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Objective: To assess the effectiveness and tolerability of brivaracetam (BRV) in adults with epilepsy by specific comorbidities and epilepsy etiologies., Methods: EXPERIENCE/EPD332 was a pooled analysis of individual patient records from several non-interventional studies of patients with epilepsy initiating BRV in clinical practice. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within prior 3 months), continuous seizure freedom (no seizures since baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Analyses were performed for all adult patients (≥ 16 years of age) and stratified by comorbidity and by etiology at baseline (patients with cognitive/learning disability [CLD], psychiatric comorbidity, post-stroke epilepsy, brain tumor-related epilepsy [BTRE], and traumatic brain injury-related epilepsy [TBIE])., Results: At 12 months, ≥ 50% seizure reduction was achieved in 35.6% (n = 264), 38.7% (n = 310), 41.7% (n = 24), 34.1% (n = 41), and 50.0% (n = 28) of patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE, respectively; and continuous seizure freedom was achieved in 5.7% (n = 318), 13.7% (n = 424), 29.4% (n = 34), 11.4% (n = 44), and 13.8% (n = 29), respectively. During the study follow-up, in patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE, 37.1% (n = 403), 30.7% (n = 605), 33.3% (n = 51), 39.7% (n = 68), and 27.1% (n = 49) of patients discontinued BRV, respectively; and TEAEs since prior visit at 12 months were reported in 11.3% (n = 283), 10.0% (n = 410), 16.7% (n = 36), 12.5% (n = 48), and 3.0% (n = 33), respectively., Conclusions: BRV as prescribed in the real world is effective and well tolerated among patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE., (© 2024. The Author(s).)

This analysis assessed the effectiveness and tolerability of brivaracetam (BRV) in older (≥65 years of age) and younger (≥16 to <65 years of age) adults with epilepsy. This was a subgroup analysis from EXPERIENCE/EPD332, a pooled analysis of individual patient records from multiple independent, non-interventional studies of patients with epilepsy starting BRV in Australia, Europe, and the United States. Included patients had ≥6 months of follow-up data. Outcomes included responders (≥50 % reduction from baseline in seizure frequency), seizure freedom (no seizures within 3 months before the time point), and continuous seizure freedom (no seizures from baseline) at 12 months; BRV discontinuation during the whole study follow-up; and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Patients with missing data after BRV discontinuation were deemed non-responders/not seizure-free. Analysis populations included the Full Analysis Set (FAS; patients who received ≥1 BRV dose and had seizure type and age documented at baseline) and the modified FAS (FAS patients who had ≥1 seizure recorded during baseline). The FAS was used for all outcomes except seizure reduction. The FAS included 147 (8.9 %) patients aged ≥65 years and 1497 (91.1 %) aged ≥16 to <65 years. Compared with the younger subgroup, patients aged ≥65 years had a longer median epilepsy duration (33.0 years [n = 144] vs 17.0 years [n = 1460]) and lower median seizure frequency at index (2.0 seizures/28 days [n = 129] vs 4.0 seizures/28 days [n = 1256]), and less commonly had >1 prior antiseizure medication (106/141 [75.2 %] vs 1265/1479 [85.5 %]). At 12 months, a numerically higher percentage of patients aged ≥65 years versus the younger subgroup achieved ≥50 % seizure reduction (46.5 % [n = 71] vs 36.0 % [n = 751]), seizure freedom (26.0 % [n = 100] vs 13.9 % [n = 1011]), and continuous seizure freedom (22.0 % [n = 100] vs 10.7 % [n = 1011]). During the whole study follow-up, 43/147 (29.3 %) patients aged ≥65 years and 508/1492 (34.0 %) aged ≥16 to <65 years discontinued BRV. The incidence of TEAEs since the prior visit was similar in both subgroups at 3 months (≥65 years vs ≥16 to <65 years: 38/138 [27.5 %] vs 356/1404 [25.4 %]), 6 months (19/119 [16.0 %] vs 176/1257 [14.0 %]), and 12 months (8/104 [7.7 %] vs 107/1128 [9.5 %]). This real-world analysis suggests BRV was effective in patients aged ≥65 years and ≥16 to <65 years, with numerically higher effectiveness in the older subgroup. BRV was well tolerated in both subgroups., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: E. Faught has received research funding from Xenon and UCB Pharma, and consulting fees from Aucta, Azurity, Biogen, the Centers for Disease Control and Prevention, LivaNova, Neurelis the State of Georgia, SK Life Science and Trevena, is on the editorial board of the Annals of Neurology and the executive board of The Epilepsy Consortium H. Besson, D. Bourikas, T. Daniels, F. Floricel, and C. Laloyaux are employees of UCB Pharma. W. D’Souza’s salary is part-funded by The University of Melbourne; he has received travel, investigator-initiated, scientific advisory board, and speaker’s honoraria from UCB Pharma Australia & Global; investigator-initiated, scientific advisory board, travel, and speaker’s honoraria from Eisai Australia & Global; advisory board honoraria from LivaNova and Tilray; educational grants from Novartis, Pfizer, and Sanofi-Synthélabo; educational, travel, and fellowship grants from GSK Neurology Australia; and honoraria from SciGen Pharmaceuticals; he has an equity interest in the device company EpiMinder. P. Klein has served as a consultant for Abbott, Arvelle Therapeutics, Neurelis, and SK Life Science; as a consultant, advisory board member, and speaker for Aquestive, Eisai, Sunovion, and UCB Pharma; is a member of the medical advisory board of Stratus and the scientific advisory board of OB Pharma; is the CEO of PrevEp; and has received research support from CURE and Department of Defense/Lundbeck. M. Reuber receives payment from Elsevier as editor-in-chief of Seizure; and has received research grants and speaker’s fees from Eisai, LivaNova, and UCB Pharma. F. Rosenow reports personal fees from Angelini Pharma, Arvelle Therapeutics, Eisai GmbH, and GW Pharmaceuticals; personal fees and other from Novartis; personal fees and grants from UCB Pharma; and grants from the Detlev-Wrobel-Fonds for Epilepsy Research Frankfurt, Deutsche Forschungsgemeinschaft, the European Union, and the State of Hessen outside the submitted work. J. Salas-Puig has received grants from Bial and UCB Pharma; and reports personal fees from Bial, Eisai, Esteve, Sanofi, and UCB Pharma outside the submitted work. V. Soto Insuga has received speaker honoraria from Bial, Eisai, and UCB Pharma. B.J. Steinhoff has received speaker’s honoraria from Al-Jazeera, Desitin, Eisai, GW Pharmaceuticals, Hikma, Novartis, Sandoz, and UCB Pharma; and has served as a consultant for Arvelle Therapeutics, B. Braun, Bial, Desitin, Eisai, GW Pharmaceuticals, and UCB Pharma. A. Strzelczyk reports personal fees and grants from Angelini Pharma, Biocodex, Desitin Arzneimittel, Eisai, GW/Jazz Pharmaceuticals, Marinus Pharma, Precisis, Takeda, UCB Pharma, UNEEG medical, and Zogenix. He is editor-in-chief of Clinical Epileptology and section editor of Neurological Research and Practice. J.P. Szaflarski has received research funding from Biogen, the Department of Defense, Eisai, GW Pharmaceuticals companies, National Institutes of Health, National Science Foundation, NeuroPace, Serina Therapeutics, Shor Foundation for Epilepsy Research, State of Alabama General Funds, and UCB Pharma; has served as a consultant or advisory board member for Elite Medical Experts, GW Pharmaceuticals, LivaNova, Lundbeck, Medical Association of the State of Alabama, NeuroPace, Serina Therapeutics, SK Life Science, and UCB Pharma; has served as an investigator on GW Research Ltd trials; and is an editorial board member for Epilepsy & Behavior, Epilepsy & Behavior Reports (associate editor), Epilepsy Currents (contributing editor), Folia Medica Copernicana, Journal of Epileptology (associate editor), and Journal of Medical Science. D. Friesen is an independent contractor for UCB Pharma. V. Villanueva has served as a consultant or on an advisory board for Arvelle Therapeutics, Bial, Eisai, Esteve, GW Pharmaceuticals, Novartis, and UCB Pharma; has received research grants from Bial, Eisai, and UCB Pharma; and has received speaker’s honoraria from Bial, Eisai, Esteve, GW Pharmaceuticals, Novartis, and UCB Pharma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Genetic factors contribute to the aetiology of epilepsy in >50% of cases, and information on the use of antiseizure medications in people with specific aetiologies will help guide treatment decisions. The PERMIT Extension study pooled data from two real-world studies (PERMIT and PROVE) to investigate the effectiveness and safety/tolerability of perampanel (PER) when used to treat people with focal and generalised epilepsy in everyday clinical practice. This post-hoc analysis of PERMIT Extension explored the use of PER when used to treat individuals presumed to have epilepsy with a genetic aetiology. Assessments included retention rate (evaluated at 3, 6 and 12 months), effectiveness (responder and seizure freedom rates; evaluated at 3, 6, 12 months and the last visit [last observation carried forward) and tolerability (adverse events [AEs]). Of the 6822 people with epilepsy included in PERMIT Extension, 1012 were presumed to have a genetic aetiology. The most common genetic aetiologies were idiopathic generalised epilepsy (IGE; 58.2%), tuberous sclerosis (1.1%), Dravet syndrome (0.8%) and genetic epilepsy with febrile seizures plus (GEFS+; 0.5%). Retention rates at 3, 6 and 12 months in the total genetic aetiology population were 89.3%, 79.7% and 65.9%, respectively. In the total genetic aetiology population, responder rates at 12 months and the last visit were 74.8% and 68.3%, respectively, and corresponding seizure freedom rates were 48.9% and 46.5%, respectively. For the specific aetiology subgroups, responder rates at 12 months and the last visit were, respectively: 90.4% and 84.4% (IGE), 100% and 57.1% (tuberous sclerosis), 100% and 71.4% (Dravet syndrome), and 33.3% and 20.0% (GEFS+). Corresponding seizure freedom rates were, respectively: 73.1% and 64.6% (IGE), 33.3% and 22.2% (tuberous sclerosis), 20.0% and 28.6% (Dravet syndrome), and 0% and 0% (GEFS+). The incidence of AEs was 46.5% for the total genetic aetiology population, 48.8% for IGE, 27.3% for tuberous sclerosis, 62.5% for Dravet syndrome, and 20% for GEFS+. Tolerability findings were consistent with PER's known safety profile. PER was effective and generally well tolerated when used in individuals with a presumed genetic epilepsy aetiology in clinical practice. PER was effective across a wide range of genetic aetiologies., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Cenobamate is a recently approved antiseizure medication that proved to be safe and effective in randomized controlled trials. However, little is known about its impact on some areas frequently affected by epilepsy. For this reason, we explored the effects of cenobamate on cognitive performance, as well as on negative affectivity and quality of life in a sample of patients with drug-resistant epilepsy., Methods: Two prospective cohort studies were carried out. In Study 1, 32 patients (22 men and 10 women) underwent a baseline (T0) and a short-term (T1) neuropsychological assessment after 3 months of cenobamate administration. In Study 2, 22 patients (16 men and 6 women) from the T1 sample also underwent a baseline and a follow-up evaluation (T2) 6 months after T0., Results: No significant differences were found in cognitive variables, negative affectivity, and quality of life either in Study 1 or Study 2. Similarly, based on the reliable change index, it was found that most patients showed no changes in these variables., Significance: These results suggest that cenobamate is a safe antiseizure medication in terms of cognition, negative affectivity, or quality of life since no adverse events have been found after 3 and 6 months of treatment., Plain Language Summary: Cenobamate is a new antiseizure medication. In patients with epilepsy, cenobamate seems to not affect cognition, anxiety, depression, or quality of life., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Purpose: To assess the impact of antiseizure medications (ASMs) with a very long half-life on long term video-EEG monitoring (LTM) in people with focal epilepsy (FE)., Methods: In this retrospective cohort study, we searched our local database for people with FE who underwent ASM reduction during LTM at the University Hospital of 'La Fe', Valencia, from January 2013 to December 2019. Taking into account the half-life of the ASM, people with FE were divided into two groups: Group A contained individuals who were taking at least one ASM with a very long half-life at admission, and Group B consisted of those not taking very long half-life ASMs. Using multivariable analysis to control for important confounders, we compared the following outcomes between both groups: seizure rates per day, time to first seizure, and LTM duration., Results: Three hundred seventy individuals were included in the study (154 in Group A and 216 in Group B). The median recorded seizure rates (1.3 seizures/day, range 0-15.3 vs.1.3 seizures/day, range 0-9.3, p-value=0.68), median time to the first seizure (24 h, range 2-119 vs. 24 h, range 2-100, p-value=0.92), and median LTM duration (4 days, range 2-5 vs. 4 days, range 2-5, p-value=0.94) were similar in both groups. Multivariable analysis did not reveal any significant differences in the three outcomes between the two groups (all p-values>0.05)., Conclusion: ASMs with a very long half-life taken as co-medication do not significantly affect important LTM outcomes, including recorded seizure rates, time to the first seizure, or LTM duration. Therefore, in general, there is no need to discontinue ASMs with a very long half-life prior to LTM., Competing Interests: Declaration of Competing Interest Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kevin G. Hampel and Carlos Morata-Martínez have no conflicts of interest. Mercedes Garcés-Sánchez has received consultant and/or speaker honoraria from Angelini-Pharma, Bial, Eisai, and UCB Pharma. Vicente Villanueva has received honoraria and/or research funds from Angelini Pharma, Bial, Eisai, Jazz Pharmaceuticals, Neuraxpharm, Novartis, Nutricia, Takeda, UCB Pharma, and Xenon., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Epilepsy is a chronic brain disease characterized by recurrent seizures. We investigated real-world management of epilepsy across treatment lines in Spain, including healthcare resource use (HRU) and associated costs., Methods: This was a retrospective study of real-life data from epilepsy patients prescribed antiseizure medication (ASM) between January 2016 and December 2021. Patients were grouped according to their line of treatment (1st, 2nd, 3rd and 4th +) during the recruitment period. Demographic and clinical characteristics, comorbidities and concomitant medications were analyzed during the baseline period (6 months before starting treatment line); antiepileptic treatments, concomitant medications, HRU and associated costs were analyzed during follow-up., Results: The study included 5006 patients. Treatment duration decreased as treatment lines progressed (mean ± SD progression time: 523.2 ± 279.1 days from 1st to 2nd line, 351.6 ± 194.4 days from 2nd to 3rd line; 272.7 ± 139.3 days from 3rd to 4th + line). Significant HRU differences were found with subsequent treatment lines, including an increase in hospital admissions and patients on sick leave. Mean (95% CI) adjusted total costs per patient were €2974/year (2773-3175) in the 1st line and €5735/year (5043-6428) in the 4th + line. There was an increase in adjusted direct and total costs with subsequent treatment lines; the mean difference in total costs between cohorts was €2761 (p < 0.001). The highest direct costs were associated with epilepsy medication, days at the hospital and specialist visits., Conclusion: Our data revealed a progressive increase in the use of resources and associated costs across subsequent epilepsy treatment lines., (© 2023. The Author(s).)

