OBJECTIVE: This study was undertaken to develop a standardized grading system based on expert consensus for evaluating the level of confidence in the localization of the epileptogenic zone (EZ) as reported in published studies, to harmonize and facilitate systematic reviews in the field of epilepsy surgery. METHODS: We conducted a Delphi study involving 22 experts from 18 countries, who were asked to rate their level of confidence in the localization of the EZ for various theoretical clinical scenarios, using different scales. Information provided in these scenarios included one or several of the following data: magnetic resonance imaging (MRI) findings, invasive electroencephalography summary, and postoperative seizure outcome. RESULTS: The first explorative phase showed an overall interrater agreement of .347, pointing to large heterogeneity among experts' assessments, with only 17% of the 42 proposed scenarios associated with a substantial level of agreement. A majority showed preferences for the simpler scale and single-item scenarios. The successive Delphi voting phases resulted in a majority consensus across experts, with more than two thirds of respondents agreeing on the rating of each of the tested single-item scenarios. High or very high levels of confidence were ascribed to patients with either an Engel class I or class IA postoperative seizure outcome, a well-delineated EZ according to all available invasive EEG (iEEG) data, or a well-delineated focal epileptogenic lesion on MRI. MRI signs of hippocampal sclerosis or atrophy were associated with a moderate level of confidence, whereas a low level was ascribed to other MRI findings, a poorly delineated EZ according to iEEG data, or an Engel class II-IV postoperative seizure outcome. SIGNIFICANCE: The proposed grading system, based on an expert consensus, provides a simple framework to rate the level of confidence in the EZ reported in published studies in a structured and harmonized way, offering an opportunity to facilitate and increase the quality of systematic reviews and guidelines in the field of epilepsy surgery.

• Klíčová slova
• Delphi, confidence, epilepsy surgery, epileptogenic zone, grading system,
• MeSH
• delfská metoda * MeSH
• elektroencefalografie * MeSH
• epilepsie * chirurgie   diagnostické zobrazování   diagnóza   MeSH
• konsensus * MeSH
• lidé MeSH
• magnetická rezonanční tomografie * normy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND AND OBJECTIVE: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. METHODS: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. RESULTS: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. DISCUSSION: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

• MeSH
• elektroencefalografie MeSH
• epilepsie parciální * diagnostické zobrazování   chirurgie   MeSH
• epilepsie temporálního laloku * chirurgie   MeSH
• epilepsie * diagnostické zobrazování   chirurgie   MeSH
• kohortové studie MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• záchvaty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

Identifying factors whose fluctuations are associated with choice inconsistency is a major issue for rational decision theory. Here, we investigated the neuro-computational mechanisms through which mood fluctuations may bias human choice behavior. Intracerebral EEG data were collected in a large group of subjects (n=30) while they were performing interleaved quiz and choice tasks that were designed to examine how a series of unrelated feedbacks affect decisions between safe and risky options. Neural baseline activity preceding choice onset was confronted first to mood level, estimated by a computational model integrating the feedbacks received in the quiz task, and then to the weighting of option attributes, in a computational model predicting risk attitude in the choice task. Results showed that (1) elevated broadband gamma activity (BGA) in the ventromedial prefrontal cortex (vmPFC) and dorsal anterior insula (daIns) was respectively signaling periods of high and low mood, (2) increased vmPFC and daIns BGA respectively promoted and tempered risk taking by overweighting gain vs. loss prospects. Thus, incidental feedbacks induce brain states that correspond to different moods and bias the evaluation of risky options. More generally, these findings might explain why people experiencing positive (or negative) outcome in some part of their life tend to expect success (or failure) in any other.

