Late-onset epilepsy has the highest incidence among all age groups affected by epilepsy and often occurs in the absence of known clinical risk factors such as stroke and dementia. There is increasing evidence that brain changes contributing to epileptogenesis likely start years before disease onset, and we aim to relate cognitive and imaging correlates of subclinical brain injury to incident late-onset epilepsy in a large, community-based cohort.

This study was undertaken to study whether high-dose folic acid (>1 mg daily) use is associated with an increased risk of cancer in all women who have given birth and in women with epilepsy. High-dose folic acid supplementation during pregnancy has been linked to increased cancer risk in children born to mothers with epilepsy.

An accurate evaluation of behavioral responsiveness during and after seizures in people with epilepsy is critical for diagnosis and management. Current methods for assessing behavioral responsiveness are characterized by substantial variation, subjectivity, and limited reliability and reproducibility in ambulatory and epilepsy monitoring unit settings. In this study, we aimed to develop and implement a novel mobile platform for deployment of automated responsiveness testing in epilepsy-the ARTiE Watch-to facilitate standardized, objective assessments of behavioral responsiveness during and after seizures.

Phenotypic heterogeneity presents challenges in providing clinical care to patients with pathogenic SCN8A variants, which underly a wide disease spectrum ranging from neurodevelopmental delays without seizures to a continuum of mild to severe developmental and epileptic encephalopathies (DEEs). An important unanswered question is whether there are clinically important subgroups within this wide spectrum. Using both supervised and unsupervised machine learning (ML) approaches, we previously found statistical support for two and three subgroups associated with loss- and gain- of- function vari-ants, respectively. Here, we test the hypothesis that the unsupervised subgroups (U1-U3) are distinguished by differential contributions of developmental and epileptic components.

This study was undertaken to determine whether admission to dedicated seizure monitoring units (SMUs) result in reduced health care use (HCU).

General anesthesia (GA) earlier than recommended (as first- or second-line treatment) was recently described to improve status epilepticus (SE) outcome. We aimed to assess the impact of early GA on outcome in matched groups. Data from a multicenter, prospective cohort of 1179 SE episodes in 1049 adults were retrospectively analyzed. Incident SE episodes were categorized as "early anesthesia" (eGA; GA as first- or second-line treatment) or "non-early anesthesia" (neGA; GA after second-line treatment or not at all). Using propensity score matching, eGA episodes were paired 1:4 with neGA episodes. We assessed survival, functional outcomes at discharge (good: modified Rankin Scale = 0-2 or no worsening), SE cessation rate, SE duration, and hospital stay. Among 1049 SE episodes, 55 (5.2%) received eGA, and 994 constituted the neGA group; 220 represented the matched controls. Patients receiving eGA were younger (median = 63, interquartile range [IQR] = 56-76 vs. median = 70, IQR = 54-80 years, p = .004), had deeper consciousness impairment (80% vs. 40% stuporous/comatose, p < .001), and had more severe SE forms (89% vs. 54% generalized convulsive SE/nonconvulsive SE in coma, p < .001). Mortality, functional outcome, SE cessation rate, and duration of SE and hospital stay were similar between the eGA group and matched controls. We conclude that early anesthesia for SE treatment did not influence prognosis.

Epilepsy is recognized increasingly as a network disease, with changes extending beyond the epileptogenic zone (EZ). However, more studies of structural connectivity are needed to better understand the behavior and nature of this condition.

The cannabinoid cannabidiol has established antiseizure effects in drug-resistant epilepsies such as Dravet syndrome and Lennox-Gastaut syndrome. Amorfrutin 2, honokiol, and magnolol are structurally similar to cannabinoids (cannabis-like drugs) but derive from non-cannabis plants. We aimed to study the antiseizure potential of these compounds in various mouse seizure models. In addition, we aimed to characterize their molecular pharmacology at cannabinoid CB and CB receptors and at T-type calcium channels, which are known targets of the cannabinoids.

The human brain undergoes an activity-dependent organization during late gestation, making it very sensitive to all effects on the spontaneous neuronal activity. Pregnant mothers with epilepsy are treated with antiepileptic drugs (AEDs) that may reach the fetus and cause altered cortical network activity after birth. However, it is not known whether these functional effects of intrauterine AED exposure persist later in childhood.

Few studies have evaluated the efficacy of antiseizure medications (ASMs) according to the etiology of neonatal acute provoked seizures. We aimed to investigate the response to ASMs in term/near term neonates with acute arterial ischemic stroke (AIS), as well as the type of seizure at presentation and the monitoring approach.

The interaction between basic science epilepsy researchers and clinical epileptologists is a longstanding issue. Efforts to provide opportunities for a dialogue between preclinical and clinical epilepsy professionals are crucial to reduce the knowledge gap between them and improve the translational success of neurobiology-based research. The International League Against Epilepsy (ILAE) Research and Innovation Task Force circulated a survey to investigate the need for an update on new clinical epilepsy concepts within the basic science community. The 336 respondents included basic scientists (BS), preclinical scientists (PCSs), and/or clinical scientists (CSs). The majority of the 237 BSs/PCSs were engaged in preclinical studies in translational epilepsy research and declared translational research as a priority research interest. Fewer respondents from low-middle-income countries than from upper-middle or high-income countries (40.7% vs 65%) considered translational research a critical aspect of their research. A broad understanding of both clinical and neurobiological aspects of epilepsy was declared by 48% of BSs/PCSs; 96% of CSs declared a superficial knowledge of neurobiology of epilepsy. Most BSs/PCSs were aware that epilepsy is a complex condition that should be investigated with the help of clinical epileptologists, even though concerns were expressed on the relationship with clinicians. A focused training program on emerging clinical epileptological aspects tailored for BSs/PCSs was recommended by 81% of the participants; the majority of respondents preferred either 1- or 2-week in-presence tutoring or continuous online training coordinated by ILAE at the regional/national level. The survey also underscored the value of educational programs on neurobiology of epilepsy targeting CSs and low-middle-income countries (LMIC) investigators.

Neuronal cell death and neuroinflammation are characteristic features of epilepsy, but it remains unclear whether neuronal cell death as such is causative for the development of epileptic seizures. To test this hypothesis, we established a novel mouse line permitting inducible ablation of pyramidal neurons by inserting simian diphtheria toxin (DT) receptor (DTR) cDNA into the Ccl17 locus. The chemokine CCL17 is expressed in pyramidal CA1 neurons in adult mice controlling microglial quiescence.

Benzodiazepine rescue medications are established as therapy for acute termination of seizure clusters. A post-hoc analysis of a clinical trial of seizure cluster treatment with diazepam nasal spray found a potential longer-term impact over a year of treatment. In this retrospective analysis, we tested the hypothesis that benzodiazepine-treated seizure clusters are associated with prolonged time to the next seizure cluster compared with untreated seizure clusters in a patient-reported real-world database.

This report is the first comprehensive update on the activities of existing epilepsy-pregnancy registries since 2010. The primary aim of these registries, which were initiated by independent international research groups some 25 years ago, has been to assess the risk of major congenital malformations (MCMs) in offspring exposed in utero to different antiseizure medications (ASMs). Progress reports are provided here from the five original registries (the International Registry of Antiepileptic Drugs and Pregnancy EURAP, the North American Antiepileptic Drug Pregnancy Registry, the UK and Ireland Epilepsy and Pregnancy Register, the Kerala Registry of Epilepsy and Pregnancy, and the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs) plus the more recently initiated West China Registry. Since their inception, the registries have published a wealth of data revealing important differences in risks across the most frequently used ASM treatments, thereby facilitating rational management of women with epilepsy who are of childbearing potential. Although the number of pregnancies enrolled in the different registries has more than doubled since the 2010 report, many questions remain. These include outcomes following prenatal exposure to most of the newer ASMs or different ASM combinations, as well as associations with specific MCMs rather than MCMs as a collective. All the registries, therefore, remain active and continue to enroll pregnancies. Administrative health care databases have been utilized more recently for the assessment of MCM risks and other adverse pregnancy outcomes associated with in utero exposure to ASMs. Although these can provide population-based complementary information, they cannot replace the specific epilepsy-pregnancy registries with their more detailed validated individual information. Given the multiple newer ASMs that are increasingly used and the continuing multiple knowledge gaps for the older ASMs, epilepsy-pregnancy registries will continue to play an important role in the future.

The Phase 3 Study 338 (NCT02834793) assessed long-term clinical outcomes of adjunctive perampanel in patients ≥2 years of age with uncontrolled seizures associated with Lennox-Gastaut syndrome (LGS).

This review systematically analyzes potential biomarker candidates for post-traumatic epilepsy (PTE) in humans who have experienced moderate to severe traumatic brain injury (TBI). Focusing on biomarkers across biofluid-based protein, genetic, neuroimaging, and neurophysiological categories, this review distinguishes between TBI patients who develop PTE and those who do not. The review adheres to established methodologies outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Data presentation follows the Meta-analyses of Observational Studies (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, Embase, and Web of Science were systematically searched and yielded 7538 records, of which 18 met inclusion criteria (moderate-severe TBI in humans, follow-up of at least 6 months, and no prior history of epilepsy). The review aggregates data from 15 cohort and 3 case-control studies (risk of bias was assessed using the Newcastle-Ottawa Scale). Statistically significant biomarkers were identified, with neurophysiological biomarkers showing the strongest effect size in a two-study meta-analysis. PTE, a severe long-term outcome of TBI affecting 2% to 53% of individuals with TBI, lacks validated biomarkers for forecasting development, crucial for designing preventive clinical trials. A multimodal approach, integrating biofluid-based protein, genetic, neuroimaging, and neurophysiological data, offers a promising strategy to enhance the predictability of PTE development and, potentially, its treatment. The study's protocol is registered in the International Prospective Register of Systematic Reviews PROSPERO (Registration ID: CRD42023470245).

This case report shows the importance of multimodal evaluation to formulate a proper diagnosis of negative motor seizures (NMSs). Only few reports in literature document NMSs with video-electroencephalographic (EEG) and electromyographic coregistration. A multimodal evaluation is crucial to exclude common mimics and propose correct therapy. We describe a case of a 62-year-old man with drug-resistant focal epilepsy and NMSs, evaluated with video-EEG recording with polygraphy, magnetoencephalography (MEG), and brain magnetic resonance imaging (MRI). Video-EEG monitoring showed 182 focal NMSs, with preserved awareness and comprehension. The patient reported complex paresthesia of the left hand followed by left facial grimace, left arm flaccid paralysis, and bradycardia. EEG showed ictal discharges in the right frontocentral region associated with sudden electromyographical silence in left limb muscles consistent with loss of tonic contraction from distal to proximal muscles of the arm. MEG localized the epileptic zone in the right opercular region, consistent with MRI evidence of type II cortical dysplasia in the right inferior frontal gyrus. Multimodal evaluation is essential to document the temporal relationship between ictal discharges, clinical onset of limb paresis, and electrophysiologic evidence of loss of tonic muscular contraction. It allows definition of the specific cortical area involved in NMSs, offering new insight into physiological brain functioning.

Deep learning methods have shown potential in automating the detection of interictal epileptiform discharges (IEDs) in electroencephalography (EEG). We compared IED detection using our previously trained deep neural network with a group of experts to assess its potential applicability.

The early onset epilepsies encompass a heterogeneous group of disorders, some of which result in drug-resistant seizures, developmental delay, psychiatric comorbidities, and sudden death. Advancement in the widespread use of targeted gene panels as well as genome and exome sequencing has facilitated the identification of different causative genes in a subset of these patients. The ability to recognize the genetic basis of early onset epilepsies continues to improve, with de novo coding variants accounting for most of the genetic etiologies identified. Although current disease-specific and disease-modifying therapies remain limited, novel precision medicine approaches, such as small molecules, cell therapy, and other forms of genetic therapies for early onset epilepsies, have created excitement among researchers, clinicians, and caregivers. Here, we summarize the main findings of presentations and discussions on novel therapeutic strategies for targeted treatment of early onset epilepsies that occurred during the Workshop on Neurobiology of Epilepsy (WONOEP XVI, Talloires, France, July 2022). The presentations discussed the use of chloride transporter inhibitors for neonatal seizures, targeting orexinergic signaling for childhood absence epilepsy, targeting energy metabolism in Dravet syndrome, and the role of cannabinoid receptor type 2, reversible acetylcholinesterase inhibitors, cell therapies, and RNA-based therapies in early life epilepsies.

Epilepsy involves significant changes in neural cells during epileptogenesis. Although the molecular mechanism of epileptogenesis remains obscure, changes in gene regulation play a crucial role in the evolution of epilepsy. This study aimed to compare changes in a subset of specific genes during epilepsy development, focusing on the period after the first spontaneous seizure, to identify critical time windows for targeting different regulators.