Purpose: Urgent seizures are a medical emergency for which new therapies are still needed. This study evaluated the use of intravenous brivaracetam (IV-BRV) in an emergency setting in clinical practice., Methods: BRIV-IV was a retrospective, multicenter, observational study. It included patients ≥18 years old who were diagnosed with urgent seizures (including status epilepticus (SE), acute repetitive seizures, and high-risk seizures) and who were treated with IV-BRV according to clinical practice in 14 hospital centers. Information was extracted from clinical charts and included in an electronic database. Primary effectiveness endpoints included the rate of IV-BRV responder patients, the rate of patients with a sustained response without seizure relapse in 12 h, and the time between IV-BRV administration and clinical response. Primary safety endpoints were comprised the percentage of patients with adverse events and those with adverse events leading to discontinuation., Results: A total of 156 patients were included in this study. The mean age was 57.7 ± 21.5 years old with a prior diagnosis of epilepsy for 57.1% of patients. The most frequent etiologies were brain tumor-related (18.1%) and vascular (11.2%) epilepsy. SE was diagnosed in 55.3% of patients. The median time from urgent seizure onset to IV treatment administration was 60.0 min (range: 15.0-360.0), and the median time from IV treatment to IV-BRV was 90.0 min (range: 30.0-2400.0). Regarding dosage, the mean bolus infusion was 163.0 ± 73.0 mg and the mean daily dosage was 195.0 ± 87.0 mg. A total of 77.6% of patients responded to IV-BRV (66.3% with SE vs. 91% other urgent seizures) with a median response time of 30.0 min (range: 10.0-60.0). A sustained response was achieved in 62.8% of patients. However, adverse events were reported in 14.7%, which were predominantly somnolence and fatigue, with 4.5% leading to discontinuation. Eighty-six percent of patients were discharged with oral brivaracetam., Conclusion: IV-BRV in emergency settings was effective, and tolerability was good for most patients. However, a larger series is needed to confirm the outcomes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: V. Villanueva has received honoraria and/or research funds from Angelini Pharma, Bial, Eisai, Jazz Pharmaceuticals, Neuraxpharm, Novartis, Nutricia, Takeda, UCB Pharma, and Xenon. X. Rodríguez-Osorio has received honoraria and/or research funds from Angelini Pharma, Bial, Eisai, Jazz Pharmaceuticals, Neuraxpharm, UCB Pharma, and LivaNova. A Juiz-Fernández declares research funding and speaking fees from Bial Pharmaceutical, Jazz Pharmaceuticals, Eisai Inc., and UCB Pharma. M. Garcés has received consultant and/or speaker honoraria from Angelini-Pharma, Bial, Eisai, and UCB Pharma. E Rubio-Nazábal has received honoraria from BIAL, Eisai, and UCB Pharma for speaking. E Santamarina reports grants and personal fees from UCB Pharma, Eisai, and Bial; personal fees from Angelini Pharma, Esteve, and Ferrer outside the submitted work. M Falip has received speaker honoraria from UCB. I Garcia-Morales has received honoraria consultant and/or speaker honoraria from UCB, EISAI, Neuraxpharm, and Angelini. Ana Belén Martínez has received consultant and/or speaker honoraria from Angelini-Pharma, Eisai, and UCB Pharma. B Chavarria has received travel support from UCB. Rodrigo Rocamora has received travel support and honoraria as advisor from UCB, EISAI, Angelini, and Jazz Pharmaceutical. D Sayas, K Hampel, A Castillo, J Montoya, D Campos, A Fernández-Cabrera, A Gifreu, G Hernández Pérez, B Parejo-Carbonell, M Massot, M Asensio, J Giménez, V Guillen, J Ruiz-Giménez, R Rocamora, and I Escalza have no conflicts of interest, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study investigated early, real-world outcomes with cenobamate (CNB) in a large series of patients with highly drug-resistant epilepsy within a Spanish Expanded Access Program (EAP)., Method: This was a multicenter, retrospective, observational study in 14 hospitals. Inclusion criteria were age ≥18 years, focal seizures, and EAP authorization. Data were sourced from patient clinical records. Primary effectiveness endpoints included reductions (100%, ≥90%, ≥75%, and ≥50%) or worsening in seizure frequency at 3-, 6-, and 12-month visits and at the last visit. Safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation., Results: The study included 170 patients. At baseline, median epilepsy duration was 26 years and median number of seizures/month was 11.3. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 12 and 3, respectively. Mean CNB dosages/day were 176 mg, 200 mg, and 250 mg at 3, 6, and 12 months. Retention rates were 98.2%, 94.5%, and 87% at 3, 6, and 12 months. At last available visit, the rate of seizure freedom was 13.3%; ≥90%, ≥75%, and ≥50% responder rates were 27.9%, 45.5%, and 63%, respectively. There was a significant reduction in the number of seizures per month (mean: 44.6%; median: 66.7%) between baseline and the last visit (P < 0.001). Responses were maintained regardless of the number of prior or concomitant ASMs. The number of concomitant ASMs was reduced in 44.7% of patients. The cumulative percentage of patients with AEs and AEs leading to discontinuation were 68.2% and 3.5% at 3 months, 74.1% and 4.1% at 6 months, and 74.1% and 4.1% at 12 months. The most frequent AEs were somnolence and dizziness., Significance: In this highly refractory population, CNB showed a high response regardless of prior and concomitant ASMs. AEs were frequent but mostly mild-to-moderate, and few led to discontinuation., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Up to 10% of people living to 80 years of age have one or more seizures; and many will not require anti-seizure medication (ASMs). In 85% of patients, the diagnosis comes from the history of the index event. One-third of patients with an apparent "first seizure" have previous events, changing their diagnosis to epilepsy. Targeted investigations are important for classification and risk prediction. Patients with a low risk of seizure recurrence are not usually offered ASM treatment. High-risk patients have multiple seizures, neurological deficits, intellectual disability and/or relevant abnormal investigations; and are offered ASMs. Individual factors modulate this decision-making. Future integrated technologies offer the game-changing potential for seizure monitoring and prediction, but are not yet robust, convenient or affordable. Therapeutic drug monitoring in patients taking ASMs may confirm ASM toxicity, or when non-adherence, malabsorption, or rapid metabolism are suspected causes of breakthrough seizures. They are less useful when these factors are intermittent or irregular. Current evidence does not favour routine monitoring of serum levels, as it neither reliably predicts control, relapse, or adverse effects. The decision to discontinue ASM should follow a full discussion with the patient of risks and benefits. Along with population risk factors for seizure recurrence, the patient's lifestyle and preferences must be considered. ASM are usually discontinued in a slow step-wise fashion, one at a time, after at least two years of remission. Seizure recurrence risk plateaus only after 2 years following ASM discontinuation, and patients need access to specialist follow-up over that period., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Aim: To evaluate the effectiveness and tolerability of cannabidiol (CBD) in patients with developmental and epileptic encephalopathies, including Dravet syndrome (DS), and Lennox-Gastaut syndrome (LGS), in a Spanish Expanded Access Program (EAP)., Methods: This was a multicenter, retrospective, observational study of patients treated with purified CBD in 14 hospitals across Spain. Patients with (1) written informed consent and (2) at least 6 months follow-up before the closure of the database were included. Primary effectiveness endpoints included reductions (100 %, ≥75 %, ≥50 %, ≥25 %, or 0 %) or worsening in seizure frequency (all seizure types and most disabling seizures) at 1-, 3-, 6-, and 12-month visits and at the last visit, and median relative seizure reduction between baseline and last visit. Secondary effectiveness endpoints included retention rate, reduction in seizure severity, status epilepticus, healthcare utilization, and quality of life. Primary safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation., Results: One hundred and two patients (DS 12 %; LGS 59 %; other epilepsy syndromes 29 %) with a mean age of 15.9 years were enrolled. Patients were highly refractory to antiseizure medications (ASMs); mean number of prior failed ASMs was 7.5 (SD 3.7). The mean CBD dose was 13.0 mg/kg/day at the last visit. The proportion of patients with ≥50 % reduction in the total number of seizures from baseline was 44.9 % at 6 months and 38.9 % at 12 months. The median number of total seizures per month reduced by 47.6 % from baseline to the last visit. At 12 months, seizure severity was lower in 33/54 patients (61.1 %) and unchanged in 17/54 patients (31.5 %). Quality of life, based on the CAVE scale, increased from a mean score of 17.9 ± 4.7 (n = 54) at baseline to 21.7 ± 5.5 (n = 51) at the last patient visit (21.2 % improvement). The mean treatment retention time was 10.3 months. There were no statistically significant changes in the number of status epilepticus episodes, but lower healthcare utilization was observed. Adverse events occurred in sixty-eight patients (66.7 %), and the most common were somnolence (34.3 %) and diarrhea (12.7 %). Cannabidiol was discontinued exclusively due to AEs in 7.8 % of patients, increasing to 25.5 % when both lack of efficacy and AEs were considered together., Conclusions: Cannabidiol demonstrated promising effectiveness and tolerability in patients with developmental and epileptic encephalopathies taking part in a Spanish EAP., Competing Interests: Declaration of Competing Interest V Villanueva has received honoraria and/or research funds from Angelini Pharma, Bial, Eisai, GW Pharmaceutical Company (now a part of Jazz Pharmaceuticals), Neuraxpharm, Novartis, Nutricia, Takeda, UCB Pharma, and Zogenix. A García-Ron has received consultant and speaker honoraria from GW Pharmaceutical Company (now a part of Jazz Pharmaceuticals). P Smeyers has received fees for conferences and other educational activities from Eisai, GW Pharmaceutical Company (now a part of Jazz Pharmaceuticals), Humana, Neuraxpharm, and UCB. V Soto has received speaker honoraria from GW Pharmaceutical Company (now a part of Jazz Pharmaceuticals). JJ Garcia-Peñas has received consultant and speaker honoraria from Bial, Eisai, GW Pharmaceutical Company (now a part of Jazz Pharmaceuticals), Nutricia, Sanofi, UCB, and Zogenix. PJ. Serrano-Castro has received consultant and/or speaker honoraria from Angelini-Pharma, Bial, Eisai, GW Pharmaceuticals (now a part of Jazz Pharmaceuticals), Roche Pharmaceuticals, UCB Pharma, and Zogenix España. A Aledo-Serrano has received funding for research and educational activities from Angelini Pharma, Bial, Biocodex, Eisai, GW Pharmaceutical Company (now a part of Jazz Pharmaceuticals), Neuraxpharm, PTC Therapeutics, Sanofi, UCB, and Zogenix. A Gil-Nagel has received grants from Jazz Pharmaceuticals, PTC Therapeutics and Zogenix, and received consultant and speaker honoraria from Bial, Biocodex, Eisai, Esteve, HealthInCode,GW Pharmaceutical Company (now a part of Jazz Pharmaceuticals), PTC Therapeutics, Stoke, Synaptia,UCB Pharma,and Zogenix. A Gómez-Ibáñez has received consultant and speaker honoraria from GW Pharmaceutical Company (now a part of Jazz Pharmaceuticals). M Falip has received consultant and speaker honoraria from GW Pharmaceutical Company (now a part of Jazz Pharmaceuticals). F J Lopez-Gonzalez has received consultant and speaker honoraria from Angelini Pharma, Bial, Eisai, Esteve, GW Pharmaceutical Company (now a part of Jazz Pharmaceuticals), LivaNova, Nutricia, and UCB. E Arias, E González-Alguacil, D Sayas, M Garcés, K Hampel, M Tomás, J Lara, M de Toledo, I Barceló, L Iacampo, R Saiz-Diaz, D Sopelana, and A Sánchez-Larsen have no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To determine the economically justifiable price (EJP) of cenobamate to become a cost-effective alternative compared with third-generation anti-seizure medications in the treatment of focal-onset seizures (FOS) in adult patients with drug-resistant epilepsy (DRE) in Spain., Methods: Cost-effectiveness analysis compared cenobamate with brivaracetam, perampanel, eslicarbazepine acetate, and lacosamide. Markov model simulation of treatment pathway over a 60-year time horizon is presented. We determined the effectiveness and quality-adjusted life-years (QALYs) of health status and disutilities associated with treatment-related adverse events. Acquisition costs and use of medical resources were obtained from published literature and expert opinion. Base-case of cenobamate's EJP calculated applying a willingness-to-pay (WTP) threshold of €21,000/QALY. Analyses were performed at different thresholds, including dominant price scenario. Result robustness was assessed through sensitivity analyses., Results: Base-case shows that cenobamate's daily EJP of €7.30 is cost-effective for a threshold of €21,000/QALY. At a daily price of €5.45, cenobamate becomes dominant over all treatment alternatives producing cost-savings for the national health system (NHS). Sensitivity analyses supported the robustness of base-case findings., Conclusions: Treatment with cenobamate produces incremental clinical benefit over third-generation ASMs, and at the base-case, EJP could represent a cost-effective option for the adjunctive treatment of FOS in adult patients with DRE in Spain.

