This report presents key insights from the 2022 annual conference held in Edinburgh, commemorating the 10th anniversary of the discovery of ATP1A3 variants in alternating hemiplegia of childhood (AHC). This milestone event marked a decade of rapid advancements in research and clinical understanding, bringing together international experts and those with lived experience to reflect on progress, identify ongoing challenges, and shape the future of ATP1A3-related disease research. Over the past 10 years, our knowledge of ATP1A3-related diseases has expanded significantly, revealing a broader clinical spectrum, complex genotype-phenotype correlations, and novel pathophysiologic mechanisms. This symposium provided new data on cardiac and respiratory involvement in AHC, the impact of Na+, K+-ATPase dysfunction on neurodevelopment, and the evolving understanding of progressive disease trajectories. The conference also showcased emerging therapeutic strategies, including gene therapy, antisense oligonucleotides, and small-molecule interventions. This article synthesizes these discussions, offering a comprehensive overview of a decade of progress while highlighting the urgent need for continued collaboration. By integrating research, clinical expertise, and lived experience advocacy, the ATP1A3 community is paving the way for improved diagnosis, enhanced care, and the development of targeted treatments for these ultra-rare conditions.

OBJECTIVE:Epilepsy surgery is a standard treatment for drug-resistant epilepsy, resulting in seizure freedom in a significant number of cases. Although frequently performed for low-grade brain tumors, it is rarely considered for high-grade tumors, despite the impact of chronic epilepsy on quality of life and cognition. METHODS:This retrospective multicenter study across 43 European centers evaluated epilepsy surgery outcomes in children with high-grade brain tumors (World Health Organization grades III and IV). Two cohorts of patients younger than 25 years were studied: (1) those undergoing epilepsy surgery after tumor resection (n = 14) and (2) those initially suspected of low-grade lesions but diagnosed with high-grade brain tumors postsurgery (n = 11). RESULTS:Eighty percent of patients achieved seizure freedom 1 year after last epilepsy surgery: 71% in Cohort 1 and 91% in Cohort 2. Eighty-four percent were free of disabling seizures (Engel IA-D) after a median follow-up period of 4.3 years (range = 1-15.9 years). No surgery-related deaths occurred. Thirty-two percent of children experienced persistent morbidity, including motor dysfunction, visual impairment, persistent seizures, cognitive deficits, and hydrocephalus. SIGNIFICANCE:Epilepsy surgery is effective for medically refractory epilepsy in children with high-grade central nervous system tumors and should be considered early, as seizure freedom is achieved in the majority of patients. Despite involving numerous epilepsy centers, only 25 patients were recruited, indicating that this method is rarely considered for high-grade brain tumor patients with medically refractory epilepsy.

Background Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder. Aims To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes. Method Euthymic individuals with bipolar disorder (N = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention. Results Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex (P = 0.025) and fell by 13.6% in the posterior cingulate cortex (P = <0.001). Conclusions These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.

BACKGROUND:Bipolar disorder is a serious mental illness, which requires new strategies for prevention and management. Recent evidence suggests that a ketogenic diet may be an effective intervention. This research aimed to explore the feasibility and acceptability of a ketogenic diet intervention for bipolar disorder, fidelity to its behavioural components and the experiences of the participants and research clinicians involved. METHODS:A mixed-methods process evaluation was conducted. Semi-structured telephone interviews were carried out with 15 participants 1-2 months after completing a 6-8 week modified ketogenic diet intervention, and 4 research clinicians from the study team following the completion of data collection. Data were thematically analysed. Fidelity checklists completed by research dietitians were analysed using descriptive count and percentage statistics. Findings are reported post-hoc, following the analysis and publication of the main pilot study findings. Reporting was guided by the COREQ checklist. RESULTS:Five themes were identified in the qualitative data: (1) 'Encouraging entry and supporting exit' (e.g. recognising and managing participants' varied motives and expectations, including around weight loss and symptom alleviation); (2) 'Challenging but potentially transformational,' which reflects that while it can be difficult to initiate and maintain a ketogenic diet day-to-day, many participants perceived physical and psychological benefits (e.g. significant weight loss, mood stability and enhanced ability to focus); (3) 'Intervention facilitators,' including a range of behavioural (e.g. goal setting), social (e.g. family and dietitians) and technological (e.g. apps for monitoring) support mechanisms; (4) 'Intervention barriers' (e.g. dietary preferences, concerns about the diet and its impact, the testing burden and capacity of the delivery team); and (5) 'The wider context' (e.g. the cost of living and sociocultural expectations) was a crucial factor explaining differential experiences. Overall, descriptive analyses indicated moderate-to-good fidelity to the behaviour change components of the study. CONCLUSION:We provide novel insight into the experiences of people living with bipolar disorder initiating and following a ketogenic diet, as well as those of research clinicians who support the intervention. Future trials may benefit from increased clinical research capacity, better-defined entry and exit routes, additional interpersonal support, and greater understanding of how social and societal factors impact participation. TRIAL REGISTRATION:Study registration number: ISRCTN61613198 (02/03/22).