• Klíčová slova
• choice, computational biology, human, iEEG, mood, neuroscience, systems biology,
• MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• mapování mozku MeSH
• mozek MeSH
• prefrontální mozková kůra MeSH
• riskování MeSH
• rozhodování * MeSH
• výběrové chování MeSH
• zpětná vazba MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies. Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database. Specifically, we considered each cortico-cortical evoked potential as the output of a transient stimulus entering the stimulated region, which directly propagated to the recording region. Both regions were modelled as coupled neural mass models, the parameters of which were estimated from the first cortico-cortical evoked potential component, occurring before 80 ms, using dynamic causal modelling and Bayesian model inversion. This methodology was applied to the data of 780 patients with epilepsy from the F-TRACT database, providing a total of 34 354 bipolar stimulations and 774 445 cortico-cortical evoked potentials. The cortical mapping of the local excitatory and inhibitory synaptic time constants and of the axonal conduction delays between cortical regions was obtained at the population level using anatomy-based averaging procedures, based on the Lausanne2008 and the HCP-MMP1 parcellation schemes, containing 130 and 360 parcels, respectively. To rule out brain maturation effects, a separate analysis was performed for older (>15 years) and younger patients (<15 years). In the group of older subjects, we found that the cortico-cortical axonal conduction delays between parcels were globally short (median = 10.2 ms) and only 16% were larger than 20 ms. This was associated to a median velocity of 3.9 m/s. Although a general lengthening of these delays with the distance between the stimulating and recording contacts was observed across the cortex, some regions were less affected by this rule, such as the insula for which almost all efferent and afferent connections were faster than 10 ms. Synaptic time constants were found to be shorter in the sensorimotor, medial occipital and latero-temporal regions, than in other cortical areas. Finally, we found that axonal conduction delays were significantly larger in the group of subjects younger than 15 years, which corroborates that brain maturation increases the speed of brain dynamics. To our knowledge, this study is the first to provide a local estimation of axonal conduction delays and synaptic time constants across the whole human cortex in vivo, based on intracerebral electrophysiological recordings.

• Klíčová slova
• axonal conduction delay, cortico-cortical evoked potential, dynamic causal modelling, neural mass models, synaptic time constant,
• MeSH
• Bayesova věta MeSH
• elektrická stimulace metody   MeSH
• epilepsie * MeSH
• evokované potenciály * fyziologie   MeSH
• lidé MeSH
• mapování mozku metody   MeSH
• mozek MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies. METHODS: Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web-based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht-like diseases. A consensus-based questionnaire was generated for each disease. RESULTS: Twenty-six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht-like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers. SIGNIFICANCE: The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers.

• Klíčová slova
• Dravet syndrome, autoimmune encephalitis, orphan disease, progressive myoclonic epilepsy, targeted therapies, tuberous sclerosis complex,
• MeSH
• antikonvulziva terapeutické užití   MeSH
• dospělí MeSH
• encefalitida imunologie   terapie   MeSH
• epilepsie myoklonické terapie   MeSH
• epilepsie patofyziologie   terapie   MeSH
• everolimus terapeutické užití   MeSH
• kohortové studie MeSH
• kojenec MeSH
• konsensus MeSH
• křeče u dětí * terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• průzkumy a dotazníky MeSH
• tuberózní skleróza * terapie   MeSH
• vzácné nemoci * MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• antikonvulziva MeSH
• everolimus MeSH

PURPOSE: Epilepsy patients consider driving issues to be one of their most serious concerns. Ideally, decisions regarding fitness to drive should be based upon thorough evaluations by specialists in epilepsy care. In 2009, an EU directive was published aiming to harmonize evaluation practices within European countries, but, despite these recommendations, whether all epileptologists use the same criteria is unclear. We therefore conducted this study to investigate routine practices on how epileptologists at European epilepsy centers evaluate fitness to drive. METHODS: A questionnaire was sent to 63 contact persons identified through the European Epi-Care and the E-pilepsy network. The questionnaire addressed how fitness-to-drive evaluations were conducted, the involvement of different professionals, the use and interpretation of EEG, and opinions on existing regulations and guidelines. RESULTS: The questionnaire was completed by 35 participants (56 % response rate). Results showed considerable variation regarding test routines and the emphasis placed on the occurrence and extent of epileptiform discharges revealed by EEG. 82 % of the responders agreed that there was a need for more research on how to better evaluate fitness-to-drive in people with epilepsy, and 89 % agreed that regulations on fitness to drive evaluations should be internationally coordinated. CONCLUSION: Our survey showed considerable variations among European epileptologists regarding use of EEG and how findings of EEG pathology should be assessed in fitness-to-drive evaluations. There is a clear need for more research on this issue and international guidelines on how such evaluations should be carried out would be of value.

