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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: 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]

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]

Objective: Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS) are rare treatment‐resistant childhood epilepsies classed as developmental and epileptic encephalopathies. ELEKTRA investigated the efficacy and safety of soticlestat (TAK‐935) as adjunctive therapy in children with DS or LGS (NCT03650452). Methods: ELEKTRA was a phase 2, randomized, double‐blind, placebo‐controlled study of soticlestat (≤300 mg twice daily, weight‐adjusted) in children (aged 2–17 years) with DS, demonstrating three or more convulsive seizures/month, or with LGS, demonstrating four or more drop seizures/month at baseline. The 20‐week treatment period comprised an 8‐week dose‐optimization period and a 12‐week maintenance period. Efficacy endpoints included change from baseline in seizure frequency versus placebo. Safety assessments included incidence of treatment‐emergent adverse events (TEAEs). Results: ELEKTRA enrolled 141 participants; 126 (89%) completed the study. The modified intent‐to‐treat population included 139 participants who received one or more doses of study drug and had one or more efficacy assessments (DS, n = 51; LGS, n = 88). ELEKTRA achieved its primary endpoint: the combined soticlestat‐treated population demonstrated a placebo‐adjusted median reduction in seizure frequency of 30.21% during the maintenance period (p =.0008, n = 139). During this period, placebo‐adjusted median reductions in convulsive and drop seizure frequencies of 50.00% (p =.0002; patients with DS) and 17.08% (p =.1160; patients with LGS), respectively, were observed. TEAE incidences were similar between the soticlestat (80.3%) and placebo (74.3%) groups and were mostly mild or moderate in severity. Serious TEAEs were reported by 15.5% and 18.6% of participants receiving soticlestat and placebo, respectively. TEAEs reported in soticlestat‐treated patients with ≥5% difference from placebo were lethargy and constipation. No deaths were reported. Significance: Soticlestat treatment resulted in statistically significant, clinically meaningful reductions from baseline in median seizure frequency (combined patient population) and in convulsive seizure frequency (DS cohort). Drop seizure frequency showed a nonstatistically significant numerical reduction in children with LGS. Soticlestat had a safety profile consistent with previous studies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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]

Summary: Objective: The definition of drug‐resistant epilepsy (DRE) affects case identification and treatment, and impacts prevalence or incidence estimates and health burden estimation in epidemiology. The objective of this systematic review is to evaluate the consistency between definitions of DRE in the literature and the official definition in the International League Against Epilepsy (ILAE) guidelines, and to estimate the incidence, prevalence, and risk factors for DRE. Methods: MEDLINE and EMBASE were searched for observational studies of DRE published between January 1980 and July 2015. The definitions of DRE in these studies were compared with the definition in the ILAE guidelines. Random‐effect model meta‐analyses were used to generate pooled estimates of prevalence or incidence and pooled odds ratios of the association with risk factors. Results: Thirty‐five studies met inclusion criteria, including 13 080 epilepsy patients and 3941 patients with DRE. The definition of DRE varied widely across studies, with only 12% meeting the requirements of the ILAE definition. The pooled prevalence proportion of DRE among epilepsy patients was 0.30 (95% confidence interval [CI] 0.19‐0.42), and the pooled incidence proportion was 0.15 (95% CI 0.11‐0.19). Age at onset, symptomatic epilepsy, abnormal neuroimaging findings, abnormal electroencephalography results, history of mental retardation, neuropsychiatric disorders, febrile seizure, and status epilepticus increased risk for DRE. Significance: There are limited high‐quality data available on DRE. Lack of consistency in definitions limits the ability to obtain robust estimates on the burden of DRE. More data based on the ILAE definition from well‐designed epidemiologic studies are needed to generate accurate and reliable results. [ABSTRACT FROM AUTHOR]

Summary: Objective: To analyze the effectiveness and tolerability of perampanel across different seizure types in routine clinical care of patients with idiopathic generalized epilepsy (IGE). Methods: This multicenter, retrospective, 1‐year observational study collected data from patient records at 21 specialist epilepsy units in Spain. All patients who were aged ≥12 years, prescribed perampanel before December 2016, and had a confirmed diagnosis of IGE were included. Results: The population comprised 149 patients with IGE (60 with juvenile myoclonic epilepsy, 51 generalized tonic–clonic seizures [GTCS] only, 21 juvenile absence epilepsy, 10 childhood absence epilepsy, 6 adulthood absence epilepsy, and one Jeavons syndrome). Mean age was 36 years. The retention rate at 12 months was 83% (124/149), and 4 mg was the most common dose. At 12 months, the seizure‐free rate was 59% for all seizures (88/149); 63% for GTCS (72/115), 65% for myoclonic seizures (31/48), and 51% for absence seizures (24/47). Seizure frequency was reduced significantly at 12 months relative to baseline for GTCS (78%), myoclonic (65%), and absence seizures (48%). Increase from baseline seizure frequency was seen in 5.2% of patients with GTCS seizures, 6.3% with myoclonic, and 4.3% with absence seizures. Perampanel was effective regardless of epilepsy syndrome, concomitant antiepileptic drugs (AEDs), and prior AEDs, but retention and seizure freedom were significantly higher when used as early add‐on (after ≤2 prior AEDs) than late (≥3 prior AEDs). Adverse events were reported in 50% of patients over 12 months, mostly mild or moderate, and irritability (23%), somnolence (15%), and dizziness (14%) were most frequent. Significance: In routine clinical care of patients with IGE, perampanel improved seizure outcomes for GTCS, myoclonic seizures, and absence seizures, with few discontinuations due to adverse events. This is the first real‐world evidence with perampanel across different seizure types in IGE. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Purpose Pooled evaluation of the key efficacy and safety profile of eslicarbazepine acetate ( ESL) added-on to stable antiepileptic therapy in adults with focal-onset seizures. Methods Data from 1703 patients enrolled in four phase III double-blind, randomized, placebo-controlled studies were pooled and analyzed. Following a 2 week titration period, ESL was administered at 400 mg, 800 mg, and 1200 mg once-daily doses for 12 weeks (maintenance period). Pooled efficacy variable was standardized (/4 weeks) seizure frequency ( SSF) analyzed over the maintenance period as reduction in absolute and relative SSF and proportion of responders (≥50% reduction in SSF). Pooled safety was analyzed by means of adverse events and clinical laboratory assessments. Results SSF was significantly reduced with ESL 800 mg ( P < 0.0001) and 1200 mg ( P < 0.0001) compared to placebo. Median relative reduction in SSF was 33.4% for ESL 800 mg and 37.8% for 1200 mg (placebo: 17.6%), and responder rate was 33.8% and 43.1% (placebo: 22.2%). ESL was more efficacious than placebo regardless of gender, geographical region, epilepsy duration, age at time of diagnosis, seizure type, and type of concomitant antiepileptic drugs ( AED). Incidence of adverse events ( AEs) and AEs leading to discontinuation was dose dependent. Most common AEs (>10% patients) were dizziness, somnolence, and nausea. The incidence of treatment-emergent AEs (dizziness, somnolence, ataxia, vomiting, and nausea) was lower in patients who began taking ESL 400 mg (followed by 400 mg increments to 800 or 1200 mg) than in those who began taking ESL 600 mg or 800 mg. Conclusions Once-daily ESL 800 mg and 1200 mg showed consistent results across all efficacy and safety endpoints, independent of study population characteristics and type of concomitant AEDs. Treatment initiated with ESL 400 mg followed by 400 mg increments to 800 or 1200 mg provides optimal balance of efficacy and tolerability. [ABSTRACT FROM AUTHOR]

Objective: The noncompetitive a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist perampanel was shown in phase III trials to be an effective and well-tolerated adjunctive treatment for partial-onset seizures. In adolescents, it is necessary to characterize cognitive, neuropsychological, and behavioral side effects of antiepileptic drugs (AEDs). The current analysis focuses on behavioral outcomes, efficacy, and safety of perampanel in adolescents. Methods: Adolescents (12-17 years) on a stable regimen of 1-3 AEDs for partial-onset seizures were randomized (2:1 ratio) to receive up to 12 mg/day perampanel or placebo. Alongside efficacy, cognitive, and neuropsychological assessments, behavioral outcomes were measured with the Child Behavior Checklist (CBCL) before and after a 19-week titration and maintenance phase. Results: Of the randomized patients, 85 received perampanel and 48 received placebo. Median reduction in seizure frequency from baseline was 58.0% for perampanel and 24.0% for placebo (p = 0.079). More patients had seizure frequency reduced by 50% after perampanel (n = 49 [59.0%]) than placebo (n = 17 [37.0%]; p = 0.0144). Changes in behavior were minimal, and there were no differences between groups on competency (p = 0.619) or problems (p = 0.174). A greater proportion of placebo patients were classified in the CBCL "clinical" range for competency at end of treatment, whereas the number in the perampanel group remained unchanged. The overall safety profile was similar to that reported previously for perampanel; most frequently reported adverse events (AEs) were dizziness (26 patients [30.6% vs. 14.6% placebo]), somnolence (13 patients [15.3% vs. 4.2%]), and headache (nine patients [10.6% vs. 14.6%]). Aggression was reported in seven patients receiving perampanel (8.2% vs. 2.1% placebo); two of these were serious AEs, with neither requiring treatment discontinuation. Significance: Adjunctive perampanel is efficacious and well tolerated in adolescents with partial-onset seizures, and appears to have no clinically important impact on behavior measured using the CBCL. [ABSTRACT FROM AUTHOR]

▪ Abstract: Supraorbital neuralgia has been identified as an infrequent cause of headache that may prove very difficult to control pharmacologically. Peripheral nerve stimulation using electrodes to stimulate the nerve segmentally responsible for the zone of pain may constitute a management alternative in such cases. We present the case of a patient with headache because of posttraumatic supraorbital neuralgia, refractory to medical treatment, with good analgesic control after peripheral nerve stimulation. Peripheral nerve stimulation may be considered a safe, reversible treatment for patients with headache secondary to supraorbital neuralgia who respond poorly to pharmacological treatment, thus avoiding irreversible alternatives such as surgery. ▪ [ABSTRACT FROM AUTHOR]

Purpose: To determine brain involvement in Lafora disease by means of 3-T MRI volumetry and 1H magnetic resonance (MR) spectroscopy. Methods: Ten patients with Lafora disease and 10 healthy controls were included in the study. The diagnosis of Lafora disease was proven genetically by the presence of mutations in the EPM2A gene in all patients, and their evolution was staged in three groups according to their functional state. MRI volumetry was performed by means of AX3DT1 images with assessment of the cerebellum and the brainstem, by using the program Stereonauta, and all the brain structures, by using voxel-based morphometry. [1H]MR spectroscopy was performed by using an Eclipse PRESS sequence probe system with 8-cc voxels positioned in the occipital and frontal cortexes, basal ganglia, pons, and cerebellar hemispheres. Spectral peak areas corresponding to NAA ( N-acetylaspartate), creatine, and choline were obtained. Results: MRI volumetry showed no statistically significant differences in patients compared with healthy controls in any of the analyzed structures. Analysis of [1H]MR spectroscopy data showed a statistically significant reduction in the NAA/creatine ratio in patients compared with controls in the frontal (p = 0.001) and occipital cortex (p = 0.043), basal ganglia (p = 0.002), and cerebellar hemispheres (p = 0.007). The NAA/choline and choline/creatine ratios were statistically significantly different in the frontal cortex (p = 0.005). No correlation was observed between the disease-evolution stage and MRI-measured volumes (range, –0.92 to 0.44) or [1H]MR spectroscopy values (range, –0.29 to 0.50). Conclusions: In our series of Lafora disease patients, [1H]MR spectroscopy was more sensitive than structural MRI to detect brain involvement. The brain cortex, especially frontal cortex, cerebellum, and basal ganglia, showed the greatest metabolic changes. [ABSTRACT FROM AUTHOR]

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.)

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.)

Objectives: Evaluate long-term effectiveness and tolerability of brivaracetam in clinical practice in patients with focal epilepsy., Materials and Methods: This was a multicenter retrospective study. Patients aged ≥16 years were started on brivaracetam from November 2016 to June 2017 and followed over 1 year. Data were obtained from medical records at 3, 6 and 12 months after treatment initiation for evaluation of safety- and seizure-related outcomes., Results: A total of 575 patients were included in analyses; most had been treated with ≥4 lifetime antiepileptic drugs. Target dosage was achieved by 30.6% of patients on the first day. Analysis of primary variables at 12 months revealed that mean reduction in seizure frequency was 36.0%, 39.7% of patients were ≥50% responders and 17.5% were seizure-free. Seizure-freedom was achieved by 37.5% of patients aged ≥65 years. Incidence of adverse events (AEs) and psychiatric AEs (PAEs) was 39.8% and 14.3%, respectively, and discontinuation due to these was 8.9% and 3.7%, respectively. Somnolence, irritability, and dizziness were the most frequently reported AEs. At baseline, 228 (39.7%) patients were being treated with levetiracetam; most switched to brivaracetam (dose ratio 1:10-15). Among those who switched because of PAEs (n = 53), 9 (17%) reported PAEs on brivaracetam, and 3 (5.7%) discontinued because of PAEs. Tolerability was not highly affected among patients with learning disability or psychiatric comorbidity., Conclusions: In a large population of patients with predominantly drug-resistant epilepsy, brivaracetam was effective and well-tolerated; no unexpected AEs occurred over 1 year, and the incidence of PAEs was lower compared with levetiracetam., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To assess the effectiveness and safety/tolerability of eslicarbazepine acetate (ESL) monotherapy in clinical practice in Europe., Materials and Methods: Euro-Esli was a pooled analysis of 14 European clinical practice studies. Responder rate (≥50% seizure frequency reduction) and seizure freedom rate (seizure freedom at least since prior visit) were assessed after 3, 6 and 12 months of ESL treatment and at last visit. Adverse events (AEs) and AEs leading to ESL discontinuation were assessed throughout follow-up. A subanalysis was conducted to assess outcomes for patients treated initially with ESL monotherapy and for patients treated at the last visit with ESL monotherapy., Results: ESL was used as monotherapy in 88/2045 (4.3%) patients initially and in 229/1340 (17.1%) patients at the last visit. At 12 months, responder and seizure freedom rates were 94.1% and 88.2%, respectively, in patients treated initially with ESL monotherapy, and 93.2% and 77.4%, respectively, in patients treated at the last visit with ESL monotherapy. Corresponding values for patients treated initially with ESL adjunctive therapy were 74.8% and 39.0%, respectively; and for patients treated at the last visit with ESL adjunctive therapy, corresponding values were 70.4% and 25.9%, respectively. Safety and tolerability were generally comparable in patients treated with ESL as monotherapy or adjunctive therapy. The most commonly reported AEs (≥5% of patients in any group) were dizziness, somnolence, instability/ataxia, and fatigue., Conclusions: These clinical practice data support the use of ESL as monotherapy, as well as adjunctive therapy, for focal-onset seizures, complementing evidence from clinical trials., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)