Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy. We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures in 36 centers from 12 European countries over 25 years. Histopathological diagnoses were determined through examination of the specimens in local hospitals (41%) or at the German Neuropathology Reference Center for Epilepsy Surgery (59%). The onset of seizures occurred before 18 years of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery as adults. The mean duration of epilepsy before surgical resection was 20.1 years among adults and 5.3 years among children. The temporal lobe was involved in 71.9% of operations. There were 36 histopathological diagnoses in seven major disease categories. The most common categories were hippocampal sclerosis, found in 36.4% of the patients (88.7% of cases were in adults), tumors (mainly ganglioglioma) in 23.6%, and malformations of cortical development in 19.8% (focal cortical dysplasia was the most common type, 52.7% of cases of which were in children). No histopathological diagnosis could be established for 7.7% of the patients. In patients with drug-resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the most common diagnosis among children. Tumors were the second most common lesion in both groups. (Funded by the European Union and others.)

Objective: To determine the incidence rates of sudden unexpected death in epilepsy (SUDEP) in different epilepsy populations and address the question of whether risk factors for SUDEP have been identified. Methods: Systematic review of evidence; modified Grading Recommendations Assessment, Development, and Evaluation process for developing conclusions; recommendations developed by consensus. Results: Findings for incidence rates based on 12 Class I studies include the following: SUDEP risk in children with epilepsy (aged 0–17 years) is 0.22/1,000 patient-years (95% confidence interval [CI] 0.16–0.31) (moderate confidence in evidence). SUDEP risk increases in adults to 1.2/1,000 patient-years (95% CI 0.64–2.32) (low confidence in evidence). The major risk factor for SUDEP is the occurrence of generalized tonic-clonic seizures (GTCS); the SUDEP risk increases in association with increasing frequency of GTCS occurrence (high confidence in evidence). Recommendations: Level B: Clinicians caring for young children with epilepsy should inform parents/guardians that in 1 year, SUDEP typically affects 1 in 4,500 children; therefore, 4,499 of 4,500 children will not be affected. Clinicians should inform adult patients with epilepsy that SUDEP typically affects 1 in 1,000 adults with epilepsy per year; therefore, annually 999 of 1,000 adults will not be affected. For persons with epilepsy who continue to experience GTCS, clinicians should continue to actively manage epilepsy therapies to reduce seizures and SUDEP risk while incorporating patient preferences and weighing the risks and benefits of any new approach. Clinicians should inform persons with epilepsy that seizure freedom, particularly freedom from GTCS, is strongly associated with decreased SUDEP risk.

Dravet syndrome (DS) is a severe developmental epileptic encephalopathy with an incidence of 1:15 700 to 1:40 900.¹ Dravet syndrome typically presents in the first year of life with frequent, pharmacoresistant convulsive seizures,^1,2 which may contribute to intellectual disability and impairments in motor control, behavior, and cognition.³ Most patients (70%-85%) have sodium voltage-gated channel alpha subunit 1 gene (SCN1A) sodium channel alterations, although diagnosis is solely based on electroclinical criteria.^1,2,4 Patients with DS who are younger than 18 years have increased risk of sudden unexpected death in epilepsy, with a mortality rate of 7% to 18%. Frequency of generalized tonic-clonic seizures is a major risk factor for this outcome.^5-7

Objective: This study assessed the efficacy and safety of the neuronal potassium channel opener ezogabine (US adopted name; EZG)/retigabine (international nonproprietary name; RTG) as adjunctive therapy for refractory partial-onset seizures. Methods: This was a multicenter, randomized, double-blind, placebo-controlled trial in adults with ≥4 partial-onset seizures per month receiving 1 to 3 antiepileptic drugs. EZG (RTG) or placebo, 3 times daily, was titrated to 600 or 900 mg/d over 4 weeks, and continued during a 12-week maintenance phase. Median percentage seizure reductions from baseline and responder rates (≥50% reduction in baseline seizure frequency) were assessed. Results: The intention-to-treat population comprised 538 patients (placebo, n = 179; 600 mg, n = 181; 900 mg, n = 178), 471 of whom (placebo, n = 164; 600 mg, n = 158; 900 mg, n = 149) entered the maintenance phase. Median percentage seizure reductions were greater in EZG (RTG)–treated patients (600 mg, 27.9%, p = 0.007; 900 mg, 39.9%, p < 0.001) compared with placebo (15.9%). Responder rates were higher in EZG (RTG)–treated patients (600 mg, 38.6%, p < 0.001; 900 mg, 47.0%, p < 0.001) than with placebo (18.9%). Treatment discontinuations due to adverse events (AEs) were more likely with EZG (RTG) than with placebo (placebo, 8%; 600 mg, 17%, 900 mg, 26%). The most commonly reported (>10%) AEs in the placebo, EZG (RTG) 600 mg/d, and EZG (RTG) 900 mg/d groups were dizziness (7%, 17%, 26%), somnolence (10%, 14%, 26%), headache (15%, 11%, 17%), and fatigue (3%, 15%, 17%). Conclusions: In this dose-ranging, placebo-controlled trial, adjunctive EZG (RTG) was effective and generally well tolerated in adults with refractory partial-onset seizures. Classification of evidence: This study provides Class II evidence that adjunctive EZG/RTG reduces the occurrence of partial-onset seizures.