This report presents key insights from the 2022 annual conference held in Edinburgh, commemorating the 10th anniversary of the discovery of ATP1A3 variants in alternating hemiplegia of childhood (AHC). This milestone event marked a decade of rapid advancements in research and clinical understanding, bringing together international experts and those with lived experience to reflect on progress, identify ongoing challenges, and shape the future of ATP1A3-related disease research. Over the past 10 years, our knowledge of ATP1A3-related diseases has expanded significantly, revealing a broader clinical spectrum, complex genotype-phenotype correlations, and novel pathophysiologic mechanisms. This symposium provided new data on cardiac and respiratory involvement in AHC, the impact of Na+, K+-ATPase dysfunction on neurodevelopment, and the evolving understanding of progressive disease trajectories. The conference also showcased emerging therapeutic strategies, including gene therapy, antisense oligonucleotides, and small-molecule interventions. This article synthesizes these discussions, offering a comprehensive overview of a decade of progress while highlighting the urgent need for continued collaboration. By integrating research, clinical expertise, and lived experience advocacy, the ATP1A3 community is paving the way for improved diagnosis, enhanced care, and the development of targeted treatments for these ultra-rare conditions.

AIM:To evaluate improvement in knowledge and clinical behaviour among healthcare professionals after attendance at paediatric epilepsy training (PET) courses. METHOD:Since 2005, 1-day PET courses have taught evidence-based paediatric epilepsy management to doctors and nurses in low-, middle-, and high-income countries. A cohort study was performed of 7528 participants attending 252 1-day PET courses between 2005 and 2020 in 17 low-, middle-, and high-income countries, and which gathered data from participants immediately after the course and then 6 months later. Training outcomes were measured prospectively in three domains (reaction, learning, and behaviour) using a mixed-methods approach involving a feedback questionnaire, a knowledge quiz before and after the course, and a 6-month survey. RESULTS:Ninety-eight per cent (7217 of 7395) of participants rated the course as excellent or good. Participants demonstrated knowledge gain, answering a significantly higher proportion of questions correctly after the course compared to before the course (88% [47 883 of 54 196], correct answers/all quiz answers, vs 75% [40 424 of 54 196]; p < 0.001). Most survey responders reported that the course had improved their epilepsy diagnosis and management (73% [311 of 425]), clinical service (68% [290 of 427]), and local epilepsy training (68% [290 of 427]). INTERPRETATION:This was the largest evaluation of a global epilepsy training course. Participants reported high course satisfaction, showed knowledge gain, and described improvements in clinical behaviour 6 months later. PET supports the global reduction in the epilepsy 'treatment gap' as promoted by the World Health Organization.

Epilepsy and obstructive sleep apnea syndrome (OSAS) are each relatively common in children. OSAS may affect cognition, such that recognition of OSAS is important for children and young people with epilepsy (CYPWE). Published pilot data reported 55 https://www.clinicaltrials.gov/study/NCT03103841 ; Identifier: NCT03103841.