Objective: This post hoc analysis of four open-label extension (OLEx) studies evaluated the long-term efficacy and safety of adjunctive perampanel in adolescent patients (aged 12 to ≤17 years) with focal-onset seizures (FOS), with/without focal to bilateral tonic-clonic seizures (FBTCS), or generalized tonic-clonic seizures (GTCS)., Methods: Patients who completed one of six double-blind, placebo-controlled studies could enter one of four OLEx studies comprising a blinded Conversion Period (6-16 weeks) followed by a Maintenance Phase (27 to ≤256 weeks; perampanel dose: ≤12 mg/day). Exposure, retention, seizure outcomes, and treatment-emergent adverse events (TEAEs) were analyzed. Efficacy outcomes were analyzed using observed case and last observation carried forward (LOCF) approaches; the latter was used to account for early dropouts., Results: The Full Analysis Set comprised 309 adolescents with FOS (FBTCS, n = 109) and 19 with GTCS, and the Safety Analysis Set comprised 311 with FOS (FBTCS, n = 110) and 19 with GTCS. Mean (standard deviation) cumulative duration of perampanel exposure (weeks) was: FOS, 77.7 (58.7); FBTCS, 88.7 (63.8); and GTCS, 97.0 (35.5). Retention rates were maintained for ≤2 years (FOS, 50.0 %; FBTCS, 57.1 %; GTCS, 41.7 %). Seizure control (median percent reduction in seizure frequency/28 days) was sustained for up to 2 years; FOS (59.4 %, n = 113), FBTCS (64.6 %, n = 53), and GTCS (86.5 %, n = 17). At Year 2, 50 % responder rates were: FOS, 58.4 % (n = 66); FBTCS, 54.7 % (n = 29); and GTCS, 82.4 % (n = 14); seizure-freedom rates were: FOS, 5.3 % (n = 6); FBTCS, 24.5 % (n = 13); and GTCS, 35.3 % (n = 6). Long-term seizure control was observed even in LOCF analyses. The incidence of TEAEs was highest during Year 1 (FOS, n = 269 [86.5 %]; FBTCS, n = 95 [86.4 %]; GTCS, n = 15 [78.9 %]), compared with Years 2-4; the most common (≥10 % of patients) were dizziness, somnolence, and nasopharyngitis. No new safety signals emerged with long-term treatment., Conclusions: This post hoc analysis suggests that long-term (≤2 years) adjunctive perampanel (≤12 mg/day) is efficacious and generally well tolerated in adolescent patients with FOS, with or without FBTCS, or GTCS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J Eric Piña-Garza has served as an advisor and speaker for Aquestive, Eisai, Jazz/Greenwich Biosciences, Neurelis, SK Life Science, Sunovion, Supernus, and UCB Pharma. Vicente Villanueva has participated in advisory boards and pharmaceutical-industry–sponsored symposia for Angellini, Arvelle, Bial, Eisai, Esteve, GW Pharmaceuticals, Novartis, Pfizer, Takeda, UCB Pharma, and Zogenix. William Rosenfeld has served on the speaker’s bureau for Eisai, Greenwich Biosciences, SK Life Science, Sunovion, and UCB Pharma, has received research support from GW Pharmaceuticals, Marinus, Medtronic, SK Life Science, Takeda, UCB Pharma, and Upsher-Smith, and is a consultant for SK Life Science. Kazunori Saeki is an employee of Eisai Co., Ltd. Harumi Yoshinaga has served as the chairman of the appropriate use committee for Sabril; as a consultant for Sanofi; and as a speaker for Eisai, Takeda, and UCB Japan. Anna Patten is an employee of Eisai Europe Ltd. Manoj Malhotra is a former employee of Eisai Inc., (Copyright © 2022. Published by Elsevier Inc.)

Dravet syndrome (DS) is a severe, rare, and complex developmental and epileptic encephalopathy affecting 1 in 16 000 live births and characterized by a drug-resistant epilepsy, cognitive, psychomotor, and language impairment, and behavioral disorders. Evidence suggests that optimal treatment of seizures in DS may improve outcomes, even though neurodevelopmental impairments are the likely result of both the underlying genetic variant and the epilepsy. We present an updated guideline for DS diagnosis and treatment, taking into consideration care of the adult patient and nonpharmaceutical therapeutic options for this disease. This up-to-date guideline, which is based on an extensive review of the literature and culminates with a new treatment algorithm for DS, is a European consensus developed through a survey involving 29 European clinical experts in DS. This guideline will serve professionals in their clinical practice and, as a consequence, will benefit DS patients and their families., (© 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Anti-seizure medications (ASMs) have been related to poor cognitive function, but their relationship with intracarotid amobarbital procedure (IAP) results remains unclear., Aims of the Study: To elucidate whether the number and drug load of ASMs are associated with memory scores of the IAP and the neuropsychological assessment., Methods: Fifty-nine adult patients with drug-resistant epilepsy (mean age = 36.1, SD = 11.6) underwent bilateral IAP (with drawings and words as memory items) and a neuropsychological assessment to assess the risk of post-surgical memory decline. Total ASM drug load was calculated by summing the daily dose/defined daily dose ratio of every ASM of each patient. Pearson's correlations and hierarchical regressions were computed., Results: Total IAP memory score was associated with total ASM drug load (r = -0.30, p = 0.02) and seizure frequency (r = -0.25, p = 0.05). After controlling clinical variables, total ASM drug load explained 16% of the variance of total IAP memory score. This relationship was especially prominent in patients with left hemisphere focus (r = -0.33, p = 0.04). The number of current ASMs was not related to IAP memory score (r = -0.16, p = 0.24). The number or drug load of ASMs were not related to neuropsychological assessment results (for all, p > 0.07)., Conclusions: Our findings suggest that total drug load can be a confounding variable in the IAP memory performance that could explain, at least in part, the reverse asymmetries reported in different studies., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Epilepsy is a serious neurological disease, ranking high in the top causes of disability. Approximately 40% of patients with epilepsy are pharmacoresistant after their seizures failed at least two antiseizure medications (ASMs). Adult patients experiencing focal-onset seizures (FOS) account for approximately 60% of all patients with epilepsy and they are more likely to become drug-resistant epilepsy (DRE) than those with generalized onset. Drug-resistant epilepsy is associated with mortality, morbidity, and reduced quality of life. The information available on the clinical management, health outcomes, and unmet needs of the disease within the Spanish healthcare environment is very limited. Multi-Criteria Decision Analysis (MCDA) allows determination of what represents value in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner and from the perspective of relevant stakeholders., Purpose: The aim of this study was to identify the burden of DRE (clinical, quality of life, and economic) and the unmet needs in Spain and to determine what represents value in the treatment of FOS in DRE patients from the perspective of Spanish epileptologists., Methods: The steps taken to carry out the MCDA were based on previously published good methodological practices. A systematic literature review (combining biomedical databases and gray literature sources) was performed between March and April 2020. Results were reviewed and validated with three epileptologists in June 2020 and used to develop a MCDA value framework, adapted for FOS in DRE, composed of 12 quantitative criteria and 3 contextual criteria. A group of six Spanish epileptologists from four Spanish regions were trained in MCDA methodology before individually validating value criteria (and their definitions based on literature review findings) and assigned relative weights using an ordinal 6-points scale. Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology., Results: Drug-resistant epilepsy is considered a very severe health problem with important unmet needs affecting a considerably sized population. While safety and impact on quality of life of available ASMs are considered adequate, efficacy remains insufficient for patients to achieve seizure freedom and maintain it over time. Hence, the therapeutic benefit of pharmacological treatments currently used is regarded as suboptimal. Drug-resistant epilepsy management is associated with moderate pharmacological, relevant direct medical and high indirect costs. Quality of evidence available for current treatments is moderate. It is considered that DRE does not currently stand as a key priority for the Spanish healthcare system., Conclusions: Drug-resistant epilepsy is considered a very severe health problem associated with relevant unmet needs. These include the lack of availability of specific treatment protocols, the need to improve early diagnosis by increasing the number of referrals to specialized epilepsy units and the availability of specific ASMs with improved efficacy and safety profiles, allowing to reach treatment objectives. Reflective MCDA provided a standardized, transparent approach to evaluate multiple criteria ascertaining what represents value from a holistic point of view and from the perspective of clinical experts, facilitating decision-making., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Villanueva has participated in advisory boards and industry-sponsored symposia by Arvelle, Bial, Eisai Inc, Esteve, GW Pharmaceuticals, Novartis, Sandoz, UCB Pharma and Zogenix. Dr. Carreño has received honoraria for advisory boards/consultancy from Arvelle, Bial, Eisai Inc, GW Pharmaceuticals, Sanofi and UCB Pharma; speaking fees from Bial, Eisai, Sanofi and UCB Pharma; and research grants from Eisai Inc. Dr. Gil-Nagel reports receiving research grants, or honoraria from speakers or advisory boards from Arvelle, Bial, Biocodex, Eisai Inc, Esteve, GW Pharmaceuticals, Stoke, UCB Pharma and Zogenix. Dr. Serrano-Castro has received honoraria or served as a paid consultant for Arvelle, BIAL, Eisai Inc, GW Pharmaceuticals, Novartis and UCB Pharma. No other potential conflicts of interest are reported. Dr. Serratosa has received research grants or honoraria as speaker or participant in advisory boards from Arvelle, BIAL, Eisai Inc, Esteve, GW Pharmaceuticals, Sanofi, UCB Pharma for participation in advisory boards or pharmaceutical industry-sponsored symposia. Dr. Toledo has participated in DRE clinical trials with different ASMs development and reports receiving consulting fees from Arvelle, Bial, Eisai Inc, GSK, GW Pharmaceuticals and UCB Pharma., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the opinions of physicians on the use of complementary and alternative medicine (CAM) in patients with epilepsy (PWE) worldwide., Methods: Online survey addressed to neurologists and psychiatrists from different countries., Results: Totally, 1112 physicians from 25 countries (different world region: Europe, North America, South America, Middle-East, Africa, Former Soviet Union Republics) participated; 804 (72.3%) believed that CAM might be helpful in PWE. The most commonly endorsed CAM included meditation (41%) and yoga (39%). Female sex, psychiatry specialization, and working in North and South America were associated with the belief that CAM is helpful in PWE. Two-hundred and forty five out of 1098 participants (22.3%) used/prescribed CAM to PWE; among them, 174 (71%) people perceived CAM to be less effective and 114 (46.5%) people found CAM to be safer than conventional antiseizure medications (ASMs). The most common reasons to prescribe CAM for PWE were: to satisfy the patient (49.9%), dissatisfaction with the efficacy (35.6%), and dissatisfaction with the adverse effects (31.2%) of conventional therapies., Conclusion: Although the evidence supporting the use of CAM for the treatment of epilepsy is extremely sparse, most physicians worldwide believe that it could be integrated with the use of conventional ASMs, at least in some patients. High-quality controlled trials are warranted to provide robust evidence on the usefulness of CAM options in PWE., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies., Methods: Members of the European Reference Network for rare and complex epilepsies ( EpiCARE) were invited to participate in a web-based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht-like diseases. A consensus-based questionnaire was generated for each disease., Results: Twenty-six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht-like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers., Significance: The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers., Competing Interests: Sameer M Zuberi has conducted randomized controlled trials for GW Pharma and Zogenix Ltd in patients with Dravet syndrome. He has participated in advisory boards for Zogenix, GW Pharma, Biocodex, and Encoded Genomics. Katarzyna Kotulska was supported by the 7th Framework Programme of European Commission within the Large‐scale Integrating Project EPISTOP (Proposal No: 602 391‐2; Proposal title: “Long term, prospective study evaluating clinical and molecular biomarkers of epileptogenesis in a genetic model of epilepsy – tuberous sclerosis complex”; www.EPISTOP.eu) and the Polish Ministerial funds for science (years 2014‐2018) for the implementation of international co‐financed project and the grant EPIMARKER of the Polish National Center for Research and Development No STRATEGMED3/306306/4/2016. All other authors have no conflict of interest related to this survey to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (© 2020 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objectives: To assess the effectiveness and safety/tolerability of eslicarbazepine acetate (ESL) in patients included in the Euro-Esli study who had focal seizures associated with post-stroke epilepsy (PSE)., Materials and Methods: Euro-Esli was a pooled analysis of 14 European clinical practice studies. Effectiveness assessments (evaluated after 3, 6 and 12 months of ESL treatment and at final follow-up ["last visit"]) included rates of response (≥50% seizure frequency reduction), seizure freedom (no seizures since at least the prior visit) and retention. Safety/tolerability was assessed throughout ESL treatment by evaluating adverse events (AEs) and discontinuation due to AEs. A post hoc analysis was conducted of patients with PSE versus patients without PSE ("non-PSE")., Results: Of 1656 patients included in the analysis, 76 (4.6%) had PSE and 1580 (95.4%) had non-PSE. Compared with non-PSE patients, PSE patients were significantly older, had significantly shorter epilepsy duration, significantly lower total baseline seizure frequency, and were treated with significantly fewer prior and concomitant antiepileptic drugs (P < .001 for all). At the last visit, the responder rate was significantly higher in PSE versus non-PSE patients (72.9% vs 60.6%; P = .040), as was the seizure freedom rate (48.6% vs 31.7%; P = .003). After 12 months, retention was significantly higher in PSE versus non-PSE patients (87.8% vs 77.4%; P = .035). The incidence of AEs was similar for PSE versus non-PSE patients (36.0% vs 35.8%; P = .966)., Conclusions: These findings suggest that ESL may be an effective and well-tolerated treatment option for patients with focal seizures due to PSE., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The aim of the study was to evaluate the effectiveness and tolerability of eslicarbazepine acetate (ESL) when used as monotherapy for 1 year or more in routine clinical use in patients with focal seizures in epilepsy clinics in Spain., Methods: This is a retrospective, observational, noninterventional study. Eligible patients were aged ≥18 years, had focal seizures, and started on ESL ≥1 year before database closure. Primary endpoint was the following: proportion seizure-free for ≥6 months at 1 and 2 years. Secondary endpoints included retention on ESL monotherapy at 1 and 2 years, seizure frequency change, seizure worsening, and side effects. Other analyses included seizure freedom from baseline to 1 and 2 years and outcomes in special populations., Results: Four hundred thirty-five patients were included (127 on first-line monotherapy and 308 converting to ESL monotherapy): median daily dose was 800 mg at all time points; 63.2% were seizure-free at 1 year, 65.1% at 2 years, and 50.3% for the entire follow-up. Mean duration of ESL monotherapy was 66.7 months; retention was 88.0% at 1 year and 81.9% at 2 years. Mean reduction in seizure frequency was 75.5% at last visit. Over the entire follow-up, seizure worsening was seen in 22 patients (5.1%), side effects in 28.0%, considered severe in 1.8%, and leading to discontinuation in 5.7%. Dizziness, hyponatremia (sodium <135 mEq/l), and somnolence were the most frequent side effects. Outcomes in special populations (patients aged ≥65 years and those with psychiatric history or learning difficulty) were consistent with the overall population., Conclusions: Patients with focal seizures taking ESL monotherapy had excellent retention, high seizure-free rates, and good tolerability up to 2 years., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Psychiatric and intellectual comorbidities are common in patients with epilepsy. However, data on the use of antiepileptic drugs in these patients are still lacking. This study assessed the real-world effectiveness and safety/tolerability of eslicarbazepine acetate (ESL) in patients with intellectual disability and psychiatric comorbidities, including a separate analysis specifically in those with depression, using data from the Euro-Esli study. Effectiveness measures included responder and seizure freedom rates. Safety and tolerability were assessed by evaluating adverse events (AEs) and ESL discontinuation due to AEs, respectively. Of the 2058 patients initially included in the Euro-Esli study, 952 patients had intellectual disability data available, 1138 had psychiatric comorbidity data available and 1134 had depression data available. Of those who had intellectual or psychiatric comorbidity data available, 11.3% (108/952) suffered from intellectual disability, 24.9% (283/1138) had a psychiatric disorder, including depression, and 12.4% (141/1134) specifically had depression. Responder and seizure freedom rates were generally comparable between patients with psychiatric comorbidity and those without, and patients with depression and those without. However, responder and seizure freedom rates were significantly lower in patients with intellectual disability compared with those without. Overall, patients with psychiatric and intellectual comorbidities experienced more AEs and AEs leading to ESL discontinuation than patients without these comorbidities. The incidence of psychiatric AEs was not significantly different for patients with psychiatric comorbidities or depression than those without, and the incidence of cognitive AEs was not significantly different for patients with intellectual disability than those without. These findings suggest that ESL is effective in patients with psychiatric and intellectual comorbidities and that its use in these patients is unlikely to exacerbate existing psychiatric or cognitive disturbances., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To investigate the relative contribution of factors non-directly related to seizures such as negative affectivity, social support, somatic symptoms and memory performance on quality of life (QOL) in patients with drug-resistant epilepsy., Methods: This is a cross-sectional study. Seventy patients with drug-resistant epilepsy were consecutively recruited from the inpatient Epilepsy Unit, Hospital Universitario y Politécnico La Fe, between April 2015 and October 2017. Medical history provided demographic characteristics of the patients (sex, age, and educational level), and clinical data (age at epilepsy onset, duration of epilepsy in years, frequency of seizures per month, type of seizures and number of AEDs). Pre-surgical assessment included diagnosis of the type of epilepsy and the lateralization of the epileptogenic area. All the patients underwent a neuropsychological assessment in which QOL (QOLIE-31), negative affectivity, social support, somatic symptoms, and memory were evaluated., Results: Negative affectivity (including anxiety-trait and depression), social support, neurosensory symptoms, and long-term verbal memory were significantly related to QOL composite score (for all, p < .009), subscales of QOL showing different sensitivities to them. Even after controlling for negative affectivity, neurosensory symptoms and long-term verbal memory significantly contribute to QOL composite score (p = .0001)., Conclusion: Results suggest that clinical management of patients with drug-resistant epilepsy should consider the treatment of verbal memory impairments at an early stage. Recognition of negative affectivity, poor social support and high somatic symptoms would also lead health professionals to develop different strategies to improve the QOL of patients with drug-resistant epilepsy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To pool observational data on the routine use of perampanel to obtain information on real-world outcomes and data in populations typically underrepresented in clinical trials., Methods: Individual-level data of people with epilepsy treated with perampanel at 45 European centers were merged into a single dataset. Prespecified outcomes were: 1-year retention rate, 1-year seizure freedom rate (duration ≥6 months), and incidence of treatment-emergent adverse events (TEAEs). In addition, relationships were explored with logistic regression analyses., Results: The full analysis set comprised 2396 people: 95% had focal seizures; median epilepsy duration was 27 years; median number of concomitant antiepileptic drugs (AEDs) was 2; and median prior AEDs was 6. One-year retention rate was 48% (1117/2332; 95% confidence interval [CI] 46-50%), and 1-year seizure-free rate (≥6-month duration) was 9.2% (74/803; 95% CI 7-11%). Median treatment duration was 11.3 months (1832 patient-years); median dose was 8 mg. In 388 individuals with available data at 3, 6, and 12 months, responder rates were 42%, 46%, and 39%, respectively. During the first year, TEAEs were reported in 68% of participants (1317/1497; 95% CI 66-70%). Logistic regression found higher age at perampanel initiation was associated with higher seizure-free rate, and higher number of prior AEDs with lower seizure-free rate and lower rates of somatic TEAEs. In 135 individuals aged ≥65 years, 1-year retention rate was 48% and seizure-free rate was 28%., Significance: Across a large, treatment-resistant population, add-on perampanel was retained for ≥1 year by 48% of individuals, and 9% were seizure-free for ≥6 months. TEAEs were in line with previous reports in routine clinical use, and less frequent than in the clinical trial setting. No new or unexpected TEAEs were seen. Despite the limitations of observational studies, our data indicate that some individuals may derive a marked benefit from the use of perampanel., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Background: The choice of antiepileptic drug (AED) therapy in patients with brain tumor-related epilepsy (BTRE) is complicated, and there are a lack of robust clinical trial data to date., Methods: The NEOPLASM (Neuroncologic Patients treated with LAcoSaMide) study was a 6-month, multicenter, retrospective, observational study in patients with BTRE treated with lacosamide. Patients were started on lacosamide because of a lack of efficacy or adverse events (AEs) with prior AEDs or suitability versus other AEDs, according to clinical practice. The primary efficacy variable was the seizure-free rate at 6months. Safety variables included the proportion of patients with an AE and the proportion with an AE that led to discontinuation., Results: Overall, 105 patients from 14 hospital centers were included in the analysis. Treatment with lacosamide for 6months resulted in a 30.8% seizure-free rate, and 66.3% of patients had a ≥50% seizure reduction (responders). In the subset of patients included because of a lack of efficacy with prior AEDs, seizure-free rates were 28.0%, and 66.7% of patients were responders. No statistically significant differences in efficacy were observed according to the mechanism of action or enzyme-inducing properties of concomitant AEDs. Adverse events were reported by 41.9% of patients at 6months, and 4.7% of them led to discontinuation. The most common AEs were somnolence/fatigue and dizziness. Notably, 57.1% of the patients who were switched to lacosamide because of AEs with their previous therapy did not report any AE at 6-month follow-up., Conclusions: In this open-label, observational study, lacosamide appeared to be effective and well tolerated in a large population of patients with BTRE. Lacosamide may therefore be a promising option for the treatment of patients with BTRE., (Copyright © 2016 Elsevier Inc. All rights reserved.)

