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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]

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

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: 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. [ABSTRACT FROM AUTHOR]

Objectives. People with drug-resistant epilepsy are potential candidates for epilepsy surgery, a subset of whom requires intracranial video-EEG monitoring (IVEM) to determine the seizure onset zone (SOZ). The purpose of this study is to investigate noninvasive predictors of SOZ focality and surgical outcome in order to optimise case selection for this procedure. Materials and Methods. We performed a retrospective cohort study of patients who underwent IVEM at our centre from January 2006 to July 2021. We applied a multivariate logistic regression model to estimate the effect of potential noninvasive data as influencing factors for both SOZ focality and surgical outcome. A focal SOZ included a sublobar onset on IVEM, and a good surgical outcome was defined as Engel class I. Results. A total of 783 underwent a presurgical evaluation, 102 of them with IVEM. Ninety-seven patients were included in the SOZ focality analysis, and 64 were included in the surgical outcome analysis. The presence of focal to bilateral tonic-clonic seizures (p = 0.03) and generalised interictal epileptiform discharges (IEDs) during scalp EEG (p = 0.02) predicted a nonfocal SOZ. A weekly (p = 0.01) or daily seizure frequency (p < 0.01), focal to bilateral tonic-clonic seizures (p = 0.01), nonlesional MRI (p < 0.01), and multifocal (p = 0.02) or generalised IEDs (p < 0.01) were associated with a poor surgical outcome. Conclusions. A high seizure frequency, positive history of focal to bilateral tonic-clonic seizures, nonlesional MRI, and generalised and multifocal IEDs are noninvasive factors that may aid in selecting candidates for IVEM. [ABSTRACT FROM AUTHOR]

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. [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]

Aims. In this Virgo Environment Traced in CO (VERTICO) science paper, we aim to study how the star formation process depends on the galactic environment and gravitational interactions in the context of galaxy evolution. We explore the scaling relation between the star formation rate surface density (ΣSFR) and the molecular gas surface density (Σmol), also known as the Kennicutt-Schmidt relation, in a subsample of Virgo cluster spiral galaxies. Methods. We used new Atacama Compact Array and Total Power (ACA+TP) observations from the VERTICO-Atacama Large Millimeter/submillimeter Array (ALMA) Large Program at 720 pc resolution to resolve the molecular gas content, as traced by the 12CO (2 − 1) transition, across the disks of 37 spiral galaxies in the Virgo cluster. In combination with archival UV and IR observations used to determine the star formation rate (SFR), we estimated the parameters of the Kennicutt-Schmidt (KS) relation for the entire ensemble of galaxies, and within individual galaxies. Results. We find the KS slope for the entire population to be N = 0.97 ± 0.07, with a characteristic molecular gas depletion time of 1.86 Gyr for our full sample, which is in agreement with previous work in isolated, nearby star-forming galaxies. In individual galaxies, we find that the KS slope ranges between 0.69 and 1.40, and that typical star formation efficiencies of molecular gas can vary from galaxy to galaxy by a factor of ∼4. These galaxy-to-galaxy variations account for ∼0.20 dex in scatter in the ensemble KS relation, which is characterized by a 0.42 dex scatter. In addition, we find that the HI-deficient galaxies in the Virgo cluster show a steeper resolved KS relation and lower molecular gas efficiencies than HI-normal cluster galaxies. Conclusions. While the molecular gas content in galaxies residing in the Virgo cluster appears – to first order – to behave similarly to that in isolated galaxies, our VERTICO sample of galaxies shows that cluster environments play a key role in regulating star formation. The environmental mechanisms affecting the HI galaxy content also have a direct impact on the star formation efficiency of molecular gas in cluster galaxies, leading to longer depletion times in HI-deficient members. [ABSTRACT FROM AUTHOR]