyond icEEG seizure onset likely contribute.

Anatomical Variation of Abdominal Wall Musculature: An Objective Assessment Using Cross-Sectional Imaging.

Purpose: To determine normal anatomical variation of abdominal wall musculature. Methods: A retrospective analysis of CT scans was performed on adults (>18 years) with normal abdominal wall muscles. Two radiologists analysed the images independently. Distances from three fixed points in the midline were measured. The fixed points were; P1, mid-way between xiphoid and umbilicus, P2, at the umbilicus, and P3, mid-way between umbilicus and pubic symphysis. From these three fixed points the following measurements were recorded; midline to lateral innermost border of the abdominal wall musculature, midline to lateral edge of rectus abdominis muscle, and midline to medial edges of all three lateral abdominal wall muscles. To obtain aponeurotic width, rectus abdominis width was subtracted from the distance to medial edge of lateral abdominal wall muscle. Results: Fifty normal CT scan were evaluated from between March 2023 to August 2023. Mean width of external oblique aponeurosis at P1 was 16.2 mm (IQR 9.2 mm to 20.7 mm), at P2 was 23.5 mm (IQR 14 mm to 33 mm), and at P3 no external oblique muscle was visible. Mean width of the internal oblique aponeurosis at P1 was 32.1 mm (IQR 17.5 mm to 45 mm), at P2 was 10.13 (IQR 1 mm to 17.5 mm), and at P3 was 9.2 mm (IQR 3.0 mm to 13.7 mm). Mean width of the transversus abdominis aponeurosis at P1 was -25.1 mm (IQR 37.8 mm to -15.0 mm), at P2 was 29.4 mm (IQR 20 mm to 39.8 mm), and at P3 was 20.3 mm (IQR 12 mm to 29 mm). Conclusion: In this study we describe normal anatomical variation of the abdominal wall muscles. Assessing this variability on the pre-operative CT scans of ventral hernia patients allows for detailed operative planning and decision making.

Therapeutic strategies during cenobamate treatment initiation: Delphi panel recommendations.

The goal of epilepsy treatment is seizure freedom, typically with antiseizure medication (ASM). If patients fail to attain seizure control despite two trials of appropriately chosen ASMs at adequate doses, they are classified as having drug-resistant epilepsy (DRE). Adverse events (AEs) commonly occur in people with DRE because they are typically on ⩾2 ASMs, increasing the potential for drug-drug interactions. Early emerging AEs may impact adherence, decrease quality of life, and delay achieving optimal treatment dosages. Cenobamate is an oral ASM with a long half-life which has proven to be highly effective in clinical trials. An international Delphi panel of expert epileptologists experienced in the clinical use of cenobamate and other ASMs was convened to develop consensus best practices for managing patients during and after cenobamate titration, with consideration for its known pharmacokinetic and pharmacodynamic interactions, to allow patients to reach the most appropriate cenobamate dose while limiting tolerability issues. The modified Delphi process included one open-ended questionnaire and one virtual face-to-face meeting. Participants agreed that cenobamate can be prescribed for most patients experiencing focal-onset seizures. Patients initiating cenobamate therapy should have access to healthcare professionals as needed and their treatment response should be evaluated at the 100-mg dose. Patients with intellectual disabilities may need additional support to navigate the titration period. Proactive down-titration or withdrawal of sodium channel blockers (SCBs) is recommended when concomitant ASM regimens include ⩾2 SCBs. When applicable, maintaining a concomitant clobazam dose at ~5-10 mg may be beneficial. Patients taking oral contraceptives, newer oral anticoagulants, or HIV antiretroviral medications should be monitored for potential interactions. Because clinical evidence informing treatment decisions is limited, guidance regarding dose adjustments of non-ASM drugs was not developed beyond specific recommendations presented in the Summary of Product Characteristics.

Addressing ethnic disparities in neurological research in the United Kingdom: An example from the prospective multicentre COVID-19 Clinical Neuroscience Study.

BACKGROUND: Minority ethnic groups have often been underrepresented in research, posing a problem in relation to external validity and extrapolation of findings. Here, we aimed to assess recruitment and retainment strategies in a large observational study assessing neurological complications following SARS-CoV-2 infection. METHODS: Participants were recruited following confirmed infection with SARS-CoV-2 and hospitalisation. Self-reported ethnicity was recorded alongside other demographic data to identify potential barriers to recruitment. RESULTS: 807 participants were recruited to COVID-CNS, and ethnicity data were available for 93.2%. We identified a proportionate representation of self-reported ethnicity categories, and distribution of broad ethnicity categories mirrored individual centres' catchment areas. White ethnicity within individual centres ranged between 44.5% and 89.1%, with highest percentage of participants with non-White ethnicity in London-based centres. Examples are provided how to reach potentially underrepresented minority ethnic groups. CONCLUSIONS: Recruitment barriers in relation to potentially underrepresented ethnic groups may be overcome with strategies identified here.