There is currently a lack of guidance on methodology and special considerations for transitioning patients from oxcarbazepine (OXC) or carbamazepine (CBZ) to eslicarbazepine acetate (ESL), if deemed clinically necessary. An advisory panel of epilepsy experts was convened to share their experience on the use of adjunctive ESL in clinical practice and to provide practical recommendations to help address this gap. When changing over from OXC to ESL, an OXC:ESL dose ratio of 1:1 should be employed to calculate the ESL target dose, and the changeover can take place overnight. No changes to comedication are required. Since CBZ has a different mechanism of action to ESL and is a stronger inducer of cytochrome P450 (CYP) enzymes, the transitioning of patients from CBZ to ESL requires careful consideration on a patient-by-patient basis. In general, a CBZ:ESL dose ratio of 1:1.3 should be employed to calculate the ESL target dose, and patients should be transitioned over a minimum period of 1-2weeks. Special considerations include adjustment of titration schedule and target dose in elderly patients and those with hepatic or renal impairment and potential adjustment of comedications metabolized by CYP enzymes. In summary, due to structural distinctions between ESL, OXC, and CBZ, which affect mechanism of action and tolerability, there are clinical situations in which it may be appropriate to consider transitioning patients from OXC or CBZ to ESL. Changing patients over from OXC to ESL is generally more straightforward than transitioning patients from CBZ to ESL, which requires careful consideration., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Zonisamide is an antiepileptic drug firstly approved in Europe as add-on therapy in adult patients with partial seizures and recently as monotherapy., Aim: To analyze the clinical development of zonisamide in Europe and USA., Development: It is a sulfonamide derivative that exerts its antiepileptic effect through different mechanisms, ion channels, neurotransmitters and free radicals. It has a lineal pharmacokinetic at usual doses, an hepatic metabolism without induction of other drugs and a half life of 60 hours. For his approval in USA and Europe four clinical randomized regulatory trials were performed. The efficacy of the drug was evaluated between 100 and 500 mg, showing a seizure reduction with respect to basal period between 24.7% (100 mg) and 52.5% (500 mg). The most frequent side effects were dizziness, fatigue, somnolence and weight loss. There is broad experience in conditions close to clinical practice in patients with partial epilepsy and different degree of refractoriness, pediatric population, monotherapy, generalized epilepsy and other special populations. Recently the results of a clinical trial in monotherapy have proved its efficacy in a no-inferiority design with carbamazepine. The seizure-free rate in the zonisamide group was 79.4%., Conclusions: At this moment, zonisamide represents a robust option in the treatment of a large number of patients with epilepsy, based on its multiple mechanism of action and efficacy in different situations.