• Klíčová slova
• Driving license, Driving regulations, EEG, Epilepsy,
• MeSH
• dospělí MeSH
• elektroencefalografie MeSH
• epilepsie epidemiologie   MeSH
• lékařská praxe - způsoby provádění statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neurologové statistika a číselné údaje   MeSH
• postoj zdravotnického personálu * MeSH
• posuzování pracovní neschopnosti * MeSH
• průzkumy a dotazníky MeSH
• řízení motorových vozidel zákonodárství a právo   statistika a číselné údaje   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH

In patients with pharmaco-resistant focal epilepsies investigated with intracranial electroencephalography (iEEG), direct electrical stimulations of a cortical region induce cortico-cortical evoked potentials (CCEP) in distant cerebral cortex, which properties can be used to infer large scale brain connectivity. In 2013, we proposed a new probabilistic functional tractography methodology to study human brain connectivity. We have now been revisiting this method in the F-TRACT project (f-tract.eu) by developing a large multicenter CCEP database of several thousand stimulation runs performed in several hundred patients, and associated processing tools to create a probabilistic atlas of human cortico-cortical connections. Here, we wish to present a snapshot of the methods and data of F-TRACT using a pool of 213 epilepsy patients, all studied by stereo-encephalography with intracerebral depth electrodes. The CCEPs were processed using an automated pipeline with the following consecutive steps: detection of each stimulation run from stimulation artifacts in raw intracranial EEG (iEEG) files, bad channels detection with a machine learning approach, model-based stimulation artifact correction, robust averaging over stimulation pulses. Effective connectivity between the stimulated and recording areas is then inferred from the properties of the first CCEP component, i.e. onset and peak latency, amplitude, duration and integral of the significant part. Finally, group statistics of CCEP features are implemented for each brain parcel explored by iEEG electrodes. The localization (coordinates, white/gray matter relative positioning) of electrode contacts were obtained from imaging data (anatomical MRI or CT scans before and after electrodes implantation). The iEEG contacts were repositioned in different brain parcellations from the segmentation of patients' anatomical MRI or from templates in the MNI coordinate system. The F-TRACT database using the first pool of 213 patients provided connectivity probability values for 95% of possible intrahemispheric and 56% of interhemispheric connections and CCEP features for 78% of intrahemisheric and 14% of interhemispheric connections. In this report, we show some examples of anatomo-functional connectivity matrices, and associated directional maps. We also indicate how CCEP features, especially latencies, are related to spatial distances, and allow estimating the velocity distribution of neuronal signals at a large scale. Finally, we describe the impact on the estimated connectivity of the stimulation charge and of the contact localization according to the white or gray matter. The most relevant maps for the scientific community are available for download on f-tract. eu (David et al., 2017) and will be regularly updated during the following months with the addition of more data in the F-TRACT database. This will provide an unprecedented knowledge on the dynamical properties of large fiber tracts in human.

• Klíčová slova
• Brain atlas, Connectivity mapping, Cortico-cortical evoked potentials, Epilepsy, Intracranial electroencephalogram,
• MeSH
• atlasy jako téma MeSH
• databáze faktografické MeSH
• dítě MeSH
• dospělí MeSH
• elektrokortikografie metody   MeSH
• epilepsie diagnostické zobrazování   patofyziologie   MeSH
• evokované potenciály fyziologie   MeSH
• konektom metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozková kůra diagnostické zobrazování   patofyziologie   MeSH
• nervové dráhy diagnostické zobrazování   MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

OBJECTIVE: Resective surgery is effective in treating drug-resistant focal epilepsy, but it remains unclear whether improved diagnostics influence postsurgical outcomes. Here, we compared practice and outcomes over 2 periods 15 years apart. METHODS: Sixteen European centers retrospectively identified 2 cohorts of children and adults who underwent epilepsy surgery in the period of 1997 to 1998 (n = 562) or 2012 to 2013 (n = 736). Data collected included patient (sex, age) and disease (duration, localization and diagnosis) characteristics, type of surgery, histopathology, Engel postsurgical outcome, and complications, as well as imaging and electrophysiologic tests performed for each case. Postsurgical outcome predictors were included in a multivariate logistic regression to assess the strength of date of surgery as an independent predictor. RESULTS: Over time, the number of operated cases per center increased from a median of 31 to 50 per 2-year period (p = 0.02). Mean disease duration at surgery decreased by 5.2 years (p < 0.001). Overall seizure freedom (Engel class 1) increased from 66.7% to 70.9% (adjusted p = 0.04), despite an increase in complex surgeries (extratemporal and/or MRI negative). Surgeries performed during the later period were 1.34 times (adjusted odds ratio; 95% confidence interval 1.02-1.77) more likely to yield a favorable outcome (Engel class I) than earlier surgeries, and improvement was more marked in extratemporal and MRI-negative temporal epilepsy. The rate of persistent neurologic complications remained stable (4.6%-5.3%, p = 0.7). CONCLUSION: Improvements in European epilepsy surgery over time are modest but significant, including higher surgical volume, shorter disease duration, and improved postsurgical seizure outcomes. Early referral for evaluation is required to continue on this encouraging trend.

• MeSH
• časové faktory MeSH
• dítě MeSH
• dospělí MeSH
• elektrofyziologické jevy MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• neurochirurgické výkony statistika a číselné údaje   MeSH
• neurozobrazování MeSH
• pooperační komplikace epidemiologie   MeSH
• předškolní dítě MeSH
• refrakterní epilepsie epidemiologie   chirurgie   MeSH
• retrospektivní studie MeSH
• výsledek terapie * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH

PURPOSE: The European Union-funded E-PILEPSY network aims to improve awareness of, and accessibility to, epilepsy surgery across Europe. In this study we assessed current clinical practices in epilepsy monitoring units (EMUs) in the participating centers. METHOD: A 60-item web-based survey was distributed to 25 centers (27 EMUs) of the E-PILEPSY network across 22 European countries. The questionnaire was designed to evaluate the characteristics of EMUs, including organizational aspects, admission, and observation of patients, procedures performed, safety issues, cost, and reimbursement. RESULTS: Complete responses were received from all (100%) EMUs surveyed. Continuous observation of patients was performed in 22 (81%) EMUs during regular working hours, and in 17 EMUs (63%) outside of regular working hours. Fifteen (56%) EMUs requested a signed informed consent before admission. All EMUs performed tapering/withdrawal of antiepileptic drugs, 14 (52%) prior to admission to an EMU. Specific protocols on antiepileptic drugs (AED) tapering were available in four (15%) EMUs. Standardized Operating Procedures (SOP) for the treatment of seizure clusters and status epilepticus were available in 16 (59%). Safety measures implemented by EMUs were: alarm seizure buttons in 21 (78%), restricted patient's ambulation in 19 (70%), guard rails in 16 (59%), and specially designated bathrooms in 7 (26%). Average costs for one inpatient day in EMU ranged between 100 and 2200 Euros. CONCLUSION: This study shows a considerable diversity in the organization and practice patterns across European epilepsy monitoring units. The collected data may contribute to the development and implementation of evidence-based recommended practices in LTM services across Europe.

• Klíčová slova
• Epilepsy, Epilepsy monitoring unit, Long-term monitoring, Presurgical evaluation, Safety, Video-EEG monitoring,
• MeSH
• dítě MeSH
• dospělí MeSH
• elektroencefalografie statistika a číselné údaje   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• monitorování fyziologických funkcí statistika a číselné údaje   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• refrakterní epilepsie diagnóza   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH