Abstract Text

Abstracts

1 - 18: Healthcare & Epidemiology 19-31: Comorbidities

32 - 38: Paediatrics 39 - 70: Treatments

71 - 86: Diagnostics 87 - 96: Basic & Translational

1 - 18: Healthcare & Epidemiology

Systematic review of under- and over-reporting of seizures in epilepsy: prevalence, mechanisms and clinical implications

Naveen Kumar¹, Joao Pizarro², Rohan Kandasamy³, Matthew Walker^2,4, Mahinda Yogarajah⁵

¹King’s College Hospital, ²Chalfont Centre for Epilepsy, ³Department of Clinical Neurophysiology, The National Hospital for Neurology & Neurosurgery, ⁴Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, ⁵Institute

of Neurology, Queen Square

Introduction: Seizure frequency guides clinical decisions, driving advice, and trial endpoints, yet commonly patients both under- and over-report. Under-reporting may reflect impaired awareness/recall, but this cannot explain over-reporting. This review aims to quantify under- and over-reporting, identify predictive factors for both, and discuss possible mechanisms.

Methods: Following PRISMA (2020) standards, we searched Medline, Embase, and PsycINFO (1990–present) for articles comparing patient-reported to EEG-determined seizure frequency. All seizure types were included, and paediatric-only and carer reporting-only studies were excluded. Article screening/data extraction were completed in duplicate.

Results: Fifteen studies were included. 62.2% (38.6%-98.3%) of seizures were unreported and 48% (26%-76%) were over-reported. Under-reporting was highest for nocturnal and impaired-awareness seizures, while over-reporting was commonest with absence-type seizures and in female patients.

Conclusions: Seizure misreporting is highly prevalent and bi-directional. Traditional explanations, focusing on impaired consciousness and recall, do not account for missed pre- or postictal cues, and cannot explain over-reporting. Altered interoception, and hence altered bodily self-awareness, may contribute to unrecognised or misattributed seizures, providing a parsimonious mechanism for seizure misreporting, and highlighting potential markers to identify patients at risk of diary inaccuracy.

A Disappearing Disease? Epidemiologic Trends of Hippocampal Sclerosis in a Multicentre Cohort

Nicholas Fearns¹, Paula Albert i Gracenea², Selina Trapp², Kai Michael Schubert¹, Luisa Delazer¹, Jan Rémi², Christian Vollmar², Josemir Sander¹, Ingmar Blümcke³, Christoph Helmstaedter⁴, Elisabeth Kaufmann², Matthias Koepp¹

¹UCL Queen Square Institute Of Neurology, ²LMU University Hospital, Department of Neurology, ³University Hospital Erlangen, Institute of Neuropathology, ⁴University Hospital Bonn, Department of Epileptology

Rationale: Hippocampal sclerosis (HS) is the classic structural basis of mesial temporal lobe epilepsy and has historically been the most common histopathological diagnosis in epilepsy surgery. Single-center studies suggest a decline in HS and changes in its clinical phenotype, but large-scale multicenter analyses with histopathological validation are lacking. This study examined temporal trends in the frequency and clinical profile of HS in a large European multicenter cohort. We tested the hypotheses that (1) the proportion of HS among epilepsy surgery specimens decreases over time and (2) the age at epilepsy onset in patients with HS increases, particularly as a birth-cohort–dependent effect.

Methods: We conducted a retrospective multicenter cohort study based on the European Epilepsy Brain Bank (EEBB), including 9,147 patients operated on between 2000 and 2012 at 36 European epilepsy centers. HS was defined histopathologically per the ILAE classification. Primary analyses comprised temporal trends in the proportion of HS and changes in age at epilepsy onset. To address selection and referral bias, analyses were performed both by year of surgery and by year of epilepsy onset.

Results: HS was diagnosed in 3,260 of 9,147 cases (35.6%). The proportion among all surgical specimens decreased significantly from 42.2% in 2000 to 25.2% in 2012 (–1.57 percentage points/year; p<0.001), reflecting a moderate reduction in absolute HS cases alongside a marked increase in non-HS procedures. Analyzed by epilepsy onset, the trend was more pronounced: HS fell from ~47% for onset in the 1960s–1970s to 14.5% for onset in 1995–2012, and below 10% in the most recent cohorts. In parallel, age at onset in HS rose significantly. By year of surgery, mean onset age increased from 15.6 to 18.2 years (p<0.001), whereas non-HS patients showed the opposite trend. This effect was stronger by year of onset: mean onset age in HS rose from 12.5 years (1960–1979) to 21.7 years (1995–2009; p<10⁻¹⁸), versus 8.8 to 11.1 years in non-HS patients, widening the group gap from 3.7 to 10.6 years.

Conclusions: This large multicenter analysis confirms a clear decline in HS and a shift toward later epilepsy onset across several decades, suggesting that classic HS-associated temporal lobe epilepsy is becoming increasingly rare and clinically changing. Possible explanations include improved treatment of prolonged febrile seizures, viral encephalitides, and autoimmune encephalitides.

Mind the Epilepsy Treatment Gap: Structural, Social and Health-system Barriers

Paola Favarato^1,2, Sena Kaya^1,2, Rebecca Yerin Im^1,2, Kasturi Kannan^1,2, Prem Jareonsettasin^1,2, Josemir W. Sander^1,2

¹UCL Queen Square Institute of Neurology, ²Social Determinants of Health in Epileptic Disorders (SdHIELD) Research Group

The epilepsy treatment gap (TG) is the proportion of people with epilepsy who require treatment but do not receive it. Despite many campaigns, TG remains large and persistent, particularly in low-resourced settings. We review the available evidence on TG, particularly potential causes and modifiable factors. We used the PRISMA extension for scoping reviews. We searched PubMed, Web of Science, Embase, Scopus, Ovid Global Health, PsychINFO and identified 393 relevant articles.

TG is not a single problem but a cascade of barriers (the 5 ‘A’s):1) Epilepsy Awareness, 2) Care Availability, 3) Treatment Accessibility, 4) Treatment Affordability, and 5) Treatment Adherence. The TG varies geographically, between and within countries. TG severity and patterns of underlying causes vary geographically between and within countries. This variation is largely driven by social determinants of health (SDH).

The awareness gap comprises multiple failure points. These include awareness, in which seizures are misattributed to supernatural, moral, or contagious causes; community awareness, in which social exclusion shapes health-seeking behaviour; and provider awareness, which can delay or divert treatment. Many studies measure TG among recognised cases and fail to include those who fail to enter the care pathway. Availability of neuroimaging, EEG, basic antiseizure medications, and epilepsy surgery is low in low-income countries. High-income countries show a geographical mismatch between supply and demand for specialist services, contributing to socioeconomic and racial inequality. The accessibility gap persists even where services exist. Factors include rurality, opportunity cost and medication distribution constraints. The affordability of antiseizure medications (ASM) remains a large problem that goes beyond drug price alone. It includes travel costs, wage loss, repeated appointments, and costs of long-term treatment. Adherence gaps are driven more by clinic-demographic factors, including ASM costs, availability, tolerability, and polytherapy, than by beliefs in low-income settings. Higher literacy is a protective factor, as it improves perceptions of treatment need. Seizure remission and employment status paradoxically increase non-adherence by reducing perceived need or making regular medication harder to sustain. Recent work has shown that exposure to environmental toxins, such as air pollutants, can affect pharmacokinetics and, consequently, ASM tolerability.

Despite progress in understanding potential causes of TG, significant knowledge gaps remain and require further work. The TG is particularly worse amongst disadvantaged groups such as ethnic minorities and those of low socioeconomic status. An understanding of SDH and local factors is needed to develop optimal intervention strategies.

Non-attendance at first seizure education sessions: associated factors and potential solutions

Dr Rhys Thomas, Raphaëlle Landais, Laure Juliette Landais, Mary Thornton, Joanne Glenton

Newcastle University

Purpose: As per NICE, all patients should see an epilepsy specialist nurse after receiving a diagnosis of epilepsy. At the Royal Victoria Infirmary (RVI), this is carried out through a group consultation. A previous audit (2022) found that this was poorly attended, particularly by patients from more deprived socioeconomic backgrounds. To encourage attendance, these sessions were reframed as a necessary part of the treatment pathway and video links were provided to non-attenders. This re-audit evaluates the effectiveness of this intervention.

Methods: We reviewed all patients who were invited to attend the group consultations at the RVI in Newcastle between July 2025 to March 2026. Information was collected on patient demographics, intellectual disability, and mental health, drug and alcohol history. Postcodes were used to calculate the index of multiple deprivation (IMD), and distance from the RVI.

Results: 211 patients were invited to the group consultation; 105 (50%) attended. 63% of attenders and 56% of non-attenders were male (not significant). Attenders had a mean age of 40y (17-83y), which was higher than the mean of 35y for non-attenders (17-81y, p=0.013). Attenders did not differ from non-attenders with regards to learning difficulties, or drug/alcohol problems (3.8% vs 6.6%; 17.1% vs 27.4% respectively), however the incidence of mental health problems was greater in non-attenders (55% vs 38%, p=0.015). Mental health (37.8% v 37.8%) was not found to be a factor for non-attendance in the previous audit. Attenders lived a mean of 9.0miles (0.5-57.7mi) from the hospital, similar to non-attenders (8.3mi, 1.0-33.7mi). Both groups had low average deprivation deciles (mean decile 4.0 vs 4.3 for attenders, p=0.39), compared to the previous audit which showed non-attendance correlated with lower deprivation scores (mean decile 3.5 vs 4.9 for attenders, p<0.005).

Discussion: This intervention reduced the discrepancy in attendance between socioeconomic backgrounds; however attendance was poorer amongst younger patients and those with mental health problems. To improve access to the information delivered in the session, we designed an easy-read leaflet with simple explanations and pictorial representations. The information was taken from the NHS website and checked by an experienced clinician. This leaflet offers an adjunct to group consultation sessions and aims to empower every patient, regardless of literacy level, by providing them with an easily accessible source of clinical information outside of the doctor’s office.

A rationalised approach to the management of newly diagnosed seizures in hospital

Piotr Wasilewski², Cameron Pinn², Andrew Dimech¹, Emily Bligh¹, Nilesh Mundil¹

¹Department of Neurosurgery, Wessex Neurological Centre, ²University of Southampton Medical School

Purpose: Epilepsy is the second commonest neurological condition. Its diagnosis carries significant physical, psychological and lifestyle implications for patients.

Not every suspected seizure represents epilepsy, particularly in an acute setting, where seizures may be provoked by structural, metabolic, infective or iatrogenic causes. NICE recommends urgent specialist assessment after a first suspected seizure and institution of AED therapy once epilepsy is confirmed.

We aimed to evaluate the investigation, treatment and follow up of newly diagnosed seizures in hospital with a view to rationalising and standardising future management.

Methods: A retrospective review of adult and paediatric patients admitted to Wessex Neurological Centre (neurosurgery, neurology and Neuro-ICU) between 01/12/2024 and 31/01/2025. Patients were identified using a search of seizure- and epilepsy-related ICD-10 codes.

Electronic records were reviewed for semiology, collateral history, diagnostic classification, investigations, aetiology, AED initiation/modification, prescribing rationale and follow-up.

Results: Of 73 records, 41 fulfilled our inclusion criteria: 21 adult neurology, 9 adult neurosurgery and 11 paediatric neurology admissions. AED therapy was started, changed or continued in 36 patients (87.8%). Levetiracetam was the most frequently prescribed AED, (75.6%): 15/21 adult neurology, 5/9 adult neurosurgery and 11/11 paediatric neurology cases.

Treatment prior to formal diagnosis occurred in 8/21 adult neurology patients (38.1%), 6/9 adult neurosurgical patients (66.7%) and 6/11 paediatric neurology patients (54.5%).

An electroencephalogram was requested in 39.0% cases, while cranial imaging was performed in 82.9% patients. Neurology/neurosurgical follow-up was arranged in 70.7% cases, with 26.9% patients reviewed within 8 weeks of ictus and 73.1% reviewed thereafter.

Safety-netting was documented in 85.4% patients, with specific driving advice/restrictions recorded in only 16.7% adult cases. Documentation regarding intended AED duration and continuation planning was by and large absent or unclear.

Conclusions: Prescribing anticonvulsants on presumption of epilepsy was more often initiated in surgical patients. Levetiracetam was the commonest anticonvulsant used, in keeping with its more favourable side effect profile. Long-term dosing plans, driving advice and timing of follow-up were inconsistently documented. Future multi-centre studies could evaluate variation in local inpatient post-first seizure review protocols.

Epilepsy remains poorly understood in an acute inpatient setting and improved education about its management and long-term implications would be beneficial. A suspected seizure proforma was generated, to be issued to medical and nursing professionals alongside targeted education sessions before a closed-loop re-audit is performed to assess the impact of rationalising seizure diagnosis and management in this setting.

Improving maternity care for women with epilepsy in the UK: a national quality improvement initiative

Jen Cannon

Epilepsy Action

The Ockenden¹ and Amos² reports deliver a damning finding: without urgent action, maternity care in the UK will continue to put women and babies at risk. For pregnant people with epilepsy (PWE), the risks are even more significant: a ten-fold higher risk³ and the fifth leading cause⁴ of maternal death, alongside increased risks of miscarriage, complications and infant mortality⁵. These dangers persist in the UK despite clear national guidance⁶,⁷. The gap is not a lack of evidence, but inconsistent implementation, leaving preventable harm unaddressed. With epilepsy named as a priority in the NHS England Maternal Care Bundle (NHSE MCB)⁸, services face a pressing challenge: turning national guidance into reliable care in everyday clinical practice.

In collaboration with two regional maternity providers in England, Epilepsy Action led a quality improvement initiative to address gaps in care for PWE. A mixed-methods approach was used in one pilot region, including regional gap analysis across providers, UK-wide surveys, and engagement with healthcare professionals and PWE. Identified barriers included limited awareness of guidance, insufficient preconception counselling, disparate multidisciplinary care, and a lack of confidence and trust among patients.

To address these issues, a self-assessment and benchmarking tool was co-produced with healthcare professionals in the pilot region. This tool aided the evaluation of adherence of current services to existing guidance, including the NHSE MCB.

Baseline benchmarking revealed substantial variation in care. In one region, providers met an average of 40% of minimum standards (range 24–69%), with governance-related measures showing particularly low adherence (13%), while pregnancy care and discharge planning showed higher adherence (56%). In the second region, overall adherence was 47% (range 30–69%), with governance again the lowest scoring domain (18%).

Following implementation, providers reported greater confidence in reducing mortality and stronger assurance against the epilepsy standards in the NHSE MCB. As a result of this work, one region’s Maternal Medicine Network has commissioned an epilepsy specialist midwife role to support patients with complex epilepsy.

This initiative shows the value of collaboration between the NHS and the third sector on healthcare improvement projects. It demonstrates that co-produced, practical tools enable providers to translate national guidance into a standardised, routine practice and support implementation of the NHSE MCB. If this initiative is adopted across the UK, this will enable consistent, safe maternity care for PWE, which have the potential to reduce maternal mortality and improve outcomes for pregnant PWE and their babies across the UK.

Area-Level Deprivation and Clinic Non-Attendance in a Regional Maternal Epilepsy Service: A Retrospective Audit

Gemma Clarke, Katie Cranfield, James Cameron, Dr Rhys Thomas

Newcastle University

Background: Pregnant women with epilepsy require timely specialist review to optimise seizure control, minimise maternal and foetal complications, and ensure appropriate medication management. Regional guidance recommends early risk stratification and regular antenatal follow-up; however, clinic non-attendance may delay delivery of this care. Identifying patients at higher risk of non-attendance could allow targeted interventions. This audit assessed whether socioeconomic deprivation, measured using the Index of Multiple Deprivation (IMD), was associated with clinic non-attendance.

Methods: A retrospective audit was performed of consecutive maternal epilepsy clinic appointments between January and May 2026. Attendance status was recorded for each clinic encounter. Patients who were no longer pregnant were excluded. Residential postcodes were mapped to IMD scores to obtain overall deprivation and seven domain-specific scores (income, employment, education and skills, health and disability, crime, living environment, and barriers to housing and services). Mean deprivation scores were compared between attendees and non-attendees. The average age of non-attendees and number of telephone appointments were recorded. As this was a service evaluation audit, analyses were descriptive.

Results: 97 clinic encounters were analysed, of which 11 were recorded as non-attendances (DNA rate 11.3%). Non-attendees demonstrated higher mean IMD scores overall (65.1 vs 61.2) and across five of seven deprivation domains. Median IMD score were 70 for non-attendees compares to 65 for attendees. However, differences between groups were consistently below 10%, with substantial variability within both cohorts. Patients from highly deprived neighbourhoods frequently attended appointments, while some individuals from relatively low-deprivation areas did not, indicating considerable overlap between groups. Although 11 appointments were not attended, 9 patients were subsequently reviewed during later antenatal appointments, with only two patients remaining unseen within the audit period.

Of the 11 non-attendances, the average age was 22.5 years. 5 patients were not previously known to the service and 5 of the missed consultations were scheduled as telephone appointments. No patient missed more than 1 scheduled appointment within the audit window.

Conclusion: Within this cohort, area-level deprivation measured using the IMD was not sufficiently discriminatory to identify women at increased risk of clinic non-attendance. The findings suggest that deprivation alone is unlikely to be an effective basis for targeted intervention. Future work should evaluate individual-level predictors, including previous engagement with healthcare services, co-existing mental health conditions, social support and safeguarding concerns, to improve attendance and optimise maternal epilepsy care.

Menopause and Epilepsy: An interim analysis of baseline data from the Epilepsy and Menopause Register

Emily Pegg^1,2, Rebecca Bromley²

¹Manchester Centre For Clinical Neurosciences/ University Of Manchester, ²Division of Neuroscience, University of Manchester

Background: Previous studies on menopause and epilepsy are sparse but suggest earlier menopause and increased perimenopausal seizure frequency in some women with epilepsy. Despite a lack of strong evidence of increased seizure susceptibility with HRT, concerns may deter use and limit its benefits. To address these knowledge gaps, the Epilepsy and Menopause Register was established to improve understanding of interactions between epilepsy, hormones, and comorbidities during the menopause transition.

Methods: Women with epilepsy aged 40-65 years were recruited via clinics and social media for a questionnaire-based study of menopausal stage, epilepsy characteristics, HRT use, and comorbidities. Validated questionnaires included GAD-7, PHQ-9, and PROMIS Sleep Disturbance. Baseline data from the first 6 months were analysed.

Results: 177 (77%) of enrolled participants (N=252) completed the study in 6 months. Most participants are white (92.2%) and living in areas of low socioeconomic deprivation. 35.5% were seizure free. 6.5% were premenopausal, 44.3% were perimenopausal, and 28.2% were postmenopausal. Peri- and post-menopause could not be distinguished in 11%, and menopausal status was unclassified in 8.5%.

Mean menopause age was 48.6 years. 38% of peri/post-menopausal participants used systemic HRT. Menopause status (pre- compared to peri- or post-menopause) was not associated with significant differences in seizure freedom rates. Peri/postmenopausal women using HRT were more likely to be seizure free than those not using HRT, χ2 (1, N=119) =4.05, p=0.044. 76% of participants met criteria for depression, 60% for anxiety, 62.1% for sleep disturbance, and 80% reported poor memory in the preceding four weeks. Depression and anxiety severity were higher in peri/postmenopausal than premenopausal women (mean PHQ-9 9.44 vs 5.92, t=-2.8, df=15.4, p=0.012, mean GAD-7 7.17 vs 3.33, t=-3.2, df=15.7, p=0.06). Menopause status was not associated with differences in sleep disturbance severity.

Conclusions: Menopause age was similar to the UK average. Depression, anxiety, and sleep disturbance were common, with depression and anxiety severity increasing from perimenopause onwards. In this cohort, HRT use is higher than in the general population, and HRT use is associated with higher seizure freedom rates. Longitudinal research is needed to determine whether this pattern reflects greater reluctance to use HRT among women with frequent seizures, or their clinicians, than when epilepsy is well controlled, or whether HRT itself may reduce seizure vulnerability, for example by reducing hormonal fluctuations. This is the largest study of menopause and epilepsy to date. Future recruitment should focus on premenopausal women and those from underrepresented groups.

Transforming Epilepsy Care in Pregnancy in Swansea Bay: Delivering Safe, Coordinated and Effective Multidisciplinary Care

Dimitri Akrivis, Jenny Edwards, Sharon Brown, Jorden Llewellyn, Owen Pickrell, Robert Powell, Madhuchanda Dey, Samantha Thalayasingam, Sara Williams, Inder Sawhney

Swansea Bay University Health Board

Background: Women with epilepsy are a high-risk obstetric group and require coordinated specialist care before, during and after pregnancy to minimise maternal and fetal complications. MBRRACE-UK has repeatedly identified epilepsy as a significant contributor to indirect maternal mortality. National guidance recommends preconception counselling, medication optimisation, seizure-risk assessment and coordinated obstetric and neurological care. A local review in Swansea Bay University Health Board identified similar findings to MBRRACE-UK, including fragmented pathways in which women attended separate obstetric and epilepsy appointments, often across different hospital sites, leading to duplication, inconsistent advice and delayed specialist input.

Aim: The aim was to establish a dedicated multidisciplinary Epilepsy in Pregnancy Clinic to provide timely, evidence-based, patient-centred care throughout pregnancy and the postnatal period, reducing variation and improving safety, experience and efficiency.

Method: In March 2021, Swansea Bay established the first dedicated multidisciplinary Epilepsy in Pregnancy Clinic in Wales, bringing together obstetricians, epilepsy specialist midwives, epilepsy specialist nurses and neurologists. The clinic introduced early referral, joint obstetric-neurology review, individualised epilepsy management plans, standardised counselling on anti-seizure medication adherence and SUDEP risk, birth planning, infant safety advice and structured postnatal follow-up.

Outcome: This clinic successfully integrated neurology and obstetric care into a single coordinated pathway, reducing fragmentation and improving communication between specialties. The service has seen an average of 40 women per year and supported each woman across her pregnancy journey for approximately seven months on average. Compared with the previous pathway, the integrated model reduced average antenatal appointments from eight to four by replacing separate specialty visits with one coordinated clinic. More than 90% of women were seen within two weeks of referral. Seventy-five percent remained seizure free during pregnancy; no women experienced an intrapartum seizure or developed status epilepticus. Overall, the obstetric intervention rates (e.g. Caesarean sections) remained comparable to the wider maternity population. Outcomes also include reduced clinic visits, consistency of advice, improved patient satisfaction.

Conclusion: Patient and clinician feedback showed improved continuity, clearer communication and greater confidence in medication decisions, seizure-risk management, birth planning, breastfeeding, contraception and postnatal safety. This project showcases that a multidisciplinary “epilepsy in pregnancy” clinic is feasible and sustainable, using existing resources. It demonstrates how a locally identified safety gap can be addressed through evidence-based pathway redesign and sustained collaboration. The Swansea Bay model aligns with MBRRACE-UK, RCOG and NICE recommendations and is informing wider service development through the All-Wales Epilepsy in Pregnancy Task Group.

Epilepsy care in pregnancy - a scoping survey

Emily Pegg, Dr Fahmida Chowdhury, Pooja Dassan, Christina Giavasi, Ana Garcia, Robert Powell, Ronan McGinty, Kasia Sieradzan, Janine Winterbottom, Ela Akay

Manchester Centre For Clinical Neurosciences/ University of Manchester

Background: Optimal epilepsy management during pregnancy is essential to reduce maternal morbidity and mortality while minimising foetal risk. National guidance, including NICE, MBRRACE-UK and the recently published NHS England Epilepsy Maternal Care Bundle, emphasises the need for multidisciplinary epilepsy-in-pregnancy services. Postnatal review and medication management is also recognised as a critical component of epilepsy care.

Currently, there is variation in the organisation and delivery of epilepsy care during pregnancy and there is limited consensus on the management of key aspects of clinical management of epilepsy in pregnancy.

This scoping survey, undertaken by the Epilepsy in Pregnancy Specialist Interest Group, aims to explore current models of care, identify variation in service provision and clinical practice, and highlight priorities for standardisation of practice and service development.

Methods: Neurologists and Epilepsy Specialist Nurses (ESN) were invited to complete a 30-item online questionnaire from May-June 2026. The survey was disseminated via the ABN, ESNA, and the ILAE through conference promotion and member newsletters.

Results: There were 141 respondents, representing services across England, Northern Ireland, Scotland, and Wales. A joint neurology-obstetric clinic was available in around 50% of regions. Appointments were delivered via face-to-face, video, and telephone consultations. Clinics were led by consultants or ESN, and new appointments lasted 30-60 minutes.

88% of respondents recommended 5mg folic acid pre-conception and during the first trimester. However, 38% continued high-dose supplementation throughout pregnancy.

Variation was observed in antiseizure medication (ASM) monitoring and dose-adjustment practices. Although 74% measure ASM levels preconception and 88% monitor ASM levels during pregnancy, practices varied widely regarding monitoring frequency, selection of ASMs for monitoring, and dose-adjustment strategies.

Turnaround times for ASM level results ranged from a few days to 6 weeks. Postnatal ASM dose adjustments and follow-up practices also varied considerably.

SUDEP risk was assessed by 86% of respondents and discussed with patients by 80%.

Common themes identified by respondents for future guideline development included ASM monitoring and interpretation, timing of reviews, folic acid dosing, breastfeeding advice, and discussion of SUDEP risk.

Conclusions: There is currently substantial variation in how maternal epilepsy care is delivered, particularly in relation to ASM level monitoring and dose adjustments, clinic design, and postnatal care. Alongside implementation of the Epilepsy Maternal Care Bundle in England, these findings underscore the need for consensus-driven guidelines and standardised care pathways to ensure safer, more equitable care for women with epilepsy during pregnancy and the postpartum period.

From inequity to action: Co-producing equitable access to specialist epilepsy care for adults - findings and approach from the PROPEL project (UK)

Adam Noble

University Of Liverpool

Objective: Ensuring equitable access to specialist epilepsy care within resource-constrained health systems is a global challenge. However, how inequities arise in high-income countries — and how they might be reduced without major new resources — remains poorly understood. We examined how inequities in ongoing adult epilepsy care emerged within an exemplar English epilepsy service, patient experience impact, and co-produced feasible service improvements. Importantly, PROPEL also provides a rare and potentially transferable framework for co-producing epilepsy service redesign within existing resource constraints.

Methods: PROPEL was an 18-month, multi-stage mixed-methods study. Six knowledge-exchange focus groups involving clinicians, administrators, people with epilepsy, and significant others first explored experiences of care and barriers to access. Findings informed iterative discussions by a 6-member multidisciplinary panel about required service revisions which were then refined through a mixed-stakeholder workshop. Data were analysed using rapid techniques.

Results: Across workshops involving 24 participants, stakeholders identified fragmented access pathways and inconsistent triage as contributors to delayed and inequitable specialist support. Access was perceived to depend partly on patients’ ability to navigate complex systems rather than need. Stakeholders also discussed increasing use of ‘Patient-Initiated Follow-Up’ (PIFU), in which patients request appointments when needed instead of offering scheduled follow-up appointments. PIFU was viewed positively for flexibility, but concerns remained regarding patients’ understanding of when and how to seek help. Following seven service-development panel meetings and a further stakeholder workshop involving 8 participants, two linked service modifications were co-produced: (1) a Single Point of Access to centralise and triage support requests; and (2) enhanced PIFU communication and safety-netting through clearer information and reminders.

Significance: Organisational complexity may itself drive inequities in epilepsy care. This co-produced redesign identified practical changes that may improve equity, responsiveness, and patient navigation without substantial workforce expansion. PROPEL offers a potentially transferable framework for strengthening specialist epilepsy services across health systems.

This work is part of a Collaborative Working project that was funded by Angelini Pharma UK-I Limited.

Scalable Home Video-Audio Monitoring (Nelli) in Adults With Epilepsy and Intellectual Disability

Dr Rhys Thomas, Vivienne Evans, Keith Young, Henry Bullogh

Newcastle University

Rationale: People with epilepsy, intellectual disability (ID) and autism are at high risk of seizure-related harm, and misdiagnosis, but are often poorly served by conventional diagnostic pathways. Inpatient video-EEG maybe difficult to tolerate, and carer diaries or ad hoc smartphone videos undercount events, particularly nocturnal seizures. Domiciliary monitoring offers the opportunity to capture typical events in the person’s usual environment. Nelli is a contactless, AI-informed video-audio monitoring system designed to identify and prioritise review of possible motor seizure events at home. We established this study to assessfeasibility, diagnostic yield and clinical utility in adults with epilepsy, and ID.

Methods: Patients are being recruited through our complex epilepsy service at the Royal Victoria Infirmary, Newcastle, with a target of 32 adults during 2026. Nelli operates as a device preparation, rental and installation service, with GDPR-compliant data storage. Possible seizure events are reviewed by medical personnel, with rapid reporting via a secure web platform that allows video review and, where appropriate, sharing with families. We will report demographics, seizure/event types, monitoring duration, event capture, diagnostic conclusions, safety, acceptability, report turnaround time, and management changes. The cohort is enriched by eight adults with Dravet syndrome who are also participating in the SCN1A Horizons natural history study with regular caregiver seizure diaries, and by two participants in REAL-ASE undergoing ultra long-term subcutaneous EEG, allowing exploratory comparison between routine diaries, prior home videos, video-audio event detection, and continuous EEG-derived seizure counts.

Results: At the time of abstract submission, 16/30 participants had been recruited, ahead of the expected recruitment trajectory. No adverse events, withdrawals due to tolerability, or patient/carer complaints have been reported. Reporting has been rapid, with reports returned within 10 days. Our analyses will include the complete 30-participant cohort and will summarise the proportion with clinically useful event capture, change in seizure classification or diagnostic confidence, discrepancy between carer-reported and recorded events, comparison with prior videos, and subsequent treatment or care-plan changes,including antiseizure medication adjustment, rescue medication review, nocturnal supervision planningand decisions about further EEG investigation.

Conclusions: Early experience supports the feasibility, acceptability and scalability of at-home AI-informed video-audiomonitoring for adults with epilepsy, ID and or autism in a busy tertiary NHS epilepsy service. This model of diagnostic support aligns with the NHS’ 10 Year Health Plan’s priorities of moving care closer to homeand supporting safe, clinically governed digital innovation. This approach may offer a flexible route to improving diagnostic confidence and guiding safer, treatments.

How Much Can We Trust Witnesses? The Accuracy of Eyewitness Recall of First Transient Loss of Consciousness Event Details at Clinically Relevant Time Intervals

Adam Noble

University of Liverpool

Background: Diagnosis after a first transient loss of consciousness (TLOC) often depends on eyewitness accounts, particularly when distinguishing epileptic seizures from functional/dissociative seizures (FDS), where clinical history is central and objective diagnostic tests may be limited. Despite their pivotal role, the accuracy of eyewitness accounts over clinically relevant delays is unknown. We therefore examined eyewitness recall of epileptic seizures and FDS immediately and after delays representative of UK clinical practice, assessed whether witness confidence predicts accuracy, and investigated whether immediate structured questioning improves subsequent recall.

Methods: Two parallel UK experimental studies recruited adults from the general population to view a standardised video of either an epileptic seizure (n=304) or an FDS (n=300). Participants were randomised to immediate free recall or immediate structured questioning before reassessment at either 2 or 7 weeks, reflecting recommended and typical UK waiting times for first seizure assessment. Recall accuracy was measured using 15 standardised semiology questions scored against consensus ratings from five consultant neurologists. We also evaluated the relationship between witness confidence and accuracy, and the effect of structured questioning on later recall.

Results: Eyewitness recall was only modest immediately after witnessing a seizure under optimal conditions (63–67% correct) and declined substantially over time. By two weeks, participants correctly recalled only 54–59% of key semiological features, with further deterioration at seven weeks. Witness confidence was consistently poorly correlated with objective accuracy. Several clinically important seizure features were especially vulnerable to forgetting. Immediate structured questioning improved later recall after epileptic seizures by 6.7% (95% CI 3.3–10.0), but conferred no meaningful benefit following FDS.

Conclusions: These studies provide the first experimental evidence quantifying the reliability of eyewitness recall across the two principal diagnostic considerations in patients presenting with undifferentiated TLOC. Eyewitness memory was inherently limited, declined over clinically relevant intervals, and was not reliably reflected by witness confidence. Although immediate structured questioning modestly improved later recall of epileptic seizures, it did not overcome these broader limitations. Clinicians should therefore interpret delayed eyewitness accounts with caution when distinguishing epileptic from functional seizures. These findings identify an important source of diagnostic uncertainty and highlight the need for new approaches to capture contemporaneous witness observations and support earlier diagnostic decision-making.

An audit of outpatient standards of care for patients with a diagnosis of epilepsy in a large male category B prison.

Laura Sewell, Sharon Brown, Jenny Edwards, Jorden Llewellyn, Inder Sawhney, Rob Powell, Owen Pickrell

Department of Neurology, Morriston Hospital, Swansea Bay University Health Board, Heol Maes Eglwys, Swansea, SA6 6NL

Purpose: Following the death of a male prisoner due to sudden unexpected death in epilepsy (SUDEP), all prisoners in a male category B prison, with a diagnosis of epilepsy, were identified as part of a pilot on-site prison epilepsy clinic run by Swansea Bay University Health Board. We aimed to assess standards of care, in line with National Institute for Health and Care Excellence (NICE) epilepsy guidelines, to optimise outpatient management and prevent avoidable deaths.

Methods: Thirty-nine prisoners were identified by the Prison Healthcare Team. Electronic clinical record data (clinic letters, GP referrals, discharge summaries and investigation results) from Welsh Clinical Portal were retrospectively reviewed. Twelve patients were excluded prior to analysis, due to never having been seen in a secondary care setting. One patient was excluded as an epilepsy diagnosis was refuted.

Twenty-six patients were reviewed in secondary care. Data regarding demographic information, prisoner status, epilepsy diagnosis and investigation results, risk factors for SUDEP, anti-seizure medications, comorbidities and availability of and compliance with follow up appointments were collected. Emergency Department attendances and hospital admissions due to epilepsy in a 12-month period prior to an outpatient appointment were also reviewed.

Results: Seventeen patients resided in this category B prison during data collection and analysis. Mean age was 45.6 years. Fourteen patients had generalised seizures, of which one had been seizure free for at least one year. Five had seizures from sleep. Three patients were in a cell alone. SUDEP was discussed with five patients. Three patients received sleeping advice. Eight patients were compliant with anti-seizure medications. Five patients had regular follow up arranged. Did not attend (DNA) rates for appointments were between 0 and 50 %. Twelve patients had either open access or no follow up. There were no Emergency Department attendances nor hospital admissions due to epilepsy in the preceding 12 months.

Nine patients had been released or transferred to another prison. No patient received a transfer of care letter from the Prison Medical Team. Only four patients had regular follow up arranged.

Conclusions: Standards of care for patients with epilepsy in prison, as outlined by NICE, are not being met, based on a hospital-based outpatient clinic model.

Implementing a monthly prison-based outpatient epilepsy clinic, offering review of six patients per clinic, supported by prison healthcare staff, could allow each patient to be seen biannually and help mitigate the risk of substandard care and SUDEP in this vulnerable population.

Clinical Nurse Specialists across Wales: A workforce report

Malisa Pierri

Neurological Conditions Network for Wales: NHS Wales: Performance and Improvement

Introduction: National guidelines such as NICE, (National Institute for Health and Care Excellence) and SIGN (Scottish Intercollegiate Guidelines Network) recommend all patients with epilepsy have access to an Epilepsy Specialist Nurse (1,2). The CNS in epilepsy has become a front line post in epilepsy care. 94% of CNS in Epilepsy are monitoring and adjusting-seizure medications (1), Studies also suggest that a lack of effective care from an CNS result in increased risk of hospital admission, injury, sudden unexpected death in epilepsy, and a poorer quality of life (2).

A national scoping exercise was undertaken with the aim to identify the numbers of CNS’s and the variations across Wales.

Method: With no recognised career pathway to become a CNS in Epilepsy the roles vary. This makes it very difficult to identify using employment systems such as Electronic Staff Record (ESR). Collection of data for this workforce report was undertaken using a grassroot cascade method. Stakeholders were identified by establishing through face-to-face meetings and by using the Welsh Epilepsy Nurses Group (WEN) and information about the scope cascaded out.

Results: The data was separated into geographical area, area of clinical practice (for example paediatrics or adults) and whole-time equivalents (WTE). There were two UHB’s that employed specific CNS’s to work with epilepsy in learning disability. Some nurses were employed by one UHB but some time outsourced to another and so the results were reflected according to WTE available in each UHB.

Recommendations for caseloads of CNS in Epilepsy vary, with the Royal College of Physicians and the Association of British Neurologists suggesting 9 CNS in Epilepsy per 500,000 population 54 (3). Wales has an estimated population of 3,186,600 (4) and according to the above should have 57.6 WTE.

The data shows that the current CNS in Epilepsy workforce across paediatrics and adults is 32.3 WTE posts. An additional 25.3 additional 25.3 WTE CNS in Epilepsy are therefore required in Wales to meet recognised guidelines for care.

Conclusion: The profile of a CNS in Epilepsy has increased immensely over the last 20 years. Disappointingly, however, this exercise has outlined large discrepancies of availability of CNSs in Epilepsy across the Wales. This leaves some patients living in some areas of Wales with no access to a CNS in Epilepsy. More work is needed to highlight the essential nature of these posts in particular, areas where access to neurology services on a whole is limited

Incidence and excess disease burden of acquired epilepsy across 20 brain insults in 4.4 million adults

Kai Michael Schubert^1,2, Miranda Stattmann², Carolina Ferreira-Atuesta², Katharina Schuler², Philip Curman^3,4, Ralf J. Ludwig³, Anton Schmick^2,3, Matthias Koepp¹, Marian Galovic^2,3

¹University College London, ²Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, ³Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany, ⁴Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

Background: Epilepsy is a frequent and feared consequence of brain injury, yet how often it arises after different insults, and whether the seizures themselves worsen outcomes or merely mark sicker patients, remains unclear. Burden-of-disease frameworks rarely treat acquired epilepsy as a distinct entity, obscuring the morbidity attributable to epilepsy itself. We aimed to estimate the incidence of acquired epilepsy across diverse brain insults, quantify the excess morbidity and mortality independently associated with it, and examine whether antiseizure-medication (ASM) treatment is associated with outcomes.

Methods: In a global federated network of electronic health records (TriNetX), we identified 4,435,452 adults meeting criteria for one of 20 structural, infectious, or inflammatory epileptogenic aetiologies. Ten-year cumulative incidence of acquired epilepsy was estimated using Aalen-Johansen methods with death as a competing risk. In aetiology-stratified landmark analyses, individuals who developed epilepsy were matched 1:1 by propensity score on 62 covariates to those who did not, and 1-year outcomes were pooled by inverse-variance synthesis. Prespecified negative-control outcomes and E-values assessed residual confounding.

Results: Acquired epilepsy occurred in 191,904 adults (4.3%), most often after ischaemic stroke (37.1%), traumatic brain injury (21.4%), and brain tumours (8.4%). Ten-year cumulative incidence ranged from 1.5% (95% CI 1.4 to 1.6) after multiple sclerosis to 36.9% (31.0 to 42.8) after neurocysticercosis. After matching (99.4% of standardised differences below 0.05), acquired epilepsy was independently associated with higher 1-year mortality (HR 1.20, 95% CI 1.16 to 1.24) and with excess emergency visits (HR 1.22), hospitalisations (HR 1.31), major bleeding (HR 1.38), head or facial injury (HR 1.64), pneumonia (HR 1.30), dysphagia (HR 1.37), depression (HR 1.30), and dementia (HR 1.36). Negative-control outcomes were near-null with small E-values, in contrast to high E-values for the main analyses. Among individuals with epilepsy, ASM treatment was associated with lower 1-year mortality (HR 0.70, 95% CI 0.62 to 0.78) despite more recorded seizures, consistently across the eight largest aetiologies.

Conclusion: Across 20 brain insults, acquired epilepsy is common and an independent contributor to death and disability, while antiseizure-medication treatment is associated with lower mortality. These findings support vigilant detection and timely management after brain injury.

Adult epilepsy care in the North East: workforce provision, clinical outcomes and economic burden compared with other English regions

Thurstan Moncrieff, Dr Rhys Thomas, Hannah Steele

Purpose: Regional inequalities in epilepsy prevalence and workforce provision are well established across England, but do not align. Following new Association of British Neurologists (ABN) workforce recommendations (1.6 consultant neurologists and 0.6 adult Epilepsy specialist nurses (ESNs) WTE per 100,000 population), we evaluated workforce provision, clinical outcomes and service costs in the North East (NE) compared with other regions.

Methods: Using the 2026 ABN epilepsy workforce report, Epilepsy Action’s 2024 report and NHS workforce statistics, we calculated consultant neurologist and adult (ESN) WTE per 100,000 population by ICB. NHS pay scales were used to estimate the cost of achieving recommended workforce provision in the NE.

Clinical outcomes, including A&E attendance, emergency admissions and years of life lost (YLL), were compared using data from the Royal College of Emergency medicines report: ‘A Dangerous Wait: Addressing the NHS Epilepsy Crisis’ Medicine and other sources.

NHS costings were used to estimate costs of unscheduled epilepsy care and potential savings.

Results: Only 50% of English regions met the recommended consultant levels, while no region met ESN recommendations. The NE had the highest epilepsy prevalence (1.1%) but the lowest neurologist provision (1.31 WTE per 100,000 population). Although ESN provision in the NE was around the national median (0.20 WTE per 100,000), this remained only one-third of the recommended minimum (0.60). Meeting workforce recommendations in the NE would come to £2.13m additional spend annually.

The NE demonstrated consistently poor outcomes, with the highest YLL rate (3.7), second-highest standardised mortality rate (1.3) and excess bed-day rate (4.63 per 100,000 population). It also had the third-highest rates of ambulance use (200.1 per 100,000) and A&E attendance (178.3 per 100,000). The region recorded 1,611 epilepsy-related emergency admissions annually (54.6 per 1,000 people with epilepsy).

Estimated annual spending on unscheduled epilepsy care in the NE was £4.48m, with per-capita costs that were 59.1%, 15.2% and 28.5% higher than London, the East of England and the South West respectively. Excess YLL was associated with estimated annual economic losses of £1.58m compared with London, £0.85m compared with the East of England, and £1.96m compared with the South West.

Conclusion: Significant disparities exist between epilepsy workforce provision in the NE and national recommendations. The region experiences poorer outcomes and higher unscheduled care costs. Although various factors, including deprivation, contribute to regional variation, the findings suggest that investment in consultants and ESNs could improve outcomes and reduce healthcare expenditure.

Implementing Emerging Epilepsy Therapies in Resource-Limited Settings: Healthcare-Worker Readiness, Awareness, and Access Barriers to Ketogenic Dietary Therapies and Pharmaceutical Cannabidiol in Kenya

Phyllis Kimani, Lucia Keter, Calvin Omolo

Neuro Reach Africa CIC

Background: The WHO Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders (IGAP) 2022-2031 calls for improved access to evidence-based epilepsy care. Ketogenic dietary therapy (KDT) and pharmaceutical cannabidiol (CBD) are increasingly used for drug-resistant epilepsy, yet whether the workforce in resource-limited settings is prepared to support them is unclear. In Kenya, where epilepsy care is constrained by workforce shortages, a substantial treatment gap and limited structured KDT services, healthcare-worker readiness is central to implementation.

Methods: We report an integrated two-phase study. Phase 1, now complete, was a rapid scoping evidence review of healthcare-worker awareness of KDT and pharmaceutical CBD for epilepsy, focused on Kenya, Africa and other low- and middle-income countries. Phase 2 is a cross-sectional mixed-methods survey of 40-60 healthcare workers across pharmacist, nursing, medical-officer, clinical-officer, nutritionist and specialist cadres with direct epilepsy contact, recruited via hospital and professional-network routes in urban and peri-urban Kenya. The questionnaire, developed and translated into Kiswahili, assesses familiarity with KDT variants and pharmaceutical CBD (including distinguishing CBD from recreational cannabis), counselling confidence, perceived effectiveness and safety, and referral pathways and barriers, with key informant interviews in a purposive sub-sample. Ethical review is underway through the KEMRI Scientific and Ethics Review Unit, with data collection beginning on approval. Quantitative data will be analysed descriptively across cadres and qualitative data by thematic analysis within a healthcare-equity framework.

Results: Phase 1 established a clear evidence gap. In Kenya, KDT awareness has been measured only among dietitians, where about two-thirds reported knowledge but fewer than one in ten answered all knowledge items correctly. CBD awareness for epilepsy has been surveyed mainly in Europe, North America and the Gulf, while the African evidence identified related largely to medical cannabis/CBD broadly rather than pharmaceutical CBD for epilepsy. No study was identified assessing awareness of both therapies across the broader practising epilepsy-care workforce in Kenya, and none evaluating awareness of pharmaceutical CBD for epilepsy among practising Kenyan healthcare workers. These findings frame Phase 2.

Conclusions: This review identifies a clear Kenyan evidence gap in healthcare-worker awareness of KDT and pharmaceutical CBD for epilepsy. Phase 2 is designed to provide the first Kenya-based evidence on broader workforce readiness for these therapies across multiple epilepsy-care cadres, informing continuing medical education, referral pathways, and implementation and equity-focused policy aligned with IGAP.

19 - 31: Comorbidities

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Evaluating the clinical utility of the Refractory Epilepsy Screening Tool for Lennox-Gastaut Syndrome (REST-LGS) in a specialised adult epilepsy and intellectual disability clinic.

Hannah Humble¹, Vivienne Evans², Dr Rhys Thomas^3,4

¹Newcastle University, ²Clinical Research Department (Neurology), Royal Victoria Infirmary, ³Translational and Clinical Research Institute, Royal Victoria Infirmary, ⁴Neurosciences, Royal Victoria Infirmary

Background: Lennox-Gastaut Syndrome (LGS) is an electroclinical syndrome with diagnostic criteria ratified by the ILAE. However, many adults are not diagnosed due to a lack of recognition, or uncertainty in adult teams. The Refractory Epilepsy Screening Tool (REST-LGS) was created to help with identification. The prevalence of LGS worldwide is suggested to be at least one million people. Screening tools are a cornerstone in preventative medicine, when used in the correct setting and their caveats understood. The aim of this study is to evaluate the clinical utility of REST-LGS and make recommendations for improving its’ specificity.

Methods: We retrospectively collected data from electronic patient records who attended a specialised adult clinic (March 2023 to 2026, to account for follow up). REST-LGS has 4 major criteria: ≥2 seizure types, onset before age 12, generalised slow spike-and-wave discharges on EEG and cognitive impairment, and 4 minor criteria: seizure persistence, helmet use, history of VNS, ketogenic diet or surgery and other specific EEG findings. The outcome is ‘likely’ if three of the major and at least two minor criteria are met or ‘unlikely’. Gold-standard diagnoses were based on ILAE criteria and where this was not possible, clinical experience with EEG support.

Results: 495 individuals were identified for screening, 122 were excluded due to limited information or failed clinic attendance. Of the 373 included, 56 patients had a gold-standard diagnosis of LGS, and 16 patients had Dravet syndrome. REST-LGS suggested an outcome of ‘likely’ for 47.45% (n=177) and ‘unlikely’ for 52.55% (n=196). For those with a known LGS diagnosis the tool suggested 98.21% (n=55) were ‘likely’ and 1.79% (n=1) ‘unlikely’. All known LGS patients had ≥2 seizure types, onset before age 12 and persistent seizures. The sensitivity of REST-LGS in this population was 98.21%, however the specificity was 61.51%; positive predictive value of 31.1%. This is shown as those with confirmed Dravet syndrome (n=16), all identified as ‘likely-LGS’.

Conclusion: We must review the 122 ‘likely’ patients to identify any missed cases, or if the tool is over-identifying. However, an ‘unlikely’ result is very helpful with a negative predictive value of 99.5%. REST-LGS could be used to prompt referral to a specialist epileptologist. However, the lack of specificity limits its use as a standalone tool. Solutions targeting improved specificity could include inclusion of cognitive specific criteria highlighting regression or using negative marking if another diagnosis is known or equally as likely.

Why the way we measure deprivation in studies of people with epilepsy matters

Kathryn Bush¹, Dr Rhys Thomas¹, Andrew Kingston¹, Sheena E Ramsay¹, Owen Pickrell²

¹Newcastle University, ²Swansea University

Introduction: Epilepsy is associated with socioeconomic deprivation in the United Kingdom, with the highest rates observed in the most deprived populations. In large population studies area-level measures of deprivation are frequently available and widely used. This study aims to understand how different measures of socioeconomic deprivation influence population-level risk estimates for incident epilepsy.

Methods: We created a Welsh Cohort study of 2.4 million individuals with linked medical, death, area-level demographic and census data, in the Secure Anonymised Information Linkage (SAIL) databank. Individuals were followed up between 2011-2024 and there were 17,455 all-age incident epilepsy cases observed. Measures of deprivation were recorded at study baseline, prior to epilepsy diagnosis. We examined the correlation between area-level and household-level measures of deprivation at a population-level. We used Cox-proportional hazard ratios to compare the risk of epilepsy in the most deprived versus least deprived groups, using: i) census household-deprivation scores, ii) individual-level factors (education and occupation), and iii) Welsh Index of multiple deprivation (WIMD) area-level measures.

Results: All methods used showed graded associations between socioeconomic deprivation and incident epilepsy in Wales, with the highest rates of incident epilepsy in the most deprived populations. Area-level and household-levels of deprivation were highly correlated (p <0.001), but area-level measures will mis-classify some individuals. Models were adjusted for age, sex and rural-urban classification. The all-age adjusted hazard ratio (AHR) of epilepsy in the most deprived areas versus least was AHR:1.66 (1.55-1.77). In the most deprived households versus least all-age AHR:3.20 (2.50-4.10). Adults (16-64 years) with no educational qualifications versus level-4 (degree) AHR 2.23 (2.01-2.47). Adults in occupational social-class 8 (most deprived) had an AHR 4.23 (3.55-5.04) compared to social-class 1.

Conclusions: In this population-level study, individual-level and household-level deprivation measures produce higher incident epilepsy risk estimates, compared to area-level measures. Studies using area-level measures of deprivation may under-estimate deprivation associated risk. Studies seeking to understand the influence of socioeconomic factors on epilepsy incidence or outcomes, should consider using household-level or individual-level measures (available in census-data), in preference to area-level data.

Verbal memory recall and retrieval in Temporal Lobe Epilepsy

Amrita Gupta^1,2, Carissa Kelley^1,2, Marzena Arridge^2,3, Sherry Liu^1,2, Hannah Bergman³, Andrea Hill³, Christopher Chua Yuan Kit⁴, John Sidney Duncan^1,2,3, Sallie Baxendale^1,2, Meneka Kaur Sidhu^1,2,3

¹UCL Queen Square Institute of Neurology, ²Department of Epilepsy, National Hospital for Neurology and Neurosurgery, ³MRI Unit, Chalfont Centre for Epilepsy, ⁴Division of Neurology, University Medical Centre, National University Hospital

Introduction: Temporal lobe epilepsy (TLE) affects cognitive networks and is associated with episodic memory impairment. We previously described reorganization of memory encoding networks in TLE using functional magnetic resonance imaging (fMRI). The impact of TLE on verbal memory retrieval networks are less well understood. We investigated verbal memory retrieval networks in left (LTLE) and right TLE (RTLE) compared to healthy controls (HC).

Methodology: 26LTLE (median age 36.5 (32.0–48.2), 29RTLE (37(30–49)) and 25HC (40(35–44)) underwent verbal memory fMRI encoding, recall and recognition paradigms with a baseline of odd/even number judgement. BIRT Memory and Information Processing Battery (BMIPB-II) was used to assess verbal learning (VL) and delayed recall (DR) with Mann-WhitneyU tests on age-normed z-scores for group comparisons.

SPM 12 was used for one-sample t-tests to assess within group activations; two-sample t-tests for group differences. Extra-temporal activations are reported at p<0.01 uncorrected (specific subtraction contrasts) with small-volume correction for medial temporal lobe (MTL) (FWE, p<0.05).

Results: Neuropsychology: LTLE performed significantly worse than RTLE on both VL and DR; VL (median z = −1.18 vs −0.67; U = 226.5, p = .011) and DR (median z = −1.44 vs −0.42; U = 201.0, p = .003). Both patient groups performed worse than controls.

Encoding: Controls showed L>R parahippocampal gyrus (PHG) activations. Compared to controls, both LTLE and RTLE had reduced neocortical activations bilaterally (LTLE: left middle temporal, middle frontal, bilateral supramarginal, RTLE: right lingual, cuneus).

Free Recall: Controls showed right PHG, entorhinal, left insula, left thalamus, right middle temporal and inferior frontal gyrus activations. LTLE showed greater bilateral fusiform, left insula, superior temporal activations compared to controls.

Recognition: Controls showed right hippocampus, PHG, right middle occipital activation. LTLE showed increased activation in the right hippocampus and PHG, left insula, left superior temporal and right fusiform gyrus compared to controls.

RTLE showed reduced right hippocampus and PHG gyrus activations compared to controls for both recognition and recall.

Conclusions: In LTLE, both recall and recognition engaged greater left insula and right-MTL network (including the fusiform gyrus) more than HC. For recall this was more extra-temporal reorganisation whilst recognition engaged the contralateral MTL. In RTLE, right MTL activation was reduced for both recognition and recall compared to controls but relatively preserved at encoding. These findings suggest recall and recognition rely on distinct networks that are altered in both LTLE and RTLE, with corresponding deficits in neuropsychological memory scores seen in both groups.

Both Face Encoding and Recognition Network Disruption is Seen in Left and Right Temporal Lobe Epilepsy

Carissa Kelley^1,2, Amrita Gupta^1,2, Marzena Arridge^2,3, Sherry Liu^1,2, Hannah Bergmann³, Andrea Hill³, Christopher Chua Yuan Kit⁴, John S. Duncan^1,2,3, Sallie Baxendale^1,2, Meneka K. Sidhu^1,2,3

Purpose: Visual episodic memory difficulties occur in primarily non-dominant temporal lobe epilepsy (TLE). Functional magnetic resonance imaging (fMRI) has demonstrated visual memory encoding network reorganization in TLE, but retrieval networks remain poorly understood. We investigated face encoding and recognition network reorganization in left TLE (LTLE) and right TLE (RTLE).

Methods: 25 controls and 55 TLE patients (26 left) performed a neutral and fearful face encoding and recognition task with a baseline task of odd/even number judgement. SPM12 was used to investigate within-group activations (one-sample t-test) during encoding and recognition and between-group differences (two-sample t-tests). Group differences in BIRT Memory and Information Processing Battery (BMIPB II) design learning (DL) and delayed recall (DR) were assessed using Mann-Whitney U tests on age-normed z-scores.

Mesial temporal activations are reported using small volume correction (6mm) at FWE p<0.05 and neocortical activations at p<0.01, as stringent subtraction contrasts were used.

Results: There was no significant difference between LTLE and RTLE for DL or DR; LTLE (median: -0.89, IQR: -1.32 to -0.51) and RTLE (-0.73, -1.21 to 0.17) for DL, LTLE (0, -0.95 to 0.48) and RTLE (-0.57, -1.49 to 0.65) for DR.

Encoding: Both patient groups showed fewer mesial temporal lobe (MTL) activations (anterior parahippocampal gyrus/amygdala) than controls. RTLE showed increased right posterior hippocampal and increased left neocortical activations, and LTLE showed reduced left neocortical and increased right neocortical activations compared to controls.

Recognition: Both patient groups showed greater fusiform and anterior cerebellum activations than controls, and RTLE showed bilateral posterior cerebellar activations exceeding both other groups. RTLE showed increased bilateral activations in the MTL with additional bilateral neocortical activations. LTLE showed reduced left inferior parietal lobule/supramarginal gyrus activation and increased right posterior hippocampal activation and additional predominantly right neocortical activations.

Key default mode network hubs (posterior cingulate cortex/precuneus) were more active in RTLE compared to controls or LTLE during both encoding and recognition.

Recognition vs Encoding: RTLE had greater cerebellar activation during recognition than encoding, while LTLE showed increased left posterior hippocampal activation with no cerebellar increase.

Conclusions: These findings suggest face encoding and recognition networks are disrupted in TLE. LTLE showed reduced left and increased right hemisphere activations during encoding and recognition, compared to controls. RTLE showed more extensive bilateral reorganization, including default mode and cerebellar regions, with cerebellar activation greatest during recognition. As the cerebellum contributes to emotion and visual recognition, this pattern may reflect compensatory efforts for network dysfunction.

Mortality and comorbidities in people with Functional/Dissociative Seizures in Wales

Russell Khan¹, Beata Fonferko-shadrach¹, Huw Strafford¹, Kathryn Bush⁴, Owen Bodger¹, Kelly Price², Kathryn Cullen¹, Inder Sawhney¹, Ronan Lyons¹, Arron Lacey¹, Ashley Akbari¹, Joe Anderson, Phil Smith⁵, Teja Zeribi⁷, Bridget Mildon⁷, Rob Powell^1,2, Markus Reuber³, Owen Pickrell^1,2

¹Swansea University Medical School, ²Neurology Department, Morriston Hosptial, Swansea Bay University Health Board, ³School of Medicine and Population Health, Academic Neurology Unit, University of Sheffield, ⁴Population Health Sciences Institute, Newcastle University, ⁵Neurology Department, University Hospital Wales Cardiff, Cardiff and Vale University Health Board, ⁶Neurology Department, Royal Gwent Hospital Newport, Aneurin Bevan University Health Board, Newport., 7FND Hope International

Purpose: There is increasing evidence that people with Functional/dissociative seizures (pwFDS) have increased mortality and comorbidity risks. We aimed to characterise these using population-level, routinely collected data in Wales.

Method: Using a previously validated algorithm (sensitivity=47.7%, specificity=99.8%), within the SAIL Databank, we identified people with FDS (pwFDS) in Wales diagnosed between 2003 and 2023. We matched (deprivation, age and sex) each pwFDS to three cases: with epilepsy and without FDS (epilepsy cohort); and without epilepsy or FDS (non-seizure comparators). We compared socioeconomic measures, mortality, comorbidities and healthcare utilisation in pwFDS, people with Epilepsy (pwE), and non-seizure comparators.

Results: There were 2857 pwFDS (8571 people in both epilepsy and non-seizure comparator cohorts). 75% of pwFDS were female, 29% had epilepsy, and 27% were from the most deprived area (quintile). For the FDS, epilepsy, and non-seizure comparator cohorts: 76%, 53% and 28% had a common mental illness; 10%, 7% and 1.2% had a severe mental illness; 28%, 26%, and 57% were currently working; 35%, 23%, and 7% had long-term sickness.

11%, 18%, and 6% of the FDS, epilepsy and non-seizure comparator cohorts died during the study. Corresponding mortality hazard ratios, for the FDS and epilepsy cohorts (when compared to non-seizure comparators) were: 2.0 (95%CI=1.7–2.4) and 2.4 (95%CI=2.2–2.7). When adjusted for common and serious mental health disorders the trend for higher mortality hazard ratios remained: HR= 2.0 (95%CI=1.7–2.3) and 3.5 (95%CI=3.1–3.8). pwFDS and pwE were more likely to die of: external, neurological or mental health causes when compared to people without seizure disorders.

pwFDS, pwE and people with both epilepsy and FDS were estimated to have 3.8, 2.8 and 6.0 the costs of non-seizure comparators in terms of hospital admissions, emergency department attendance and outpatient appointments.

Significance: People with FDS have significant higher rates of psychiatric comorbidities, unemployment, mortality and healthcare utilisation when compared to age, sex and deprivation matched comparators. Mortality hazard ratios remained elevated for people with FDS even when adjusting for psychiatric comorbidities. It is important for healthcare professionals and service planners to recognise the burden of FDS. Further work is necessary to understand the causes of increased mortality and to prioritise treatments.

Vulnerability factors for non-epileptic seizures in patients with epilepsy – a retrospective cross-sectional study

Benjamin Sacks, Bonnie Chow, Akihiro Koreki, Rohan Kandasamy, Mahinda Yogarajah

National Hospital For Neurology & Neurosurgery

Background: Functional seizures occur in approximately 5–20% of people with epilepsy, a prevalence substantially higher than the general population. The reasons for this co-occurrence remain unclear and may relate to psychiatric comorbidity, medication exposure, or disease-specific vulnerability factors.

Methods: We compared patients with a confirmed dual diagnosis of epilepsy and NES (n=131) with a control group of patients with epilepsy alone (n=131) treated at the National Hospital for Neurology & Neurosurgery and the Chalfont Centre for Epilepsy. Demographic and clinical characteristics were described, and differences in anti-seizure, anti-psychotic and anti-depressant medication exposure were assessed using propensity score matching and binary logistic regression.

Results: There were no significant differences in seizure frequency, age of epilepsy onset and age at first anti-epileptic medication between groups. Abnormal MRI scans (p=<0.001) and epileptiform EEGs (p=0.007) were significantly correlated with the epilepsy only group. Females were significantly over-represented in the dual diagnosis group (73% vs 54%, p=0.001). The dual diagnosis group had significantly higher rates of psychological trauma (15% vs 5%, p=0.012) and mood disorders (76% vs 55%, p=<0.001). No significant anti-seizure medication associations were identified in either group. Antipsychotic prescriptions were significantly lower in the dual diagnosis group, compared to the epilepsy only group with an odds ratio of 0.21 [0.05 - 0.89] (p=0.034) after correction for medication indication & psychiatric comorbidities.

Discussion: In this analysis, dual diagnosis was associated with female sex & history of mood or anxiety disorders. They appeared to have a lower incidence of focal epilepsy & abnormal, however, we hypothesise that this represents selection bias. It is reassuring to note that no anti-seizure medications are associated with the development of functional seizures in epileptic patients. In this study, antipsychotics were a protective factor against the development of functional seizures in patients with epilepsy. In a predictive processing model of functional neurological disorders, dopamine codes the misattribution of salience to otherwise benign stimuli. Our results in this study, where patients with epilepsy who received dopamine blocking agents had a lower incidence of functional seizures, are consistent with this model.

Impaired cerebrovascular reactivity to carbon dioxide indicates cerebral vasomotor dysfunction in patients with late onset unprovoked seizures and epilepsy

Josephine Mayer^1,2,3, Rehan Junejo^2,4, Helen Shantsila^1,2, Laura Bonnett¹, Gregory Lip^1,2, Tony Marson^1,3

¹University Of Liverpool, ²Liverpool Centre for Cardiovascular Sciences, ³The Walton Centre, ⁴Manchester Metropolitan University

Background: Late-onset unprovoked seizures and epilepsy (LOUE) is associated with an increased risk of stroke. Cerebrovascular reactivity to carbon dioxide (CVR CO₂) is used to index cerebrovascular health and cerebral vasomotor function. Impaired CVR CO₂ suggests a brain vulnerability to ischaemic events. We sought to investigate cerebrovascular health in LOUE; we hypothesised that LOUE have lower CVR CO₂ compared to controls, indicating reduced cerebral vasodilatory reserve and vasomotor dysfunction to explain stroke risk. Methods: Thirty LOUE participants without an identified cause were recruited from a tertiary Neurology centre (age = 60 ± 9 [mean ± standard deviation] years) and were compared to twenty-one hypertensive (HTN; 62 ± 8 years) and twenty-one healthy (59 ± 9 years) controls. Participants with prior stroke were excluded. Transcranial doppler recorded middle cerebral artery blood velocity (MCAVm) at rest (five minutes) and during step increase (4 minutes) and decrease (2 minutes) in end tidal CO₂(PETCO₂) with 5% CO₂ administration and hyperventilation. Cerebrovascular conductance index (CVCi) was defined as ratio of MCAVm and mean arterial pressure (MAP). CVR CO₂ was calculated as the linear slope for MCAVm and CVCi versus PETCO₂. QRisk3 score (a validated score for 10-year risk of myocardial infarction and stroke) was calculated for each participant.

Results: Baseline MCAVm and CVCi were lower in LOUE (59.69 ± 12.89 cm.s−1; 0.55 ± 0.13 cm.s−1.mmHg−1) and HTN (59.22 ± 8.70 cm.s−1, 0.54 ± 0.10 cm.s−1.mmHg−1 ) versus healthy (64.64 ± 9.53 cm.s−1, 0.622 ± 0.14 cm.s−1.mmHg−1 ) but were not significantly different. MCAVm and CVCi CVR CO₂ were lower in LOUE (1.37 ± 0.43 cm.s−1, 0.012 ± 0.004 cm.s−1.mmHg−1) than HTN (1.49 ± 0.33 cm.s−1, 0.013 ±0.004 cm.s−1.mmHg−1) and healthy (1.68 ± 0.3 cm.s−1 [p = 0.015; one-way ANOVA], 0.015 ± 0.005 cm.s−1.mmHg−1 [p = 0.02]). Post-hoc analysis revealed significant differences between LOUE and healthy controls (p < 0.015). Stepwise multiple regression identified LOUE, increasing age and chronic kidney disease as statistically significant predictors of reduced MCAVm CVR CO₂ and CVCi CVR CO₂ . QRisk3 score was higher (indicating increased risk of vascular events) in LOUE and HTN compared to healthy controls (median (IQR) 14.2 (11.1), 15.4 (10.6), 9.0 (8.6); p=0.031 respectively).

Conclusion: LOUE was associated with impaired CVR CO₂ and elevated QRisk3 score compared to healthy controls. Vascular risk factors and cerebral vasomotor dysfunction may contribute to stroke risk in this group and may be a treatment target to reduce stroke risk.

Network structure of epilepsy and SUDEP-related risk in a real-world digital self-assessment cohort

Jake Ahern^1,2, Sammy Ashby³, Ben Donovan³, Peter Hannon⁴, Lance Watkins^2,5,6, Richard Laugharne^2,10, Brendan Mclean^2,7,8, Rohit Shankar^2,8, John Terry^2,9

¹University Of Birmingham, ²CIDER, University of Plymouth, ³SUDEP Action, ⁴Suvo Limited, ⁵University of South Wales, ⁶Mental Health and Learning Disabilities Service Group, Swansea Bay University Health Board, ⁷Cornwall Partnership NHS Foundation Trust, ⁸Neurology Department, Royal Cornwall Hospitals NHS Trust, ⁹Neuronostics Ltd., ¹⁰Department of Intellectual Disability Neuropsychiatry, Research Team, Cornwall Partnership NHS Foundation Trust

Background: Sudden unexpected death in epilepsy (SUDEP) and epilepsy related mortality risk is multifactorial, dynamic, and spans seizure control, mental health, substance use, and medication and healthcare access. Here, the structure of epilepsy and SUDEP-related risk factors captured by EpSMon (an epilepsy self-assessment risk app) is characterized using network analysis. We determine whether the digital self-assessment data contains clinically meaningful risk structure.

Methods: For each risk factor captured by EpSMon, multivariable mixed-effects logistic regression models estimated pairwise associations with all other variables. A directed, weighted network was constructed from associations after false discovery rate correction and backbone extraction. Network community structure, node centrality, bridging factors, and the directed subnetwork of pathways leading to worsening generalised tonic-clonic seizures (GTCS) were analysed.

Results: The final cohort comprised 337 users contributing 1569 self-assessments (median 4 assessments; mean age 37 years; 68% female). Network analysis revealed five stable risk communities corresponding to seizure severity, mental health, substance use, healthcare utilisation, and comorbid medical conditions. Anxiety and depression were the most broadly influential predictors of other risk factors. Substance use variables were the most strongly predicted nodes in the network. Nocturnal seizures were a prominent predictor of worsening GTCS after multivariable adjustment; other seizure-related factors contributed through indirect pathways.

Conclusion: Epilepsy and SUDEP-related risk factors captured by routine digital self-assessment form a structured system with clinically interpretable communities, distinct functional roles, and indirect pathways to convulsive seizure deterioration. These findings are hypothesis-generating and support the prospective evaluation of more dynamic approaches to digital risk assessment in epilepsy. Validation in independent cohorts and co-design with patients and clinicians are required before these structural findings can inform clinical tools.

Characteristics and themes of pregnancy-related SUDEP: a registry-based case series using the Epilepsy Deaths Register.

Jiwon Kim¹, Alex Grundmann^2,3, Ben Donovan⁴, Dr Rhys Thomas^2,3

¹University Hospital Of North Tees, ²Translational and Clinical Research institute, Newcastle University, ³Royal Victoria Infirmary, ⁴SUDEP Action

Background: Pregnancy is a high-risk period for women with epilepsy, associated with adverse outcomes, including sudden unexpected death in epilepsy (SUDEP). National guidelines emphasise effective risk communication, specialist-led care, and optimisation of anti-seizure medication (ASM). However, real-world adherence to these standards remains unclear.

Aim: To identify recurring themes in pregnancy-related SUDEP and assess adherence to guideline-recommended care.

Methods: We conducted a retrospective analysis of pregnancy-related SUDEP cases from the SUDEP Action Epilepsy Deaths Register (2013–2025), which contains data derived from third-party reports provided by bereaved contacts. Quantitative analysis assessed adherence to guideline-recommended care domains where sufficient information was available, and qualitative analysis identified recurring themes in clinical management and risk communication.

Results: Thirteen pregnancy-related deaths were identified, all consistent with definite or probable SUDEP. Median age at death was 25 (range 17-37). The majority were cohabiting (85%), antepartum (85%), found at home (92%) and found prone (54%). Adherence to epilepsy care standards in pregnancy was variable, particularly in the domain of risk communication and awareness. Among 5 assessable cases, specifically referring to SUDEP risk communication, 4 cases did not meet the guideline recommendation and 1 case partially met it. The most recurrent theme from the narrative data, emerging in 9 out of 13 cases, was limited communication and awareness of SUDEP and pregnancy-related risks. Challenges surrounding ASM management were identified, including medication changes in the month prior to death (8/11), concerns about ASM (4/13) and increasing seizure frequency during pregnancy or following ASM changes (5/13). Most individuals were under a form of specialist care (11/12), had seen a specialist in the last 12 months (9/11) and prescribed ASM (9/11).

Conclusion: Despite the limitation of third-party derived data being susceptible to recall or reporting bias, these pregnancy-related SUDEP cases highlight potential areas for improvement in risk communication and medication management. Most individuals were under specialist care, prescribed ASM and recently reviewed, suggesting pregnancy-related SUDEP may occur even among women engaged with specialist services.

A System-Wide Approach to SUDEP Prevention: Implementation of a Safety Checklist and Workforce Training Programme in South Yorkshire

Anita Winter¹, Ben Donovan², Jane Hanna²

¹NHS South Yorkshire ICB, 2SUDEP Action

Background: Over 1,000 epilepsy-related deaths occur annually in the UK, with mortality rates around three times higher in people with epilepsy than the general population. Sudden Unexpected Death in Epilepsy (SUDEP) is a significant and potentially preventable cause of premature mortality, particularly among people with a learning disability and autistic people. Learning from the South Yorkshire LeDeR Programme and the NHS England STEP TOGETHER – Mind the Gap epilepsy benchmarking report identified variation in SUDEP awareness, inconsistent risk discussions and limited use of structured safety planning.

Aim: To improve SUDEP awareness, standardise risk assessment, and support consistent seizure safety planning through workforce training and implementation of the SUDEP & Seizure Safety Checklist.

Methods: South Yorkshire ICB commissioned SUDEP Action to deliver a SUDEP & Seizure Safety Programme comprising multi-sector SUDEP awareness training, promotion of the adult and children’s SUDEP & Seizure Safety Checklists, and development of an accessible electronic SUDEP leaflet. Nine 90-minute training sessions were delivered between June 2025 and March 2026 using the ECHO model, incorporating clinical expertise and lived experience. Evaluation used a mixed-methods approach, combining quantitative pre- and post-training surveys with qualitative feedback to assess knowledge, confidence and intended practice change.

Results: The programme engaged 1,135 participants across health, social care, education and VCSE sectors, demonstrating strong system-wide engagement and attracting interest beyond South Yorkshire.

Evaluation demonstrated measurable improvements in self-rated knowledge and confidence. On a 1–7 scale, where 1 represented the highest level of knowledge/confidence, mean scores improved across all measures: knowledge of SUDEP (4.4 to 2.9), awareness of modifiable risk factors (4.5 to 3.0), awareness of good practice resources (4.6 to 2.9), and knowledge of good practice following a sudden epilepsy-related death (4.6 to 3.0). The proportion of respondents rating themselves within the top three categories increased from 28% pre-training to 71% post-training.

Qualitative feedback highlighted increased confidence in discussing SUDEP, awareness of risk-reduction strategies, and improved understanding of how to use the checklist to support person-centred conversations, shared decision-making and safety planning. SUDEP Action also reported increased clinician and organisational registrations for the SUDEP & Seizure Safety Checklists, providing evidence of engagement with structured risk-reduction tools.

Conclusion: This programme demonstrates an evidence-informed, system-wide approach to reducing SUDEP risk. Combining ECHO-based training with practical risk-reduction tools improved workforce knowledge, confidence and engagement with seizure safety planning. Early findings suggest a scalable model for embedding consistent, person-centred epilepsy safety practices across health and care systems.

Learning from Prevention of Future Death Reports in Epilepsy

Julia Stirling, Ben Donovan, Jane Hanna

SUDEP Action

Introduction: At least 21 epilepsy-related deaths occur each week in the UK and young adults have the highest relative risk of epilepsy-related death, particularly from SUDEP. Up to 80% of deaths in young adults are thought to be preventable through improved epilepsy care. Prevention of Future Deaths (PFD) reports offer clear insights into failures in epilepsy care that increase risk but represent only the tip of the iceberg. Nevertheless, they are a red-flag for the true scale of preventable harm.

Coroners have a duty to report where deaths could be prevented, but the process is shaped by structural inequalities. NHS Trusts are routinely legally represented, while, due to cost, bereaved families rarely are. This imbalance affects the evidence heard and learning captured. SUDEP Action’s free, family centred casework service helps address this gap, ensuring over 70 families a year are supported through complex investigations and inquests.

Methodology: A retrospective qualitative analysis was conducted with the following complimentary sources of information around learning from epilepsy-related deaths:

- Notes from SUDEP Action’s casework service

Six PFD reports since 2024 - Charlie Marriage, Andrew Ewin Ripp, Amber Walker, David Compton, Paul Nash, and John Fisher,

- Clive Treacey’s Independent Review

Key themes were drawn out independently by two researchers prior to further analysis.

Results: A cross-cutting theme across all deaths was a systemic failure to communicate with patients about their person-centred risk including risk of SUDEP. Furthermore, analysis highlighted consistent failures in epilepsy care including:

- delays in accessing regular and emergency medications

- appointment delays

- poor discharge information

- failures in primary care and pharmacy systems.

Conclusions: Findings of this study echo concerns that have been being voiced for over two decades. Key issues around person-centred communication of risk, access to medications and epilepsy support, and systematic learning from deaths, can be traced back to the Prevent21 “Time to Listen” consensus. Despite evidence from past leading to present, many issues continue to be left unaddressed, causing preventable risks to persist and putting people with epilepsy at risk of harm and potential premature mortality.

Furthermore, learning from deaths is still hampered by inconsistent use of Royal College of Pathologists guidelines and misattributed causes of death. The Hillsborough inspired Public Authority Accountability Bill would transform the PFD system by introducing a statutory duty of candour for public bodies and funded legal support for families at inquest.

Antiseizure Medication Monotherapy and Long-Term Mortality in Epilepsy

Gashirai Mbizvo¹, Glen P. Martin², Matthew Sperrin², Josemir W. Sander³, Iain E. Buchan¹, Gregory Y.H. Lip¹, Anthony G. Marson¹

¹The University Of Liverpool, ²University of Manchester, ³UCL Queen Square Institute of Neurology

Background: People with epilepsy have an increased risk of premature death. Whether long-term mortality differs by initial antiseizure medication (ASM) selection is unclear, as prospective trials are typically underpowered to assess this. We therefore emulated a clinical trial of ASM monotherapy and mortality in newly diagnosed epilepsy using observational data.

Methods: We emulated a target trial using international health data from TriNetX. We assessed patients with newly diagnosed generalised or unclassifiable epilepsy initiating lamotrigine, levetiracetam or valproate, and patients with focal epilepsy initiating lamotrigine, levetiracetam, carbamazepine or lacosamide. Pairwise cohorts were propensity score matched on baseline demographic, clinical, laboratory, medication and healthcare-utilisation covariates. Outcomes were ten-year all-cause death and unexplained death (ICD-10-CM R99). Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). Ten-year absolute risks and numbers needed to treat (NNTs) were derived from Kaplan–Meier survival probabilities.

Results: Among 144,055 patients with generalised or unclassifiable epilepsy, 98,735 initiated levetiracetam, 25,672 valproate and 19,648 lamotrigine. Compared with levetiracetam, lamotrigine was associated with lower hazards of all-cause death (HR 0.642 [CI 0.583-0.707]) and unexplained death (0.519 [0.426-0.632]). Ten-year all-cause mortality was 8.96% with lamotrigine and 13.2% with levetiracetam, corresponding to an NNT of 24; that is, for every 24 patients treated with lamotrigine rather than levetiracetam, one death was prevented over 10 years. Lamotrigine was also associated with lower mortality than valproate, and valproate associated with lower mortality than levetiracetam. For every 38 patients treated with valproate instead of levetiracetam, one death was prevented. Among 41,230 patients with focal epilepsy, 26,713 initiated levetiracetam, 7,819 lamotrigine, 5,118 carbamazepine and 1,580 lacosamide. Lamotrigine and carbamazepine did not differ. Compared with levetiracetam or lacosamide, lamotrigine and carbamazepine were associated with 40.0-49.5% lower hazards of all-cause death and 44.7-68.4% lower hazards of unexplained death. For every 18 patients treated with lamotrigine instead of levetiracetam, one death was prevented. The corresponding figure was 22 for carbamazepine against levetiracetam.

Conclusions: Initial ASM choice may have important implications for long-term survival in epilepsy. Lamotrigine had the lowest mortality hazards and should remain a preferred first-line treatment. By contrast, levetiracetam was the most frequently initiated ASM, yet was associated with higher mortality hazards than nearly all comparators. This is concerning given the marked global shift towards levetiracetam use. Clinicians should be cautious about defaulting to levetiracetam as initial monotherapy when appropriate alternatives are available. Lacosamide may also be a less favourable initial treatment when long-term mortality is considered.

Recognising Ictal Asystole: New Seizure semiology in established epilepsy

Naseem Al Salihi¹, Khalid Hamandi²

¹Department of Neurology, University Hospital of Wales, ²The Welsh Epilepsy Centre, Department of Neurology, University Hospital of Wales

Background: Ictal asystole (IA) is a recognised manifestation of epileptic seizures, most commonly seen in temporal or insula epilepsies. It may present as a new seizure semiology associated with sudden collapse and severe injuries, and may contribute to sudden unexpected death in epilepsy (SUDEP). Therefore, early recognition is essential.

Case presentation: We present four cases of ictal asystole captured during pre-surgical video EEG telemetry and routine follow-up.

Case 1: A 58-year-old woman with right temporal lobe epilepsy for 13 years presented with recurrent collapses occurring approximately every two months. Pre-surgical video EEG telemetry admission demonstrated ictal asystole lasting 8 seconds.

Case 2: A 38-year-old man with known right parietal dysembryoplastic neuroepithelial tumour (DNET) subtotal resection at the age of 7 and drug-resistant epilepsy presented with intermittent syncopal episodes. Pre-surgical video EEG detected bradycardia and syncope during one of the episodes. An implantable loop recorder confirmed ictal asystole lasting 19 seconds. He underwent resective epilepsy surgery with dramatic improvement in seizure frequency from more than 20 seizures per day to fewer than one seizure per week.

Case 3: A 73-year-old woman with right temporal lobe epilepsy and hippocampal sclerosis since age of 18 years developed a change in seizure semiology, notably recurrent collapses resulting in bone fractures. An Implantable loop recorder identified ictal bradyarrhythmia/asystole.

Case 4: A 41-year-old man with left temporal lobe epilepsy presented after an unexplained fall and loss of consciousness with no recollection of events. Pre-surgical video EEG telemetry captured ictal asystole lasting 20 seconds.

Results: All patients were treated with permanent pacemakers due to the length of asystole and risk of future injury or fatal asystole. Case 4 had a leadless pacemaker due to his relatively young age. All patients no longer had episodes of collapse and continued their usual epilepsy follow-up.

Conclusion: A recent history of change in seizure type, with initial focal onset, followed by sudden collapse without bilateral tonic-clonic movements, was in keeping with the subsequently recorded asystole, and such a seizure pattern should prompt consideration of this phenomenon and investigation with telemetry or long-term loop recorder. Management of ictal asystole with permanent pacemakers is balanced against the risk-benefit of long-term pacemaker insertion and future lead complications.

32 - 38: Paediatrics

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From brain to heart: an update on the phenotypic spectrum of SCN1B-related diseases

Lucrezia Piccicacchi¹, Sopio Gverdtsiteli², Ingrid Scheffer³, Aeby Alec⁴, Nour Elkhateeb⁵, Laila Selim⁶, Dan Roden⁷, Gaetan Lesca⁸, Eleni Panagiotakaki⁸, Luca Bergonzini⁹, Mehran Beiraghi Toosi¹⁰, Damien Lederer¹¹, Alan Bayat², Niels Matthiesen¹², Konrad Platzer¹³, Sebastian Ortiz², Marina Trivisano¹⁴, Guido Rubboli², Elena Gardella², Rikke Steensbjerre Møller²

¹NHS Grampian , ²Danish Epilepsy Centre , ³Florey Institute of Neuroscience and Mental Health, ⁴Hôpital Universitaire de Bruxelles, ⁵Great Ormond Street Hospital , ⁶Cairo University Hospital, ⁷Vanderbilt University, ⁸Université de Lyon, ⁹Università di Bologna, ¹⁰Mashhad University of Medical Sciences, ¹¹Institut de Pathologie et de Génétique, Charleroi (IPG), ¹²Aarhus University Hospital, ¹³Institute of Human Genetics, University of Leipzig Medical Center, ¹⁴Bambino Gesù Children’s Hospital, IRCCS

SCN1B encodes for the regulatory beta 1 subunit of voltage gated sodium channels, expressed in multiple tissues, including brain and heart. Variants in SCN1B are associated with epilepsy and cardiac conduction disease. Here, we present an overview of the phenotypic spectrum of SCN1B, focusing on epilepsy and cardiac features. We gathered genetic, clinical and electrophysiological data on individuals with pathogenic and likely pathogenic variants in SCN1B through a literature review and international collaboration.

We identified 27 pathogenic/likely pathogenic variants in SCN1B in 127 individuals. Seizures were present in 87% of individuals, 94% had febrile seizures and 39 % had an epilepsy syndrome. Less than 20% of individuals had cardiac investigations and in 58 % of those tested cardiac pathology was identified. Cardiac disease included arrhythmias (71 %), heart failure (21 %), cardiomyopathy (28 %) and structural heart disease (28 %). Brugada syndrome was identified in three individuals from a SCN1B p.(Trp179*) family.

For the highly recurrent SCN1B p.(Arg85His), we identified 24 individuals, from 13 unrelated families. Seizures were present in 79 % of individuals, with 68 % having febrile seizures. An epilepsy syndrome diagnosis was present in 36 %, including GEFS+ (n=4), EIDEE (n=1) and Dravet-like (n=1) in heterozygotes and Dravet-syndrome (n=1) in a homozygous individual. Cardiac disease was identified in 29 %; however, only 37 % of individuals had appropriate investigations.

Here, we confirm the phenotypic heterogeneity of SCN1B variants and highlight a lack of cardiac follow-up in individuals with a pathogenic SCN1B variant, despite documented cases of arrhythmias, including Brugada syndrome, as well as cardiomyopathy and structural heart disease. Furthermore, we report co-existing cardiac and epilepsy phenotypes in several individuals with SCN1B R85H. Further characterisation of cardiac phenotypes in individuals with SCN1B will ensure appropriate counselling of families on management and prognosis, particularly around the risk of sudden cardiac death.

When Epilepsy Takes an Unexpected Turn: Adult Presentation of Mosaic SMC1A-Related Epilepsy

Mohamed Taha¹, Saul Crandon², Colette Mallon¹, Sharon Mulhern³, Natasha Fullerton⁴, Joseph Symonds⁵, Claire Gall¹

¹Department of Neurology, Institute of neurological sciences, NHSGGC, ²Department of Clinical Neurophysiology, Institute of neurological sciences, NHSGGC, ³Department of Clinical Neuropsychology, Institute of neurological sciences, NHSGGC, ⁴Department of Neuroradiology, Institute of neurological sciences, NHSGGC, ⁵Department of Paediatrics Neuroscience, Royal hospital for children, NHSGGC

Introduction: Refractory seizure clusters after a long period of seizure freedom in individuals with an established diagnosis of epilepsy, with no prior history of drug-resistant epilepsy, should prompt a thorough review of the underlying aetiology of epilepsy. This case highlights an unusual presentation of SMC1A-related epilepsy.

Case Presentation: We report a 25-year-old woman living with epilepsy diagnosed at age 16 years, after two unprovoked bilateral tonic-clonic seizures from waking. She has established diagnosis of childhood attention deficit disorder and dyspraxia. She remained seizure-free on Levetiracetam for eight years. In 2023, she developed abrupt recurrent seizure clusters presenting as focal to bilateral tonic-clonic seizures, focal motor seizures with impaired consciousness, and focal non-motor with impaired consciousness seizures. Clusters were often, but not exclusively, perimenstrual and led to repeated emergency department and intensive care admissions for status epilepticus despite escalation to adjuvant Lamotrigine, Lacosamide and Clobazam, with rescue Midazolam and repeated phenytoin loading.

Investigations: Pseudo-refractory causes, CNS infection, autoimmune encephalitis, metabolic disorders, mitochondrial disease and structural lesions were excluded. MRI brain showed disproportionate early volume loss, prominent Virchow-Robin spaces and a non-specific right frontal T2/FLAIR signal abnormality. Repeated EEGs demonstrated bifrontal high-amplitude slowing; five days video telemetry also showed runs of 1 Hz frontally dominant spike-and-slow-wave discharges prominent during sleep. Interictal FDG-PET showed relative bifrontal hypometabolism without convincing lateralisation. Chromosomal microarray, karyotype, mitochondrial gene testing and a 104-gene Scottish epilepsy panel were unrevealing. Review in a neuropaediatric-led genetic epilepsy clinic identified the combination of female sex, neurodevelopmental history and prominent afebrile seizure clustering as suggestive of SMC1A-related epilepsy. Additional testing identified a mosaic pathogenic SMC1A variant, c.3540C>A p.(Cys1180Ter), detected at reduced levels in blood and confirmed in saliva, predicted to introduce a premature stop codon. SMC1A loss-of-function variants typically cause female-predominant developmental and epileptic encephalopathy with early-onset drug-resistant cluster seizures; mosaicism may explain later presentation and milder cognitive features.

Management and outcome: Care was coordinated by adult epilepsy, neurophysiology, neuropsychology, neuroradiology, clinical genetics and neuropaediatric teams. Sodium Valproate was introduced with counselling and second-opinion review, producing a marked reduction in seizure burden, including a prolonged admission-free period. Neuropsychology demonstrated borderline premorbid function with stable impairments in memory, attention, executive function and visuospatial processing over time.

Conclusion: SMC1A-related epilepsy may present to adult neurologists as late-onset refractory seizure clusters after years of apparent stability. Recognition of specific genetic causes can guide early appropriate management, and help patients and families understand and live well with SMC1A-related epilepsy.

Lessons Learned from a Regional Whole Genome Sequencing Pathway for Epilepsy Patients in the West Midlands: A Genomic Practitioner-Led Approach

Larisa Trower¹, Karen Cross¹, Aung Saw², Amitav Parida³, Shanika Samarasekera², Mary O’Driscoll1

¹West Midlands Regional Clinical Genetics Service, Birmingham Health Partners, Birmingham Women’s and Children’s Hospital NHS Foundation Trust, ²Department of Neurology, University Hospital Birmingham NHS Foundation Trust, ³Department of Paediatric Neurology, Birmingham Children’s Hospital

Introduction: Over the last few decades, genomic testing has transformed epilepsy care from a syndrome-based approach to one focused on precision medicine. However, despite the National Health Service (NHS) being the first healthcare system worldwide to incorporate whole genome sequencing (WGS) into routine clinical care, equitable and efficient access to WGS remains a challenge. In 2024, a genomic practitioner-led pathway was introduced across the West Midlands region to improve access to WGS. This study describes the key lessons learned from this two-year regional pathway.

Methods: Data were collected prospectively by Genomic Practitioners between August 2024 and May 2026. Patient demographics, referral sources, indications, age at symptom onset, type of test requested, and test results were recorded. Results were reviewed by a multidisciplinary team, including neurologists and clinical geneticists.

Findings: A total of 304 patients were referred to the service; 160 samples were processed. Both adult and paediatric patients with seizure onset before two years of age and suspected epilepsy syndromes and/or additional clinical features (such as intellectual disability) were included. In keeping with NICE guideline (NG217), the main indication for referral was the presence of additional clinical features (71%; 215/304), followed by seizure onset before two years of age (26%; 80/304).

At the time of analysis, 119 results were available. The overall diagnostic yield was 32% (38/119). The highest diagnostic yield was observed in patients undergoing trio testing (21/38; 55%), compared with duo (6/38; 16%) and singleton (11/38; 29%).

A multiple-gene panel approach enhanced diagnostic yield, with most positive results obtained when the intellectual disability panel (R29) was added to the early-onset syndromic epilepsy panel (R59) (21/38; 55%), compared with R59 alone (4/38; 11%). Dravet syndrome associated with SCN1A variants was the most common diagnosis (5/38; 13%), followed by Tuberous Sclerosis associated with TSC1 variants (2/38; 5%).

The pathway demonstrated strong patient engagement, reflected by a low did-not-attend (DNA) rate of 6% (17/304) and a low dropout rate of 5% (16/304). The mean turnaround time from referral to completion of consent was 60 days.

Conclusion: The Genomic Practitioner-led WGS pathway significantly improved service efficiency by minimising incomplete referrals and reducing demands on senior clinicians’ time. Trio testing combined with multiple-gene panel analysis proved to be the most effective testing strategy. Genetic diagnoses led to changes in clinical management in 22% of patients (8/38). All patients benefited through access to condition-specific support groups, research opportunities, and information relevant to reproductive decision.

Completeness and consistency of seizure and epilepsy classification in infant medical records: Comparisons against ILAE criteria within the eLIXIR South London cohort

Jacqueline Nonweiler¹, Emma Casey¹, Despoina Mandelenaki², Sushma Goyal², Charlotte Tye¹, Michael Absoud¹, Sarah Aldridge²

¹Department of Psychology, King’s College London, ²Newcomen Neurodevelopmental Centre, Children’s Neurosciences, Evelina London Hospital,

Background: The ILAE framework classifies epilepsy across three levels: seizure type, epilepsy type, and syndrome (Scheffer 2017; Fisher 2017), with dedicated definitions for syndromes of neonatal and infantile onset (Zuberi 2022). Accurate, complete classification of seizures informs management, prognosis, and family counselling, and supports continuity across services. Although documentation in routine clinical practice is likely incomplete or inconsistent, few efforts have examined classification quality specifically in infant-onset seizures, where syndrome recognition is most prognostically consequential.

Aims: To assess the completeness, use of current terminology, and consistency of seizure and epilepsy documentation in infant medical records against current ILAE criteria.

Methods: Within the eLIXIR cohort, medical records of infants (aged <36 months) ascertained at first-instance EEG and subsequent epilepsy diagnosis (between 2021-2023) were reviewed. Documentation was assessed for: (i) completeness: whether seizure type, epilepsy type, and syndrome were each recorded; (ii) clinical ILAE classifications as noted by a consultant neurophysiologist and (iii) EEG reported classification of seizure activity. Analyses were descriptive.

Expected Results: Of n = 305 infants having EEGs, 15% (n = 46) received an epilepsy diagnosis. Presenting seizure type was documented in 90% of epilepsy diagnosed infants (n = 42), epilepsy type in 10% (n = 5) and syndrome in 10% of those with epilepsy diagnosis (n = 5); all three levels were reported only in 4% of cases (n = 2). Paediatric neurologists’ comparisons with EEG reported seizure findings are compared to medical record reports.

Anticipated Conclusions: Classification of infant-onset seizures in routine records was frequently incomplete and variably consistent with ILAE standards, and more detailed in EEG reports which are not accessible via routine electronic medical records. Findings support structured documentation (e.g. classification proformas), targeted training, and emphasis on syndrome-level diagnosis to improve prognostic communication. Suggestions and implications for clinical care, including possible AI epilepsy classification, are considered.

Developmental and educational outcomes in infants with suspected seizures: Evidence from the eLIXIR Study

Jacqueline Nonweiler¹, Emma Casey¹, Despoina Mandelenaki², Sushma Goyal², Sarah Aldridge², Charlotte Tye¹, Michael Absoud²

¹King’s College London, ²Newcomen Neurodevelopmental Centre, Children’s Neurosciences, Evelina London Hospital

Background: Epilepsy incidence peaks in the first year of life, and infant-onset seizures carry a high risk of adverse neurodevelopment. Existing cohorts typically report cognitive or developmental outcomes but rarely capture educational placement, despite this being the functional outcome most salient to families and education services. First-instance EEG, identifiable through routinely collected electronic health records, provides a consistent and early ascertainment point that enables longitudinal tracking of medical and educational outcomes across a broad clinical spectrum.

Aims: To characterise infants suspected of seizures at first-instance EEG and to examine associations between early clinical features and later developmental trajectories and educational placements.

Methods: Infants were identified within eLIXIR (Early Life Cross-Linkage in Research, Born in South London), a pseudonymised linkage of routinely collected maternity, neonatal, and child health records from Guy’s and St Thomas’ and King’s College Hospital NHS Foundation Trusts, serving a large, diverse, urban population. Retrospective review of electronic health records was conducted for infants aged under 36 months undergoing first-instance EEG. Extracted variables include age at seizure onset, predominant seizure type, history of status epilepticus, and aetiological classification per ILAE criteria. Outcomes were developmental status and educational placement; for the primary analysis, placement was dichotomised as mainstream without support versus any additional educational support. Associations were assessed using chi-square and Fisher’s exact tests as appropriate. Records with missing outcome data were compared with complete records on baseline features to assess potential ascertainment bias.

Expected Results: We report developmentally typical, impaired, and unknown proportions for n = 305 infants, alongside educational placement where available. Status epilepticus, predominant seizure type, and younger age at onset were most strongly associated with developmental delay and specialist school placement. Missing data analysis indicated comparable baseline features between groups.

Anticipated Conclusions: In this infant cohort, younger age at first seizure and history of status epilepticus were most strongly associated with developmental delay and requirement for additional educational support. Reporting educational placement alongside developmental data offers a practical, meaningful outcome description that is under-represented in the infant epilepsy literature, with implications for early counselling, service planning, and resource allocation for families requiring additional support.

Expanding the UK Epilepsy and Pregnancy Register to Capture Child Neurodevelopmental Outcomes

Ellie Preece¹, Matthew Bluett-Duncan¹, John Craig², Craig Heath³, Beth Irwin², Graeme Sills⁴, Ngawai Moss⁵, Victoria Taylor¹, Kathryn Burrell¹, Rebecca Bromley¹

¹University of Manchester, ²Belfast Health and Social Care Trust, ³NHS Greater Glasgow and Clyde, ⁴University of Glasgow, ⁵Queen Mary University of London

Background: Pregnancy pharmacovigilance and initiatives regarding antiseizure medications (ASMs) have predominantly focused surveillance on infant congenital anomaly outcomes, with less routine investigation of neurodevelopmental outcomes. Due to this, there are large knowledge gaps pertaining to the child neurodevelopmental outcomes for even relatively widely used monotherapy ASMs and polytherapy combinations. A series of studies have been undertaken in preparation for adapting the traditional pregnancy register methodology to incorporate routine longer-term neurodevelopmental follow-up for the UK Epilepsy and Pregnancy Register (UKEPR). The results of the 12-month child screening outcomes from these studies are presented here.

Methods: Women were recruited during pregnancy and provided health and pregnancy information prospectively. Post-birth child health and demographic information was collected through an expert-developed questionnaire. Child neurodevelopment was assessed using the parental completed Ages and Stages, 3rd Edition (ASQ-3) and the 12-month ASQ-3 outcomes are presented here.