A Ventral Hernia Management Pathway; A "Getting It Right First Time" approach to Complex Abdominal Wall Reconstruction.

INTRODUCTION: Abdominal wall reconstruction (AWR) is an emerging specialty, involving complex multi-stage operations in patients with high medical and surgical risk. At our hospital, we have developed a growing interest in AWR, with a commitment to improving outcomes through a regular complex hernia MDT. An MDT approach to these patients is increasingly recognized as the path forward in management to optimize patients and improve outcomes. METHODS: We conducted a literature review and combined this with our experiential knowledge of managing these cases to create a pathway for the management of our abdominal wall patients. This was done under the auspices of GIRFT (Getting It Right First Time) as a quality improvement project at our hospital. RESULTS: We describe, in detail, our current AWR pathway, including the checklists and information documents we use with a stepwise evidence and experience-based approach to identifying the multiple factors associated with good outcomes. We explore the current literature and discuss our best practice pathway. CONCLUSION: In this emerging specialty, there is limited guidance on the management of these patients. Our pathway, the "Complex Hernia Bundle," currently provides guidance for our abdominal wall team and may well be one that could be adopted/adapted by other centers where challenging hernia cases are undertaken.

A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN.

Objectives: Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments. Methods: We studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves. Results: In TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions. Conclusions: This study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.

The promise of AI Large Language Models for Epilepsy care.

Artificial intelligence (AI) has been supporting our digital life for decades, but public interest in this has exploded with the recognition of large language models, such as GPT-4. We examine and evaluate the potential uses for generative AI technologies in epilepsy and neurological services. Generative AI could not only improve patient care and safety by refining communication and removing certain barriers to healthcare but may also extend to streamlining a doctor's practice through strategies such as automating paperwork. Challenges with the integration of generative AI in epilepsy services are also explored and include the risk of producing inaccurate and biased information. The impact generative AI could have on the provision of healthcare, both positive and negative, should be understood and considered carefully when deciding on the steps that need to be taken before AI is ready for use in hospitals and epilepsy services.

Corruption and hierarchy: a replication of studies 1c and 6 of Fath & Kay 2018.

Corruption represents a complex problem firmly embedded within our societal structures, governments, and organizations. The current study aimed to build a clearer consensus on the extent to which perceptions of organizational corruption are associated with organizational hierarchy. Two high-powered close replications of studies 1c and 6 by Fath and Kay provide further evidence for the claim that taller organizational structures are associated with greater perceived potential for corruption, and that these perceptions may compromise subsequent trust-related outcomes. Our results reinforce the importance of organizational design and aim to inspire future works to consider the ways in which researchers and organizations can minimize corruption. Preregistration, data and materials can be found on the OSF: https://osf.io/zb5j2.

A guide for social science journal editors on easing into open science.

Journal editors have a large amount of power to advance open science in their respective fields by incentivising and mandating open policies and practices at their journals. The Data PASS Journal Editors Discussion Interface (JEDI, an online community for social science journal editors: www.dpjedi.org ) has collated several resources on embedding open science in journal editing ( www.dpjedi.org/resources ). However, it can be overwhelming as an editor new to open science practices to know where to start. For this reason, we created a guide for journal editors on how to get started with open science. The guide outlines steps that editors can take to implement open policies and practices within their journal, and goes through the what, why, how, and worries of each policy and practice. This manuscript introduces and summarizes the guide (full guide: https://doi.org/10.31219/osf.io/hstcx ).

Exploring critical intervention features and trial processes in the evaluation of sensory integration therapy for autistic children.

BACKGROUND: We evaluated the clinical and cost-effectiveness of manualised sensory integration therapy (SIT) for autistic children with sensory processing difficulties in a two-arm randomised controlled trial. Trial processes and contextual factors which may have affected intervention outcomes were explored within a nested process evaluation. This paper details the process evaluation methods and results. We also discuss implications for evaluation of individual level, tailored interventions in similar populations. METHODS: The process evaluation was conducted in line with Medical Research Council guidance. Recruitment, demographics, retention, adherence, and adverse effects are reported using descriptive statistics. Fidelity of intervention delivery is reported according to the intervention scoring manual. Qualitative interviews with therapists and carers were undertaken to explore the acceptability of the intervention and trial processes. Qualitative interviews with carers explored potential contamination. RESULTS: Recruitment, reach and retention within the trial met expected thresholds. One hundred thirty-eight children and carers were recruited (92% of those screened and 53.5% of those who expressed an interest) with 77.5% retained at 6 months and 69.9% at 12 months post-randomisation. The intervention was delivered with structural and process fidelity with the majority (78.3%) receiving a 'sufficient dose' of intervention. However, there was considerable individual variability in the receipt of sessions. Carers and therapists reported that trial processes were generally acceptable though logistical challenges such as appointment times, travel and COVID restrictions were frequent barriers to receiving the intervention. No adverse effects were reported. CONCLUSIONS: The process evaluation was highly valuable in identifying contextual factors that could impact the effectiveness of this individualised intervention. Rigorous evaluations of interventions for autistic children are important, especially given the limitations such as limited sample sizes and short-term follow-up as faced by previous research. One of the challenges lies in the variability of outcomes considered important by caregivers, as each autistic child faces unique challenges. It is crucial to consider the role of parents or other caregivers in facilitating access to these interventions and how this may impact effectiveness. TRIAL REGISTRATION: This trial is registered as ISRCTN14716440. August 11, 2016.

The direct and spillover effects of diabetes diagnosis on lifestyle behaviours.

Using blood sample data we exploit an arbitrary cut-off of diabetes risk and through a fuzzy regression kink design we estimate the effect of a diabetes diagnosis on own and partner health-related behaviours. Diabetes diagnosis increases the probability of exercising, both for those diagnosed with diabetes and their partner. We also conduct mediation analysis which suggests that joint household participation is the channel behind this effect. Our results have significant implications for the understanding of the channels that induce behavioural change, and household decision making, as well as, for the evaluation of diabetes related policies.

Pragmatic randomised controlled trial of guided self-help versus individual cognitive behavioural therapy with a trauma focus for post-traumatic stress disorder (RAPID).

Background: Guided self-help has been shown to be effective for other mental conditions and, if effective for post-traumatic stress disorder, would offer a time-efficient and accessible treatment option, with the potential to reduce waiting times and costs. Objective: To determine if trauma-focused guided self-help is non-inferior to individual, face-to-face cognitive-behavioural therapy with a trauma focus for mild to moderate post-traumatic stress disorder to a single traumatic event. Design: Multicentre pragmatic randomised controlled non-inferiority trial with economic evaluation to determine cost-effectiveness and nested process evaluation to assess fidelity and adherence, dose and factors that influence outcome (including context, acceptability, facilitators and barriers, measured qualitatively). Participants were randomised in a 1 : 1 ratio. The primary analysis was intention to treat using multilevel analysis of covariance. Setting: Primary and secondary mental health settings across the United Kingdom's National Health Service. Participants: One hundred and ninety-six adults with a primary diagnosis of mild to moderate post-traumatic stress disorder were randomised with 82% retention at 16 weeks and 71% at 52 weeks. Nineteen participants and ten therapists were interviewed for the process evaluation. Interventions: Up to 12 face-to-face, manualised, individual cognitive-behavioural therapy with a trauma focus sessions, each lasting 60-90 minutes, or to guided self-help using Spring, an eight-step online guided self-help programme based on cognitive-behavioural therapy with a trauma focus, with up to five face-to-face meetings of up to 3 hours in total and four brief telephone calls or e-mail contacts between sessions. Main outcome measures: Primary outcome: the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, at 16 weeks post-randomisation. Secondary outcomes: included severity of post-traumatic stress disorder symptoms at 52 weeks, and functioning, symptoms of depression, symptoms of anxiety, alcohol use and perceived social support at both 16 and 52 weeks post-randomisation. Those assessing outcomes were blinded to group assignment. Results: Non-inferiority was demonstrated at the primary end point of 16 weeks on the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [mean difference 1.01 (one-sided 95% CI -∞ to 3.90, non-inferiority p = 0.012)]. Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, score improvements of over 60% in both groups were maintained at 52 weeks but the non-inferiority results were inconclusive in favour of cognitive-behavioural therapy with a trauma focus at this timepoint [mean difference 3.20 (one-sided 95% confidence interval -∞ to 6.00, non-inferiority p = 0.15)]. Guided self-help using Spring was not shown to be more cost-effective than face-to-face cognitive-behavioural therapy with a trauma focus although there was no significant difference in accruing quality-adjusted life-years, incremental quality-adjusted life-years -0.04 (95% confidence interval -0.10 to 0.01) and guided self-help using Spring was significantly cheaper to deliver [£277 (95% confidence interval £253 to £301) vs. £729 (95% CI £671 to £788)]. Guided self-help using Spring appeared to be acceptable and well tolerated by participants. No important adverse events or side effects were identified. Limitations: The results are not generalisable to people with post-traumatic stress disorder to more than one traumatic event. Conclusions: Guided self-help using Spring for mild to moderate post-traumatic stress disorder to a single traumatic event appears to be non-inferior to individual face-to-face cognitive-behavioural therapy with a trauma focus and the results suggest it should be considered a first-line treatment for people with this condition. Future work: Work is now needed to determine how best to effectively disseminate and implement guided self-help using Spring at scale. Trial registration: This trial is registered as ISRCTN13697710. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/97) and is published in full in Health Technology Assessment; Vol. 27, No. 26. See the NIHR Funding and Awards website for further award information.

Post-traumatic stress disorder is a common, disabling condition that can occur following major traumatic events. Typical symptoms include distressing reliving, avoidance of reminders and feeling a current sense of threat. First-choice treatments for post-traumatic stress disorder are individual, face-to-face talking treatments, of 12­16 hours duration, including cognitive behavioural therapy with a trauma focus. If equally effective treatments could be developed that take less time and can be largely undertaken in a flexible manner at home, this would improve accessibility, reduce waiting times and hence the burden of disease. RAPID was a randomised controlled trial using a web-based programme called Spring. The aim was to determine if trauma-focused guided self-help provided a faster and cheaper treatment for post-traumatic stress disorder than first-choice face-to-face therapy, while being equally effective. Guided self-help using Spring is delivered through eight steps. A therapist provides a 1-hour introductory meeting followed by four further, fortnightly sessions of 30 minutes each and four brief (around 5 minutes) telephone calls or e-mail contacts between sessions. At each session, the therapist reviews progress and guides the client through the programme, offering continued support, monitoring, motivation and problem-solving. One hundred and ninety-six people with post-traumatic stress disorder to a single traumatic event took part in the study. Guided self-help using Spring was found to be equally effective to first-choice face-to-face therapy at reducing post-traumatic stress disorder symptoms at 16 weeks. Very noticeable improvements were maintained at 52 weeks post-randomisation in both groups, when most results were inconclusive but in favour of face-to-face therapy. Guided self-help using Spring was significantly cheaper to deliver and appeared to be well-tolerated. It is noteworthy that not everyone benefitted from guided self-help using Spring, highlighting the importance of considering it on a person-by-person basis, and personalising interventions. But, the RAPID trial has demonstrated that guided self-help using Spring provides a low-intensity treatment option for people with post-traumatic stress disorder that is ready to be implemented in the National Health Service.

Complementary structural and functional abnormalities to localise epileptogenic tissue.

BACKGROUND: When investigating suitability for epilepsy surgery, people with drug-refractory focal epilepsy may have intracranial EEG (iEEG) electrodes implanted to localise seizure onset. Diffusion-weighted magnetic resonance imaging (dMRI) may be acquired to identify key white matter tracts for surgical avoidance. Here, we investigate whether structural connectivity abnormalities, inferred from dMRI, may be used in conjunction with functional iEEG abnormalities to aid localisation of the epileptogenic zone (EZ), improving surgical outcomes in epilepsy. METHODS: We retrospectively investigated data from 43 patients (42% female) with epilepsy who had surgery following iEEG. Twenty-five patients (58%) were free from disabling seizures (ILAE 1 or 2) at one year. Interictal iEEG functional, and dMRI structural connectivity abnormalities were quantified by comparison to a normative map and healthy controls. We explored whether the resection of maximal abnormalities related to improved surgical outcomes, in both modalities individually and concurrently. Additionally, we suggest how connectivity abnormalities may inform the placement of iEEG electrodes pre-surgically using a patient case study. FINDINGS: Seizure freedom was 15 times more likely in patients with resection of maximal connectivity and iEEG abnormalities (p = 0.008). Both modalities separately distinguished patient surgical outcome groups and when used simultaneously, a decision tree correctly separated 36 of 43 (84%) patients. INTERPRETATION: Our results suggest that both connectivity and iEEG abnormalities may localise epileptogenic tissue, and that these two modalities may provide complementary information in pre-surgical evaluations. FUNDING: This research was funded by UKRI, CDT in Cloud Computing for Big Data, NIH, MRC, Wellcome Trust and Epilepsy Research UK.

The burden of chronic drug-refractory focal onset epilepsy: Can it be prevented?

Despite the many therapeutic options for epilepsy available today, a third of patients still have poorly controlled epilepsy. Over the years, their transition through lines of treatment exposes them to increased risk of disease progression, mortality, morbidity, mental distress, and not least significantly impaired quality of life (QoL). The present review explores the multiple factors contributing to the impairment of health-related QoL in PWE-including both seizure-related and non seizure-related. The analysis aims to identify potential areas of intervention and strategies for a more holistic approach to epilepsy care and inform policy-makers and healthcare providers in their approach to this condition.

SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy.

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10-9) and 10p11.21 (P = 3.6 × 10-8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10-3). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10-3) and increased seizure-like events (P = 6.8 × 10-7). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10-3). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease.