Membrane potential states gate synaptic consolidation in human neocortical tissue.

Synaptic mechanisms that contribute to human memory consolidation remain largely unexplored. Consolidation critically relies on sleep. During slow wave sleep, neurons exhibit characteristic membrane potential oscillations known as UP and DOWN states.

Analysis of 1386 epileptogenic brain lesions reveals association with DYRK1A and EGFR.

Lesional focal epilepsy (LFE) is a common and severe seizure disorder caused by epileptogenic lesions, including malformations of cortical development (MCD) and low-grade epilepsy-associated tumors (LEAT). Understanding the genetic etiology of these lesions can inform medical and surgical treatment. We conducted a somatic variant enrichment mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( > 1600x) targeted panel sequencing.

Anatomy-guided resections for paralimbic tumors in the temporo-insular region: combining tumor and epilepsy surgery concepts.

Object: Tumors in the temporo-mesial region often extend into the insula and vice versa. The present study investigated the results of a surgical strategy that combines principles of tumor and epilepsy surgery.

Methods: We retrospectively analyzed 157 consecutive patients with intrinsic brain tumors in the temporo-mesial region, with varying degrees of extensions into the insula (44 patients, 28.

Directed and acyclic synaptic connectivity in the human layer 2-3 cortical microcircuit.

The computational capabilities of neuronal networks are fundamentally constrained by their specific connectivity. Previous studies of cortical connectivity have mostly been carried out in rodents; whether the principles established therein also apply to the evolutionarily expanded human cortex is unclear. We studied network properties within the human temporal cortex using samples obtained from brain surgery.

Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

Objective: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE).

Methods: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents.

Deep histopathology genotype-phenotype analysis of focal cortical dysplasia type II differentiates between the GATOR1-altered autophagocytic subtype IIa and MTOR-altered migration deficient subtype IIb.

Focal cortical dysplasia type II (FCDII) is the most common cause of drug-resistant focal epilepsy in children. Herein, we performed a deep histopathology-based genotype-phenotype analysis to further elucidate the clinico-pathological and genetic presentation of FCDIIa compared to FCDIIb. Seventeen individuals with histopathologically confirmed diagnosis of FCD ILAE Type II and a pathogenic variant detected in brain derived DNA whole-exome sequencing or mTOR gene panel sequencing were included in this study.

Hemispherotomy in children: A retrospective analysis of 152 surgeries at a single center and predictors for long-term seizure outcome.

Objective: Completeness as a predictor of seizure freedom is broadly accepted in epilepsy surgery. We focused on the requirements for a complete hemispherotomy and hypothesized that the disconnection of the insula contributes to a favorable postoperative seizure outcome. We analyzed surgical and nonsurgical predictors influencing long-term seizure outcome before and after a modification of our hemispherotomy technique.

Ganglioglioma with adverse clinical outcome and atypical histopathological features were defined by alterations in PTPN11/KRAS/NF1 and other RAS-/MAP-Kinase pathway genes.

Exome-wide sequencing studies recently described PTPN11 as a novel brain somatic epilepsy gene. In contrast, germline mutations of PTPN11 are known to cause Noonan syndrome, a multisystem disorder characterized by abnormal facial features, developmental delay, and sporadically, also brain tumors. Herein, we performed a deep phenotype-genotype analysis of a comprehensive series of ganglioglioma (GG) with brain somatic alterations of the PTPN11/KRAS/NF1 genes compared to GG with common MAP-Kinase signaling pathway alterations, i.

Epilepsy Surgery in Extratemporal vs Temporal Lobe Epilepsy: Changes in Surgical Volumes and Seizure Outcome Between 1990 and 2017.

Background And Objectives: Seizure outcome after extratemporal lobe epilepsy (exTLE) surgery has often been poorer than after temporal lobe epilepsy (TLE) surgery, but recent improvements in diagnostics and surgery may have changed this. Our aim was to analyze the changes in presurgical and surgical volumes and seizure outcome 2 years after surgery for patients with exTLE compared with those with TLE.

Methods: We performed a retrospective, single-center cohort study including patients from the Bethel presurgical-surgical-postsurgical database from 1990 to 2017.

Enhancing Safety in Epilepsy Surgery (EASINESS): Study Protocol for a Retrospective, Multicenter, Open Registry.

Optimizing patient safety and quality improvement is increasingly important in surgery. Benchmarks and clinical quality registries are being developed to assess the best achievable results for several surgical procedures and reduce unwarranted variation between different centers. However, there is no clinical database from international centers for establishing standardized reference values of patients undergoing surgery for mesial temporal lobe epilepsy.

DNA methylation-based classification of malformations of cortical development in the human brain.

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.

Development and Validation of Prediction Models for Developmental and Intellectual Outcome Following Pediatric Epilepsy Surgery.

Background And Objectives: To identify predictors of postoperative intelligence and developmental quotients (IQ/DQ) and develop and validate clinically applicable IQ/DQ prediction models.

Methods: We retrospectively analyzed neuropsychological outcomes and their possible determinants for children treated in Bethel and Utrecht since 1990. We performed separate analyses for patients with IQ and those with only DQ available.

Clinical characteristics and postoperative seizure outcome in patients with mild malformation of cortical development and oligodendroglial hyperplasia.

Objective: We describe for the first time clinical characteristics in a series of 20 pre-surgically investigated patients with mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE) who were operated on in our epilepsy center. We aimed to better diagnose this entity and help surgical planning.

Methods: Data on 20 patients with histologically confirmed MOGHE were retrospectively evaluated as to age at epilepsy onset and operation, seizure semiology, magnetic resonance imaging (MRI) localization, electroencephalography (EEG) patterns, extent of the operative resection, and postoperative seizure outcome.

Reading and the visual word form area (VWFA) - Management and clinical experience at one epilepsy surgery center.

Objective: Presurgical evaluation has no established routine to assess reading competence and to identify essential "not to resect" reading areas. Functional models describe a visual word form area (VWFA) located in the midfusiform gyrus in the dominant ventral occipito-temporal cortex (vOTC) as essential for reading. We demonstrate the relevance and feasibility of invasive VWFA-mapping.

Epilepsy associated with tuberous sclerosis complex in childhood: Long-term outcome in children after epilepsy surgery and children non-eligible for epilepsy surgery.

Objective: Drug-resistant epilepsy is one of the major disease burdens in patients with tuberous sclerosis complex (TSC). Epilepsy surgery has been shown to be effective in TSC, but making a decision for surgery is often more complex than in other surgically amenable epilepsy syndromes and not all patients with TSC are eligible. We investigated long-term outcomes (after ≥one year; median, 6.

Stereotactic depth electrode placement surgery in paediatric and adult patients with the Neuromate robotic device: Accuracy, complications and epileptological results.

Objective: The number of patients requiring depth electrode implantation for invasive video EEG diagnostics increases in most epilepsy centres. Here we report on our institutional experience with frameless robot-assisted stereotactic placement of intracerebral depth electrodes using the Neuromate® stereotactic robot-system.

Methods: We identified all patients who had undergone robot-assisted stereotactic placement of intracerebral depth electrodes for invasive extra-operative epilepsy monitoring between September 2013 and March 2020.

Hyperkinetic Seizures with Ictal Fear as Localizing Ictal Signs in MRI-Negative Medial Frontal Lobe Epilepsy.

Purpose: Hyperkinetic seizures are described as seizure onset in the frontal or temporal lobe. Additional localizing information is important for diagnostic workup and surgical therapy. We describe diagnostic workup and surgical outcomes in three patients with pharmacoresistant focal emotional seizures with hyperkinetic elements.

Operative posterior disconnection in epilepsy surgery: Experience with 29 patients.

Objective: It has been suggested that multilobar epilepsies caused by lesions restricted to the posterior cerebral quadrant (ie, the parietal, temporal, and occipital lobes) can be treated successfully by a procedure termed posterior disconnection. The objective of the present paper was to identify determinants of the epileptological outcome following posterior disconnection surgery.

Methods: The authors retrospectively analyzed a series of 29 consecutive patients undergoing posterior disconnection surgery between 2005 and 2017 for the treatment of refractory posterior quadrantic epilepsy.

Differences in pediatric and adult epilepsy surgery: A comparison at one center from 1990 to 2014.

Objective: Surgical volumes at large epilepsy centers are decreasing. Pediatric cohorts, however, show a trend toward more resections and superior outcome. Differences in pediatric and adult epilepsy surgery were investigated in our cohort.

Partial resection of presurgical fMRI activation is associated with a postsurgical loss of language function after frontal lobe epilepsy surgery.

We describe five patients with frontal lobe epilepsy who underwent electrocortical stimulation (ES) for language localization and language functional magnetic resonance imaging (fMRI) prior to epilepsy surgery. Six months after surgery, three patients suffered from a drop of verbal fluency. In all of them, frontal areas with presurgical language fMRI activity were resected.

Trends in epilepsy surgery: stable surgical numbers despite increasing presurgical volumes.

Introduction: Despite the success of epilepsy surgery, recent reports suggest a decline in surgical numbers. We tested these trends in our cohort to elucidate potential reasons.

Patients And Methods: Presurgical, surgical and postsurgical data of all patients undergoing presurgical evaluation in between 1990 and 2013 were retrospectively analysed.