Results: A total of 341 children were included in this analysis. Exposure groups comprised lamotrigine (LTG) monotherapy (n=107), levetiracetam (LEV) monotherapy (n=76), other monotherapies (n=31), polytherapy (n=86), and no ASM exposure (n=41). Across the total cohort, the proportion of children scoring within the typical developmental range was 88.3% (n = 301) for communication, 63.5% (n= 216) for gross motor, 70.9% (n= 241) for fine motor, 66.2% (n= 225) for problem-solving, and 78.3% (n= 267) for personal-social skills. Among those exposed to polytherapy, the proportions in the typical developmental range were 89.5% (n=77) for communication, 60.5% (n= 52) for gross motor, 66.3% (n=57) for fine motor, 58.1% (n=50) for problem-solving, and 79.1% (n=68) for personal-social skills.

Overall, 44.1% (n=152) of children scored at least 1 standard deviation (SD) below the mean in two or more developmental domains. Continued follow-up beyond 12 months of age is needed to better characterise the risk profiles of commonly used ASMs in pregnancy.

Conclusions: Follow-up through 24 months of age will enable delineation of ASM-specific outcomes following prenatal ASM exposure. The LIFETIME Framework is feasible for neurodevelopmental follow-up and provides a standardised approach which can be integrated into pregnancy pharmacovigilance initiatives worldwide.

Development of transition clinic for epilepsy patients moving from paediatric to adult services

Erin Lilley, Russell Hewett

Institute Of Neurological Sciences, Glasgow

Transition is a period of planned and structured multidisciplinary review between both paediatric and adult teams with the aim of optimising the care and treatment of young people with epilepsy as they move from children’s to adult services.

In 2025, 37 young adults in NHS Greater Glasgow and Clyde were transitioned from paediatric care to adult service over 6 clinics. The epilepsy team saw a need to improve the pathway for transition clinics. In the previous year, loss to follow-up with the team resulted in patients experiencing missed reviews, delays in treatment, poorer outcomes and increased exposure to risks of harm.

The pathway improvement involved:

1. A set proforma for clinical information transfer prepared by the paediatric service.

2. Changing the location of the transition clinic from the paediatric to the adult hospital.

3. The adult rather than the paediatric Neurologist to lead the transition appointment.

By following a pathway the epilepsy team were able to streamline transition appointment allowing for patient centred approach to care with the ultimate aim of improving patient outcomes.

The adult epilepsy team also developed two questionnaires targeting the young adults and carers to support the development of transition clinic:

1. The primary function of the first was to guide the initial conversations between the patient and their new adult neurologist.

They were asked to prioritise from 1st to 4th in level of importance:

a) Discussion with regard to current medication

b) Discussion with regards to seizure frequency

c) Discussion of longer term planning

d) To meet the adult epilepsy neurologist and epilepsy nurse

The top priority in 53% of the respondents was to meet the team. 47% consider longer term planning as the most popular second priority choice.

2. Feedback on the clinic appointment was also sought through a secondary questionnaire. This quantitative research approach allowed clinicians to adapt treatment plan for patients next appointment within Neurology department..

The adaptation of the transition pathway follows ‘SIGN Epilepsies in children and young people: investigative procedures and management’ suggestions that healthcare professionals should consider the use of a planned, structured, educational approach directed at both patients and carers, to help prepare young people with epilepsy for the move to adult healthcare services.

References: Epilepsies in children and young people: investigative procedures and management (revised June 2026) SIGN 159 – A national clinic guideline

39 - 70: Pharmacological & Surgical Treatment

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Barriers and enablers to antiseizure medication adherence in children with epilepsy: a qualitative study.

Eric Amankona Abrefa Kyeremaa¹, Andy Stewart², Caroline Smith³, Charlotte Lawthom⁴, Majed Alorabi¹, Meera Naran⁵, Sion Scott³, David Wright¹

¹University Of Leicester, ²Desitin Pharma Ltd, ³University of East Anglia , ⁴Aneurin Bevan University Health Board, ⁵Patient and Public Involvement Lead

Background: Antiseizure medications (ASMs) help to control seizures in about 70% of people with epilepsy [1]; however, up to 79% of children with epilepsy do not take their ASMs as prescribed [2]. Although a range of interventions have been developed to improve ASM adherence, evidence for their effectiveness in paediatric epilepsy is limited [3].

Aim: The aim of this study is to explore the barriers and enablers to ASM adherence in children with epilepsy and their carers to inform the development of a tailored intervention.

Method: A qualitative study was conducted between November 2025 and February 2026 using semi-structured interviews among children with epilepsy aged 5 to 12 years and their carers. Participants were recruited using maximum variation sampling through epilepsy charities. Interviews were conducted on Microsoft Teams lasting 35 to 84 minutes. Data were analysed using reflective thematic analysis in NVivo 14, with attention to both child and carer perspectives.

Results: Ten interviews were conducted; three with carers only and seven with children and their carers. Four main themes emerged from the analysis which were; medication-related beliefs and experiences, organisation of medicine management, physical and formulation related challenges and the role of social and professional support. While children were primarily concerned about medication formulation, particularly taste, parents were more concerned about medication side effects and reported that establishing routines supported adherence. Children with recognised learning disabilities additionally expressed concerns about the colour of their medication.

Discussion/Conclusion: This study highlights the importance of prescribing child-appropriate formulations for child with epilepsy. Healthcare professionals (HCPs) should proactively identify and address formulation-related challenges to support adherence. HCPs should prioritise clear communication about treatment expectations, address concerns about efficacy and adverse effects particularly when seizure is uncontrolled. Prescribers should consider specifying particular brands or formulations to minimise unintended switching which may affect medication adherence.

References

1. World Health Organization. Epilepsy. 2024 [cited 2026 29/03/2026]; Available from: https://www.who.int/news-room/fact-sheets/detail/epilepsy.

2. Malek, N., C.A. Heath, and J. Greene, A review of medication adherence in people with epilepsy. Acta Neurol Scand, 2017. 135(5): p. 507-515.

3. Kangwal, C., et al., Interventions to promote medication adherence among children with epilepsy: An integrative review. Journal of Pediatric Nursing, 2024. 78: p. e51-e58.

Effectiveness and Safety of Cannabidiol in Adult Patients with Lennox-Gastaut Syndrome: A Post hoc Analysis of Phase 3 and Open-Label Extension Data

Matt Callaghan¹, Kishan Vyas², Teresa Greco³, Miranda Harrison², Simona Lattanzi⁴

¹Jazz Pharmaceuticals, ²Jazz Pharmaceuticals, UK Ltd., ³Jazz Pharmaceuticals, Inc., Gentium Srl, ⁴Department of Experimental and Clinical Medicine, Neurological Clinic, Marche Polytechnic University

Purpose: The randomised controlled trials (RCTs) of highly purified cannabidiol (CBD; Epidyolex® [EU]/Epidiolex® [US], 100 mg/mL oral solution) in patients with Lennox-Gastaut syndrome (LGS) reflected mixed-age populations, including paediatric patients. Analysing adult data from the pooled phase 3 RCTs (NCT02224560, NCT02224690) and their open-label extension (OLE; NCT02224573) allows the evaluation of CBD effectiveness and safety specifically in adults with LGS.

Method: This post hoc analysis included adults (≥18 years at randomisation) in the RCTs (RCT Set; 10 or 20 mg/kg/day CBD [pooled], or placebo), and those who continued in the OLE (OLE/Safety Set). Baseline characteristics, demographics, efficacy, and safety data were analysed at RCT/OLE baselines and ends (RCT Week 14, OLE Week 156) using descriptive statistics. This exploratory analysis was not intended to compare CBD versus placebo.

Results: The RCT and OLE sets, respectively, included 125 and 116 adults (49% and 48% male; median 8 prior and 3 current antiseizure medications). Median (Q1, Q3) age was 24.8 (20.5, 31.5) and 25.2 (20.7, 32.3) years; baseline 28-day drop-seizure frequency was 59.7 (25.4, 101.0) and 58.8 (24.0, 97.5). One- and 3-year OLE retention rates were, respectively, 80% (95% CI: 72, 86) and 70% (60, 77). In the pooled CBD group (N=74), median (Q1, Q3) drop- and total-seizure frequency reductions from baseline to RCT end were, respectively, -33.9% (-59.6, 8.6) and -31.6% (-54.5, -1.4); overall OLE-end reductions were -68.8% (-84.8, -40.7) and -64.6% (-80.6, -37.0). Response (≥50% reduction) for drop and total seizures was seen in 29% and 31% of patients in the CBD group at RCT end. Most frequent adverse events in the Safety Set were diarrhoea (51%), convulsion (37%), pyrexia (28%), and somnolence (28%).

Conclusions: This descriptive post hoc analysis supports the effectiveness and tolerability of CBD for adults with LGS. The safety profile was consistent with previous studies.

Funding: Jazz Pharmaceuticals, Inc.

First presented at EEC 2026 (Vyas et al. [2026]. Abstract 415).

Use of Fenfluramine and Cannabidiol in daily practice: An update of a retrospective analysis of German prescription claims

Felix von Podewils¹, Milka Pringsheim^2,3, Claudio Schiener⁴, Elian Amani⁴, Manuela Molzan⁵, Viraj Pindoria⁶, Luis Möckel⁵, Iryna Leunikava⁵

¹Universitätsmedizin Greifswald, Klinik und Poliklinik für Neurologie, Epilepsiezentrum, ²Schön Klinik Vogtareuth, Neuropädiatrie/Epilepsizentrum, ³Deutsches Herzzentrum München, Klinik für Kinderkardiologie und angeborene Herzfehler, ⁴Insight Health, Waldems-Esch, ⁵UCB, ⁶UCB

Introduction: Fenfluramine (FFA) and cannabidiol (CBD [in conjunction with clobazam]) are indicated for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) as add-on therapies for patients ≥2 years old in Germany. A retrospective prescription claims analysis reported first evidence of the use of FFA and CBD in patients with LGS or DS in Germany. The present data are an update of this analysis with a greater sample size and a longer follow-up period.

Methods: Prescription claims from December 2020 until October 2024 were analysed covering 64 million statutorily health-insured patients. Date of first FFA or CBD prescription was the index date. DS group: patients with stiripentol and without felbamate or rufinamide. Group LGS: felbamate or rufinamide and without stiripentol. Excluded patients: patients who received CBD and everolismus or vigabatrin. Patient characteristics, change in prior and concomitant antiseizure medications (co-ASMs) were analysed.

Results: A total of 494 patients who received FFA (mean age±SD [standard deviation] 14.8±13.9 years; 35.2% female; 39.1% male) and 1,509 patients who received CBD (18.5±16.1 years; 36.3% female; 38.9% male) were identified. Of these, 70 FFA (17.1±13.6 years) and 238 CBD (17.7±13.4 years) receiving patients were assigned to LGS and 108 FFA (12.7±14.8 years) and 87 CBD (14.9±13.3 years) patients were assigned to DS. Remaining 316 FFA and 1,184 CBD receiving patients could not be assigned to LGS or DS based on available data. For FFA patients with 1, 2, and 3 years of pre-index data, mean number±SD of ASMs received pre-index were 3.2±1.6 (median 3.0; n=443), 3.5±1.6 (3.0; n=304), 3.6±1.6 (4.0; n=214), and for CBD patients, 2.7±1.6 (3.0; n=1,231), 2.8±1.7 (3.0; n=793) and 2.9±1.8 (3.0; n=463), respectively. In the total FFA population, reductions in mean number of co-ASM prescriptions of 11%, 17% and 38% were observed for the periods 15-180, 181-365 and 366-546 days post-index relative to prior ASM prescriptions in the reference pre-index period of −180 to −15 days (Table 1). In those treated with CBD, the number of co-ASMs decreased by 8%, 9% and 24% for the respective periods versus the reference period. Reduction of co-ASMs was strongest in LGS patients compared to DS patients treated with FFA.

Conclusions: the reduction of co-ASM prescriptions was numerically higher in FFA patients, especially in the LGS group.

UCB-funded

Association of Fenfluramine Treatment and Everyday Executive Functioning in Adult Patients With Lennox-Gastaut Syndrome

Delphine Breuillard, Kelly Knupp, Adam Strzelczyk, Danielle M. Andrade, Patrick Healy, Jayne Abraham, Clare Makepeace, Amélie Lothe, Rima Nabbout

¹Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Université de Paris Cité, ²University of Colorado, Anschutz Medical Campus, ³Goethe University Frankfurt, Epilepsy Center Frankfurt Rhine-Main, University Medicine Frankfurt, ⁴Institute of Medical Science, University of Toronto, ⁵UCB, ⁶UCB, ⁷UCB, ⁸Reference Centre for Rare Epilepsies, Necker Enfants Malades Hospital, APHP, Member of the European Reference Network (ERN) EpiCARE, ⁹Institut Imagine, U 1163, 10Université Paris Cité

Rational: A previous post hoc analysis of the fenfluramine phase 3 randomized controlled trial (RCT; NCT03355209) was performed to evaluate everyday executive function (EEF) by Behavior Rating Inventory of Executive Functioning®-Adult Version (BRIEF®-A) and demonstrated improvement in patients (pts) aged 18-35y with LGS. In this post hoc analysis, we describe fenfluramine-associated changes in EEF by BRIEF®-A scores in patients from this RCT and its open-label extension (OLE; final database lock).

Methods: Patients with LGS (2–35 years) were randomized (14-week RCT, NCT03355209) to fenfluramine 0.7 mg/kg/d (maximum 26 mg/d), 0.2 mg/kg/d, or placebo; then, could enter the OLE (fenfluramine 0.2 mg/kg/d flexibly titrated up to 0.7 mg/kg/d).

Patients (18–35 years) with caregiver-completed baseline and RCT end-of-study (EOS; Day 99) BRIEF®-A were included in RCT analyses; OLE analyses included patients with BRIEF®-A at RCT baseline and OLE Month 12. Clinically meaningful improvement/worsening (Reliable Change Index≥90%/≥80%) in median BRIEF®-A T-scores (Behavioral Regulation Index [BRI], Metacognition Index [MI], Global Executive Composite [GEC]), changes in T≥65 patient frequency, and Spearman’s correlations between change in seizures associated with a fall and T-scores were analyzed.

Results: RCT and OLE data from 67 (fenfluramine [0.7 mg/kg/d, n=18; 0.2 mg/kg/d, n=24]; placebo, n=25) and 41 adults with LGS, respectively, were included.

On GEC, percentage of fenfluramine -treated patients with T≥65 at RCT baseline ranged from 36%–56%. In fenfluramine groups, percentage of patients with T≥65 numerically decreased from baseline to RCT EOS on MI (fenfluramine 0.2: 54%–33%; fenfluramine 0.7: 67%–56%) and GEC (fenfluramine 0.2: 50%–33%; fenfluramine 0.7: 56%–50%) but numerically increased in the placebo group (MI: 44%–52%; GEC: 36%–52%). In the OLE, percentage of patients with T ≥65 treated with fenfluramine <0.3 mg/kg/d numerically decreased on BRI and GEC (26%–11%; 47%–32%); a decrease in percentage of patients was also observed with fenfluramine ≥0.5 mg/kg/d on GEC (25%–0%). Median changes in T-scores for all BRIEF®-A Indexes/Composite indicated improvement or no change in RCT fenfluramine and OLE groups and worsened in the placebo group. Correlations between change in frequency of seizures associated with a fall and BRIEF®-A Indexes/Composite were negligible to weak (RCT: −0.232 to 0.024; OLE: −0.239 to −0.206).

Conclusion: Adults with LGS treated with fenfluramine had clinically meaningful EEF improvements during a 14-week RCT and its 12-month OLE. Reductions in seizures associated with a fall and EEF improvements were partially independent of each other.

UCB-funded

Bexicaserin for Seizure Treatment in Developmental and Epileptic Encephalopathies: Interim Analysis of an Expanded Access Program for Participants on Treatment for up to 2 Years

Caitlin Sylvia¹, Shikha Polega¹, Nadine Knowles¹, Randall Kaye², Henrik Loft¹, Tolga Uz¹

¹H. Lundbeck A/S, ²Longboard Pharmaceuticals (now a part of H. Lundbeck A/S)

Objectives: Developmental and epileptic encephalopathies (DEEs) are the most severe epilepsies, characterized by treatment-resistant seizures, frequent epileptiform activity, and developmental slowing or regression [1]. The clinical trial program for bexicaserin – an investigational, highly selective superagonist of the 5-hydroxytryptamine type 2C (5-HT2C) receptor – includes the first regulatory-endorsed study design to enroll patients with any type of DEE in a single trial. Bexicaserin was well tolerated in the Phase 1b/2a PACIFIC randomized controlled trial (RCT) and 12-month open-label extension (OLE), with a favorable safety profile and similar countable motor seizure frequency reductions in participants with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), and other DEEs (DEE Other). The expanded access program (EAP) provides further access to bexicaserin in this underserved population. Here, we report an interim analysis of the EAP in the group of participants who rolled over from the OLE and have received up to 2 years of bexicaserin treatment (OLE + EAP).

Methods: This analysis included participants who completed the PACIFIC RCT and OLE and enrolled in the EAP. Data reflect staggered entry into the EAP and/or staggered seizure diary data entry.

Results: Of 38 participants who completed the PACIFIC OLE, 36 enrolled immediately in the EAP and continued their maintenance dosing regimen. At approximately 18 months’ treatment (OLE + EAP), 1 participant was lost to follow-up and 1 participant was reported as deceased (unrelated to study drug). The remaining 34 EAP participants on bexicaserin received approximately 24 months of treatment. Compared with the safety profile during the OLE, no new safety signals were observed. Relative to RCT baseline, the median percentage change in countable motor seizure frequency was −60.2% (n=30) at ~18 months and −53.7% (n=17) at ~24 months. Seizure frequency reductions were seen across participant subgroups at ~18 months (DS, −73.0% [n=3]; LGS, −51.2% [n=12]; DEE Other, −61.5% [n=15]) and ~24 months of treatment (DS, −100% [n=1]; LGS, −37.1% [n=6]; DEE Other, −73% [n=10]).

Conclusions: Bexicaserin continues to exhibit a favorable safety and tolerability profile in participants with a variety of DEEs for up to 2 years of treatment. Comparable reductions in countable motor seizure frequencies between the PACIFIC RCT, OLE, and EAP reinforce the sustainability and consistency of bexicaserin efficacy across DEEs, further validating its progression into Phase 3 trials.

Funding: This study was sponsored by Longboard Pharmaceuticals, Inc., now a part of H. Lundbeck A/S.

Reference: 1. Scheffer I, et al. Epilepsia. 2025;66:1014–1023.

Bexicaserin Seizure Treatment in Developmental and Epileptic Encephalopathies: Response Over Time and Responder Rates in the Phase 1b/2a PACIFIC Trial Open-Label Extension

David G. Vossler¹, Dennis Dlugos², Kate Riney^3,4, Nadine Knowles⁵, Tolga Uz⁶, Randall Kaye⁷, Sidsel Jensen⁶, Shikha Polega⁶

¹University of Washington School of Medicine, ²Children’s Hospital of Philadelphia, ³Queensland Children’s Hospital, ⁴University of Queensland, ⁵H. Lundbeck A/S, ⁶H. Lundbeck A/S, ⁷Longboard Pharmaceuticals (now part of H. Lundbeck A/S)

Objectives: In the Phase 1b/2a PACIFIC randomized controlled trial (RCT) and its 12-month open-label extension (OLE), bexicaserin – an investigational, highly selective 5-hydroxytryptamine type 2C (5-HT2C) receptor superagonist – was well tolerated, had a favorable safety profile, and demonstrated reductions in countable motor seizure frequency that included clinically meaningful responder rates in participants with a variety of developmental and epileptic encephalopathies (DEEs; Dravet syndrome, Lennox-Gastaut syndrome, and other DEEs). This post-hoc analysis evaluated the effect of bexicaserin on countable motor seizure frequency reductions over time in the RCT and OLE, as well as the sustainability of responses for up to 1 year, including ≥50%, ≥75%, and ≥90% responder rates.

Methods:Participants were aged 12–65 years and had a diagnosis of DEE; they could enter the OLE after completing the RCT. Baseline seizure frequency was determined from the 28-day screening period before initiation of bexicaserin or placebo. The median percentage change from baseline in countable motor seizure frequency was assessed during the RCT (bexicaserin vs placebo; Weeks 1–2/1–6/1–8/total RCT) and OLE (bexicaserin only; Month(s) 1/1–6/1–9/total OLE). The sustainability of response was evaluated as proportions of participants with ≥50%, ≥75%, and ≥90% reductions in seizure frequency during the OLE.

Results:Median percentage change from baseline in countable motor seizure frequency with bexicaserin (n=35) diverged from placebo (n=9) by Weeks 1–2 (−49.6% vs 1.5%) and was sustained for Weeks 1–6 (−58.0% vs −24.3%), Weeks 1–8 (−60.5% vs −22.0%), and over the entire RCT (−59.8% vs −17.4%). In the OLE (n=40), seizure frequency reductions were maintained through 1 year (−59.3%). Responder rates (≥50%, ≥75%, ≥90%) with bexicaserin during the RCT (60%, 31.4%, 11.4%) were maintained in the OLE (55%, 40%, 17.5%); placebo administration in the RCT only yielded a ≥50% responder rate in 33% (n=3/9) of participants, with no ≥75% or ≥90% responders.

Conclusions: Bexicaserin showed a rapid onset in countable motor seizure frequency reductions across DEEs that was sustained over time, with consistent responder rates throughout the RCT and OLE. The data indicate no loss of long-term therapeutic benefit with bexicaserin, reinforcing the rationale for the ongoing global Phase 3 DEEp program.

Funding: This study was sponsored by Longboard Pharmaceuticals, Inc., now a part of H. Lundbeck A/S.

Unintended consequences? Potential harms associated with the prescribing of midazolam as a rescue medication for people with epilepsy

Phil Tittensor^1,2, Zygimantas Puras⁴, Charlotte Hodgetts³, Sally-Ann Remnant⁵, Rohit Shankar³

¹Royal Wolverhampton NHS Trust, ²University of Wolverhampton, ³University of Plymouth, ⁴Southern Trust SHSCT, ⁵University Hospitals Sussex NHS Foundation Trust

Purpose: Midazolam is a short-acting benzodiazepine used in the emergency management of seizures mainly within the community. Despite its clinical effectiveness, there is limited literature specifically examining misuse, diversion, and harm related to midazolam prescribed for epilepsy. Community prescribing of midazolam presents unique challenges, as administration is frequently undertaken by caregivers or family members rather than healthcare professionals.

Method: We undertook a literature review of 70 papers for existing safeguards for midazolam misuse and developed an initial survey to gather commentary using a modified DELPHI method. From this review, a pilot questionnaire was developed and distributed to 80 members of the Epilepsy Nurses Association (ESNA) at their conference in June 2026. The results informed a final questionnaire, which was sent to epilepsy specialist nurses, pharmacists, doctors, service leads and safeguarding leads, from organisations including the International League Against Epilepsy - ILAE British Branch, ESNA, Cornwall Intellectual Disabilities Equitable Research network (CIDER), and NHS Trusts. Ethical approval was obtained from the University of Plymouth.

Results: Clinician perspectives for the potential of misuse, diversion, and harm associated with midazolam prescriptions intended for epilepsy-related use will be analysed. We will identify high-risk prescribing patterns, opportunities for inappropriate self-administration, and improvements in the detection of patients who obtain midazolam frequently or administer midazolam outside of recommended clinical indications. Final data will be presented at the Scientific Meeting.

Conclusion: Preliminary evidence suggests substantial knowledge gaps and variability in practice surrounding community midazolam use. This study seeks to provide clinician-derived data to inform future guidance, education, and safeguarding measures, with the aim of improving patient safety and reducing preventable harm associated with emergency seizure medication in the community.

Drivers of prescribing decision-making for nasal midazolam spray for the treatment of acute seizures in Sweden

Annabel Bowden¹, Tommy Stödberg^2,3

¹Spire Outcomes Limited, ²Neuropediatric Unit, Department of Women’s and Children’s Health, Karolinska Institutet, ³Department of Pediatric Neurology, Astrid Lindgren Children’s Hospital, Karolinska University Hospital

Purpose: Midazolam is effective in the management of acute seizures; currently available formulations can be difficult to administer, compromising seizure control. This study sought to identify drivers for prescribing a novel, unlicensed, single-dose nasal midazolam spray for the management of acute seizures.

Methods: Healthcare professionals from adult and paediatric centres in Sweden documented their reasons for prescribing a single-dose nasal midazolam spray for the prehospital management of acute seizures and sedation, in cases where rectal or buccal rescue medication had been experienced as inefficient or otherwise problematic. The data, recorded in 2024, consisted of unstructured free text. Analysis focused on cases that specifically referenced epilepsy. Thematic analysis with inductive and deductive coding was used to identify themes and categories in the data. An initial coding framework was developed from a review of literature and patient-reported outcome measures and developed iteratively. MAXQDA software was used to facilitate the thematic analysis.

Results: From 228 records, data were available for 161 patients with reference to an epilepsy diagnosis and/or various phenotypes, etiologies and comorbidities recorded. Nasal midazolam spray 2.5 mg was administered to 61 patients and 5 mg to 100, for the treatment of seizures. The initial coding framework comprised nine parent codes which were refined through the thematic analysis to ten. The most common reason given for prescribing nasal midazolam was mode of administration/method of treatment (n=122, 76%), with prescribers referring to difficulties with buccal administration (e.g. because of issues with drool and mucus), rectal administration or intravenous administration. The second most common reason for prescribing the nasal formulation was the ability to treat seizures effectively (n=105, 65%), with references to prolonged seizures that are difficult to manage, a perception that nasal treatment is most effective, and concerns with Buccolam® (midazolam) oromucosal solution and Stesolid® (rectal diazepam) in the treatment of prolonged seizures. Further reasons for prescribing single-dose nasal midazolam included ease of use (n=30, 19%), side-effects (n=11, 7%), social acceptability/privacy (n=5, 3%) (rectal administration being considered unacceptable) and frequency of use in patients experiencing daily seizures (n=5, 3%).

Conclusions: Despite an inherent selection bias, given all patients had prior difficulties or dissatisfaction with other administration routes, this analysis indicates a preference among prescribers for single-dose nasal midazolam spray over alternatives for the management of acute seizures in some patients, scenarios and semiologies, due to perceived better effectiveness and ease of use. These findings will inform future qualitative research with parents/caregivers.

Does a Short Shelf-Life of Epilepsy Rescue Medications Lead to an Increased Wastage Burden? The Impact of Buccal Midazolam Shelf-Life on UK Patients and Pharmacists

Matthias Koepp¹, Tim Rider², Phil Tittensor³, Ramandeep Sandhu⁴

¹Department of Clinical & Experimental Epilepsy, UCL Queen Square Institute of Neurology, ²The Leeds Road Practice, ³The Royal Wolverhampton NHS Trust, ⁴SDSmyhealthcare GP Federation, West Heath Medical Centre

Background: Unused or partially used medicines are estimated to generate £300 million of waste annually in England, around half of which is considered avoidable. In epilepsy, key buccal midazolam optimisation challenges include medicine wastage and repeat prescribing requirements. Disposal of controlled drugs also creates administrative burden and expense for pharmacies. This market research evaluated the impact of buccal midazolam shelf-life on patients, carers and pharmacists, focusing on wastage, operational burden, patient experience and quality-of-life.

Methods: Patients (n=21) and carers (n=25) completed a 12-question online survey, distributed through Epilepsy Action, assessing experiences with rescue medication and expiry-related concerns. A separate 28-question online survey was completed by UK pharmacists involved in epilepsy rescue medication supply, procurement and demand planning (community pharmacist n=80; primary care network (PCN) pharmacists n=20). Pharmacists were recruited through a specialist market research company using verified healthcare professional panels.

Results: Over the preceding 6 months, 65% (30/46) of patients/carers reported discarding at least one expired unit of rescue medication, with a mean of 2.5 discarded units per patient over 6 months. One in five participants (20%, 9/46) required an emergency prescription due to expired medication, while 13% (6/46) reported being unable to administer medication when needed. Expiry dates also negatively affected wellbeing, with 24% (11/46) reporting stress or anxiety related to medication expiry. Most patients/carers agreed that longer shelf-life would be beneficial (78%, 36/46) and would reduce waste (76%, 35/46). Among pharmacists, 21% of Buccolam units (n=96) and 16% of Epistatus units (n=71) arrived at the pharmacy with ≤6 months remaining shelf-life. Similarly, 25% of Buccolam units (n=76) and 15% of Epistatus units (n=60) dispensed to patients had ≤6 months shelf-life remaining. Disposal of expired-stock contributed additional burden, with 57% (55/96) and 42% (30/71) of pharmacists reporting disposal of Buccolam and Epistatus stock, respectively, within the past 6 months. Pharmacists agreed that extending shelf-life could reduce medicines wastage (94%, 94/100), lost revenue (92%, 92/100) and disposal cost (88%, 88/100).

Conclusion: Short shelf-life of epilepsy rescue medications contributes to avoidable medicine wastage, increased pharmacy and healthcare burden and patient/carer anxiety regarding access to emergency seizure treatment. Extending shelf-life may improve medicines optimisation, reduce operational inefficiencies and support patient confidence and continuity of care. Further evaluation of the socio-economic impact of extended rescue medication shelf-life is warranted to quantify the health-economic and service-level benefits.

Alturix funded this survey-based research. Alturix and all authors participated in the development of this abstract.

Real-World Prescribing Patterns of Buccal Midazolam: Implications for Pack Size and Resource Utilisation

Alison Paterson

Neuraxpharm

Background: Prolonged acute convulsive seizures (PACS) require timely rescue medication to reduce seizure duration and the risk of progression to status epilepticus. In the United Kingdom, two branded buccal midazolam oromucosal solutions are available: Epistatus®, supplied as single syringes, and Buccolam®, supplied in four-syringe packs. Previous Delphi-based modelling of PACS frequency and prescribing suggested that 4 pack Buccolam® was being wastefully prescribed to low risk PACS patients who may be more economically managed using Epistatus® single-unit dispensing and therefore reduce waste. There is limited real-world evidence describing how pack size aligns with prescribing patterns in patients who require multiple rescue doses annually.

Methods: This study describes real-world prescribing of branded buccal midazolam in Scotland, the relationship between dispensed syringe volumes, patient-level utilisation, cost and estimated resource use. Retail pharmacy prescription data were obtained from IQVIA, covering approximately 51% of community pharmacies in Scotland over a 12-month period (May 2024 to April 2025). Metrics included syringes dispensed per patient per year, syringes per prescription, and the distribution of patients receiving three or fewer versus four or more syringes annually. Cost estimates used British National Formulary list prices, applying conservative assumptions due to the absence of dosage-level data

Results: A total of 5,300 prescriptions were analysed, representing 19,926 syringes dispensed across both products. Of these, 28.7% were Buccolam® syringes and 71.3% were Epistatus® syringes. The mean number of Epistatus® syringes dispensed per patient was 7.32 per year, with an average of 3.4 syringes per prescription. Overall, 65.7% of patients receiving Epistatus® were dispensed four or more syringes annually, accounting for 91.3% of all Epistatus® syringes. Patients requiring four or more syringes annually would incur much lower medication costs if prescribed Buccolam® four-syringe packs (£296,391) compared with Epistatus® single syringes (£566,869).

Conclusions: In this real-world Scottish cohort, most Epistatus® single syringes were dispensed to patients requiring four or more rescue doses annually. These findings contrast with prior model-based analyses using six-month time horizons, highlighting the value of real-world prescribing data when evaluating pack size strategies. Resource implications appear sensitive to patient-level demand and pack size. Multi-unit pack formats appear well aligned with the needs of patients requiring higher annual syringe volumes and may support more efficient resource utilisation in this population. Further evaluation across broader UK populations may support evidence-informed prescribing and health-economic decision-making for the community management of PACS.

Drug-Resistant Temporal Lobe Epilepsy Responding To Weekly Pulsed Clobazam Therapy

Amogh Ravi, Sean Slaght

University Hospital Southampton

Benzodiazepines are used in epilepsy as adjunctive anti-seizure medications (ASM), rescue therapy for seizure clusters and status epilepticus, and prophylactically in catamenial epilepsy. The long-term efficacy with regular use is often limited by tolerance. We describe a patient with temporal lobe epilepsy refractory to multiple ASMs who achieved sustained seizure freedom with an unconventional weekly pulsed clobazam regime.

A 19-year-old right-handed woman of normal developmental background and no significant medical history developed her first bilateral tonic-clonic seizure from sleep. Subsequently, she experienced focal impaired awareness seizures characterised by oral automatisms, chewing, lip-smacking, deja-vu, gradual rightward head version which often progressed to bilateral tonic-clonic seizures. Seizures initially occurred at approximately 27-day intervals. Following epilepsy onset, temporary amenorrhoea obscured a suspected catamenial pattern.

Despite treatment with lamotrigine, levetiracetam, lacosamide, pregabalin, perampanel and regular clobazam, seizures remained drug resistant. Clustering was common and frequently resulted in hospital admissions with status epilepticus, responding to intravenous phenytoin.

Investigations for epilepsy surgery demonstrated a normal magnetic resonance imaging (MRI) of her brain. Repeated prolonged video electro-encephalograms failed to capture habitual seizures despite drug reduction but demonstrated inter-ictal left temporal abnormalities. Neuropsychological assessment revealed impaired verbal memory, particularly when compared to her non-verbal memory and impaired naming consistent with dominant temporal lobe dysfunction. A functional MRI confirmed left hemispheric language dominance. FDG-PET demonstrated subtle left temporal hypometabolism within normal statistical limits. The investigations were supportive of a left temporal lobe onset epilepsy but inconclusive of it. A surgical option was not pursued further due risk of post-operative language deficits and uncertain seizure freedom.

The patient trialled a progesterone implant for 6 months with no meaningful effect on seizure control. Reintroduction of clobazam or an increased rescue dose of 30mg when on a regular 10mg dose was effective in abating a cluster of seizures but the response was found to be diminishing after successive months. 6 years after the onset of seizures, patient independently trialled clobazam 20mg once a week alongside maintenance lacosamide. She achieved seizure freedom for over a year on this regime and has even applied for a driving licence.

To our knowledge, this is the first reported case of sustained seizure freedom using a weekly pulsed oral clobazam regime. Intermittent scheduled benzodiazepine administration may reduce tolerance while maintaining anti-seizure efficacy and could represent a novel strategy in selected patients with drug-refractory epilepsy who exhibit transient responsiveness to benzodiazepines. Further investigation of this approach is warranted.

Clinical outcomes following discontinuation of sodium valproate in women of child- bearing age: A retrospective review from NHS Greater Glasgow and Clyde (NHSGGC)

Mya Win¹, Sean MacBride-Stewart², Craig Heath^1,3

¹Department of Neurology, Queen Elizabeth University Hospital, Glasgow., ²Medicines Management Resources, NHS Greater Glasgow and Clyde, Glasgow., ³School of Health and Wellbeing, University of Glasgow.

Introduction: In response to new regulatory measure by the Medicines and Healthcare products Regulatory Agency (MHRA) regarding the use of sodium valproate in women of childbearing potential, women with epilepsy dispensed valproate were recalled and treatment plans reviewed. The aim was to reduce exposure to this teratogenic medicine. However, concerns were raised regarding the impact valproate withdrawal may have on epilepsy control, particularly in women with generalised epilepsy.

Aim: This study aims to describe the clinical outcomes of valproate withdrawal in women of childbearing potential within NHSGGC.

Methods: Patients were identified through Pharmacy Information System (PIS), an administrative dataset containing all community pharmacy dispensed medication within NHSGGC. Adult women were included if they were between the age of 16-54 and had discontinued valproate since 2017. Discontinuation was defined as an absence of prescription for a period of at least 365 days.

We conducted a retrospective case note to obtain key clinical variables including indication for use. Adverse clinical outcomes were considered at the last point of contact and defined as deterioration in seizure control, either by emergence of breakthrough seizures or increase in seizure frequency from baseline, epilepsy related unscheduled care (unplanned emergency appointment with epilepsy service, epilepsy related Emergency Department (ED) attendance or hospital admission), and epilepsy related deaths.

Results: Since March 2017, 94 women discontinued valproate as a result of the MHRA process. Mean age at withdrawal was 35.63 years (SD ±8.69). Mean follow up period was two years. A generalised epilepsy was identified in 42/94 (44.7%). 61/94 (64.9%) had been dispensed valproate for more than ten years. 39/94 (41.5%) had complete seizure freedom within preceding 12 months. At the time of withdrawal, 58/94 (61.7%) women were on at least another adjunctive anti-seizure medication. Deterioration in seizure control was observed in 10/94 (10.6%); 3 patients experienced breakthrough seizures following a mean seizure-free period of 56 months, 2 patients with myoclonic jerks developed generalised tonic-clonic seizures at 10.5 months, and 5 patients experienced >50% increase in seizure frequency. Epilepsy related healthcare encounters were noted in 8/10.

Two deaths were recorded during 2-year follow up, one within a week of valproate withdrawal as a result of SUDEP. The other patient’s cause of death was unknown.

Conclusion: Although in the majority of cases, withdrawal of valproate was undertaken without adverse effects within NHSGGC, it is important that women with epilepsy are counselled regarding the risk of adverse outcomes including SUDEP.

Towards an emulated sequential target trial design of valproate discontinuation: baseline characteristics, hospitalisations and deaths

Sneha Mary George^1,2, Molly Wells³, Georgie Schofield⁴, Hayley Jones⁴, Alan Griffiths, Naheed Tahir, Laura J. Bonnett⁵, Gregory Y. H Lip^2,6, Iain Buchan⁴, Anthony G. Marson^1,7, Glen P. Martin³, Matthew Sperrin³, Gashirai Mbizvo^1,2,7

¹Institute of Systems, Molecular and Integrative Biology, University of Liverpool, ²Liverpool Centre for Cardiovascular Science, University of Liverpool, ³Faculty of Biology, Division of Informatics, Imaging and Data Science, University of Manchester, ⁴Department of Public Health, Policy and Systems, University of Liverpool, ⁵University of Liverpool Department of Biostatistics, Liverpool, ⁶Department of Clinical Medicine, Danish Centre for Health Services Research, Aalborg University, ⁷The Walton Centre NHS Foundation Trust, Liverpool

Background: Valproate is the most effective treatment for generalised epilepsy. Current guidance restricts its use in women of childbearing potential and more recently men aged <55 years also. It is unclear whether those who discontinue valproate will come to harm. This study aims to establish that and develop a tool to predict which the safest drug switches are. Our approach is an emulation of a target trial designed to reproduce the conditions of a randomised controlled trial, thereby minimising bias and allowing more confident causal inferences to be made from the observational data. The study is ongoing. Presented here are steps taken thus far to engineer the data, select covariates, model outcomes, design sequential trials, and involve the public.

Method: Anonymised UK Clinical Practice Research Datalink (CPRD) data were processed using SQL and DuckDB to create a research database linking primary care with mortality, A&E, inpatient, outpatient, pregnancy, and deprivation data. An analysis-ready dataset was used to design a series of emulated target trials each month from 01/01/2013-11/09/2023 (129 trials). Each trial included patients aged 16-54 years with epilepsy and ≥2 valproate prescriptions in the previous 12 months. A directed acyclic graph (DAG), domain knowledge, and public consultation informed baseline covariate selection. These included age, sex, ethnicity, deprivation, seizure frequency, number of antiseizure medications (ASMs), hospitalisations, outpatient neurology attendance, alcohol excess, neurodevelopmental disorders, psychiatric comorbidities, valproate treatment duration, and Charlson Comorbidity Index (CCI). Their distributions were assessed in relation to subsequent hospitalisation and mortality outcomes. A public involvement workshop refined covariates and outcomes.

Result: An 11.5 GB health dataset was engineered, containing 72m consultations, 198m observations, 138m prescriptions. Of 19,357 eligible patients in the first sequential trial, 63.8% were men, 36.2% women. All-cause mortality was higher in patients with alcohol excess, neurodevelopmental disorders, and psychiatric comorbidity compared with those without these conditions (21.0% vs 7.0%, 10.1% vs 7.3%, and 14.4% vs 6.9%, respectively). Mortality also increased with higher ASM use (1: 6.6%; 2: 9.0%; ≥3: 11.9%) and CCI scores (0: 4.6%; 1-3: 11.9%; >3: 29.0%;). All cause hospitalisation was also higher with alcohol excess (91.8% vs 82.0%), psychiatric comorbidity (93.0% vs 80.0%), and increasing ASM use (1: 79.6%, 2: 86.0%, ≥3: 90.3%).

Conclusion: CPRD data can support sequential emulated target trials of valproate discontinuation. Hospitalisation and mortality varied by comorbidity, psychiatric history, alcohol excess and ASM burden. These findings support careful covariate adjustment when estimating discontinuation and treatment switching safety.

The Patient Voice: Valproate, Topiramate and MHRA Regulation

Jane Hanna¹, Professor Ley Sander², Faye Waddams³, Sarah Jones⁴, Rachel Arkell⁵, Elly Nowell¹, Ben Donovan¹, Heather Angus-Leppen⁶

¹SUDEP Action, ²UCL Queen Square Institute of Neurology, ³Crown Prosecution Service, ⁴Royal National Orthopaedic Hospital, ⁵Kent Law School, University of Kent, ⁶University of East London, Royal Free London NHS Foundation Trust, UCL Queen Square Institute of Neurology

Valproate and Topiramate use is increasingly restricted by government regulations, such as those of the MHRA. The views of people with epilepsy and their families affected by these are largely unstudied.

This qualitative project examines the views of 22 people with epilepsy and their families about valproate prescription and restrictions. Themes explored include informed consent, shared decision making, negative consequences of avoiding valproate or topiramate (including SUDEP), missed opportunities and disruption of belief systems.

There were 5/22 deaths in the group and in 13/22 increased seizures and/or serious injuries. All 22 reported significant disruptions in life choices, employment and/or education. Recommendations to align the regulations to human rights and true informed decision making are made.

Cenobamate in the treatment of rare monogenic epilepsies

Ben Waters¹, Alexander Hagan¹, Vivienne Evans², Hester Garratt², Ela Akay², Shan Ellawela², Dr Rhys Thomas^1,2

¹School of Medicine, Newcastle University, ²Department of Neurology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary

Introduction: Cenobamate is a novel antiseizure medication with a dual mechanism of action, involving the inhibition of sodium currents and positive allosteric modulation of GABA-A receptors. In the United Kingdom, cenobamate is currently approved as adjunctive treatment for focal-onset seizures in adults with drug-resistant epilepsy. There is growing recognition of its additional therapeutic role in treating generalised seizures, with cenobamate now approved for both focal and generalised seizures in the United States. The current project aims to evaluate the utility of cenobamate on seizure frequency in rare monogenic epilepsies.

Methods: We conducted a retrospective review of patients with treatment-resistant, monogenic epilepsies being treated with cenobamate between October 2021 and February 2026. Patients were categorised into three groups based on their genetic epilepsy; group 1 (possible indication of cenobamate - TSC and LGS), group 2 (replication of cenobamate efficacy- SCN1A, SCN2A, SCN8A), group 3 (novel use of cenobamate - CHD2, DCX, POLG mitochondrial). Seizure frequency was reported by patients and/or caregivers at follow-up appointment as >25% reduction, >50% reduction, >75% reduction, no change, or worsening of seizures.

Results: Eighteen patients (11 males, 7 females) were identified, with an average age of epilepsy onset of 10 years (12 months - 14 years 6 months). The average age at which cenobamate was initiated was 28 years 5 months (21 years 6 months - 32 years). At the time of initiation, patients were on a median of 3 other anti-seizure medications (range 2-5). If discontinued (n = 7), the average duration of cenobamate treatment was 29 months. The greatest response to cenobamate was seen in group 1 (n = 9) with 56% of participants demonstrating a reduction of >50% in seizure frequency at follow-up appointment, of which 2 patients achieved seizure freedom. Group 2 (n = 6) demonstrated the poorest response to cenobamate with one participant becoming seizure-free and three participants reporting worsening seizure frequency. Group 3 (n = 3) demonstrated varying degrees of seizure reduction.

Discussion: Our findings indicate the potential utility of cenobamate beyond focal-onset seizures, with observed clinical benefit across a spectrum of epilepsy classifications - generalised, focal, mixed, and DEEs. While careful interpretation is required due to the small cohort size, heterogeneous epilepsy phenotypes, incomplete reporting and subjective interpretation of seizure frequency, our findings offer preliminary evidence supporting the use of cenobamate in broader epilepsy populations.

Long-Term Retention of Cenobamate in a Large Single-Centre Cohort of Adults With Drug-Resistant Epilepsy

Luisa Delazer^1,2,3, Isabella Farren^1,2,3, Kazuki Fukuma^1,2, Kajaal Shah⁴, Evelyn Frank⁴, Archie Jaques¹, Rezane Kajashi¹, Dilahxsi Vijayakumar¹, Fei Zhu^1,2, Adolfo Mazzeo^1,2, Thaera Arafat^1,2, Nicholas Fearns^1,2, Sanjeev Rajakulendran^1,2, Simona Balestrini^1,2, Matthias Koepp^1,2, Josemir Sander^1,2,3

¹UCL Queen Square Institute of Neurology, ²National Hospital for Neurology & Neurosurgery, ³Chalfont Centre for Epilepsy, ⁴Pharmacy, National Hospital for Neurology & Neurosurgery

Rationale: Cenobamate (CNB) demonstrated substantial efficacy in drug-resistant epilepsy (DRE), yet large observational studies evaluating long-term retention are scarce. Retention rate is a composite of drug efficacy and tolerability and provides a pragmatic measure of treatment effectiveness in clinical practice. We assessed long-term CNB retention in a large cohort of people attending tertiary epilepsy care centre.

Methods: We prospectively enrolled adults with epilepsy who had failed at least two antiseizure medications (ASMs) at the time of the prescription of CNB at the National Hospital of Neurology and Neurosurgery London at Queen Square and Chalfont sites. We retrospectively reviewed the records of those who were first prescribed CNB between 18 May 2021 and 30 August 2024. Follow-up data were collected up to May 2026. The primary outcome was CNB retention, defined as ongoing CNB therapy at the last available follow-up. Retention was estimated using Kaplan–Meier survival analysis.

Results: A total of 1,037 people were prescribed CNB during the study period. Of these, 1,000 initiated treatment and were included in the analysis. At last follow-up, 774 (77.4%) remained on CNB. Mean treatment duration was 24.9 months (SD 12.9), and median treatment duration was 26.5 months (IQR 16.5–34.7). Kaplan–Meier retention estimates were 89.1% (95% CI 87.2–91.1) at 6 months, 84.8% (82.6–87.1) at 12 months, 81.5% (79.1–84.0) at 18 months, 79.1% (76.6–81.7) at 24 months, 75.5% (72.6–78.5) at 36 months, and 69.3% (62.8–76.5) at 48 months. Among those who discontinued treatment, median time to discontinuation was 6.8 months (IQR 2.0–14.7).

Conclusions: In this large cohort of adults with DRE, CNB demonstrated high long-term treatment retention, with approximately 80% remaining on treatment after 2 years. Median retention was not reached, supporting sustained treatment effectiveness and tolerability in routine clinical practice. Most discontinuations occurred within the first year, suggesting that people who tolerate and benefit from CNB early may be more likely to remain on treatment long term.

Post-Licensing Population Data on Cenobamate Exposure and Mortality in Epilepsy

Isabella Farren^1,2, Luisa Delazer^1,2,3, Kazuki Fukuma^1,2,4, Kai Michael Schubert^1,2,5, Kajal Shah⁶, Katarzyna Saunders², Sanjeev Rajakulendran^1,2,7, Simona Balestrini^1,2,7,8, Josemir Sander^1,2,7,9, Matthias Koepp^1,2,7

¹UCL Institute of Neurology, ²National Hospital of Neurology and Neurosurgery, ³Department of Neurology, Medical University of Innsbruck, ⁴Department of Neurology, National Cerebral and Cardiovascular Center, ⁵Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, ⁶Pharmacy, National Hospital for Neurology & Neurosurger, ⁷Chalfont Centre for Epilepsy, ⁸Neuroscience and Human Genetics Department, Meyer Children’s Hospital IRCCS, ⁹Department of Neurology, West China Hospital, Sichuan University

Purpose: Cenobamate became available for routine clinical use in the UK in 2022. However, post-licensing data on its potential impact on mortality are limited.

Method: As part of routine retention audits of newer antiseizure medications, we identified all individuals who initiated cenobamate within a single tertiary epilepsy service. This provided a denominator-based assessment across the full spectrum of epilepsy severity. Cenobamate exposure was modelled as a time-dependent variable, with only on-treatment time contributing.

Results: A total of 12,737 clinic attendees contributed approximately 36,272 patient-years of follow up. Between March 1, 2022, and March 31, 2026, CNB was prescribed to 1,454 individuals, yielding approximately 2,299 patient years of cenobamate exposure. Eleven deaths occurred during cenobamate treatment (4.78 per 1,000 patient years), compared with 299 deaths during 34,098 patient-years without cenobamate exposure (8.77 per 1,000 patient years), corresponding to an incidence ratio of 0.55 (95% CI, 0.30-0.96; p=0.048).

Conclusion: Although immortal time bias cannot be fully excluded and cause-of-death adjudication was incomplete, these findings are relevant to the discussion of sudden unexpected death in epilepsy (SUDEP). Because SUDEP is intrinsically under-reported and remains a diagnosis of exclusion, all-cause mortality represents a conservative but robust endpoint. Given the dominant contribution of uncontrolled convulsive seizures to SUDEP risk, these post-licensing data raise the critical question of whether potent seizure suppression with cenobamate may translate into a measurable reduction in epilepsy related mortality.

Evaluating the impact of adjunctive cenobamate in the management of patients with drug resistant focal epilepsy- a retrospective real world observational study

Craig Heath, Eleanor Arthur, Yousif Mohamed, Sarah Nichol, Sean MacBride Stewart, Giorgio Di Dato, Stephen Bolan, Alex Marshall, Susan Yule

NHS Greater Glasgow and Clyde

Introduction: Cenobamate (CNB) is the latest anti-seizure medication (ASM) to be licensed in the UK as an adjunctive treatment for adults with focal epilepsy. Clinical trials and expanded access programmes have shown positive results in terms of seizure reduction and retention rates, however further evidence is required to assess the performance of cenobamate in real world practice.

Since approval by the Scottish Medicines Consortium, we have been collecting audit data on all patients receiving cenobamate. Thanks to the unique clinical and administrative data available within NHS GGC, this study has the potential to provide unique insight into this ASM in a complete cohort of patients with treatment resistant epilepsy.

Methods: Patients living with epilepsy (PWE) dispensed CNB within NHS GGC between March 2022 and December 2025 were identified from the Prescribing Information System. Patients with generalised epilepsy and those younger than 18 years old at initiation were excluded.

Key clinical variables were obtained by manual review of patient records. The primary outcome of interest was change in seizure frequency. Secondary outcomes included epilepsy-related admissions, changes in ASMs and healthcare resource utilisation costs.

Results: 290 patients received at least 1 CNB prescription.

Median age of patients at CNB initiation was 40.3 years (IQR 29.8–53.8)

232/290 (80%) had a favourable response - as of most recent point of contact 34/290 (11.7%) patients were seizure free, 137/290 (47.2%) had a greater than 50% reduction in seizure frequency, 61/290 (21.1%) had a less than 50% reduction in seizure frequency. 58/290 (20%) discontinued cenobamate - 40 stopped due to side effects, 11 due to lack of efficacy and the remainder did not cite a specific reason.

Median length of treatment was 542 days (IQR 329 - 846 days), with a median dose of 200mg/d (range 25-400mg/d). median number of previous ASMs was 5 (range 1-22).

4 patients died during the study period (one as a result of SUDEP).

Early analysis suggests a reduction in health care resource utilisation as a result of a decrease in epilepsy-related emergency department (ED) attendances.

Conclusion: These results offer insights for clinicians regarding the real-world utility of CNB in a cohort of patients with drug resistant focal epilepsy. A positive response of 80% in a population of PWE who had previously failed to respond to, on average 5 previous ASMs, and a reduction in health care resource use, highlights that cenobamate should be considered early within this population.

What can existing evidence tell us about treatment decisions after the first antiseizure medication failure in focal epilepsy?

Isaac Egesa^1,2, Gashirai Mbizvo^2,3,4, Richard Emsley⁵, Laura J. Bonnett¹, Anthony G. Marson^2,4, Catrin Tudur Smith¹

¹Department of Health Data Science, Institute of Population Health, University of Liverpool, ²Liverpool Interdisciplinary Neuroscience Centre, University of Liverpool, ³Liverpool Centre for Cardiovascular Science, University of Liverpool, ⁴The Walton Centre NHS Foundation Trust, Liverpool, UK, ⁵Institute of Psychiatry, Psychology and Neuroscience, King’s College London

Background: The first antiseizure medication (ASM) tried in epilepsy often fails because it does not control seizures or causes unacceptable side effects. Clinicians and patients are then faced with a difficult decision about whether to switch or add another ASM, and which ASM to use. We currently do not know which decision is best or what patient characteristics should guide it, despite a growing number of available ASMs.

Aim: To assess whether evidence can inform subsequent treatment decisions after the first ASM failure in focal epilepsy and identify the uncertainties requiring further comparative evaluation.

Methods: We synthesised four sources of evidence: a systematic review of randomised trials of subsequent ASM effectiveness after first ASM failure; a scoping review of prognostic factors; treatment pathways observed in Standard and Newer Antiepileptic Drug (SANAD) trials; and a survey of UK epilepsy clinicians. We examined what each source contributed to three decisions: why treatment failed, whether to switch or add treatment, and which ASM to select next.

Results: Six trials involving 961 patients evaluated subsequent ASMs after the first failed. The trials were small, heterogeneous and did not support one ASM over the other or switch over add-on strategy to be superior for seizure remission. Prognostic factors focused mainly on factors assessed at diagnosis rather at the point of first ASM failure. Understanding the reason for first ASM failure could help in inform subsequent treatment decisions. In SANAD and SANAD II, 38.6% and 31.7% of participants failed their initial ASM and started at least one further ASM. The most frequently selected second ASMs were carbamazepine, lamotrigine and valproate in SANAD, and lamotrigine, levetiracetam and carbamazepine in SANAD II. After failure due to inadequate seizure control, switching versus adding ASM was 60:40 in SANAD and 47:53 in SANAD II. Forty-six UK clinicians also differed in whether they would switch (48.0%) or add (52.0%) treatment, and their preferred next ASM depended on the drug that had failed.

Conclusion: The available evidence shows discrepancies in practice on treatment decisions after first ASM failure. Sequential decisions are poorly supported because trials tend to evaluate a single initial choice in isolation. Future evaluation should instead capture the patient’s whole treatment journey, randomise successive decisions and tailor them by reason for failure. Existing data can be used to design and test the feasibility of such an approach.

Psychological Predictors of Antiseizure Medication Side Effects: Findings from a Systematic Review and Ongoing Longitudinal Study

Liam Jarvis¹, Adam Noble¹, Rajiv Mohanraj^2,3, Paul Christiansen¹, Saif Ahmed¹, Chris Huntley¹

¹University Of Liverpool, ²University of Manchester, ³Salford Royal Hospital

Background: Antiseizure medications (ASMs) are the cornerstone of epilepsy treatment, yet their benefits are often complicated by adverse effects; ~60% of people with epilepsy (PWE) reporting at least one. While pharmacological factors such as dosage explain some variation in side-effect burden, psychological factors may also contribute. Metacognitive beliefs—beliefs about one’s own thinking—may represent one mechanism. This project comprises two complementary studies: a systematic review of psychological predictors of ASM side effects and an ongoing 9-month longitudinal study testing a theory-driven psychological model.

Methods: Study 1: A PROSPERO-registered review examined psychological factors associated with ASM side effects in adults with epilepsy. SCOPUS and Ovid MEDLINE were searched from 1971 to 2025. Screening, extraction, and risk of bias evaluations were conducted with two reviewers.

Study 2: An ongoing three-wave longitudinal study is testing whether metacognitive beliefs, derived from the Self-Regulatory Executive Function (S-REF) model, predict ASM side effect experience, medication adherence, and healthcare utilisation. Adults with self-reported epilepsy prescribed ≥1 ASM, and significant others, were recruited through a regional NHS epilepsy service and national epilepsy networks. Time 1 measures included epilepsy characteristics, metacognitive beliefs, side-effect burden, adherence, and healthcare utilisation.

Results: Study 1: Forty-three studies met the inclusion criteria, comprising over 31,000 participants and evaluating side effects associated with 24 ASMs. Most were cross-sectional. Side effects were assessed using patient-reported measures (predominantly the Liverpool Adverse Events Profile) or healthcare record review. Although a broad range of psychological factors was examined, these were often poorly defined and rarely theory-driven. Mental health variables (e.g., depression and anxiety) showed the most consistent associations with side-effect burden, with small-to-moderate effects often remaining after adjustment for epilepsy- and treatment-related factors.

Study 2: 723 participants (407 PWE and 316 significant others) have completed the Time 1 assessment. Cross-sectional analyses are underway to test whether metacognitive beliefs explain side-effect burden beyond established demographic, epilepsy, and treatment-related predictors. Preliminary findings will be presented.

Conclusions: This programme of research is the first to systematically synthesise evidence on psychological predictors of ASM side effects while also evaluating a theory-driven model of individual vulnerability. The review identifies mental health as a robust correlate of side-effect burden while highlighting the lack of theory-driven research into underlying psychological mechanisms. Findings from the longitudinal study will provide the first test of whether metacognitive beliefs contribute to ASM side effects in PWE and their significant others, informing psychologically informed side-effect management.

Blown Pupils and a Normal Scan: Severe Carbamazepine Toxicity Mimicking Acute Structural Brain Injury. A case report.

Donald Adjorlolo, Joanna Kitley

University Hospital Southampton NHS Foundation Trust

Background: Severe carbamazepine toxicity is an uncommon but important cause of acute symptomatic seizures and profound neurological dysfunction. Patients may present with coma, absent brainstem reflexes which mimicks acute structural brain injury, however, with normal neuroimaging. Early recognition is essential, as prompt toxin elimination therapy can result in complete neurological recovery.

Case: A previously fit and well 17-year-old male collapsed at home with a generalised tonic-clonic seizure. The seizure did not terminate following 10 mg intravenous (IV) diazepam but ceased after administration of 2 mg IV midazolam. Due to reduced consciousness (Glasgow Coma Scale score of 3), he underwent pre-hospital rapid sequence induction and intubation by the Helicopter Emergency Medical Service.

On arrival, he was noted to have bilaterally dilated pupils. Initial CT brain imaging was normal. Following withdrawal of sedation, neurological examination remained abnormal with persistent coma and absent corneal, gag and cough reflexes, raising concern for severe brainstem dysfunction. Repeat CT brain imaging, CT angiography, MRI brain, MR venography and cerebrospinal fluid analysis were all unremarkable. Electroencephalography showed diffuse encephalopathy without evidence of ongoing epileptiform activity. Nerve conduction studies showed a diffuse large fibre sensorimotor neuropathy affecting both motor and sensory fibres, suggesting a toxic-metabolic process. This was done to evaluate for a peripheral neuromuscular disorder.

Further collateral history identified possible ingestion of carbamazepine prescribed for his sister, who has epilepsy. Serum carbamazepine concentration was 38 mg/L. Treatment with repeated activated charcoal and renal replacement therapy was initiated, resulting in rapid recovery of brainstem reflexes, purposeful motor responses and progressive neurological improvement.

Conclusion: This case highlights severe carbamazepine toxicity as a reversible mimic of acute structural brain injury. Acute symptomatic seizures may be followed by profound but reversible brainstem dysfunction despite normal neuroimaging. Clinicians should consider antiseizure medication toxicity in patients presenting with unexplained coma after seizures, particularly when the neurological examination appears disproportionately severe in relation to neuroimaging findings. Early toxicological evaluation, collateral medication history and prompt initiation of enhanced elimination therapies can be lifesaving and may prevent inappropriate neuroprognostication.

VNS Therapy is Associated with Reduced Severe Disabling Seizure Burden in Children Early in Treatment (3 months) of DRE with Continued Improvement Over 36 Months

J Wheless¹, M Zafar², G Motamedi³, F Babtain⁴, MP Fry⁵, G Giannicola⁶, R El Tahry⁷, G Groepper⁸, TJ O-Brien⁹, P Lyons¹⁰, K Liow¹¹, J O’Flaherty⁶, K Nichol⁶, M Dibue⁶, C Gordon⁶, F Beraldi⁶, A Sen¹², M Boffini⁶, COREVNS Study Group

¹University of Tennessee Health Science Center & Le Bonheur Children’s Hospital, ²Duke University Hospital, ³Medstar Georgetown University Hospital, Department of Neurology, ⁴King Faisal Specialist Hospital and Research Centre, Neurosciences Department, ⁵National Hospital for Neurology and Neurosurgery, Department of Neurosurgery, ⁶LivaNova PLC (or a subsidiary), ⁷Universite Catholique de Louvain, Centre for Refractory Epilepsy, Department of Neurology, Cliniques Universitaires Saint-Luc, and Institute of Neuroscience, ⁸Johannes Kepler University, ⁸Department of Pediatrics and Adolescent Medicine, ⁹epartment of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Department of Neurology, Alfred Hospital, ¹⁰Virginia Comprehensive Epilepsy Program, ¹¹Comprehensive Epilepsy Center, Hawaii Pacific Neuroscience, Hawaii Pacific Neuroscience, University of Hawai’i at Mānoa, John A. Burns School of Medicine, ¹²Oxford Epilepsy Research Group, John Radcliffe Hospital

Purpose: Evaluate the effectiveness and safety of VNS Therapy in children <18 years of age.

Method: The CORE-VNS (NCT03529045) study collected data on seizure and non-seizure outcomes following treatment with VNS Therapy. Participants <18 (children) who received their first VNS Therapy were selected for this analysis. Seizure frequency reduction of defined most severe seizures and patient-described outcome measures (quality of life and quality of sleep) were collected at baseline and at 3, 6, 12, 24, and 36 months.

Results: VNS therapy devices were implanted for the first time into 241 (54% male, 47% female, median age=9 years, median duration of epilepsy = 5.5 years, median number of anti-seizure medications at baseline = 6) paediatric study participants (0-18 years of age). The responder rate (≥50% reduction in seizure frequency over the previous 3 months compared to baseline) for all paediatric participants was 69.1% (all seizures), 76.2% (focal seizures), and 63.3% (generalized seizures). An ≥80% reduction in seizure frequency was also noted in 51.7%, 60.1%, and 46.9%, for all seizures, focal, and generalised, respectively. Freedom from all seizures was reported by 19.7% of paediatric participants at the 36-month study visit and most participant reported either improvement or no change in quality of life. The most commonly reported treatment emergent adverse events included respiratory, thoracic and mediastinal disorders including dysphonia and cough.

Conclusion: This analysis of the CORE-VNS Study represents a large cohort of prospectively gathered paediatric data on the effectiveness of responsive adjunctive VNS therapy for DRE. Seizure reduction was noted, regardless of type, over the course of 36 months and seizure freedom was reported as early as the first 3-month visit. The long-term experience of VNS therapy in paediatric patients demonstrates significant therapeutic promise.

