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Objective: To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic-clonic seizures (GTCS). Methods: This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure-free rate after 3, 6, and 12 months and tolerability throughout the follow-up. Results: A total of 98 patients (mean age = 49.6 ± 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of How to cite this article: Toledano DelgadoR, García-Morales I, Parejo-Carbonell B, et al. Effectiveness and safety of perampanel monotherapy for focal and generalized tonic-clonic seizures: Experience from a national multicenter registry.

Malformations of cortical development (MCD) comprise a broad spectrum of structural brain lesions frequently associated with epilepsy. Disease definition and diagnosis remain challenging and are often prone to arbitrary judgment. Molecular classification of histopathological entities may help rationalize the diagnostic process. We present a retrospective, multi-center analysis of genome-wide DNA methylation from human brain specimens obtained from epilepsy surgery using EPIC 850 K BeadChip arrays. A total of 308 samples were included in the study. In the reference cohort, 239 formalin-fixed and paraffin-embedded (FFPE) tissue samples were histopathologically classified as MCD, including 12 major subtype pathologies. They were compared to 15 FFPE samples from surgical non-MCD cortices and 11 FFPE samples from post-mortem non-epilepsy controls. We applied three different statistical approaches to decipher the DNA methylation pattern of histopathological MCD entities, i.e., pairwise comparison, machine learning, and deep learning algorithms. Our deep learning model, which represented a shallow neuronal network, achieved the highest level of accuracy. A test cohort of 43 independent surgical samples from different epilepsy centers was used to test the precision of our DNA methylation-based MCD classifier. All samples from the test cohort were accurately assigned to their disease classes by the algorithm. These data demonstrate DNA methylation-based MCD classification suitability across major histopathological entities amenable to epilepsy surgery and age groups and will help establish an integrated diagnostic classification scheme for epilepsy-associated MCD.

This retrospective study reports the early experience with lacosamide (LCM) as adjunctive therapy in Spanish patients with refractory focal epilepsy. Sixty patients (mean age 38.3 years, 54% women, mean epilepsy duration 27.2 years, mean seizure rate 9.7/month, and 28% with mainly nocturnal seizures) taking ≥2 antiepileptic drugs (mean 2.2) were included. LCM maintenance doses were 200, 300, 400, and 500mg/day in 31, 16, 10, and 3 patients, respectively. Patients were followed up for 13-24 months. Twenty-eight patients (47%) reported a ≥50% reduction in seizure frequency. A ≥50% reduction in seizure frequency was reported by 65% and 40% of patients in the nocturnal seizure and diurnal seizure subgroups, respectively (p>0.05). Of the 28 responders, 2 achieved stable periods of seizure freedom of 6 and 11 months after starting LCM. Twenty patients (33%) reported drug-related adverse events (AEs); the most common was dizziness (16 patients). LCM was withdrawn in 8 patients (13%). There were no serious AEs. These results support the efficacy and safety of adjunctive LCM in patients with partial-onset seizures.

In our sample of patients with suspected PD, SN hyperechogenicity predicted PD diagnosis in the long term with a high odds ratio. Conversely, a baseline normal SN echogenicity was associated with a poorer response to PD therapy and change to a different diagnosis from PD. Normal SN appears to be a caveat for clinicians to check for atypical parkinsonism features during follow-up.

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Objectives. To investigate the effectiveness, safety, and tolerability of perampanel (PER) when used as monotherapy to treat focal or generalized epilepsy in everyday clinical practice, using data from the PERMIT study. Methods. PERMIT was a pooled analysis of 44 real-world studies from 17 countries, in which people with focal and generalized epilepsy were treated with PER. This post hoc analysis included people with epilepsy (PWE) from PERMIT who were treated with PER monotherapy at baseline. Retention and effectiveness were assessed after 3, 6, and 12 months. Effectiveness assessments included ≥50% responder rate and seizure freedom rate (no seizures since at least the prior visit). Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. Results. Overall, 268 PWE were treated with PER monotherapy at baseline. Retention was assessed for 168 PWE, effectiveness for 183 PWE, and safety and tolerability for 197 PWE. Retention rates were 91.1%, 87.3%, and 73.3% at 3, 6, and 12 months, respectively. At 12 months, responder rates were 84.2% overall, 82.9% in PWE with only focal-onset seizures at baseline, and 88.0% in those with only generalized-onset seizures at baseline; corresponding freedom rates were 62.9%, 57.7%, and 80.0%, respectively. AEs were reported for 45.2% of PWE. The most frequently reported AEs (≥5% of PWE) were dizziness/vertigo (16.8%), irritability (11.2%), somnolence (9.1%), and depression (6.6%). Over 12 months, 13.7% discontinued due to AEs. Conclusions. PER was effective when used as monotherapy in clinical practice, particularly in those with generalized-onset seizures, and was generally well tolerated.