Objective: The goal of the study described here was to obtain psychometric validation of the Spanish version of the 38-item Side Effects and Life Satisfaction (SEALS) Inventory., Methods: A cross-cultural adaptation of the inventory was performed. A total of 595 patients with epilepsy were included in a multicenter cross-sectional study. The SEALS Inventory was completed, together with the Hospital Anxiety and Depression Scale and SF-12 Health Survey., Results: The mean SEALS score was 60.7. SEALS presented high internal consistency, with a Cronbach alpha coefficient of 0.93, and good test-retest reliability, with an intraclass correlation coefficient of 0.92. The pattern of correlations with the Hospital Anxiety and Depression Scale and SF-12 Health Survey indicated good convergent and divergent validity. SEALS scores discriminated patients according to epilepsy-related factors, emotional disturbances, and the generic quality of life., Conclusion: The Spanish version of the SEALS Inventory is a valid psychometric instrument. It may be used in routine clinical practice and in clinical trials in patients with epilepsy to capture the cognitive and behavioral aspects of quality of life.

Introduction: Comorbidity between epilepsy and cancer is elevated. As a life-time condition, it is not impossible for a patient with epilepsy to have a cancer at some point. Besides, at least 30% of patients with primary brain tumors have epileptic seizures, but also in patients with metastatic infiltrating lesions of the central nervous system and with extracerebral tumors, epilepsy can be related. Seizures may also appear associated with paraneoplastic syndromes, such as limbic encephalitis and metabolic and infectious complications of chemotherapy and radiotherapy., Results: The precise mechanisms by which brain tumors and the other conditions mentioned above produce seizures are not fully understood, but are reviewed in this article, as well as the many different therapeutic options that may be used in the treatment of epileptic seizures. Pharmacological treatment poses various controversies, such as the utility of prophylactic treatment, interactions between antiepileptic drugs (AEDs) and chemotherapeutic drugs and the complications derived from the adverse effects of AEDs in this population. Finally, other treatments are proposed such as chemotherapy, radiotherapy and surgery, the rational application of which allows for an improvement in the patients' quality of life., Conclusion: In order to arrive at a diagnosis, the different causes that could condition the appearance of epileptic seizures in cancer patients must be known. After this, the most adequate treatment should be chosen, thus ensuring the comprehensive treatment of cancer and epilepsy.

Background: Despite the correct use of antiepileptic drugs, control of seizures is not possible in 20% to 30% of people with epilepsy. This group of patients is considered to suffer from drug-resistant epilepsy, a clinical situation that can be caused by certain syndromes in which surgery can be used to bring the seizures under control., Review Summary: Determining the suitability of the surgical treatment and the best approach always requires a full assessment, which includes video-electroencephalogram (EEG) monitoring, neuropsychological examination, and structural magnetic resonance imaging. In some patients it may be necessary to perform functional imaging tests and intracranial electrode recordings. These tests make it possible to confirm that the patient does indeed have epilepsy, identify the type of epilepsy, determine the severity of the seizures, and locate the epileptogenic zone. The best surgical results are obtained in patients with small epileptogenic lesions which can be totally resected. Nevertheless, in many patients in whom complete control is not achieved after surgery, the improvement in control of the seizures also has a positive impact on their quality of life. Some surgical techniques (partial resections, corpus callosotomy, subpial transection, electrical stimulation of the vagus nerve, and deep brain stimulation) have a palliative effect., Conclusion: The aim of this review is to update knowledge on the indications for surgery and electrical stimulation in the management of epilepsy.

To assess whether performance in attention and executive functions evaluated with the Epitrack screening tool before surgery can differentiate memory and quality of life (QOL) profiles, and detect different post-surgical change patterns in these variables in patients with epilepsy. This is a longitudinal study. Seventy-seven patients with drug-resistant epilepsy (mean age = 37.91) underwent a neuropsychological assessment before and one year after surgery. Epitrack, a screening tool that exclusively evaluates attention and executive functioning, was administered in the pre-surgical assessment, and verbal and visual memory and QOL were assessed before and after surgery. Patients with impaired Epitrack performance had poorer verbal and visual memory than those with intact Epitrack performance, regardless of the time point (for all, p < 0.0001). They also showed a post-surgical decline in immediate verbal recall (p = 0.04) and discriminability (p = 0.001). Patients with intact Epitrack performance did not exhibit this decline. Epitrack total score significantly contributed to 13 and 11% of the variance of post-surgical changes in immediate verbal recall and discriminability, respectively. Epitrack groups did not differ in QOL profiles or changes, but post-surgical immediate verbal recall improvements were related to post-surgical QOL improvements. Our findings underline the utility of Epitrack screening tool to detect different patterns of verbal and visual memory dysfunction, as well as to predict post-surgical verbal memory decline in patients with drug-resistant epilepsy. Patients with lower pre-surgical Epitrack scores appear to be at increased risk for post-surgical memory decline. [ABSTRACT FROM AUTHOR]

Objective: Cenobamate is an antiseizure medication (ASM) associated with high rates of seizure freedom and acceptable tolerability in patients with focal seizures. To achieve the optimal cenobamate dose for maximal potential effectiveness while avoiding or minimizing drug‐related adverse events (AEs), the administration of cenobamate with other ASMs must be managed through concomitant ASM load reduction. A panel of Spanish epilepsy experts aimed to provide a Spanish consensus on how to adjust the dose of concomitant ASMs in patients with drug‐resistant epilepsy (DRE) in order to improve the effectiveness and tolerability of adjunctive cenobamate. Methods: A three‐stage modified Delphi consensus process was undertaken, including six Spanish epileptologists with extensive experience using cenobamate. Based on current literature and their own expert opinion, the expert panel reached a consensus on when and how to adjust the dosage of concomitant ASMs during cenobamate titration. Results: The expert panel agreed that tailored titration and close follow‐up are required to achieve the best efficacy and tolerability when initiating cenobamate in patients receiving concomitant ASMs. When concomitant clobazam, phenytoin, phenobarbital, and sodium channel blockers are taken at high dosages, or when the patient is receiving two or more sodium channel blockers, dosages should be proactively lowered during the cenobamate titration period. Other concomitant ASMs should be reduced only if the patient reports a moderate/severe AE at any stage of the titration period. Significance: Cenobamate is an effective ASM with a dose‐dependent effect. To maximize effectiveness while maintaining the best tolerability profile, co‐medication management is needed. The recommendations included herein provide practical guidance for proactive and reactive management of co‐medication in cenobamate‐treated patients with DRE and a high drug load. Plain Language Summary: Patients with epilepsy may continue to have seizures even after treatment with several different antiseizure medications (ASMs). Cenobamate is an ASM that can reduce seizures in these patients. In this study, six Spanish experts in epilepsy discussed the best way to use cenobamate in drug‐resistant epilepsy. They provide practical guidance on when and how the dose of other ASMs might be adjusted to reduce side effects and optimize the use of cenobamate. [ABSTRACT FROM AUTHOR]

Introduction: It is important to assess the effectiveness of an antiseizure medication in treating different epilepsy aetiologies to optimise individualised therapeutic approaches. Data from the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) Extension study were used to assess the effectiveness and safety/tolerability of perampanel (PER) when used to treat individuals with a range of epilepsy aetiologies in clinical practice. Methods: A post hoc analysis was conducted of PERMIT Extension data from individuals with a known aetiology. Retention was assessed after 3, 6 and 12 months. Effectiveness was assessed after 3, 6 and 12 months and at the last visit (last observation carried forward). Effectiveness assessments included responder rate (≥ 50% seizure frequency reduction) and seizure freedom rate (no seizures since at least the prior visit). Safety/tolerability was assessed by evaluating adverse events (AEs) and AEs leading to discontinuation. Results: PERMIT Extension included 1945 individuals with structural aetiology, 1012 with genetic aetiology, 93 with an infectious aetiology, and 26 with an immune aetiology. Retention rates at 12 months were 61.1% (structural), 65.9% (genetic), 56.8% (infectious) and 56.5% (immune). At the last visit, responder rates (total seizures) were 43.3% (structural), 68.3% (genetic), 37.0% (infectious) and 20.0% (immune), and corresponding seizure freedom rates were 15.8%, 46.5%, 11.1% and 5.0%, respectively. AE incidence rates were 58.0% (structural), 46.5% (genetic), 51.1% (infectious) and 65.0% (immune), and corresponding rates of discontinuation due to AEs over 12 months were 18.9%, 16.4%, 18.5% and 21.7%, respectively. The types of AEs reported were generally consistent across aetiology subgroups, with no idiosyncratic AEs emerging. Conclusion: Although PER was effective and generally well tolerated when used to treat individuals with a range of epilepsy aetiologies in clinical practice, variability in its effectiveness and tolerability across the subgroups indicates that PER may be particularly useful for individuals with specific epilepsy aetiologies. [ABSTRACT FROM AUTHOR]

Objective The aim was to examine the effect of polytherapy (i.e. the number of administered anti-seizure medications (ASMs)) on memory, and whether the interaction between the number of ASMs and attentional/executive functioning affect presurgical memory functioning and postsurgical memory changes in patients with drug-resistant epilepsy. Methods Two studies were carried out. Study 1 consisted of a presurgical assessment of 125 adult patients, in which attention/executive function (EpiTrack screening tool) and memory were assessed (cross-sectional study). Of them, 72 patients underwent a second postsurgical evaluation, in which memory was assessed (Study 2). Patients were distributed into groups based on EpiTrack performance and number of ASMs. Results The interaction between the number of ASMs and the attentional/executive functioning significantly affected presurgical memory, with patients with impaired EpiTrack performance taking three-four ASMs having poorer scores than patients with intact EpiTrack performance taking three-four ASMs (for all, p  < .0001). This interaction also affected postsurgical memory changes, with patients with impaired Epitrack performance taking three-four ASMs having higher postsurgical decline than those with intact Epitrack performance taking three-four ASMs (for all, p  < .005). No differences were found in patients taking two ASMs. Furthermore, the number of ASMs was associated with presurgical memory performance and postsurgical memory changes only in patients with impaired EpiTrack performance (for all, p  < .05). Conclusions Our findings underline the utility of EpiTrack, together with the clinical information on the number of prescribed ASMs, to corroborate the impact of polytherapy on memory and to optimize the prediction of postsurgical memory changes. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to evaluate perampanel (PER) when used under real‐world conditions to treat people with idiopathic generalized epilepsy (IGE) included in the PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study. Methods: The multinational, retrospective, pooled analysis PERMIT explored the use of PER in people with focal and generalized epilepsy treated in clinical practice across 17 countries. This subgroup analysis included PERMIT participants with IGE. Time points for retention and effectiveness measurements were 3, 6, and 12 months (last observation carried forward, defined as "last visit," was also applied to effectiveness). Effectiveness was evaluated by seizure type (total seizures, generalized tonic–clonic seizures [GTCS], myoclonic seizures, absence seizures) and included ≥50% responder rate and seizure freedom rate (defined as no seizures since at least the previous visit). Safety/tolerability was monitored throughout PER treatment and evaluated by documenting the incidence of adverse events (AEs), including psychiatric AEs and those leading to treatment discontinuation. Results: The Full Analysis Set included 544 people with IGE (51.9% women, mean age = 33.3 years, mean epilepsy duration = 18.1 years). At 3, 6, and 12 months, 92.4%, 85.5%, and 77.3% of participants were retained on PER treatment, respectively (Retention Population, n = 497). At the last visit, responder and seizure freedom rates were, respectively, 74.2% and 54.6% (total seizures), 81.2% and 61.5% (GTCS), 85.7% and 66.0% (myoclonic seizures), and 90.5% and 81.0% (absence seizures) (Effectiveness Population, n = 467). AEs occurred in 42.9% of patients and included irritability (9.6%), dizziness/vertigo (9.2%), and somnolence (6.3%) (Tolerability Population, n = 520). Treatment discontinuation due to AEs was 12.4% over 12 months. Significance: This subgroup analysis of the PERMIT study demonstrated the effectiveness and good tolerability of PER in people with IGE when administered under everyday clinical practice conditions. These findings are in line with clinical trial evidence, supporting PER's use as broad‐spectrum antiseizure medication for the treatment of IGE. [ABSTRACT FROM AUTHOR]

Introduction: Drug-resistant epilepsy has been proposed as a chronic stress model. Stress can be measured in terms of chronicity (epilepsy duration) and intensity (comorbidities), with depression and anxiety among the most important comorbidities in epilepsy due to its prevalence and its relationship with cognitive functioning and quality of life. This study aims to establish phenotypes according to how patients face a stressful condition (epilepsy) and examine differences in cognition and quality of life depending on these phenotypes. We hypothesize that there will be an interrelationship between epilepsy duration and negative affectivity, and these variables will influence cognition and quality of life. Methods: 170 patients (82 men and 88 women) underwent a neuropsychological evaluation in which trait anxiety, depression, attention and executive function, verbal and visual memory, language, emotional recognition, and quality of life were assessed. Hierarchical clustering was performed using z-scores for three variables: trait anxiety; depression; and epilepsy duration. Results: Three clusters were found: vulnerable (high negative affectivity and short duration); resilient (moderate negative affectivity and long duration); and lowimpact group (low negative affectivity and short duration). Results show that the vulnerable group had poorer cognitive functioning and quality of life than the other groups. Specifically, the vulnerable group had poorer scores than the lowimpact group on verbal memory, visual confrontation naming, and quality of life (except seizure worry). Furthermore, resilient patients had better scores than the low-impact group on cognitive flexibility variables, but lower scores on some quality-of-life subscales (i.e., overall quality of life, emotional well-being, and energy). Finally, the vulnerable group had poorer scores than the resilient group in executive functioning, naming, and quality of life. Discussion: These results suggest that dealing with stress in patients with epilepsy is related to cognitive performance and quality of life. These findings underline the relevance of considering comorbidities in epilepsy and may be useful for detecting vulnerable or resilient profiles as risk or protective factors for cognitive and quality of life decline. [ABSTRACT FROM AUTHOR]

To assess the effectiveness, overall tolerability of eslicarbazepine acetate (ESL) as an initial or early monotherapy treatment of adult patients with focal epilepsy under real-world practice conditions. We focused on real-world longitudinal studies that included or separately reported the results of at least one of the efficacy outcomes of interest. A DerSimonian-Laird random effects model was used with the presentation of the 95% confidence intervals of the estimate 5 studies met our selection criteria and were included in the quantitative synthesis. All studies were observational and uncontrolled studies, and all but one were retrospective studies. The pooled proportion of patients who were seizure-free for the entire study period was 64.6% (95% CI, 45.7 to 79.8) at month 6 and 56.6% (95% CI, 50.2 to 62.8) at month 12. Pooled retention rates were 95.0% (95% CI, 90.3 to 97.5) at 6 months and 83.6% (95% CI, 73.9 to 90.1) at 12 months. The pooled proportion of patients who reported at least one adverse event was 27.2% (95% CI, 21.7 to 33.6), and the pooled proportion of patients who discontinued ESL due to adverse events was 8.9% (95% CI 6.2 to 12.6). Our results suggest that initial or early monotherapy with ESL is effective and well-tolerated for the management of adult patients with focal epilepsy in clinical practice, with results that are at least similar to those reported in the pivotal randomized clinical trial of ESL monotherapy. No new safety signals with ESL have been identified in this systematic review. [ABSTRACT FROM AUTHOR]

Introduction: The PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date. Methods: This post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three ormore previous antiseizuremedications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. Results: The Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p=0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p < 0.001), focal seizures (65.0% vs. 36.8%; p < 0.001) and GTCS (83.7% vs. 67.2%; p < 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p < 0.001]; focal seizures, 29.4% vs. 8.7% [p < 0.001]; GTCS, 69.0% vs. 48.1% [p < 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p < 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031). Discussion: This study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures. [ABSTRACT FROM AUTHOR]

Purpose: Memory deficits are very frequent in patients with drug-resistant epilepsy, but they predict a small proportion of variance of their quality of life (QOL) in previous studies, possibly due to the lack of consideration of mediating factors of this relationship. This study aimed to examine whether trait anxiety mediates the relationship between memory and QOL in this population, controlling the influence of demographic and seizure-related factors. Methods: In this cross-sectional study, 119 adults with drug-resistant temporal lobe epilepsy (TLE) underwent a neuropsychological evaluation, in which memory, anxiety, and QOL were assessed. Results: In the total sample, better delayed memory had an effect on better QOL indirectly through lower trait anxiety (B = 0.13, SE = 0.06, p = 0.04, abcs = 0.13; κ2 = 0.18; PMind = 0.76). Additionally, delayed memory has not a direct association with QOL (B = 0.04, SE = 0.09, p = 0.64, Cohen's f 2 = 0.005; PMdir = 0.24), and the total effect of delayed memory on QOL tended to reach statistical significance (B = 0.17, SE = 0.10, p = 0.08). The proposed mediation model yielded excellent fit (CFI = 1.00, RMSEA = 0.0001, SRMR = 0.009, and χ2 (1) = 0.50, p = 0.48) and explained 38% of the variance of QOL. Conclusion: These findings suggest that trait anxiety is an important factor in understanding the relationship between memory and QOL in patients with TLE, considering the influence of demographic and seizure-related variables, and may have relevant implications for decision-making in this population. [ABSTRACT FROM AUTHOR]

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Objective: We conducted a post hoc analysis of two randomized controlled trials, GWPCARE1 (NCT02091375) and GWPCARE2 (NCT02224703), to estimate the time to onset of cannabidiol (CBD) treatment effects (seizure reduction and adverse events [AEs]) in patients with Dravet syndrome (DS). Methods: Patients received either plant‐derived highly purified CBD (Epidiolex in the United States; 100 mg/ml oral solution) 10 mg/kg/day (CBD10; GWPCARE2) or 20 mg/kg/day (CBD20; GWPCARE1&2), or matching placebo for 14 weeks. Treatment started at 2.5 mg/kg/day, reached 10 mg/kg/day on Day 7, and went up to 20 mg/kg/day on Day 11 during the 14‐day titration period. Percentage change from baseline in convulsive seizure frequency was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were also evaluated. Results: Overall, 124 patients received placebo and 194 received CBD (CBD10, n = 64; CBD20, n = 130). Mean age was 9.5 years (range = 2.2–18.9). Patients had discontinued a median of four antiepileptic drugs (range = 0–26) and were currently taking a median of three (range = 1–5). Differences in convulsive seizure reduction between placebo and CBD emerged during titration and became nominally significant by Day 12 for CBD20 (p =.02) and Day 13 for CBD10 (p =.03). Additionally, differences in the 50% responder rate between placebo and CBD became apparent during titration. Onset of the first reported AE occurred during the titration period in 48.4% of placebo patients and 54.1% of CBD patients. The three most common AEs of somnolence, decreased appetite, and diarrhea resolved within 4 weeks of onset in the majority of CBD‐treated patients (56.3%–72.9%). Significance: The therapeutic effect of CBD in DS may start within 2 weeks of treatment in some patients. Although AEs lasted longer for CBD than placebo, most resolved within the 14‐week study period. [ABSTRACT FROM AUTHOR]

Objective: To estimate time to onset of cannabidiol (CBD) treatment effect (seizure reduction and adverse events [AEs]), we conducted post hoc analyses of data from two randomized, placebo‐controlled, Phase 3 trials, GWPCARE3 (NCT02224560) and GWPCARE4 (NCT02224690), of patients with Lennox–Gastaut syndrome. Methods: Patients received plant‐derived pharmaceutical formulation of highly purified CBD (Epidiolex, 100 mg/ml oral solution) at 10 mg/kg/day (CBD10; GWPCARE3) or 20 mg/kg/day (CBD20; both trials) or placebo for 14 weeks. Treatment started at 2.5 mg/kg/day for all groups and reached 10 mg/kg/day on Day 7 and 20 mg/kg/day (CBD20 and matching placebo only) on Day 11. Percentage change from baseline in drop seizure frequency was calculated by cumulative day (i.e., including all previous days). Time to onset and resolution of AEs were evaluated. Results: Overall, 235 patients received CBD (CBD10 [GWPCARE3 only], n = 67; CBD20 [pooled GWPCARE3&4], n = 168) and 161 received placebo. Mean (range) age was 15.3 years (2.6–48.0). Patients had previously discontinued a median (range) of six (0–28) antiepileptic drugs (AEDs) and were currently taking a median of three (0–5) AEDs. Differences in drop seizure reduction between placebo and CBD emerged during the titration period and became nominally significant by Day 6 (p =.008) for pooled CBD treatment groups. Separation between placebo and CBD in ≥50% responder rate emerged by Day 6. Onset of the first reported AE occurred during the titration period in 45% of patients (CBD10, 46%; CBD20, 52%; placebo, 38%). In patients with AEs, resolution occurred within 4 weeks of onset in 53% of placebo and 39% of CBD patients and by end of study in 63% of placebo and 61% of CBD patients. Significance: Treatment effect (efficacy and AEs) of CBD may occur within 1 week of starting treatment. Although AEs lasted longer for CBD than placebo, most resolved within the 14‐week period. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy, safety and tolerability of eslicarbazepine acetate (ESL) in patients transitioning from carbamazepine or oxcarbazepine to ESL in clinical practice, by analysing data from the Euro-Esli study.Methods: Euro-Esli was a pooled analysis of 14 European clinical practice studies. Effectiveness assessments included responder rate (≥50 % seizure frequency reduction) and seizure freedom rate (seizure freedom at least since prior visit), assessed after 3, 6 and 12 months of ESL treatment, and at the last visit. Safety and tolerability were assessed throughout follow-up by evaluating adverse events (AEs) and ESL discontinuation due to AEs, respectively. Data were analysed for cohorts of patients who transitioned from carbamazepine and oxcarbazepine to ESL either due to lack of efficacy or poor tolerability.Results: Euro-Esli included 2058 patients, of whom 233 (11.3 %) transitioned from carbamazepine to ESL and 134 (6.5 %) transitioned from oxcarbazepine to ESL. After 12 months of ESL treatment, responder and seizure freedom rates for patients transitioning from carbamazepine due to lack of efficacy (n = 163) were 70.0 % and 30.9 %, respectively. Corresponding values for patients transitioning from oxcarbazepine due to lack of efficacy (n = 90) were 57.1 % and 25.0 %, respectively. Among patients who transitioned from carbamazepine and oxcarbazepine to ESL due to poor tolerability (n = 64 and n = 61, respectively), 26.6 % and 39.5 % experienced AEs, and 8.3 % and 6.8 % discontinued ESL due to AEs, respectively.Conclusion: ESL was efficacious and generally well tolerated in patients transitioning from carbamazepine or oxcarbazepine in clinical practice due to inadequate seizure control or intolerable AEs with these agents. [ABSTRACT FROM AUTHOR]

The epileptogenic focus is a brain area that may be surgically removed to control of epileptic seizures. Locating it is an essential and crucial step prior to the surgical treatment. However, given the difficulty of determining the localization of this brain region responsible of the initial seizure discharge, many works have proposed machine learning methods for the automatic classification of focal and non-focal electroencephalographic (EEG) signals. These works use automatic classification as an analysis tool for helping neurosurgeons to identify focal areas off-line, out of surgery, during the processing of the huge amount of information collected during several days of patient monitoring. In turn, this paper proposes an automatic classification procedure capable of assisting neurosurgeons online, during the resective epilepsy surgery, to refine the localization of the epileptogenic area to be resected, if they have doubts. This goal requires a real-time implementation with as low a computational cost as possible. For that reason, this work proposes both a feature set and a classifier model that minimizes the computational load while preserving the classification accuracy at 95.5%, a level similar to previous works. In addition, the classification procedure has been implemented on a FPGA device to determine its resource needs and throughput. Thus, it can be concluded that such a device can embed the whole classification process, from accepting raw signals to the delivery of the classification results in a cost-effective Xilinx Spartan-6 FPGA device. This real-time implementation begins providing results after a 5 s latency, and later, can deliver floating-point classification results at 3.5 Hz rate, using overlapped time-windows. [ABSTRACT FROM AUTHOR]