CORE-VNS Study Full Cohort at 36 Months Demonstrates Significant Reduction in Severe Disabling Seizures

A Sen¹, P Kwan², R Verner³, J Wheless⁴, R El Tahry⁵, G Motamedi⁶, F Fahoum⁷, TJ O’Brien², K Keough⁸, J Boggs⁹, A Suller Marti¹⁰, M Zafar¹¹, Dr Rhys Thomas¹², K Liow¹³, M Tzadok¹⁴, P Lyons¹⁵, M Keezer¹⁶, S Baeesa¹⁷, J Valeriano¹⁸, KA Myers¹⁹, F Babtain¹⁷, R Lee²⁰, Y Al Said¹⁷, J Ferreira²¹, K Kotulska²², J O’Flaherty³, C Gordon³, F Beraldi²³, K Eggleston³, K Nichol³, COREVNS Study Group

¹LivaNova PLC (or a subsidiary), London, United Kingdom, ²Oxford Epilepsy Research Group, John Radcliffe Hospital , ³The Alfred Hospital. Monash University and Royal Melbourne Hospital, ⁴University of Tennessee Health Science Center & Le Bonheur Children’s Hospital, ⁵Universite Catholique de Louvain, Centre for Refractory Epilepsy, Department of Neurology, Cliniques Universitaires Saint-Luc, and Institute of Neuroscience, ⁶Medstar Georgetown University Hospital, Department of Neurology, ⁷Medical & Health Sciences, Tel Aviv University; Neurological Institute, Tel Aviv Sourasky Medical Center, ⁸Child Neurology Consultants of Austin, ⁹Comprehensive Epilepsy Center, Wake Forest University, ¹⁰Department of Clinical Neurological Sciences, Department of Pediatrics, Schulich School of Medicine and Dentistry, Western University, ¹¹Duke University Hospital, ¹²Translational and Clinical Research Institute, Newcastle University, Royal Victoria Infirmary Hospital, ¹³Comprehensive Epilepsy Center, Hawaii Pacific Neuroscience, Hawaii Pacific Neuroscience, University of Hawai’i at Mānoa, John A. Burns School of Medicine, ¹⁴Pediatric Neurology Unit, Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel- Hashomer, Sackler Faculty of Medicine, Tel Aviv University, ¹⁵Virginia Comprehensive Epilepsy Program, ¹⁶Universite de Montreal, Department of Neurosciences and School of Public Health, ¹⁷King Faisal Specialist Hospital and Research Centre, Neurosciences Department, ¹⁸Allegheny General Hospital, ¹⁹Research Institute of the McGill University Medical Center, ²⁰Ascension Via Christi Health, ²¹St. Joseph’s Children’s Hospital, School of Medicine, Department of Pediatrics, and Pediatric Neurology, ²²The Children’s Memorial Health Institute, Department of Neurology and Epileptology, ²³Valos, LivaNova Partner CRO

Purpose: In this analysis, we describe how VNS Therapy reduces the frequency of severe seizures that result in loss of consciousness in people receiving their first neuromodulation device.

Method: Participants enrolled in the CORE-VNS (NCT03529045) study who received their first VNS Therapy implant were selected. Seizure frequency changes using the 2017 ILAE classification scheme for each seizure type as well as seizure and non-seizure outcomes and safety were collected. Participants were asked to identify their most disabling seizure type at each visit and report on the severity of that seizure type (which may have changed throughout the study). In this analysis, severe seizures that result in loss-of-consciousness are analysed: Focal Impaired Awareness Motor and Non-motor (FIA-M, FIANM), Focal-to-Bilateral Tonic-Clonic (FBTC), and Generalised Tonic-Clonic (GTC).

Results: Of those meeting criteria, 531 proceeded to first implantation, 526 had at least one post-implantation follow-up visit, and 426 completed the study with at least 36 months of follow-up. At 36 months the median change in FIA-M seizures was -80.1% (95%CI: -90, -66.7), FIA-NM seizures was -94.4% (95%CI:-100, -77.3), FBTC seizures was -95.0% (95%CI: -100, -72.7), and GTC seizures was -84.0% (95%CI: -100, -66.7). The median monthly frequency of GTC seizures decreased from 4.0 (95%CI: 2.3, 6.7) at baseline to 1.00 (95%CI: 0.0, 1.7) at 36 months. Post-ictal severity for the patient’s self-reported “most disabling seizure” also decreased. Finally, participants tended to report less use of rescue medication, the emergency department, and seizure-related hospitalisation in the follow-up. For all participants, n=92/794 (11.6%) reported an adverse event that was causally, possibly, or probably related. Commonly reported adverse events were consistent with the safety profile of VNS Therapy and included dysphonia, dyspnea, and cough.

Conclusion: VNS Therapy reduces the frequency of severe disabling seizures with loss of consciousness, resulting in a reduced risk of serious health sequelae.

Structural morphometry distinguishes vagus nerve stimulation outcomes in individuals with epilepsy

Harry Clifford¹, Sonja Fenske¹, Peter Taylor^1,2,3

¹CNNP Lab, ²Faculty of Medical Sciences, ³UCL Queen Square institute of Neurology

Introduction: Vagus nerve stimulation (VNS) is a commonly used treatment for drug-resistant epilepsy. However, response to VNS is variable, with understanding of this response variability being limited. The vagus afferent network (VagAN), the neural circuits thought to be involved in response to vagal afferents, has been implicated in response prediction in modalities such as diffusion weighted imaging, functional imaging, and neurophysiology. Structural abnormality in the VagAN from T1w MRI has not yet been studied.

Methods: We assessed if VagAN abnormalities, derived from pre-implantation T1w MRI, were associated with VNS response in 92 individuals with epilepsy two-years post-implantation (42 responders, 50 non-responders). We used the first principal component (PC1) from a robust principal component analysis for a variety of region sets trained using 100 healthy controls. We investigated two primary hypotheses. (i) If VagAN regions’ PC1 differentiates response groups, (ii) if other region sets did not differentiate response groups.

Results: Non-responders had significantly higher VagAN PC1 abnormality scores than both responders (r = 0.30, p = 0.008) and controls (r = 0.37, p < 0.005). In contrast, non-VagAN PC1 showed no discriminatory value (r = −0.03, p > 0.05). VagAN outperformed all other region sets.

Significance: Structural abnormality of VagAN was associated with non-response to VNS. This suggests that volume abnormalities in key VNS regions correlate negatively with reduction of seizures. Abnormalities in other regions, such as the non-VagAN region set, were not associated with VNS response. This metric, when combined with other modalities, may be a useful measure to improve the selection of individuals with drug-resistant epilepsy for VNS therapy.

Vagus nerve stimulation in adults in Newcastle: a retrospective notes audit

Alexander Wright-Todd^1,2, Dr Rhys Thomas^2,1, Hester Garratt²

¹Medical School, Newcastle University, ²Newcastle upon Tyne NHS Hospitals NHS Foundation Trust

Introduction: Vagus nerve stimulation therapy is a recognized treatment for drug refractory epilepsy and has been established in the UK for decades. We set out to review our clinical service.

Methods: We used the electronic patient record system to identify patient demographics, to classify their epilepsy and capture change in seizures following VNS implantation. We categorised this a worse, improved (but not seizure free), seizure free and unclear/unascertainable. We looked at patterns of seizures at two and at five years where data were available.

Results: We identified 139 unique patients. As of June 2026, 121 were alive (87%) and 73 were male (52.5%). 57 had an intellectual disability (41%). 94 had focal epilepsy (68%), 27 had DEE (19%) and 16 had GGE (12%), 2 had types of epilepsy that were unable to be determined (1%). The median age of VNS implantation was 30 years old; the youngest patient was 3 years and the oldest 68 years.

10% had seizure aggravation, and 45% were improved; including the 10% who were seizure free. In 45% we could either not identify a seizure change or there was no discernable difference.

VNS peak efficacy was seen at two years – with no significant changes seen between two and five years; noting that 73 people could not be used for the five year analysis: unable to determine original seizure frequency, unable to determine frequency at 5 years, patients deceased, no notes either from time of VNS implant or from after 5 years. Of the 10 with a DEE at five years we saw a 70% improvement (20% unchanged and 10% worse)

Conclusion: Clinical records are commonly used for retrospective analysis but data are frequently captured in a structure that prevents us to analyse the impact of our clinical decisions. For VNS therapy this is regrettable as not only is the treatment invasive, but we need the ability to better select who will and who won’t respond to neuromodulation. The NIHR funded VNS-ALERT randomised clinical trial will seek to report on VNS therapy efficacy and cost efficacy across the UK.

Optimising EASEE^® Device Placement through Integrated multimodal Structural and Functional Imaging, and Electroclinical Modelling

Sherry Liu, Hak Kei (Antonia) Wong, Thomas Jensen, Anna Miserocchi, Mr Andrew Mcevoy, Roman Rodionov, John S Duncan, Meneka K Sidhu

University College London, Institute of Neurology, Department of Epilepsy, Queen Square Institute of Neurology

Introduction: Epilepsy is recognised as a network disorder, in which abnormalities in distributed networks may contribute to seizure generation and propagation. This concept is especially relevant for patients unsuitable for resective surgery, who may benefit from network-level modulation. The EASEE® system is an emerging form of individualized epicranial neuromodulation, with approximately 60% of patients achieving >50% reduction in seizures at 2 years. Optimal device placement remains uncertain in current practice, particularly in individuals with prior resections, in whom the impact of large surgical cavities on stimulation efficacy is poorly understood. We developed a novel approach for optimising EASEE® device placement and report preliminary 6-month outcomes in first four patients, including individuals with previous cerebral resection.

Methods: We developed a workflow integrating 3D-neuroimaging data to guide individualized EASEE® implantation planning using our in-house surgical planning software, EpiNav. Structural lesions, previous resection cavities, and relevant functional abnormalities, including PET and SPECT data were integrated into 3D models with scalp and intracranial EEG data to define the most likely region of seizure generation. A virtual EASEE® electrode simulation model was then created using SimNibs to simulate volume of tissue receiving various levels of stimulation (V/m), with a current of 2 and 4mA, to optimise stimulation of the putative epileptogenic zone, accounting for resection cavities, and differential electrical conductivity.

Results: To date, ten patients underwent EASEE® implantation using this approach, four of which had available 6-month follow up data. 3/4 patients had >50% reduction in seizures, including two patients who had prior resection.

Conclusion: Our preliminary experience suggests that individualized, image-guided EASEE® placement is feasible, including in patients with previous resections. Integrating structural, functional, and electroclinical data may help to optimise electrode positioning, particularly when conventional anatomical targeting is difficult because of prior surgery or complex epileptogenic networks. Early outcomes are encouraging, but larger cohorts and longer follow-up are underway to determine whether this approach improves patient selection, device placement, and seizure outcomes.

SEEG for Delineating the Epileptogenic Zone in Extensive Structural Lesions

Mohammed Elkider, Samden Lhatoo

University of Texas Health Science Center at Houston (UTHealth Houston)

Background: SEEG may be particularly beneficial in patients with extensive structural lesions, such as large focal cortical dysplasia, post-traumatic encephalomalacia, polymicrogyria, or perinatal stroke, because the visible lesion on MRI does not necessarily correspond to the full extent of the epileptogenic zone (EZ).

Methods: We report a 19-year-old right-handed male with drug-resistant focal epilepsy following two intracerebral hemorrhages due to ruptured arteriovenous malformation. He underwent left craniotomy at age six and developed medically refractory epilepsy after recurrent hemorrhage in 2017. MRI demonstrated extensive left parietal, posterior temporal, and occipital encephalomalacia. SEEG implantation sampled temporal, parietal, and occipital regions to define the EZ and perform functional cortical mapping.

Results: Interictal SEEG demonstrated continuous slowing over the left temporal pole, periodic discharges in the left mesial occipital and medial temporo-occipital (lingual) regions, and persistent epileptiform activity involving the left lateral posterior temporal cortex and angular gyrus. Frequent epileptiform discharges were also recorded from the amygdala with propagation to the mesial hippocampus and temporal pole, predominantly during sleep.

Twenty-one electrographic seizures were recorded. Ten originated from the left angular gyrus with early involvement of the left lateral posterior temporal cortex, eight from the medial temporo-occipital (lingual) region, two from the calcarine cortex, and one from the occipital cuneus. Two habitual electroclinical seizures were captured, both characterized by impaired awareness and rightward eye deviation, with one preceded by apnea. In both seizures, ictal onset localized to the left angular gyrus and lateral posterior temporal cortex, followed by spread to the amygdala and mesial hippocampus after 5–6 seconds, excluding the mesial temporal structures as the primary seizure onset zone.

Electrical stimulation of the lingual and calcarine cortices elicited contralateral visual phenomena. Language mapping demonstrated impaired visual naming with posterior basal temporal stimulation, while language, calculation, and working memory were preserved during stimulation of the angular gyrus and lateral posterior temporal cortex. SEEG localized a non-contiguous posterior quadrant EZ involving the left angular gyrus, posterior temporal cortex, lingual gyrus, and cuneus.

Conclusions: This case demonstrates the value of SEEG in patients with extensive post-hemorrhagic encephalomalacia, where MRI alone may not accurately define the epileptogenic network. SEEG excluded mesial temporal seizure onset, identified a multifocal posterior quadrant EZ, and provided essential functional mapping that predicted complete right homonymous hemianopia if the entire EZ were resected. These findings directly informed surgical decision-making by balancing the likelihood of seizure freedom against anticipated visual morbidity.

Role of MEG in SEEG Implantation Planning

Mohammed Elkider, Pedro Balaguera, Abdulrahman Alwaki

University of Texas Health Science Center at Houston (UTHealth Houston)

Background: Magnetoencephalography (MEG) is an important non-invasive functional imaging modality in the presurgical evaluation of drug-resistant epilepsy. In addition to localizing interictal epileptiform activity, MEG can inform stereoelectroencephalography (SEEG) implantation by identifying epileptogenic regions that may not be evident on MRI or scalp EEG. Incorporating MEG into SEEG planning may optimize electrode placement, reduce unnecessary sampling, and improve localization of the seizure onset zone, particularly in MRI-negative or multilobar epilepsy.

Methods: We report a 44-year-old right-handed man with medically refractory focal epilepsy. His habitual seizures began with arousal from sleep followed by sitting upright, right facial numbness and a pulling sensation associated with an urge to touch his face. He subsequently developed body-directed automatisms characterized by alternating hand movements covering his mouth, accompanied by sialorrhea without impaired awareness. Seizures lasted 20–30 seconds with rapid recovery. Scalp EEG demonstrated repetitive spikes over the left temporo-centro-parietal region (T7/P7>C3/P3), consistent with a tangential dipole across the insular-opercular region. MRI was initially interpreted as non-lesional. MEG demonstrated abundant clustered dipoles with uniform orientation localized to the left lateral frontal cortex immediately anterior to the precentral sulcus, guiding SEEG implantation.

Results: Phase II SEEG evaluation captured five habitual electroclinical seizures. Ictal onset consistently localized to the left frontal operculum (MSIN contacts 5–10), with early propagation to the left rolandic operculum and subcentral gyrus (PSIN contacts 3–11). Interictal recordings demonstrated continuous focal slowing and near-continuous epileptiform discharges involving the same regions, supporting a highly localized epileptogenic network. Functional cortical stimulation showed preserved visual naming, auditory naming, and reading during stimulation of the superior temporal gyrus, pars opercularis, and adjacent frontal operculum. Stimulation of MSIN contacts 7–8 and 8–9 reliably reproduced the patient’s habitual aura and electroclinical seizure, further confirming localization of the epileptogenic zone.

Conclusions: SEEG localized the epileptogenic zone to the left frontal operculum, concordant with the tightly clustered MEG dipoles. The combined electrophysiological findings were highly suggestive of focal cortical dysplasia. Prompted by the concordant MEG and SEEG findings, repeat review of the MRI identified subtle imaging features suspicious for focal cortical dysplasia that had not been recognized initially. This case illustrates the complementary role of MEG in SEEG implantation planning for MRI-negative epilepsy, demonstrating how MEG-guided electrode placement can accurately localize the epileptogenic zone, improve diagnostic confidence, and uncover subtle structural abnormalities that directly influence surgical planning.

Murray Alexander Falconer (1910–1977): his contribution to the modern International League Against Epilepsy (ILAE) classification of epilepsies and British epilepsy surgery

Amisha Vastani, Harutomo Hasegawa, Richard Selway

Department Of Neurosurgery, King’s College Hospital, London, Uk

A pioneer of epilepsy surgery whose work led to describing mesial temporal sclerosis, focal cortical dysplasia and the en bloc temporal lobectomy. We present M. Falconer’s scientific and operative contribution to the modern ILAE framework, emphasising pathological substrates, surgical outcomes, and prevention strategies defined during his 26-year tenure directing the Guy’s–Maudsley Neurosurgical Unit.

Design: Structured historical literature review alongside his personal archive at King’s containing his and colleagues’ work. We outline key publications and operative innovations, appraising each against contemporary ILAE position papers on hippocampal sclerosis, focal cortical dysplasia, seizure classification, and surgical outcome measurement.

Subject: M. Falconer FRCS FRACS (Dunedin 1910 – London 1977): Nuffield Dominions Clinical Fellow, Oxford 1938 (under Sir Hugh Cairns); RAMC Major, St Hugh’s Military Hospital for Head Injuries 1940–1945; Director, Guy’s–Maudsley Neurosurgical Unit 1949–1975. Produced approximately 50 peer-reviewed epilepsy papers in collaboration with Hill, Pond, Meyer, Serafetinides, Corsellis, Bruton, Taylor, Davidson, and Engel.

Method: A 1953–1975 chronology of scientific publications constructed from his personal archive, cross-referenced with contemporary ILAE position papers: HS-ILAE 2013; FCD ILAE 2011 and 2022; ILAE Classification of Epilepsies 2017; and the Updated Seizure Classification 2025.

Results: Key publications and ILAE relevance: the 1953 JNNP report of paediatric temporal-lobe epilepsy cured by lobectomy; the 1954 Lancet paraphilic automatism abolished by resection; the 1955 Lancet series (n=31; first standardised en bloc anterior temporal lobectomy, the operative method whose intact specimens made ILAE neuropathological classification achievable); 1957 Journal of Mental Science psychiatric outcome study, republished Epilepsy & Behavior 2004; 1958 Brain paper on Meyer’s loop visual-field defects; 1963 JNNP 100-patient ictal-speech series; 1964 Archives of Neurology paper formally naming mesial temporal sclerosis as the dominant substrate, the HS-ILAE 2013 Type 1 entity; 1971 JNNP focal cortical dysplasia (Taylor, Falconer, Bruton, Corsellis), eponymous Taylor-type FCD and foundation of ILAE FCD Type II 2011/2022; 1973 NEJM behavioural reversibility (n>250); 1974 Lancet initial-precipitating-injury MTS-prevention paper, read to the ILAE British Branch, National Hospital Queen Square, 26 April 1974, and cited in NICE guidance; 1975 Brain (Engel, Driver, Falconer) and the Engel outcome scale; and 1975 Lancet paediatric series (n=40, 1–24-year follow-up).

Conclusion: Across four decades, Falconer established the operative and pathological framework upon which the modern ILAE classifications of hippocampal sclerosis, focal cortical dysplasia, and surgical outcome are built. His previously undescribed clinical archive at King’s offers a new primary source for understanding his contributions to the ILAE and modern epilepsy management.

Focal Cortical Dysplasia in Epilepsy Surgery Candidates: A 10-year Experience at a Regional Centre

John Holden, Leach Veronica, Livingstone Shona, Athanasios Grivas, Russell Hewett

Institute Of Neurological Sciences, Glasgow

Background: Focal Cortical Dysplasia (FCD) is a major structural cause of focal drug-resistant epilepsy (DRE), accounting for up to 14% of surgical resections in the European Epilepsy Brain Bank (EEBB) registry [1]. This regional, 10-year retrospective study aims to evaluate the prevalence, patient phenotype, and surgical outcomes of histologically proven FCD.

Methods: Electronic patient records from all cases discussed at the regional epilepsy surgery multidisciplinary team (MDT) meeting (January 2015–December 2025) were retrospectively reviewed. Patients were classified into two cohorts: pathologically proven FCD (FCD-P) and radiologically suspected FCD without surgical resection (FCD-R). Extracted data included demographics, age at seizure onset/surgery, electro-clinical findings, neuroimaging, surgical interventions, histopathology (ILAE consensus guidelines), and postoperative outcomes (Engel/ILAE scales).

Results: Of 216 unique cases discussed, 55 (25%) underwent an epilepsy surgical procedure; 6 patients had historical neurosurgical procedures. Resections accounted for 93% (n=57) of total interventions. Among the 57 cases with histopathological data, the most frequent diagnoses were low grade epilepsy-associated tumours (n=17), vascular malformations (n=10), isolated FCD (n=10), hippocampal sclerosis (HS; n=7), and non-diagnostic pathology (n=7). Structural dual pathology (combined HS and FCD; ILAE FCD Type III) was identified in 3 cases. Within the FCD-P cohort, the commonest sub-classification was ILAE FCD Type II (n=8; 4 Type IIa, 3 Type Type IIb, 1 unspecified). An additional 12 cases (FCD-R) demonstrated radiological features consistent with possible FCD but did not progress to surgery.

The combined FCD cohort (FCD-P + FCD-R, n=25) had a median age of seizure onset of 9 years and a median age at MDT discussion of 35 years. Seizure frequency was predominantly daily (n=12) or weekly (n=11). Patients were prescribed a median of 3 anti-seizure medications (ASMs), with historical exposure to a median of 4 others; levetiracetam and lamotrigine were most common. Postoperatively, 61.5% of the FCD-P cohort (8/13) achieved an Engel Classification score of I.

Of note, 58 of 216 unique cases discussed (27%) with refractory focal epilepsy presented with normal MRI findings.

Conclusions: FCD represents a substantial proportion of the surgical cohort at our centre. Patients face a high seizure and treatment burden, yet operative management yields highly satisfactory outcomes in the majority of cases. These findings emphasize the benefit of epilepsy surgery in management of FCD.

References:

1. Blümcke, I., et al. (2017). “Histopathological Findings in Brain Tissue from Epilepsy Surgery.” New England Journal of Medicine, 377(17), 1648–1656.

Early UK experience with robot-assisted Visualase MR-guided LITT for drug-resistant epilepsy: workflow, technical metrics and outcomes in the first 22 cases

Amr Moursi, Thangaraj MUNUSAMY, Dr Nandini Mullatti, Harutomo Hasegawa, Richard Selway

King’s College Hospital NHS Foundation Trust

Purpose: Magnetic resonance-guided laser interstitial thermal therapy (MRg-LITT) is a minimally invasive option for drug-resistant focal epilepsy, particularly for deep or surgically challenging targets. UK experience remains limited. We describe a single-centre early experience with robot-assisted Medtronic Visualase MRg-LITT, focusing on indications, technical metrics and outcomes.

Methods: We retrospectively reviewed the first 22 consecutive patients who underwent robot-assisted Visualase MRg-LITT for epilepsy at King’s College Hospital between July 2024 and June 2026. Data included demographics, indication, preoperative workup, applicator and ablation parameters, delivered energy, follow-up duration, Engel outcome and complications.

Results: Twenty-two patients were treated: 20 adults and 2 paediatric patients; 15 were male. Median age was 32 years (range 12-56) and median epilepsy duration was 21 years. Indications were hypothalamic hamartoma (HH) in 11, mesial temporal or temporal targets in 5, cavernoma in 2, periventricular heterotopia in 2 and other focal cortical lesions in 2. A single trajectory was used in all cases. A 3 mm diffusing tip was used in 12 patients and a 10 mm tip in 10. Median ablation runs were 2.5 (range 1-5), with a median of 1.5 pull-backs and median ablation time of 628 seconds (range 120-1554). Median mean power was 4.95 W (range 2.71-8.50), approximately 33% of the 15 W maximum. Engel outcome was documented in 21 patients at median follow-up of 7 months (range 0-19): Engel I in 14 (67%), Engel II in 1 and Engel III in 6. In patients with at least six months’ follow-up (N=11), Engel I was achieved in 4 (36%), Engel II in 1 and Engel III in 6. Hypothalamic weight gain occurred in six HH patients. One small localised haemorrhage resolved without neurological deficit. No permanent neurological deficits were observed.

Conclusion: This early UK experience demonstrates the feasibility and safety of a robot-assisted Visualase MRg-LITT epilepsy service across heterogeneous indications with no permanent neurological morbidity. Applicator selection, ablation time, power, and delivered energy were reproducibly measurable and may support standardised reporting. These are early results from a small, recent series with a short follow-up. Longer follow-up is essential before firm conclusions can be drawn, and careful counselling is needed.

Reduced Preoperative Piriform-Insula Connectivity Is Associated with 5-Year Seizure Outcome After Anterior Temporal Lobe Resection

Hak Kei (Antonia) Wong, Sherry Liu, Jane de Tisi, Boyuan Song, Anna Miserocchi, Mr Andrew Mcevoy, John S Duncan, Louis Lemieux, Umair Javaid Chaudhary, Meneka K Sidhu

University College London, Institute of Neurology, Department of Epilepsy, Queen Square Institute of Neurology

Introduction: Piriform cortex has large scale network interactions: orbitofrontal-thalamic, limbic and anterior insula integrating salience network. It plays a critical role in seizure initiation, propagation and termination. This study investigates preoperative piriform cortex resting-state fMRI (rsfMRI) functional connectivity (FC) profiles associated with longer-term seizure outcomes after anterior temporal lobe resection (ATLR) for unilateral temporal lobe epilepsy (TLE).

Method: 13 healthy controls and 27 TLE patients (16 left) who underwent ATLR had preoperative rsfMRI. Seed-based FC analyses from piriform were performed using CONN22 toolbox-v2407. The effect of 5-year postoperative seizure outcome (ILAE 1-6) was investigated as a covariate (controlling for focal to bilateral tonic-clonic seizures, age at onset of epilepsy, pathology, preoperative seizure frequency). All results were reported with false discovery rate correction (FDR p<0.05) unless otherwise stated.

Results: 50% had ILAE 1-2 outcomes. Compared with controls, left TLE showed reduced connectivity between left piriform and bilateral insulae. In RTLE, there was reduced right piriform-salience network connectivity (uncorrected p=0.008) compared to controls.

In combined left and right TLE analyses, worse seizure outcomes were associated with reduced left piriform-salience network, bilateral insulae and planum polare connectivity.

In left TLE, worse seizure outcome was associated with decreased left piriform-contralateral insula connectivity. A similar trend was observed for left piriform-salience network connectivity (p-FDR=0.056).

In right TLE, seizure outcome was not significantly associated with any connectivity patterns, possibly reflecting a type II error due to smaller sample size.

Conclusion: We showed bilateral disruption of piriform cortex connectivity primarily to insulae in TLE. This hypoconnectivity was associated with worse seizure outcome after ATLR implying that more diffuse piriform network disruption is a potential biomarker for seizure outcome after ATLR. This may provide a neurobiological understanding of why adequate removal of the piriform cortex is associated with better longer term seizure free outcomes after ATLR.

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Preoperative Perivascular Space Asymmetry Predicts Memory Trajectories After Temporal Lobe Epilepsy Surgery

Thaera Arafat, Joanna Bartkiewicz, Luisa Delazer, Nicholas Fearns, Kazuki Fukuma, Matthias Koepp, Adolfo Mazzeo, Alicija Mrzyglod, Isha Puntambekar, Michael Schubert, Maria Thom

Background. MRI-visible perivascular spaces (PVS) are markers of glymphatic dysfunction that are increased in temporal lobe epilepsy (TLE). We investigated whether preoperative hemispheric PVS asymmetry is associated with verbal and visual memory trajectories after TLE surgery.

Methods. We studied 141 patients from a TLE surgery registry (56% left TLE; 54% female; mean age 38 years) with one-year neuropsychological follow-up; 47 also completed long-term assessment (mean 9.3 years). Two laterality indices (LI) were computed as (ipsilateral − contralateral) / (ipsilateral + contralateral), where ipsilateral denotes the side of the epileptic focus and positive values indicate greater PVS burden at the seizure onset zone: temporal PVS volume (T-Vol LI) and non-temporal PVS volume (nT-Vol LI). Verbal memory (word list learning + delayed recall + story delayed recall) and visual memory (design learning + delayed recall) from the Adult BMIPB battery were summarised as PCA composites (PC1: 62–77% variance, α=0.51–0.80). Outcomes were z-score change scores (postoperative − preoperative); positive values indicate less decline. Standardised OLS regression adjusted for sex, age, surgery side, and domain-specific baseline. Tau burden was quantified by AT8 immunoreactivity in resection specimens (N=108). FDR correction (Benjamini–Hochberg) was applied across 8 tests.

Results. Higher temporal PVS asymmetry (T-Vol LI) was associated with less verbal memory decline one year after surgery (β=+0.27, p=0.043, FDR=0.172), while greater non-temporal PVS asymmetry (nT-Vol LI) was associated with less long-term visual memory decline (β=+0.51, p=0.006, FDR=0.050), representing the only association to survive correction for multiple comparisons. In both cases, greater ipsilateral PVS predominance was associated with better preservation of memory. The association between non-temporal PVS asymmetry and postoperative memory trajectory diminished with increasing age, with significant nT-Vol LI×age interactions for visual (p=0.040) and verbal memory (p=0.026), whereas temporal PVS asymmetry showed no significant age interaction (all p>0.25). Neither PVS laterality measure was associated with epilepsy severity (age at onset, disease duration, seizure frequency, number of antiseizure medications; all p>0.20) or AT8-positive tau pathology in resected tissue (all p>0.15).

Conclusions. Preoperative hemispheric PVS asymmetry was associated with postoperative memory trajectories independently of epilepsy severity and local tau pathology. Together with emerging evidence linking astrocytic dysfunction, impaired glutamate homeostasis and activity-dependent tau accumulation to cognitive decline, these findings suggest that MRI-visible PVS may capture an early disturbance of brain homeostasis that precedes overt neurodegeneration. Rather than reflecting accumulated pathology, hemispheric PVS asymmetry may identify differences in network resilience that influence long-term cognitive trajectories in TLE

A systematic review of brain network and connectivity measures that predict seizure outcome after epilepsy surgery

Damjan Veljanoski^1,2, Siddarth Kannan³, Aswin Chari^1,2, Martin Tisdall^1,2, Torsten Baldeweg^1,2, Rory Piper^1,2

¹Developmental Neurosciences, UCL Great Ormond Street Institute Of Child Health, ²Department of Neurosurgery, Great Ormond Street Institute of Child Health, ³NHS University Hospitals of Liverpool

Purpose: To identify and synthesise neuroimaging brain network and connectivity measures that predict postoperative seizure outcomes following epilepsy surgery, and to evaluate their methodological characteristics and predictive performance.

Methods: A PROSPERO-registered systematic review (CRD420251004246) was conducted in accordance with PRISMA. Embase, PubMed and Web of Science were searched without date or language restrictions. Two reviewers independently screened titles/abstracts and full texts. Eligible studies used neuroimaging network/connectivity analyses to predict seizure outcome after epilepsy surgery in adults or children. Data extracted included cohort and surgical characteristics, imaging modality and field strength, network construction/metrics, outcome definitions, and model evaluation (where applicable). Studies were classified as predictor-finding or predictor-modelling with risk of bias was assessed using QUIPS and PROBAST, respectively. Findings were narratively synthesised by connectivity domain, unit of analysis (global/subnetwork/nodal), anatomical grouping, and direction of association with outcome.

Results: Eighty-one studies were included; 86% were single-centre, 70% adult-only, and 69% focused on temporal lobe epilepsy. Median minimum follow-up was 12 months (range 3–60). The predominant intervention was resection (60%), followed by neuromodulation (RNS/DBS/VNS; 13%), combined LITT/resection (9%), and LITT-only (6%). Functional (35%), diffusion (25%), and metabolic (10%) analyses were most frequent. Most studies used 3T MRI (74%); none used 7T. Outcomes were variably defined (ILAE, Engel, responder rates), with median “good outcome” proportions ranging from 45% to 64% across outcome definitions. Among 18 predictor-modelling studies reporting accuracy, median outcome-prediction accuracy was 86%. Narrative synthesis indicated that favourable outcomes were generally associated with selective disconnection/reduction of pathological connectivity and preservation or reorganisation of key networks, whereas poor outcomes aligned with widespread/bilateral abnormalities and incomplete disruption of critical pathways.

Conclusions: Imaging-based connectivity and network metrics show promising accuracy for predicting postoperative seizure outcomes, but heterogeneity in cohorts, outcome definitions, and analytic pipelines limits comparability and generalisability.

Diffusion MRI abnormalities localise the epileptogenic zone in paediatric drug-resistant epilepsy

Damjan Veljanoski^1,2, Aswin Chari^1,2, Kiran Seunarine¹, Felice D’Arco³, Kshitij Mankad³, Zubair Tahir², Chris Clark¹, Martin Tisdall^1,2, Torsten Baldeweg^1,2, Rory Piper^1,2

¹Developmental Neurosciences, UCL Great Ormond Street Institute Of Child Health, ²Department of Neurosurgery, Great Ormond Street Hospital for Children NHS Trust, ³Department of Radiology, Great Ormond Street Hospital for Children NHS Trust

Background and objectives: Seizure freedom is achieved in 67% of children undergoing surgery for drug-resistant epilepsy, but reliable imaging biomarkers are needed to improve localization of the epileptogenic zone, patient selection and outcome prediction, particularly in MRI-negative patients. We evaluated a voxelwise diffusion MRI method for detecting microstructural abnormalities, testing whether abnormalities were associated with seizure freedom when resected, aligned with stereo-EEG-defined seizure onset and interictal zones, distinguished focal from distributed epileptic networks, including patients with and without an identified seizure onset zone, and localized the epileptogenic zone in MRI lesion-negative epilepsy.

Methods: We retrospectively studied children with epilepsy undergoing focal resection (n=110) or stereo-EEG implantation (n=61) between 2015-2023, and healthy controls aged 6–18 years (n=69), scanned using the same 3T MRI and diffusion protocol. Individual voxelwise z-score maps were generated for mean diffusivity (MD) and fractional anisotropy (FA) using age- and sex-adjusted normative models. Cluster-enhanced dominant abnormalities were identified. In the resection cohort, percentage overlap between abnormalities and resection masks was related to Engel outcome at ≥12 months. In the stereo-EEG cohort, diffusion z-scores were compared across seizure onset, interictal and remaining gray matter contacts. Group maps characterized clinical subgroups. In MRI lesion-negative patients, abnormalities were assessed for concordance with PET hypometabolism and stereo-EEG findings.

Results: Greater resection of the dominant MD abnormality predicted seizure freedom, with a stronger effect when restricted to patients with >0 overlap (mean differences 17% and 23%; Pperm=0.0086 and Pperm<0.001, respectively), and increased odds of Engel I outcome (OR 1.31 per 10%; AUC 0.723; Youden threshold 36%). FA abnormalities showed similar associations. In stereo-EEG patients, seizure onset contacts had higher MD and lower FA z-scores than remaining gray matter contacts (mean differences +0.65 and −0.18; Pperm<0.001 and Pperm=0.001), with interictal contacts intermediate. Abnormalities were more widespread and contralateral in patients without an identified seizure onset zone. In MRI lesion-negative patients, abnormalities co-localized with PET hypometabolism (20/28 fully, 6/28 partially) and were concordant with stereo-EEG findings (17/24 fully, 3/24 partially).

Discussion: Diffusion MRI identified abnormalities that aligned with invasive electrophysiology, associated with seizure freedom when resected, and co-localized with PET hypometabolism and stereo-EEG findings in lesion-negative epilepsy, supporting its potential to inform presurgical evaluation.

The Role of Low-field MRI in Epilepsy

Melody Asukile^1,2, Frederik Barkhof¹, Kelly Baruteau¹, Indran Davagnanam¹, Rui Yeow³, James Cole³, Josemir W Sander^1,3, John S Duncan¹

¹UCL Queen Square Institute of Neurology, ²Department of Internal Medicine, University of Zambia School of Medicine , ³UCL Hawkes Institute, ⁴Department of Neurology, West China Hospital, Sichuan University

Background: Magnetic Resonance Imaging (MRI) is essential in the diagnostic evaluation of epilepsy. Conventional MRI scanners are inaccessible in many low- and middle-income countries (LMIC). More affordable, portable low-field (LF) MRI scanners have the potential to improve access to brain imaging in resource-limited settings. Currently, image quality is limited but may be improved by Artificial intelligence (AI) algorithms. We explored the utility of LF-MRI in the diagnosis of causes of focal epilepsy.

Methods: Adults with focal epilepsy who had a 3T high-field (HF) MRI scan within 12 months underwent a 60-minute non-contrast LF-MRI on a Hyperfine® Swoop 64mT scanner. Scans were processed for image enhancement and segmentation with SuperSynth, an AI machine-learning tool. Three neuroradiologists independently read the native LF-MRI, AI-LF-MRI, and HF-MRI. Basic participant clinical information was provided.

Results: Of 39 participants, 51% were male (mean age 42 ± 12 years). 3T MRI diagnoses included: Non-lesional (10/39, 26%) Hippocampal sclerosis (HS) (8/39, 21%)

Post-surgical or gliotic (7/39, 18%), Long-term epilepsy associated tumours (LEAT) (7/39, 18%), Cavernoma (3/39, 8%), Cortical malformations (2/39, 6%), Hypothalamic hamartoma (1/39, 3%) and post-infectious calcification (1/39, 3%). There was moderate agreement among the neuroradiologists, with Cohen’s kappa = 0.33 (95% CI 0.18-0.48) and Gwet’s AC = 0.53 (95% CI 0.34-0.72). LF-MRI scan quality was reported as poor in 96%, with signal inhomogeneity the most frequent artefact (97%). LF-MRI was reported to be diagnostic in 80% of cases. Reporting confidence was 25% confident, 19% neutral, and 56% unconfident.

Concordance with 3T MRI was highest in LEAT, with complete agreement in 5/7 (71%) cases, and partial (2 of 3 raters) in 2/7 (29%), then gliotic lesions (4/7, 57%), and HS, complete agreement (3/8 cases, 37.5%) and partial (2/6, 37.5%), with overall agreement in HS ~75%. HS agreement was more likely in unequivocal cases. In non-lesional cases, agreement was in 2/10 and partial agreement in 5/10. Concordance with 3T reports was lowest for cavernomas (1/3) and malformations of cortical development (0/2). Reporting of the AI-LF-MRI is pending.

Conclusion: Qualitative analysis of LF-MRI scans by experienced neuroradiologists showed fair to moderate agreement. There were high rates of poor MRI quality and signal inhomogeneity. Gliotic lesions, tumours and HS showed the highest concordance with 3T-MRI. There was only partial agreement for other lesions and non-lesional cases. Analysis of AI-LF-MRI scans will help determine whether LF-MRI has a role in the evaluation of focal epilepsy in LMIC.

The global prevalence of malformations of cortical development in people with epilepsy: a systematic review and meta-analysis

Rebecca Maguire^1,2, Prem Jareonsettasin^1,2, Mina Hanifi^1,2, Professor Ley Sander^1,2

¹Queen’s Square Institute of Neurology, ²Social Determinants of Health in Epileptic Disorders (SdHIELD) Research Group

Introduction: Malformations of cortical development (MCDs) are important causes of drug-resistant epilepsy (DRE) worldwide. Understanding MCD epidemiology is essential to understanding risk factors, burden and the effects of potentially modifiable factors, including social determinants of health. We conducted a systematic review and meta-analysis to determine the prevalence of MCDs worldwide.

Methods: Nine databases (PubMed, Web of Science, Global Index Medicus, Embase, Scopus, Ovid Global Health, PsychINFO, LILACS, CNKI) were searched from 01/1980 to 09/2025 to identify cohorts of people with epilepsy who underwent neuroimaging. Inclusion criteria: original research articles from a single country, people with epilepsy who have undergone an MRI scan with a breakdown of radiological diagnoses. Studies restricted to a first seizure, acute symptomatic seizures or a selective differentiated cohort such as post-stroke epilepsy only, and with fewer than 50 people were excluded. A random-effects meta-analysis was performed to estimate the pooled prevalence of MCDs. Subgroup analysis examined the effects of drug-resistance status, age group, geographical region and national income status.

Results: Forty-one studies comprising 11,103 individuals across twenty-seven countries were included. 847 participants have MRI evidence of MCDs, giving a pooled prevalence of 7.88% (95% CI 6.10-10.12). There is substantial inter-study heterogeneity (I² = 91.6%). DRE cohorts have a higher prevalence (14.04%; 95% CI 10.23-18.97) compared to cohorts with mixed (6.41%; 95% CI 4.66-8.76) or unspecified (7.09%; 95% CI 4.78-10.38) drug-resistance status (p = 0.001). Children with DRE (11.41%; 95% CI 9.58-13.55) and adults with DRE (10.34%; 95% CI 7.76-13.65) have similar prevalence. Higher-income countries have a higher prevalence of MCDs in DRE (17.19%; 95% CI 10.56-26.73) than low- and middle-income countries (LMICs) (10.37%; 95% CI 8.12-13.15). Prevalence of MCDs in DRE for studies using 1.5 Tesla MRI is 11.72% (95% CI 9.95-14.31) and 3 Tesla MRI is 14.75% (95% CI 8.25-24.97).

Discussion: Overall, the global prevalence of radiologically identifiable MCDs is substantial and nearly doubles in people with DRE. Poor maternal health, exposure to toxins, pollution, radiation and immune activation are risk factors for MCDs. The lower prevalence in LMICs may be related to differences in social determinants of health, including inequities in access to health care and the lack of sophisticated diagnostic facilities. Premature mortality in those who have MCDs cannot be excluded. The lower prevalence observed in LMICs likely reflects disparities in healthcare access and higher premature mortality rates rather than lower incidence.

Thalamic Volumetric Analysis in ESES using THOMAS: An MRI Case-Control Study

Dion Tahiri^1,2, Suresh Pujar^2,3, Aswin Chari^1,4

¹University College London , ²Developmental Neurosciences, Institute of Child Health, Great Ormond Street, ³Department of Neurology, Great Ormond Street Hospital, ⁴Department of Neurosurgery, Great Ormond Street Hospital

Introduction: Electrical status sleep epilepticus (ESES) is the terminology used to describe an epileptic pattern observed during NREM sleep of paediatric patients who present with developmental and behavioural deficits. These deficits are induced by a chronic form of NREM sleep epilepsy that can be described under an umbrella of different terms such as DEE-SWAS or CWSW. Previous studies have suggested that early lesions or developmental abnormalities of the thalami on either hemisphere may lead to the onset of ESES pathology, while others simply outline the correlation between a seemingly reduced thalamic volume and occurrence of this wave pattern; results that have been inconsistent across the literature.

Methods: We conducted a retrospective case control study of 29 ESES patients who were compared to 65 healthy controls, using post-diagnostic MRI files obtained between 2013-2022. A converted form of these files was then run through THOMAS, a docker-based container that automatically segments, labels, and measures the volumes of the thalamus and its constituents in both the left and right hemispheres. We had run various age and gender-adjusted statistical tests, including total volume comparison, individual abnormality testing using Z scores, lateralised atrophy index testing, using MATLAB.

Results: Our age and gender adjusted ANCOVA test had found that the ESES cohort had a reduced thalamic volume (-1805mm3, Cohen’s D = 1.67, p < 0.001) at a group level. Individually, 59% of ESES patients fell outside of the 95th percentile of normal volume (Z < -1.96) 8 of 11 nuclei showed significant volume decrease after Bonferroni correction, the biggest decreases being the mediodorsal-parafasicular (d=1.56), ventral lateral posterior (d= 1.56), and ventral anterior nuclei (1.52). Our lateralisation testing had showed significantly increased thalamic asymmetry in the ESES cohort (p=0.034), not be significantly linked to a specific hemisphere (sign test p = 0.15).

Discussion: Our data supports the idea seen across the literature that a reduction in thalamic volume occurs within patients with ESES, yet whether this is the cause of the disorder or an effect caused by some other factor remains unknown. Our results may lead to future thalamic studies that highlight the pathology of this condition, the way both the reduced overall thalamic volume, and the hemispheric thalamus imbalance correlate with disease severity, seizure onset, and the extent of the ESES waveform during NREM sleep.

New-Onset Refractory Status Epilepticus (NORSE) versus Refractory Status Epilepticus not meeting NORSE criteria: A Comparative Clinical and EEG-Based Study

Seren Hawksworth¹, Nina Moutonnet^2,3, Gregory Scott², Sanjeev Rajakulendran¹, Mahinda Yogarajah¹, Matthew Walker¹, Umesh Vivekananda¹

¹UCL Queen Square Institute of Neurology, ²Imperial College London, UK Dementia Research Institute, ³Imperial College London, Department of Computing

Background: New-onset refractory status epilepticus (NORSE) is a rare, severe presentation of refractory status epilepticus (RSE), with approximately half of cases cryptogenic (c-NORSE). We compared electroencephalography (EEG) findings alongside clinical features between NORSE and RSE not meeting NORSE criteria to better understand outcomes and prognostication.

Methods: This retrospective cohort study analysed 81 RSE patients admitted to the Intensive Therapy Unit (ITU) at The National Hospital for Neurology and Neurosurgery and University College London Hospital (2007-2023). Patients were categorised as RSE not meeting NORSE criteria (n=52) or NORSE (n=29). EEG features, treatment, and outcomes (ITU stay, mortality, cognitive outcome, and anti-seizure medication (ASMs) use), were evaluated.

Results: Of 29 NORSE patients (15 c-NORSE, 51.7%; 14 aetiology-identified NORSE, 48.3%), autoimmune (20.7%) and infectious (17.2%) aetiologies were most prevalent. Six-month mortality was higher in c-NORSE than aetiology-identified NORSE (20.0% vs. 7.1%), but similar between NORSE and RSE not meeting NORSE criteria (13.8% vs. 21.1%). EEG analysis revealed longer seizure duration (mean 243.38 vs. 51.67 seconds; p<0.001), a tendency to higher seizure frequency (0.013 vs. 0.009 seizures/minute; p=0.076), and increased presence of generalised periodic epileptiform discharges and stimulus-induced rhythmic, periodic, or ictal discharges in NORSE than RSE not meeting NORSE criteria. Across all patients, higher initial seizure burden correlated with longer ITU admissions and worse outcomes. Compared with RSE not meeting NORSE criteria, NORSE patients had longer ITU stays (median 51 vs. 11 days; p<0.001), more ASMs (mean 3.91 vs. 2.00; p=0.031), greater sedative use (mean 2.17 vs. 1.00; p<0.001), and more frequent cognitive impairment at discharge (88.9% vs. 62.2%; p=0.037).

Conclusions: NORSE, particularly c-NORSE, tends to follow a more severe course than RSE not meeting NORSE criteria, with more severe background electroencephalographic features including the initial EEG, greater seizure burden, longer ITU stays, and increased incidence of cognitive impairment at discharge. Six-month mortality was similar, implying additional contributing factors to mortality.

Validating SEEG Ictal and Interictal Pattern Classification

Li-Zhang Tan¹, Khalid Hamandi², Glen Brimble²

¹Cardiff University, ²Cardiff and Vale University Hospital of Wales

Aim: To identify seizure onset patterns (SOP) in patients diagnosed with hippocampal sclerosis (HS) and focal cortical dysplasia (FCD) using stereo-electroencephalography (SEEG), and to compare findings with those reported by Di Giacomo et al.

Methods: Data from 13 patients with drug-resistant focal epilepsy were retrospectively collected from the University Hospital of Wales. Diagnosis of HS and FCD were established through clinical presentation, neuroimaging, and later concluded with SEEG findings. Ictal and interictal SEEG recordings were reviewed, and SOPs were classified according to Di Giacomo’s categories: low voltage fast activity (LVFA), fast activity (FA), rhythmic sharp activity (RSA), repetitive fast spike burst (RFSB), and slow burst (SB), based on the earliest identifiable ictal changes.

Results: In total, 153 clinical seizures (99 HS, 54 FCD) and 29 electrographic seizures (22 HS, 7 FCD) were reviewed across 13 patients (9 HS, 4 FCD). In HS, LVFA was the predominant SOP (68.7%), followed by RSA (30.3%) and RFSB (1%). FCD seizures showed a more heterogeneous distribution, with RSA and RFSB each accounting for 29.6%, followed by LVFA (20.4%) and SB (20.4%). At the patient level, LVFA was present in all HS patients (100%) and 75% of FCD patients. LVFA demonstrated high sensitivity (100%) but low specificity (25%) for HS, while RFSB showed low sensitivity (25%) but higher specificity (88.9%). Fischer’s exact testing revealed no statistically significant association between any individual SOP and underlying pathology. Similar patterns were observed in electrographic seizures, with no single onset pattern reliably distinguishing HS from FCD.

Conclusion: Seizure onset patterns demonstrated substantial overlap between HS and FCD in this cohort. Although LVFA was universally observed in HS and certain patterns appeared more frequently in FCD, no single onset morphology achieved sufficient sensitivity or specificity to reliably distinguish the two pathologies. These findings contrast with those of Di Giacomo et al., suggesting that seizure onset morphology alone has limited diagnostic utility. Given that the neurophysiological mechanisms underlying this discharge patterns remain incompletely understood, establishing a direct correlation between ictal onset pattern and histopathology is inherently challenging. Electrode locations also influence recorded SEEG patterns. Therefore, the reproducibility and generalisability of previously described SEEG patterns across different centres and patient population remain important considerations. These findings reinforce the need for comprehensive multimodal evaluation in presurgical assessment rather than reliance on seizure onset morphology alone.

Clinical decision support after inconclusive EEG: evaluating the clinical utility and health economic potential of BioEP

Phil Tittensor^1,4, Anke Verhaege², Jeremy Andrews², Wessel Woldman², John Terry^2,3, Daniel Russell¹, Elizabeth Schnabel¹, Conor Smyth¹, Jacqui Rowe¹, Toni Ball¹, Hannah Johnson¹, Louise Coope, Francesco Manfredonia¹

¹Royal Wolverhampton NHS Trust, ²Neuronostics, ³University of Plymouth, ⁴University of Wolverhampton

Background: BioEP is a clinical decision-support tool designed to aid differentiation between epilepsy and non-epileptic conditions following an inconclusive electroencephalogram (EEG). The tool utilises computational biomarkers derived from routine EEG background activity, which are fed into a statistical model to output one of five ordinal classes: very unsupportive, unsupportive, neutral, supportive and very supportive of epilepsy. Inconclusive EEG results are common and can contribute to diagnostic uncertainty, the need for repeat investigations and delays in diagnosis and treatment, increasing healthcare resource use and costs. This first real-world evaluation at The Royal Wolverhampton NHS Trust assesses the potential health economic value of BioEP as well as the adoption and clinical utility of the tool in routine practice within a nurse-led seizure clinic.

Methods: Interim data were reviewed for all EEGs uploaded to BioEP up to 24 June 2026, 6 months after implementation. Four senior Epilepsy Specialist Nurses (ESNs) requested and reviewed BioEP assessments. Clinical utility and potential health economic impact were assessed using clinician-reported data collected via a structured questionnaire, including effects on diagnostic confidence, downstream clinical activity, and perceived value during patient discussions.

Results: At the interim evaluation, 96 BioEP assessments had been requested, and clinician-reported evaluation data were available for 66 cases. Of the 96 assessments, 8 (8.3%) were classified as very supportive, 12 (12.5%) supportive, 40 (41.7%) neutral, 20 (20.8%) unsupportive, and 16 (16.7%) very unsupportive of epilepsy. Use of BioEP increased during the implementation period and then remained consistent from month 3 onward. BioEP improved clinician confidence in diagnosing epilepsy in 39 of 66 evaluated cases (59%). No additional EEG investigations were requested in 37 of these 39 cases (94.8%). In cases where clinician confidence was not improved by BioEP; no further testing was requested in 23 of 27 cases (85,1%). BioEP findings were discussed with patients in 28 of 66 cases (42.4%) and were considered by clinicians to add value in 19 of those 28 discussions (67.8%).

Conclusion: BioEP was associated with improved clinician confidence, which may lead to more efficient use of clinical resources. Furthermore, the interim data confirm that BioEP can be integrated into routine clinical practice after an initial learning period, as its use increased over the first few months before stabilising. The strength of the current results is limited by the limited sample size. Ongoing data collection aims to provide further evidence regarding the impact and scalability of BioEP in routine practice.

X-SEPT: individualised, EEG based overnight music playlists for people with drug-resistant seizures – a pilot study

Phil Tittensor^1,3, Nigel Osbourne², Kit Barnes³, Rahnuma Feist-Hassan³, James Hanlon³, John Turner³, Jonathan Walton³

¹Royal Wolverhampton NHS Trust, ²University of Edinburgh, ³University of Wolverhampton, 4X System

Purpose: Up to 70% of people with epilepsy (PWE) can become seizure free using anti-seizure medication (ASM). The remaining 30% require alternative management strategies. Listening to Mozart’s K448 has been reported to reduce seizure frequency for some PWE. X-SEPT produces playlists created through a personalised process, selecting music tracks based primarily on musical feature similarity to a ‘healthy’ period of the patient’s EEG. This has been audified with the aim of encouraging healthy brain activity during sleep through neural synchronisation/entrainment. The tracks are edited to reduce sudden dynamic shifts or uncomfortable pitches. A previous exploratory study reported a mean 28.42% reduction in epileptiform spikes.

Objective: We will evaluate the efficacy, safety, and cost-effectiveness of using X-SEPT music playlists nightly by people with drug resistant epilepsy, through assessing seizure frequency, seizure severity, seizure safety, quality of sleep, quality of life and cost data, compared to listening to a nightly playlist of Mozart’s K448 or to receiving care as usual in a three arm parallel group randomised controlled trial with follow-up phase; an internal pilot study.

The secondary objective is to assess the study design in terms of participant recruitment rates, retention rates, protocol adherence, and data completion, so that any design corrections can be made (if necessary) before a larger RCT is carried out.

Method: Forty-eight PWE receiving care at The Royal Wolverhampton NHS Trust will be recruited. The study will have two phases; confirmatory phase consisting of baseline (1 month) and intervention (3 months) periods, followed by the surveillance phase that will consist of an optional follow-up period (12 months).

Participants will be randomised into an intervention group, where they will receive the X-SEPT playlist, an alternate group where they will receive Mozart K448 on loop, or a control group where they will receive care as usual.

Data will be collected through forms, seizure diaries, sleep questionnaires, saliva samples, SUDEP checklists, cost questionnaires, and quality-of-life questionnaires.

Results: Preliminary results from the first phase will be presented at conference.

Conclusion: Completion of the pilot study should support progression from an exploratory study to a full randomised controlled trial of X-SEPT in drug-resistant epilepsy. If shown to be effective, X-SEPT may offer a low-risk, non-invasive adjunctive approach for people with drug-resistant seizures.

From algorithm to patient: progress from the ATMOSPHERE (Artificial intelligence To Optimise Seizure Prediction to Empower people with Epilepsy) project.

Phil Tittensor^1,2, Amberly Brigden³, Leandro Junges⁴, Peter Kissack⁴, Yasser Qureshi⁶, Emily Quilter³, Samuel Downes³, Liz Stuart⁷, Rosie Charles⁵, Amelia Slay³, Jerussa Vasikaran³, Lauren Thompson³, Emily Nielsen³, Matthew Wragg³

¹Royal Wolverhampton NHS Trust, ²University of Wolverhampton, ³University of Bristol, ⁴University of Birmingham, ⁵Neuronostics, ⁶University of Warwick, ⁷Ulster University

Purpose: Seizure unpredictability is a research priority for people living with epilepsy (PWE). ATMOSPHERE is an interdisciplinary project to design technology that alerts individuals if seizures are likely in the near future; analogous to checking a weather forecast for the need of an umbrella.

Method: Synthetic seizure diaries and publicly available datasets were used to train an AI algorithm to forecast seizures. 22 stakeholders (clinicians, individuals with lived experience) co-designed the smartwatch and smartphone device, designed to capture the real patient data needed to optimise the AI algorithm. Stakeholders advised about the optimal design of presenting these forecasts, including an artist’s interpretation using video and pictures to explain the project. Subsequently, 14 participants used the device for up to 3 months in their lived context, providing longitudinal data for the seizureforecasting algorithm. A small subset (n=4) are using long-term implantable EEG (UNEEG Episight), with the aim of enabling accurate mapping of the forecast to seizures. The project now has ethical approval to begin a feasibility study of the device within an NHS clinic.

Results: We will present:

The algorithm pipeline based on synthetic dataset and refined in real patient data

Usability of the smartwatch and smartphone device

The optimal design of how to present forecasts, including artist designs for public engagement forums

UNEEG analysis

Usability withing NHS feasibility study

Conclusion: ATMOSPHERE is a novel concept, utilising readily available technology to forecast seizures. This has the potential to minimise risk, up to and including SUDEP, and maximise opportunities for people with epilepsy. Our results so far demonstrate high user acceptability and an ability to record the necessary data to produce a forecast. We will begin a trial to produce forecasts for people with epilepsy in 2026 and hope to be able to present preliminary results at the ILAE Scientific Meeting.

Preoperative Quantitative EEG Predicts Long-Term Tau Accumulation and Cognitive Decline Following Temporal Lobe Epilepsy Surgery

Adolfo Mazzeo^1,2, Thaera Arafat¹, Luisa Delazer¹, Isha Puntambekar¹, Kjell Erlandsson⁴, Beate Diehl^1,3, Dr Fahmida Chowdhury^1,3, Alicija Mrzyglod¹, Maria Thom¹, Matthias Koepp^1,3

¹UCL Queen Square Institute of Neurology, ²Department of Human Neurosciences, Sapienza University of Rome, ³National Hospital of Neurology and Neurosurgery, ⁴Institute of Nuclear Medicine, University College London Hospital

Background: Chronic network hyperexcitability has emerged as a potential driver of tau accumulation and accelerated brain ageing in temporal lobe epilepsy (TLE), yet electrophysiological markers identifying networks susceptible to activity-dependent tau propagation remain unknown. We investigated whether preoperative quantitative EEG (qEEG) measures are associated with postoperative tau burden measured approximately one decade later and with long-term cognitive outcome.

Methods: Patients with drug-resistant TLE underwent tau PET imaging with [¹⁸F]MK-6240 following epilepsy surgery. After preprocessing, routine preoperative EEG recordings were analysed with exact low-resolution electromagnetic tomography (eLORETA) source localisation. Regional source activity was quantified across conventional frequency bands and correlated with global and regional tau PET uptake after adjustment for age. Associations with phosphorylated tau (AT8) in surgical tissue, long-term cognitive decline and postoperative seizure outcome were also explored.

Results: Preoperative qEEG demonstrated significant associations with subsequent tau burden. Lower frontal (ρ = −0.544, p = 0.029) and central delta activity (ρ = −0.552, p = 0.027) was associated with higher global tau PET uptake, together with higher temporal alpha2 (ρ = 0.542, p = 0.030) and alpha3 activity (ρ = 0.582, p = 0.018). Similar relationships were observed for temporal neocortical tau uptake. The same qEEG pattern predicted long-term memory decline, with patients exhibiting post-operative cognitive deterioration showing lower frontal and central delta activity and higher temporal alpha2 activity. In contrast, qEEG measures were unrelated to phosphorylated tau burden within the resected tissue or postoperative seizure outcome.

Conclusions: Preoperative qEEG source activity identifies network-level physiological states associated with subsequent distributed tau accumulation and long-term cognitive decline. The dissociation between qEEG and pathological tau within the surgical specimen suggests that electrophysiological network function reflects vulnerability to future activity-dependent tau propagation rather than existing focal tau pathology. Together with recent evidence linking impaired glutamate homeostasis to chronic network hyperexcitability, these findings support a model in which preserved but chronically hyperactive neural networks promote progressive tau-associated brain ageing before overt network failure becomes clinically apparent.

Long-term EEG - Rapid Treatment Changes (LEG-RTC): a novel use of implantable EEG in a non-tertiary clinical setting.

Phil Tittensor^1,2, James Barraclough¹, Neil McNiven¹, Francesco Manfredonia¹, Daniel Konn¹, Kim Byrne³, Pia Kjaer Gauger³, Chris Young³

¹Royal Wolverhampton NHS Trust, ²University of Wolverhampton, ³UNEEG Medical

Purpose: To assess whether rapid changes of treatment could be undertaken safely with continuous EEG monitoring for people with difficult to control seizures.

Method: Five patients were selected from the caseload of the epilepsy nursing service at the Royal Wolverhampton NHS Trust (RWT). All patients reported frequent seizures, at least monthly, and had tried at least four different antiseizure medications (ASM). A long-term, two channel EEG (UNEEG) was implanted in each patient by an ENT surgeon between October 2025 and January 2026. Patients retained the device for six months from implantation. Patients had EEG reports prepared by UNEEG every two weeks, ratified by consultant neuro physiologists from RWT. Patients were remotely reviewed by a consultant nurse for the epilepsies every two weeks, with treatment changes made based upon EEG recorded events.

Results: Five patients were successfully implanted. One patient developed an infection around the implantation site and had to be explanted. The four remaining patients wore the device for more than 90% of the time. One patient was aware of every seizure. Two patients reported events they considered to be seizures without EEG correlation; both had other seizures recorded that they were unaware of. One patient recorded no seizures for five months, after which there were two clusters of seizures. All patients undertook rapid changes to antiseizure medication, reacting to recorded seizures. One patient showed significant improvements in seizure control two reported improved understanding of their seizures. Two patients UNEEG recordings showed excessive sleep, which has led to discussions about medication changes not purely based on seizure control.

Conclusion: We present the first experience of UNEEG implanted by non-neurosurgeons outside a tertiary epilepsy centre, with clinical consultations undertaken by a consultant nurse. Our experience demonstrates the potential benefit of this technology for patients who are not managed in tertiary settings.

Current availability and demand for Point-of Care EEG in the across Critical Care in the United Kingdom: A National Survey

Masumi Tanaka¹, Dr Fahmida Chowdhury², Helen Ford¹, Hannah Stapley³, Juliet Solomon³, Khalid Hamandi⁴, Tejal Mitchell⁵, Tim Fudge⁶, Rajiv Mohanraj⁶

¹Kings College Hospital, ²National Hospital for Neurology and Neurosurgery, UCLH, ³ILAE British chapter, ⁴Cardiff and Vale University Health Board, Cardiff University, ⁵Cambridge University Hospitals NHS Foundation Trust, ⁶Manchester Centre for Clinical Neurosciences, Salford Royal

There is growing evidence that point-of-care EEG (POC-EEG) may be useful or associated with improved outcomes in critical care patients in status epilepticus, subarachnoid haemorrhage and reduced consciousness of unknown aetiology. In the UK, the use and demand of POCEEG remains unknown. We conducted a national survey to determine the current use and demand of POC=EEG.

Method: A 17-question survey, subcategorised into demographics of the responder and their hospital, current provision of departmental EEG and POCEEG, and the respondents’ views on POCEEG usage in critical care, including a free comments question, was distributed electronically to members of the Neuroanaesthesia and Critical Care Society (NACCS), Faculty of Intensive Care Medicine (FICM), Advanced Critical Care Practitioner (ACCPs) and the British Association of Critical Care Nursing (BACCN) network between December 2025 and April 2026, reaching 250 intensive care units across the UK. Respondents included senior nurses, advanced critical care practitioners (ACCPs) and consultants. Where multiple responses were received from the same hospital regarding EEG provision, the most senior respondent was used.

Results: Respondents: A total of 115 responses were received (30 ACCPs, 79 consultants, and 6 senior nurses). Three types of ICUs were represented - 47 non-neuroscience ICUs (38 of which were general ICUs), 12 general ICUs managing neurocritical care patients, and 7 dedicated neuro ICUs). 10% (7/66) of hospitals have either reduced or full montage on-demand EEG, most of which are centres with neurocritical care patients (6/7). Access to departmental EEG ranged from none to 7 days, with 68% of hospitals having 5 day access. Reporting: EEGs were mostly reported by neurophysiologists (79%) and neurologists (15%) of cases. Demand: When asked if respondents would like to have better access to continuous bedside EEG (N=115), 59% said yes, 16% said maybe and 12% said no. 38% believed that better access to EEG could shorten the duration of mechanical ventilation for some patients, 33% thought that it may do, 14% were not sure whereas 3% did not believe so. Free text responses consistently highlighted the need for more efficient EEG access, availability and reporting to support decision making at the bedside.

Conclusions: A significant proportion of intensivists perceived POC-EEG to be of benefit. Our survey highlights the low availability of POC-EEG in ICUs in the UK, and the need to develop infrastructure for POC-EEG guided ICU therapy at the bedside.

Prioritising follow-up for people with suspected epilepsy using a digital EEG biomarker.

Wessel Woldman, Rosie Charles, Emanuela De Falco, Elizabeth Galizia, David Martin-Lopez, Kay Meiklejohn, David Allen, Rohit Shankar, John Terry

Neuronostics

Introduction: Diagnostic delays for suspected epilepsy remain a critical challenge. With initial routine EEGs proving non-contributory in over 70% of cases, people with suspected epilepsy can wait several months for follow-up testing. This creates substantial risks; for example, 35% experience further seizures within twelve months whilst awaiting diagnosis. We investigated whether a digital EEG biomarker could help prioritise those most likely to have epilepsy for expedited testing.

Methods: We analysed 196 non-contributory routine EEGs from six NHS sites (N=66 ultimately diagnosed with epilepsy; N=130 with alternative conditions). BioEP, a digital biomarker consisting of eight computational features (including spectral properties, network connectivity, and model-based measures) that gives a measure of the level of support for epilepsy, was calculated for each EEG. We simulated clinical prioritisation by comparing biomarker-ordered follow-up lists against standard scheduling (i.e. ordered by time of referral) across random patient subsets (N=50; stratified random sampling).

Results: Biomarker-based prioritisation consistently outperformed standard scheduling. To see 50% of epilepsy patients required significantly fewer follow-up EEGs (median 33% vs 49% of list; p<0.001). The diagnostic yield for epilepsy at the 50% follow-up mark increased from 27% with random scheduling to 33% with biomarker ordering (p<0.001). The proportion of epilepsy patients seen after 50% follow-up visits increased by 10% (median value, 95% CI 7-15%, effect size 0.76). Benefits were most pronounced in typical clinic scenarios where epilepsy prevalence was 20-50% of the total list.

Discussion: This multicentre study demonstrates that computational analysis of non-contributory EEGs can identify patients at higher risk of epilepsy, enabling more efficient resource allocation. Prioritising those most likely to benefit from second-line investigations can potentially reduce diagnostic delays and seizure burden whilst maintaining equitable access, as no one is excluded from follow-up. A prospective two-arm study (‘PRIORITISE’) is currently underway to prospectively assess the potential of this methodology.

The author-list was condensed: full author-list at: DOI: 10.1016/j.yebeh.2026.110925

A novel computational EEG biomarker to support diagnosis in paediatric epilepsy: results from the OASIS study

Wessel Woldman, Emanuela De Falco, Verity Fuller, Kay Meiklejohn, Kelly St. Pier, John Terry

Neuronostics

Background: Epilepsy is the most common long-term neurological disorder in childhood, yet diagnosis remains challenging because routine EEG has limited sensitivity, particularly when epileptiform abnormalities are absent. Recently, a computational EEG biomarker of epilepsy based on network science has demonstrated robust diagnostic performance in adults using non-contributory EEG recordings (Tait et al., 2024) and was translated into a clinical decision-support tool (BioEP). However, because this biomarker was developed in adult populations, it cannot be directly applied to paediatric EEG without accounting for fundamental differences in brain maturation, developmental network organisation, and paediatric comorbidities.

Methods: We conducted a retrospective multicentre study (OASIS) of routine non-contributory EEG recordings from children investigated for suspected epilepsy across seven NHS sites. The final cohort comprised 530 patients (ages: 2-17 years, N=261 epilepsy, N=269 differential). Biomarker development was performed on a stratified training subset (n=424), with an established set of computational EEG features extracted from each recording.

We first assessed the influence of potential confounders, including age and comorbidities. Age-subgroup analyses were performed across three clinically pre-defined age groups (2-4, 5-9, and 10-17, Meiklejohn et al. 2025). We then developed a model framework using nested cross-validation for model selection and hyperparameter optimisation to identify the best-performing model.

Results: We found that age had a substantial effect on several computational EEG features. Comparison with an adult cohort showed that these age-related trends extended into adulthood. Notably, age influenced not only the feature values but also their variability, which increased with age, highlighting the dynamic nature of EEG network organisation across development and reinforcing the need for age-aware modelling.

Despite this developmental variability, the EEG features retained diagnostic value. A tree-based classifier incorporating EEG features and demographic confounders (age, sex, comorbidity, and ASM status) achieved performance significantly above chance (AUC: 73.3%, balanced accuracy: 70%, specificity: 75%, sensitivity: 65%) and consistent across the age groups, demonstrating discrimination between epilepsy and non-epilepsy beyond what achievable with conventional EEG alone.

Conclusions: Developmental changes substantially influence computational EEG features in children and should be considered when developing diagnostic tools for paediatric epilepsy. Age-adjusted computational models can identify epilepsy with clinically meaningful accuracy even from clinically inconclusive EEGs. These findings support computational EEG biomarkers as an additional source of diagnostic evidence alongside routine clinical EEG interpretation that may contribute to earlier and more accurate diagnosis in children with suspected epilepsy.

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Evaluation of microangiopathy in epilepsy in surgical and post-mortem cohorts

Maria Thom, Tien JIN, Fabio Ribeiro Rodrigues, Hanaa EL HACHAMI, Alicja MRZYGLOD, Joanna Bartkiewicz, Matthias Koepp

UCL, Research Department of Epilepsy

There is growing interest in the role of cerebral small vessel pathology in epilepsy. Although vascular malformations and stroke are well-established causes of epilepsy, accumulating evidence indicates that recurrent, particularly refractory, seizures can also induce microvascular alterations, including blood–brain barrier disruption and acquired vascular remodelling. These vascular changes may impair cerebral perfusion and neuronal function and have been implicated in memory decline in adults. However, the prevalence and distribution of small vessel disease in epilepsy, its distinction from age-related vascular changes, and relationship to glymphatic clearance remain incompletely understood. In a previous study of a small temporal lobe epilepsy (TLE) cohort, we identified age-accelerated hyaline arteriolosclerosis (vascular sclerosis; VS), pericyte alterations, and perivascular space expansion (PVSE) which correlated with measures of cognitive decline on neuropsychological assessment (Liu et al., 2024).

In the present study, we investigated over 165 surgically resected TLE specimens using image analysis methods to quantify PVSE and VS and to assess their relationship with the accumulation of corpora amylacea (CA), an indirect marker of impaired glymphatic clearance, in cortical and white matter regions compared with controls. The relationship to focal tau burden was also explored in a subset. In a post-mortem cohort of over 100 cases representing a range of epilepsy syndromes. VS, PVSE, and perivascular macrophages (PVMs), an indirect marker of glymphatic function, were semi-quantitatively assessed bilaterally in cortical and deep regions. Selected cases were explored with vascular and glymphatic markers, including Claudin-5 (endothelial tight junctions), SLC6A12, PDGFR-beta (pericytes), AQP4 (perivascular astroglia), and LYVE1/PDPN (glymphatic-associated endothelium) to further characterise vascular integrity and structure.

Compared with controls, TLE cases demonstrated greater VS. PVSE was more pronounced in the deep cortical layers and superficial white matter than deep white matter, although its relationship with CA accumulation was less consistent. Similar patterns of preferential subcortical small vessel involvement were identified in the post-mortem cohort including some young adults, together with altered AQP4 distribution, supporting disruption of glymphatic pathways.

These findings provide evidence for degenerative small vessel pathology in a subset of patients with epilepsy, with a regional distribution that differs from normal ageing patterns. As the cerebral vasculature and glymphatic system are dynamic and interdependent, robust and validated neuropathological measures of vascular and glymphatic dysfunction are essential for meaningful correlation with in vivo neuroimaging biomarkers, including MRI-derived perivascular space measures and diffusion tensor imaging analysis along the perivascular space (DTI-ALPS), as well as with neuropsychological measures of cognitive decline.

Cellular Senescence in Temporal Lobe Epilepsy: A Neuropathological Study

Joanna Bartkiewicz, Matthias Koepp, Maria Thom

UCL

Purpose: Cellular senescence occurs towards the end of cell cycle. While most damaged cells undergo apoptosis, a programmed cell death, some enter senescence which protects the cell from apoptosis. Although neurons are postmitotic, they have also been shown to undergo senescence1. Senescence is part of normal ageing but has also been implicated in neurodegenerative diseases, as well as epilepsy. In temporal lobe epilepsy (TLE), MRI studies frequently report widespread cortical thinning that appears to progress with age. Previously, on larger cohort, we demonstrated that cortical thinning may reflect altered neuronal composition or disrupted cytoarchitectural organisation, as histological analysis did not reveal corresponding cortical thinning. Here we investigated whether there is a link between senescence and MRI-derived cortical thinning.

Methods: A subgroup of 8 patients with TLE from a cohort of 117 cases, including individuals with hippocampal sclerosis and no additional lesional pathology, were stratified into four groups based on pre-operative MRI measures of cortical thickness: left or right high cortical thinning (LHCT, n = 2; RHCT, n = 2) and left or right low cortical thinning (LLCT, n = 2; RLCT, n = 2). Temporal neocortical sections were immunohistochemically stained for double label: p16/NeuN, p16/Calretinin and p16/Iba1. For p16/Iba1 staining, an additional cohort of 20 patients was analysed (LHCT = 10 and LLCT = 10). These were quantified using cell detection and object classifiers in QuPath. Measures of positive cell counts as well as intensity of the markers were analysed.

Results: Patients with low cortical thinning in MRI, showed a narrow and localised expression of p16 at the crest of the gyrus, whereas cases with high cortical thinning revealed a ‘pan-cortical’ expression. Moreover, an inverse relationship between p16 and NeuN expression was observed in p16+/NeuN+ cells.

Conclusion: These preliminary findings indicate that senescence might be a marker of microstructural degeneration that may manifest as cortical thinning in MRI. MRI-derived cortical thinning in TLE does not necessarily correspond to widespread neuronal loss. Instead, cortical thinning may reflect altered neuronal composition in the form of neuropil loss (e.g. from dendritic retraction, spine loss, etc) associated with senescence. Although studies in mouse models of epilepsy have reported increased senescence in microglia2, we observed very few senescent microglia and with the majority of p16+ cells being neurons.

Age-dependent coupling of hyperphosphorylated tau and cognitive decline intemporal lobe epilepsy

Isha Puntambekar¹, Alicja MRZYGLOD¹, Joanna Bartkiewicz¹, Gareth Ambler³, Sallie Baxendale^1,2, Maria Thom^1,2, Matthias Koepp^1,2

¹UCL Queen Square Institute Of Neurology, ²National Hospital for Neurology and Neurosurgery, ³UCL Department of Statistical Sciences

Background: Hyperphosphorylated tau (pTau) is increasingly identified in temporal lobe epilepsy (TLE), but its contribution to cognitive function remains uncertain. While pTau accumulation is linked to neurodegeneration and progressive cognitive decline in Alzheimer’s disease, cognitive dysfunction in epilepsy arises from multiple interacting factors.We therefore examined whether pTau contributes to preoperative cognitive function and postoperative cognitive change beyond established clinical covariates.

Methods: Two-hundred and forty-four adults with drug-resistant TLE underwent standardised neuropsychological assessmentbefore and one year after unilateral temporal lobe resection. Resected temporal neocortex was analysed using AT8immunohistochemistry and semi-quantitatively scored for neuronal and dendritic pTau burden (0–5). The contribution of pTau to preoperative cognitive function, and postoperative change in function was modelled using hierarchical linear/logistic regressions adjusting for age, gender, seizure laterality and medication load.

Associations between age, pTau and verbal memory were additionally modelled in separate logistic regressions, either with a linear age term or restricted cubic splines to account for potential non-linearage effects.

Results: pTau burden increased progressively with age at surgery (ρ = 0.50, p < 0.001; range 16-67). An age cut-off of 38.5 years distinguished low (0-2) from high (3-5) pathological burden with 75% sensitivity and 73%specificity. However, pTau did not incrementally contribute to preoperative cognitive performance orearly postoperative cognitive change after accounting for established clinical covariates. Group-level age-trajectory analyses revealed a dissociation between pathology and cognition; the predicted probability ofhigh pTau linearly increased across adulthood. In contrast, the predicted probability of significant postoperative memory decline appeared to follow a non-linear trajectory, mirroring the shape of thepTau trajectory from approximately the fifth decade of life.

Conclusions: Our results suggest that progressive pTau accumulation in TLE may precede age-accelerated cognitivedecline by decades. A ‘tipping point’ for tau-associated cognitive decline may emerge in older ages with failure of compensatory reserve, but could not be identified in the observed age range. These findings position TLE as a human model for studying age-dependent interactions between pathological tauaccumulation, cognitive resilience and neurodegeneration.

Neurodegeneration Biomarkers Relate to Hippocampal Tau Signals and Sleep Spindle Activity

in Focal Epilepsy

Thaera Arafat^1,2, Tevy Chan^3,4, Jack Lam¹, Katharina Schiller⁵, Nicolas Von Ellenrieder¹, Andrea Bernasconi¹, Neda Bernasconi¹, Jean Gotman¹, Maria Thom², Matthias Koepp², Eliane Kobayashi⁶, Pedro Rosa-Neto^4,6, Boris Bernhardt¹

¹Montreal Neurological Institute-Hospital, McGill University, ²Research Department of Epilepsy, UCL Queen Square Institute of Neurology, University College London, ³Douglas Mental Health University Institute, McGill University, ⁴Research Institute of the McGill University Health Centre, ⁵Hospital Kaufbeuren, Department of Pediatric Neurology, 6Peter O’Donnell Jr. Brain Institute (OBI), University of Texas Southwestern Medical Centre (UTSW)

Rationale: Emerging evidence suggests shared pathophysiological mechanisms between epilepsy and neurodegeneration, with advances in neurodegeneration biomarkers, particularly phosphorylated tau-217 (pTau217), accelerating epilepsy research (Mo et al., 2019; Zawar, 2023). However, associations with in-vivo tau load and sleep spindle activity remain underexplored.

Methods: Seventeen patients with focal epilepsy from a multicentre cohort (mean age 35.9 ± 16.4 years; 9 females; 11 temporal lobe epilepsy) underwent (18F)MK-6240 positron emission tomography (PET) and 3T MRI. Imaging acquisition and analysis were harmonised across Montreal Neurological Institute-Hospital, Canada, and Chalfont Centre for Epilepsy, United Kingdom. Hippocampal tau uptake was quantified as mean bilateral standardized uptake value ratios (SUVRs) using the pons as the reference region. Plasma pTau217, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were measured using validated immunoassays. Overnight EEG was available in eight patients (47%), with N2 spindle rates quantified using automated detection algorithms.

Results: Mean hippocampal tau uptake showed a strong positive association with plasma GFAP (r=0.71, p=0.001), a moderate positive, non-significant association with pTau217 (r=0.44, p=0.08), and no association with NfL (r=−0.15, p=0.56). In the EEG subgroup, N2 spindle rate showed a strong negative correlation with pTau217 that did not reach statistical significance (r=−0.69, p=0.06), with no associations observed for GFAP (r=0.22, p=0.59) or NfL (r=−0.20, p=0.63).

Conclusion: These findings suggest an association between hippocampal tau uptake and astroglial activation and provide preliminary evidence that reduced sleep spindle activity may reflect early tau-related neurodegenerative processes in focal epilepsy

Loss of excitability homeostasis drives reversible tau accumulation during human brain ageing

Thaera Arafat¹, Alicja MRZYGLOD¹, Luisa Delazer¹, Kai Michael Schubert^1,3, Adolfo Mazzeo², Nicholas Fearns¹, Marian Galovic³, Maria Thom¹, Matthias Koepp¹

¹UCL, Queen Square Institute of Neurology, London, UK, ²Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy, ³Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland

Healthy cognitive ageing depends on the ability of neural circuits to maintain homeostatic regulation despite lifelong physiological stress. Progressive failure of this homeostatic reserve is thought to underlie neurodegeneration, yet the biological sequence linking early network dysfunction to later cognitive decline in humans remains poorly understood.

Here, we identify a multiscale pathway connecting impaired brain homeostasis to activity-dependent tau accumulation and cognitive ageing. By integrating magnetic resonance imaging of perivascular spaces, in vivo N-methyl-D-aspartate receptor positron emission tomography, intracranial microdialysis, human brain transcriptomics, histology, quantitative electroencephalography, longitudinal tau positron emission tomography and long-term cognitive follow-up.

We demonstrate convergent evidence that ageing is characterised by progressive disruption of excitatory homeostasis preceding structural degeneration. Reduced astrocytic glutamate transport is associated with elevated extracellular glutamate, persistent receptor overactivation and chronic network hyperexcitability within selectively vulnerable cognitive networks. Preoperative quantitative electroencephalographic markers identify physiological network states associated with subsequent distributed tau accumulation and long-term cognitive decline, whereas asymmetric enlargement of perivascular spaces consistent with altered glymphatic homeostasis is associated with memory trajectories independently of tau pathology, suggesting that impaired interstitial clearance represents an additional early contributor to network vulnerability. These processes localise to regions susceptible to tau accumulation and are markedly amplified in epilepsy, a translational model of accelerated brain ageing. Longitudinal analyses further demonstrate that successful surgical suppression of chronic network hyperexcitability is associated with lower subsequent whole-brain tau burden, whereas persistent seizures are associated with continued tau accumulation, indicating that activity-dependent tau propagation remains biologically modifiable.

Together, these findings support a unified model in which impaired glymphatic and astrocytic homeostasis progressively destabilise excitatory regulation, creating network states that facilitate tau propagation before age-dependent cognitive decompensation becomes clinically manifest. This framework identifies homeostatic failure as a fundamental mechanism of human brain ageing and highlights restoration of glutamate regulation and network activity as potential disease-modifying therapeutic strategies

Neuropathological correlates of clinical progression in childhood Rasmussen encephalitis(RE): a 30-year single-centre cohort study

Eva Ioannidou^1,2, Marios Kaliakatsos², Suresh Pujar², Torsten Baldeweg¹, Sophia Varadkar⁶, Christin Eltze², Robert Robinson², Martin Tisdall^1,7, Zubair Tahir⁷, Ashirwad Merve⁵, Tom Jacques^4,5, Helen Cross³

¹Developmental Neurosciences Department, ²Department of Paediatric Neurology, ³Director’s Office , ⁴Developmental Biology and Cancer Department, ⁵Neuropathology Department, ⁶Director’s Office , ⁷Paediatric Neurosurgery Department

Background: Rasmussen encephalitis (RE) is a rare immune-mediated encephalitis characterised by progressive unilateral hemispheric inflammation, neurological decline and drug-resistant seizures¹. While its pathological hallmarks are well recognised², their relationship with clinical phenotype and disease progression remains poorly understood.

Methods: We performed a retrospective clinico-pathological study of children with RE undergoing epilepsy surgery at Great Ormond Street Hospital over a 30-year period. Original neuropathology reports were systematically reviewed for inflammatory response, microglial nodules, perivascular lymphocytes, neuronophagia, neurodegeneration, hippocampal sclerosis (HS) and the presence of a comment of ‘dual pathology’³ within the sample. These features were correlated with demographic and clinical variables, including age at onset, epilepsia partialis continua (EPC), hemiparesis, cognitive decline and time to surgery.

Results: Fifty-seven children underwent surgery, of whom 52 (91%) had available neuropathology reports. Mean age at seizure onset was 6.3 years and median time to surgery was 3.7 years. Neurodegeneration was the commonest pathological finding (79%), followed by microglial nodules (67%) and neuronophagia (38%). A co-existing ‘dual pathology’ was reported in 29% of cases, while HS was present in 11/31 (35%) cases with available hippocampal tissue. HS was strongly associated with dual pathology (73% vs 15%; p=0.001). Neuronophagia was significantly associated with neurodegeneration (89% vs 66%; p=0.004), supporting active immune-mediated neuronal injury. Although no pathological feature predicted the presence of EPC, hemiparesis or cognitive decline, patients with reported neuronophagia and/or neurodegeneration developed EPC significantly earlier than those without these features (median 0.7 vs 1.6 years, p=0.024; and 1.0 vs 2.3 years, p=0.026, respectively). Greater inflammatory activity also showed a trend towards shorter time to surgery.

Conclusions: This represents the largest clinico-pathological analysis of paediatric RE to date, in the UK. Active neuronal injury was associated with earlier disease progression, while the strong association between HS and dual pathology suggests that consequent structural abnormalities may contribute to the pathological spectrum of RE. These findings provide new insights into the relationship between neuropathology and clinical evolution and generate hypotheses for future mechanistic studies.

References:

1. Varadkar, S. et al. Rasmussen’s encephalitis: clinical features, pathobiology, and treatment advances. Lancet Neurol. 13, 195–205 (2014).

2. Pardo, C. A. et al. The pathology of Rasmussen syndrome: stages of cortical involvement and neuropathological studies in 45 hemispherectomies. Epilepsia 45, 516–526 (2004).

3. Gilani, A. & Kleinschmidt-DeMasters, B. K. How frequent is double pathology in Rasmussen encephalitis? Clin. Neuropathol. 39, 55–63 (2020).

Somatic mosaicism in resected brain tissue: diagnostic rate and implications for patient care

Flavia Santo^1,2, Amy McTague^1,3, Natalie Chandler^2,7, Lara Menzies⁴, Thomas Cullup², Thomas S. Jacques^5,6, Martin M. Tisdall^1,8

¹Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, ²North Thames Genomic Laboratory Hub, Great Ormond Street NHS Foundation Trust , ³Department of Neurology, Great Ormond Street Hospital, London, UK; Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children., ⁴Department of Clinical Genetics, Great Ormond Street Hospital for Children, ⁵Department of Histopathology, Great Ormond Street NHS Foundation Trust, London, UK., ⁶Developmental Biology and Cancer Programme, UCL Institute of Child Health, ⁷Genetic and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, ⁸Department of Neurosurgery, Great Ormond Street Hospital for Children

Focal epilepsies may be associated with abnormal structural lesions (brain malformations) visible on MRI that are amenable to surgical resection. Somatic mosaicism, defined as post-zygotic genetic variability affecting only a subgroup of cells or tissues, may be responsible for 30%-40% of epilepsy cases with structural malformations. However, diagnosis remains challenging in routine practice, as mosaicism often occurs at low cellular fractions and may be absent from peripheral blood, limiting detection using standard NHS testing.

We performed deep next generation sequencing (NGS) on resected brain tissue from 50 paediatric patients with focal lesions, including cortical dysplasia (n=32), non-specific epilepsy-related changes (n=7), mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE; n=4), other malformations of cortical development and tuberous sclerosis complex. A targeted panel of 22 genes associated with focal epilepsy and mosaicism was used, achieving a median read depth of 1531× and detection sensitivity of 1% variant allele fraction. All pathogenic variants detected were validated using an orthogonal method and matched blood samples were tested, where available. Complex cases were reviewed in multidisciplinary team meetings consisting of neurology, imaging, histopathology and genomics professionals.

A genetic diagnosis was established in 25/50 patients (50%). Mosaic variants were identified in 14 patients (28%), and germline variants were detected in 10 (20%), including five copy number variants. One further patient harboured both a heterozygous germline and a mosaic variant in DEPDC5, supporting a second-hit mechanism.

Among the patients where follow-up information was available, 21/36 (58%) were seizure-free at 12 months post-surgery. Genetic findings informed various aspects of clinical management and counselling for patients and their families. For example, two patients with MOGHE and SLC35A2 variants are due to now receive D-galactose therapy. Informed reproductive counselling aided pregnancy-related counselling in a further family. In addition, further follow-up and screening was recommended for eight patients with mosaic variants in genes known to cause multi-system disorders e.g. Tuberous Sclerosis Complex, due to the risk of systemic manifestations.

These findings demonstrate that deep sequencing of brain tissue substantially improves diagnostic yield in focal epilepsy and provides clinically actionable information. Broader implementation of this approach within the NHS could reduce the proportion of undiagnosed patients and support precision medicine strategies in epilepsy care.

Focal astrocyte Kir4.1 loss drives seizures, spreading depolarisations and postictal impairments

Neela Codadu¹, Yunan Gao^1,2, Olga Tyurikova¹, Zixi Dai², Xueting Ban², Yuyan Weng², Eduard Masvidal-Codina³, Jose Garrido^3,4, Anton Guimera-Brunet^5,6, Dmitri Rusakov¹, Kevan Hashemi⁷, Nicholas Mazarakis², Rob Wykes^1,8

¹Research Department of Epilepsy, Queen Square Institute of Neurology, University College London, ² Gene Therapy, Division of Neuroscience, Department of Brain Sciences, Faculty of Medicine, Imperial College London, ³Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Campus UAB, ⁴Institució Catalana de Recerca i Estudis Avançats (ICREA), ⁵Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), ⁶Institut de Microelectrònica de Barcelona, IMB-CNM (CSIC), ⁷Open Source Instruments Inc, ⁸Division of Neuroscience & Centre for Nanotechnology applied to Medicine, University of Manchester

Introduction: Astrocytes regulate neuronal excitability through potassium buffering mediated by Kir4.1 inwardly-rectifying potassium channels. Reduced astrocytic Kir4.1 expression has been reported in human temporal lobe epilepsy, yet its causal role in epileptogenesis remains unclear. In epilepsy, spreading depolarisations (SDs), slowly propagating waves of neuronal and glial depolarisation, are temporally associated with seizures (SzSD) and have been implicated in postictal (period immediately following seizure termination) dysfunction and Sudden Unexpected Death in Epilepsy. However, whether focal astrocytic Kir4.1 loss acquired in adult brain networks is sufficient to drive seizures and SDs, and how SDs influence the postictal state, is unknown.

Methods: We generated focal Kir4.1 knockout mice (Kir4.1-cKO) by deleting the Kcnj10 gene encoding Kir4.1 channels in hippocampal astrocytes of adult Kir4.1-floxed mice using viral Cre recombinase. Ex vivo validation of Kir4.1 loss was performed using western blotting. Extracellular potassium dynamics were examined in hippocampal slices by measuring genetically encoded potassium indicator (GINKO2) fluorescence. To test seizure and SD susceptibility in vivo, optogenetics and DC-coupled graphene micro-transistor arrays were used in awake head-fixed mice. Continuous AC-coupled and video-DC-coupled iEEG telemetry recordings were employed to characterise the emergence of spontaneous seizures and SD.

Results: Kir4.1-cKO showed significantly reduced Kir4.1 protein expression (controls vs cKO: P=0.03). Electrical stimulation of Schaffer collaterals evoked larger GINKO2 fluorescence responses in CA1 stratum radiatum, indicating impaired potassium buffering. Chronic AC-coupled telemetry in Kir4.1-cKO revealed the emergence of spontaneous seizures 7–10 days post-viral injection. In awake head-fixed mice, Kir4.1-cKO hippocampal networks showed increased susceptibility to optogenetic stimulation-induced seizures-alone and SzSD. SzSD profoundly altered the postictal state, resulting in significantly prolonged postictal depression and delayed recovery compared with seizures-alone (P=0.016). Chronic video-DC-coupled telemetry (n = 6 mice, 3 weeks) revealed spontaneous seizures-alone and SzSD events. Compared with seizures-alone, SzSD exhibited higher power (P<0.0001) and greater postictal depression (P<0.0001). Video-DC-coupled iEEG analysis showed that SD-associated seizures exhibited a severe behavioural phenotype (maximum Racine score: 5-6), and postictal behaviour during the120s following seizure termination was characterised by behavioural arrest, loss of posture, and body jerks for ~87% of the postictal period, compared with ~1.7% following seizures-alone (P<0.0001), consistent with delayed functional recovery.

Conclusion: Focal hippocampal astrocytic Kir4.1 loss is sufficient to drive spontaneous seizures accompanied by frequent SDs, which markedly exacerbate postictal dysfunction. These findings provide mechanistic insight into how impaired astrocytic potassium buffering promotes epileptogenesis and seizure-associated pathology.

Modelling Depdc5 loss of function in rat primary cortical neurons

Angus Gane^1,2,3,4, Madeleine Marshall1, Marie Pronot^1,3,4, Alfredo Gonzalez-Sulser^1,3,4, Michael Cousin^1,3,4

¹University of Edinburgh, ²NHS Lothian, ³Simons Initiative for the Developing Brain, ⁴Muir Maxwell Epilepsy Centre

Background: Genetic variants in DEPDC5 are the most common cause of genetic focal epilepsy. DEPDC5 is known to form a complex with NPRL2 and NPRL3 termed GATOR1 which inhibits the mTOR signalling pathway. A rat model of Depdc5 loss of function induced by in utero electroporation produces focal seizures making the rat an exciting model to elucidate the mechanisms underlying DEPDC5-related epilepsy. We have developed a model of Depdc5 knockdown in cortical neuronal cultures to investigate the role of Depdc5 in neurons.

Methods: Lentiviruses expressing three short hairpin RNA (shRNA) systems and a scrambled control were synthesised. Rat primary cortical neuronal cultures were prepared from E16-18 embryos transduced after one day in vitro (DIV1). RNA was extracted for cDNA synthesis and quantitative PCR at 72 hours post transduction to determine the extent of knockdown. Two pairs of primers targeting the C and N termini of Depdc5 were normalised to the reference gene Tbp. Protein extraction and Western blot analysis was performed at DIV10 and normalised to total protein and βIII-Tubulin. Cells were fixed at DIV5 for immunocytochemical analysis of soma size, pS6/S6 intensity and neurite complexity using antibodies against MAP2 to determine if previously reported phenotypes are detectable in culture.

Results: Lentiviruses expressing shRNA2 and shRNA3 reduced both Depdc5 transcript expression and protein expression. No change was observed in soma size, pS6/S6 or dendritic complexity at DIV5, despite a high transduction efficiency. Excitatory and inhibitory synapse quantification, calcium imaging and multielectrode array recordings to determine culture excitability are ongoing.

Conclusion and future directions: We have established a rat primary cortical neuronal culture model of Depdc5 loss of function. At the timepoints analysed, we found no evidence of previously reported phenotypes associated with Depdc5 loss of function and mTORC1 activation. Future work will assess these phenotypes at later time points and examine whether a network level hyperexcitability phenotype using calcium imaging and multielectrode array recordings can be identified. Establishment of this model will reveal insights into the function of Depdc5 in neurons and potentially provide a platform for screening possible therapeutic targets.

A Gut Feeling About Epilepsy: A Systematic Review and Meta-Analysis of Gut Microbiota Alterations in People with Epilepsy

Pooja Goswami¹, Prem Jareonsettasin^2,3, Josemir W. Sander^2,3,4

¹Faculty of Health, Medicine and Life Sciences, Maastricht University, ²UCL Queen Square Institute of Neurology, ³Social Determinants of Health in Epileptic Disorders (SdHIELD) Research Group, ⁴Department of Neurology, West China Hospital, Sichuan University

Background: Epilepsy is a common neurological disorder associated with significant clinical and social burden. It is a symptom complex with multiple possible underlying mechanisms. Emerging work suggests that the gut microbiota may play a role in epileptogenesis through the microbiota-gut-brain axis. However, findings on gut microbiota alterations in epilepsy compared to controls remain inconsistent.

Objective: To explore gut microbiota diversity and composition between individuals with epilepsy and healthy controls, focusing on Shannon α-diversity, β-diversity, and exploratory phylum-level relative abundance. Secondary analyses explored whether gut microbiota patterns differed across subgroups, including drug-resistant epilepsy, age group, and geographical location.

Methods: A systematic search was conducted to identify studies investigating gut microbiota composition in people with epilepsy. Eligible studies comparing people with epilepsy to controls were included in meta-analysis when sufficient α-diversity data were available. Standardised mean differences (SMD) were estimated for Shannon α-diversity using a random-effects model. Reported beta diversity findings were summarised descriptively, while the relative abundance of taxa was explored using comparative statistical analyses. Subgroup and sensitivity analyses explored potential sources of heterogeneity, including age group and influential studies.

Results: Included studies (n= 31) varied substantially in population characteristics, epilepsy type, and control-group selection. Qualitative synthesis of taxonomic findings suggested alterations in major bacterial phyla, particularly Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria, although findings were inconsistent across studies. β-diversity more consistently suggested distinct clustering between epilepsy and control samples. Meta-analysis of Shannon α-diversity showed no significant overall difference between epilepsy and control groups (SMD = −0.02, 95% CI −0.92 to 0.88, p = 0.96), with substantial heterogeneity (I² = 92%). Exploratory analysis of phylum-level relative abundance showed no significant differences between epilepsy and control groups after adjustment for multiple testing. However, Proteobacteria was numerically higher in people with epilepsy. Subgroup analyses by age group, drug sensitivity and geographical location showed no significant difference.

Conclusion: No significant differences in Shannon w-diversity or phylum-level relative abundance were identified between epilepsy and controls. β-diversity findings suggested differences in overall microbial community composition, indicating that epilepsy may be associated with compositional shifts. Subgroup analyses reported no statistical differences. However, reverse causality cannot be ruled out, as seizure burden, long-term ASM use, and disease- or lifestyle-related factors may also contribute to alterations in microbiota. Current evidence remains heterogeneous, and larger standardised studies with detailed participant data are needed to identify epilepsy-associated microbiome signals.

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ILAE British Branch

ILAE British Branch 2026 | 8 - 10 October | Harrogate Conference Centre