Objectives: Cenobamate is an antiseizure medication (ASM) with proven effectiveness in individuals with highly refractory epilepsy. This study investigated the effectiveness and tolerability of cenobamate in different treatment lines and a less refractory setting. Methods: This was a multicenter, retrospective, observational study. Adults with focal epilepsy, 2–6 prior ASMs, and ≥12 months between cenobamate initiation and database closure were included. Data from patients' charts were collected and included in the Drug‐Resistant Epilepsy Registry of the Spanish Epilepsy Society using Research Electronic Data Capture. Primary effectiveness endpoints included changes in seizure frequency at 3, 6, and 12 months after cenobamate initiation according to different treatment lines. Primary safety endpoints included the percentage of patients with adverse events (AEs). Results: In total, 486 patients were included (mean age 42.8 years). The mean number of prior ASMs was 4.4 (2–6); the mean number of concomitant ASMs at cenobamate initiation was 2.5 (1–5). At 12 months, treatment retention was 92% and median dose was 200 mg. One‐year seizure‐freedom rates were 32.5%, 33.3%, 21.4%, 24.2%, and 11.4% in those treated with 2–6 prior ASMs, respectively. The proportions of patients achieving ≥50%, ≥75%, ≥90%, and 100% reductions in seizure frequency at 12 months were significantly higher in patients with 2–3 (earlier treatment lines) vs 4–6 prior ASMs (later treatment lines; p ≤ .004). Improvements in seizure severity were reported in 71.9% of patients during follow‐up (82.5% and 62.1% in those with 2 and 6 prior ASMs, respectively). At 12 months, 56.4% of patients had reported AEs, with somnolence the most frequent, and 4.9% had AEs requiring cenobamate discontinuation. Significance: Cenobamate was effective and well tolerated in patients who had tried 2–6 prior ASMs in a real‐world setting. High effectiveness was confirmed at 1 year, with better outcomes in earlier users.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β plaques, tau hyperphosphorylation, and chronic neuroinflammation. Emerging evidence suggests a crucial role of lipid signaling pathways in AD pathogenesis, particularly those mediated by autotaxin (ATX) and lysophosphatidic acid (LPA). ATX, an enzyme responsible for LPA production, has been implicated in neuroinflammatory processes, blood–brain barrier dysfunction, and neuronal degeneration. LPA signaling, through its interaction with specific G-protein-coupled receptors, influences neuroinflammation, synaptic plasticity, and tau pathology, all of which contribute to AD progression. This review synthesizes recent findings on the ATX/LPA axis in AD, exploring its potential as a biomarker and therapeutic target. Understanding the mechanistic links between ATX, LPA, and AD pathology may open new avenues for disease-modifying strategies.

• Depression was screened in 82 epilepsy outpatients using the NDDIE. • 42.7% of patients screened positive; 29.3% were confirmed depressed by psychiatry. • NDDIE showed substantial agreement with psychiatric diagnosis (κ = 0.71). • Significant NDDIE score reduction was observed after SSRI treatment (p < 0.001). • Routine use of NDDIE may improve detection and management of depression in epilepsy.

Objective: Developmental and epileptic encephalopathies (DEEs) are characterized by drug‐resistant seizures and developmental slowing/regression. We examined the efficacy and tolerability of fenfluramine (FFA) in pediatric and adult patients with Lennox–Gastaut syndrome (LGS), Dravet syndrome (DS), and other DEEs. Methods: In this multicenter, retrospective, real‐world study, FFA treatment was initiated ≥12 months before database closure. Data from patients' charts at 3, 6 and 12 months were recorded in the Spanish Epilepsy Society's DEEs registry. Effectiveness endpoints included seizure reductions of 100%, ≥75%, and ≥50% (responder), median percent seizure reduction, and seizure worsening. Safety endpoints included adverse event (AE) rates. Results: The study included 166 patients (LGS, n = 84; DS, n = 42; other DEE, n = 40; mean age 16.6 ± 12.1 years [111 pediatric, median 10.1 years; 55 adult, median 26.5 years]). Patients had a median of 3 prior failed anti‐seizure medications (ASMs). At 12 months, the median FFA dose was 0.49 mg/kg/day, with 77.1% treatment retention. There was a 68.8% median reduction in seizure frequency between baseline and 12 months ( p < .001), with significant reductions across all diagnostic groups (LGS, p < .001; DS, p < .001; other DEE, p = .004). The 12‐month ≥50% responder rate was 61%, with no statistically significant differences according to age. At 12 months, there were significant reductions in the mean number of concomitant ASMs ( p = .004) and the proportion of patients requiring rescue medication ( p < .001). Meaningful improvements in Clinical Global Impression scores for cognition (59.3% of patients), behavior (40.9%), sleep (24.3%), and caregiver (44.8%) domains were observed. At 12 months, AEs were reported in 68.1% of patients (mostly mild‐to‐moderate) and AEs leading to discontinuation in 12%, with no significant differences according to age. Significance: FFA was effective, with predictable tolerability, in patients with different DEEs and seizure types, supporting its use as an effective treatment option in pediatric and adult patients with DEEs.

Objective: To evaluate the effectiveness, tolerability, and retention of PER as monotherapy in adults with focal or idiopathic generalized epilepsy over a 12‐month period in routine clinical practice. Methods: In this single‐center, ambispective, noninterventional observational study, 74 patients (age 18–90 years) initiated PER monotherapy—either as first‐line treatment (n = 21) or conversion from another antiseizure medication (n = 53)—and were followed for 12 months. Demographic and clinical variables, prior antiseizure regimens, indication for PER initiation (suboptimal seizure control, adverse effects, or sleep improvement), PER dosage, seizure outcomes (seizure freedom and ≥ 50% reduction), and adverse events (AEs) were recorded at 6‐ and 12‐month visits. Retention rates were calculated, and safety was assessed by AE reports and discontinuations. Results: The mean PER dose was 7.22 ± 1.71 mg/day, with 85.1% of patients remaining on monotherapy at 12 months (first‐line: 90.5%; conversion: 83.0%). Overall, 70.3% of patients achieved seizure freedom at 12 months (first‐line: 81.0%; conversion: 66.0%), and 79.7% were ≥ 50% responders (first‐line: 85.7%; conversion: 75.5%). In patients initiated for sleep improvement (n = 24), hypnotic medications were withdrawn in 87.5%, and 79% reported better sleep. AEs were reported in 46.2% of patients at 12 months, most commonly somnolence (28.4%), dizziness (18.9%), and irritability (10.8%). Severe AEs leading to discontinuation occurred in 6.7% of cases. Significance: In a real‐world cohort, PER monotherapy demonstrated high rates of seizure freedom and retention, with a manageable safety profile. These findings support PER as an effective and tolerable monotherapy option for adult patients with focal or idiopathic generalized epilepsy, corroborating similar observations in recent Epilepsia Open studies of antiseizure monotherapy. Plain Language Summary: Perampanel (PER) is approved as an add‐on treatment for seizures, but information on its use alone (monotherapy) is scarce. We studied 74 adults who started PER by itself—either as their first treatment or after stopping another medication—over 1 year. Eighty‐five percent stayed on PER for the full year. Seventy percent became seizure‐free, and nearly 80% had their seizures cut by at least half. In those taking PER to improve sleep, most could stop sleep‐aid drugs and reported better rest. Side effects (mostly mild sleepiness, dizziness, or irritability) occurred in about half of patients, but only 7% stopped PER because of them. Our results suggest that PER alone works well and is generally well tolerated in everyday clinical practice.