Background Many infancy-onset epilepsies have a poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in older children and adults unresponsive to antiseizure medicines. We aimed to determine the effectiveness of the ketogenic diet in reducing seizure frequency compared to further antiseizure medicine in infants with drug-resistant epilepsy. Methods In this randomised, open-label trial, 136 infants with epilepsy, aged 1–24 months, with > 4 seizures/week and a previous trial of ≥ 2 antiseizure medicines were recruited from 19 hospitals in the United Kingdom. Following a 1- or 2-week observation period, participants were randomised to receive the classical ketogenic diet or a further antiseizure medicine for 8 weeks, using a computer-generated schedule without stratification. Treatment allocation was concealed from research nurses involved in patient care, but not from participants. The primary outcome was the number of seizures/day recorded during weeks 6–8. All analyses were intention to treat. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). Findings Between 1 January 2015 and 30 September 2021, 136 eligible infants were randomised. Sixty-one (78%) of 78 assigned to a ketogenic diet and 47 (81%) of 58 assigned to antiseizure medicine had primary outcome data. At 8 weeks, the number of seizures per day, accounting for the baseline rate and randomised group, was not significantly different between groups [median (interquartile range) ketogenic diet 5 (1, 16); antiseizure medicine 3 (2, 11), incidence rate ratio 1.33, 95%, confidence internal 0.84 to 2.11; p = 0.22]. A similar number of infants reported at least one serious adverse event in both groups [antiseizure medicine: 24/56 (43%), ketogenic diet: 40/78 (51%)]. The most common serious adverse events were seizures in both groups. Three infants died during the course of the trial, all of whom were randomised to the ketogenic diet arm; deaths were considered to be unrelated to treatment. Interpretation There was no evidence that a ketogenic diet was better than further antiseizure medicine in achieving seizure control in infants with epilepsy. The two treatments were similarly tolerated and a ketogenic diet appears safe to use in infants with epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite trial of two standard antiseizure medicines. Study registration This study was registered as EudraCT 2013-002195-40. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/10/18) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 16. See the NIHR Funding and Awards website for further award information. Plain language summary Many babies with epilepsy continue to have seizures (‘fits’), despite taking medicines. These babies are unlikely to make the same developmental progress as babies without epilepsy. Ketogenic diets are high in fat and low in carbohydrate and have been shown to reduce seizures in older children and adults. Babies (age 1–24 months) with epilepsy, who still had seizures despite having tried medicines, either started a ketogenic diet or another medicine. They then stayed on this treatment for 8 weeks. We wanted to know whether there was a difference in the number of seizures in the last 2 weeks of treatments compared to before. Seventy-eight babies started a ketogenic diet and 58 started another medicine. Overall, the number of seizures babies had every day was similar in both groups. A similar number of babies in both groups either had to go to hospital for some reason or stay in hospital for longer. This was mostly because of seizures. Two babies suffered ‘sudden unexpected death in epilepsy’ and another died during a planned surgery. These deaths were not thought to be related to the ketogenic diet. Both the ketogenic diet and the medicines helped to reduce the number of seizures in the babies. Babies in both groups had similar side effects. Doctors could consider starting a ketogenic diet in babies who continue to have seizures even though they have tried medicines to stop their seizures. Scientific summary Background Many infancy-onset epilepsies are poorly responsive to antiseizure medicines (ASMs) with poor prognosis for neurodevelopmental outcome. Ketogenic diets (KDs), which are high-fat, low-carbohydrate diets, have been shown to reduce seizures in older children with drug-resistant epilepsy. No high-quality evidence is available for infants. Objectives In this open-label randomised controlled trial, we compared the efficacy of the classical KD to a further appropriate ASM in infants with drug-resistant epilepsy. The primary outcome was the number of seizures recorded during weeks 6–8, accounting for the baseline rate and randomised group. Secondary outcomes at 8 weeks were the number of infants seizure-free in weeks 6–8 of the intervention period, responder rate (defined as the number showing more than a 50% improvement in seizure frequency compared to baseline), tolerance to KD and relationship between medium-chain fatty acids and seizure control. Secondary outcomes at 12 months were retention on treatment, quality of life and neurodevelopmental outcome. Adverse events were recorded throughout the trial. Serious adverse events were reported to the study sponsor. Methods Infants (age 1–24 months) with epilepsy, with an average ≥ 4 seizures/week and previous trials of ≥ 2 ASMs were recruited from 19 hospitals in the UK. Following a 1- or 2-week observation period, during which there were no changes to regular ASMs (emergency seizure treatments continued as required), participants were randomised to receive a classical KD or a further ASM for 8 weeks, using a computer-generated schedule without stratification. An allocation ratio of 1 : 1.35 was used to account for the therapist effect in the KD group only. Treatment allocation was concealed from research nurses involved in patient care, but not from participants. The primary outcome was the number of seizures/day recorded during weeks 6–8. All analyses were intention to treat. The following assessments were performed in all infants prior to randomisation: medical history, physical examination, administration of the Infant Toddler Quality of Life Questionnaire™ (ITQOL-97; © HealthActCHQ Inc. 2013) and Vineland Adaptive Behaviour Scales (Vineland™-II), and clinical laboratory assessments. Food diaries required for diet calculation were returned from parents/guardians of all participants a maximum of 1 week into the observation period. Parents/carers were asked to keep daily seizure diaries throughout the 8-week treatment periods for participants in both arms. Thereafter, they were requested to reduce seizure recording to at least 1–2 days per week, as clinically indicated, until 28 days before the final 12-month visit, when daily seizure recording recommenced. Follow-up visits were arranged at 4 weeks, 8 weeks, and 6, 9 and 12 months. Assessments included clinical review, physical examination, documentation of seizure frequency from seizure diaries, review of adverse events and concomitant medication, clinical laboratory assessments (8 weeks, and 6 and 12 months) and completion of tolerability questionnaire by parents/carers together with research nurses, the ITQOL-97 (8 weeks and 12 months) and Vineland-II (12 months). After the 8-week assessment, according to the infant’s clinical response to treatment (seizure outcome and tolerability), KD or ASM was then continued or changed; those randomised to the ASM arm then had the opportunity to start KD. Results Of 136 eligible infants, 78 were randomised to KD and 58 to ASM. Of 78 infants who started KD, 67 (86%) continued to 8 weeks, of which 61 (78%) had primary outcome data available; 53 (91% of those randomised to ASM group) started a further ASM, 49 (84%) continued to 8 weeks and 47 (81%) had primary outcome data available. The median number of daily seizures was not significantly different in both groups at 8 weeks [KD 5 (1, 16); ASM 3 (2, 11), incidence rate ratio (IRR) 1.33, 95% confidence interval (CI) 0.84 to 2.11; p = 0.22]. The odds ratio (OR) of achieving ≥ 50% seizure reduction was 1.21 (95% CI 0.55 to 2.65) and 0.88 (0.27 to 2.80) for seizure freedom. A total of 7/63 infants (11%) in the KD group were seizure-free, compared with 6/48 (13%) in the ASM group (OR 0.88, 95% CI 0.27 to 2.80). A higher proportion of infants in the ASM group changed the number or dose of concurrent ASMs during the intervention period [24/48 (50%)] compared to KD [9/66 (14%)]. The side-effect score at 8 weeks was similar in both groups [KD median 40; interquartile range (IQR) 38–42; ASM median 41 IQR 39‒44) and there were no clinically significant differences other than those expected in clinical or laboratory parameters between groups. At 8 weeks, median scores within the ITQOL-97 were numerically higher (suggesting better health) in the KD group for 7 of the 12 concepts. The infant’s pain, its global behaviour, impact on parental time and family cohesion were equal between the two groups, although general perceptions of the infant’s health were numerically higher in the ASM arm. A numerically larger proportion of parents/guardians of infants in the KD group perceived their child’s health to be ‘much better than a year ago’ (10/40, 25%) compared to those in the ASM group (3/32, 9%); numerically more parents/guardians of infants in the ASM group perceived their child’s health to be ‘much worse than a year ago’ (8/32, 25%) compared to those in the KD group (2/40, 5%). Of 66 infants randomised to KD > 12 months before the study end date, 31 (47%) continued the diet to 12 months; of 47 randomised to further ASM > 12 months before the study end date, 21 (45%) continued the ASM to 12 months. For those who reported data, there were no differences between groups for any concept within the ITQOL-97 at 12 months, except for the infant’s temperament and mood (coefficient −6.09, 95% CI −11.63 to −0.54) and the infant getting along with others (coefficient −6.79, 95% CI −12.97 to −0.60), which favoured the ASM group. A similar proportion of parents/guardians of infants in both groups perceived their child’s health to be ‘much better than a year ago’ (12/24 50% ASM; 11/30 37% KD) or ‘much worse than a year ago’ (0/24, 0% ASM; 1/30, 3% KD). Within the Vineland-II there were neither significant differences between groups in the overall standardised score nor domain standard scores at 12 months. The Daily living domain sum of v-scale scores was nominally improved in the ASM group (coefficient 2.23, 95% CI −4.22 to −0.25). A total of 73 serious adverse events (SAEs) were reported in the ASM group and 161 in the KD group. A similar proportion of infants in both groups reported at least 1 SAE (43% ASM; 51% KD) – most commonly seizures. Three infants died in the KD arm, all considered unrelated to treatment. Conclusions There was no evidence that KD was better than further ASM in achieving seizure control in infants with epilepsy. The two treatments were similarly tolerated and KD appeared safe to use in infants with epilepsy. KD could be a treatment option in infants whose seizures continue despite trial of two standard ASMs. Further trials are needed with larger cohorts at 12-month follow-up and beyond, particularly to look at quality of life and neurodevelopment, perhaps with alternative study design. Study registration This study was registered as EudraCT 2013-002195-40. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/10/18) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 16. See the NIHR Funding and Awards website for further award information.

Background Many infancy-onset epilepsies have poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in children older than 2 years and adults who are unresponsive to antiseizure medicines. We aimed to establish the efficacy of a classic ketogenic diet at reducing seizure frequency compared with further antiseizure medicine in infants with drug-resistant epilepsy. Methods In this phase 4, open-label, multicentre, randomised clinical trial, infants aged 1-24 months with drug-resistant epilepsy (defined as four or more seizures per week and two or more previous antiseizure medications) were recruited from 19 hospitals in the UK. Following a 1-week or 2-week observation period, participants were randomly assigned using a computer-generated schedule, without stratification, to either a classic ketogenic diet or a further antiseizure medication for 8 weeks. Treatment allocation was masked from research nurses involved in patient care, but not from participants. The primary outcome was the median number of seizures per day, recorded during weeks 6-8. All analyses were by modified intention to treat, which included all participants with available data. Participants were followed for up to 12 months. All serious adverse events were recorded. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). The trial was terminated early before all participants had reached 12 months of follow-up because of slow recruitment and end of funding. Findings Between Jan 1, 2015, and Sept 30, 2021, 155 infants were assessed for eligibility, of whom 136 met inclusion criteria and were randomly assigned; 75 (55%) were male and 61 (45%) were female. 78 infants were assigned to ketogenic diet and 58 to antiseizure medication, of whom 61 and 47, respectively, had available data and were included in the modifified intention-to-treat analysis at week 8. The median number of seizures per day during weeks 6-8, accounting for baseline rate and randomised group, was similar between the ketogenic diet group (5 [IQR 1-16]) and antiseizure medication group (3 [IQR 2-11]; IRR 1 center dot 33, 95% CI 0 center dot 84-2 center dot 11). A similar number of infants with at least one serious adverse event was reported in both groups (40 [51%] of 78 participants in the ketogenic diet group and 26 [45%] of 58 participants in the antiseizure medication group). The most common serious adverse events were seizures in both groups. Three infants died during the trial, all of whom were randomly assigned a ketogenic diet: one child (who also had dystonic cerebral palsy) was found not breathing at home; one child died suddenly and unexpectedly at home; and one child went into cardiac arrest during routine surgery under anaesthetic. The deaths were judged unrelated to treatment by local principal investigators and confirmed by the data safety monitoring committee. Interpretation In this phase 4 trial, a ketogenic diet did not differ in efficacy and tolerability to a further antiseizure medication, and it appears to be safe to use in infants with drug-resistant epilepsy. A ketogenic diet could be treatment option in infants whose seizures continue despite previously trying two antiseizure medications. Funding National Institute for Health and Care Research. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Background Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date. Aims To assess the recruitment and feasibility of a ketogenic diet intervention in bipolar disorder. Method Euthymic individuals with bipolar disorder were recruited to a 6–8 week trial of a modified ketogenic diet, and a range of clinical, economic and functional outcome measures were assessed. Study registration number: ISRCTN61613198. Results Of 27 recruited participants, 26 commenced and 20 completed the modified ketogenic diet for 6–8 weeks. The outcomes data-set was 95% complete for daily ketone measures, 95% complete for daily glucose measures and 95% complete for daily ecological momentary assessment of symptoms during the intervention period. Mean daily blood ketone readings were 1.3 mmol/L (s.d. = 0.77, median = 1.1) during the intervention period, and 91% of all readings indicated ketosis, suggesting a high degree of adherence to the diet. Over 91% of daily blood glucose readings were within normal range, with 9% indicating mild hypoglycaemia. Eleven minor adverse events were recorded, including fatigue, constipation, drowsiness and hunger. One serious adverse event was reported (euglycemic ketoacidosis in a participant taking SGLT2-inhibitor medication). Conclusions The recruitment and retention of euthymic individuals with bipolar disorder to a 6–8 week ketogenic diet intervention was feasible, with high completion rates for outcome measures. The majority of participants reached and maintained ketosis, and adverse events were generally mild and modifiable. A future randomised controlled trial is now warranted.

To report incidence, demographic and clinical characteristics, and symptom outcome of functional neurological disorder (FND) in children.

One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted 'gold-standard' subcohort of seizure-free patients with FCD type IIB who had T1 and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions in individuals with epilepsy.

Aims Epilepsy is reported to affect 63,400 young people in the UK,1 with focal epilepsy accounting for 60% of paediatric epilepsy syndromes.2 Here we report clinical outcomes in a population cohort with focal epilepsy and factors predicting outcomes. Methods An epilepsy database was created using routinely collected clinical data including: age at diagnosis, sex, pre-existing neurological conditions, neurodevelopmental comorbidities, seizure frequency (multiple daily, 1-7 per week, 2-4 per month, 1-12 per year), onset type of seizure (motor or non-motor), awake status during seizure, awareness during seizure, education type, epilepsy syndrome diagnosis, secondary generalisation, number of anti-epileptic drugs, side effects, nonpharmacological management, and outcomes of seizure control one and two years after diagnosis. This database was linked to a neurophysiology and neuroimaging database to collect EEG and MRI findings. Data were analysed by descriptive statistics and binomial logistic regression to determine the predictive effect of the previously described variables on seizure control one and two years post diagnosis. ANOVA chi-square test was used to determine statistical significance. Odds were interpreted by exponentiating the coefficient outcomes. Rstudio Version 1.1.456 software was used. Results One year after diagnosis, 53% of children reached seizure control, increasing to 58% after two years (table 1). Predictors of control at one year include; Presence of a neurodevelopmental condition (p<0.05), awareness level during a seizure (p<0.05), onset type of seizure (p<0.05), Education type (p<0.05) and number of anti-epileptic drugs used (p<0.05). Presence of a neurodevelopmental condition made control of seizure at one year 42% less likely, mixed motor and non-motor onset decreased likelihood by 92%, and mainstream education with support, specialist schooling, and not yet being in nursery at diagnosis decreased likelihood of control at one year by 81%, 91%, and 34% respectively. Being on one, two and more than two antiepileptic drugs decreased odds of seizure control by 8%, 78%, and 85%. Loss of awareness during seizure indicated a 6.71 times increase in odds of seizure control, while a non-motor onset of seizure indicated a 1.09 increase in odds. Age at diagnosis (p<0.001) was a predictor for seizure control after two years. Conclusion We report outcomes of paediatric focal epilepsy from a population database. We found statistically significant positive predictive factors of seizure control one year post diagnosis including awareness loss during seizures and non-motor onset of seizure. Negative predictive factors include having neurodevelopmental conditions, mixed onset and non-motor onset, mainstream education with support, specialist schooling, not yet being in nursery, and requiring antiepileptic drugs. Age at diagnosis was a statistically significant predictor for seizure control two years after diagnosis. This data may help clinicians counsel families on potential epilepsy outcomes. References Epilepsy prevalence, incidence and other statistics, Joint Epilepsy Council. Partial seizures in children-incidence, EEG and CT scan as diagnostic aid. Chandra, et al.