Search

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., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

The hippocampus is generally considered to have relatively late involvement in recognition memory, its main electrophysiological signature being between 400 and 800 ms after stimulus onset. However, most electrophysiological studies have analyzed the hippocampus as a single responsive area, selecting only a single-site signal exhibiting the strongest effect in terms of amplitude. These classical approaches may not capture all the dynamics of this structure, hindering the contribution of other hippocampal sources that are not located in the vicinity of the selected site. We combined intracerebral electroencephalogram recordings from epileptic patients with independent component analysis during a recognition memory task involving the recognition of old and new images. We identified two sources with different responses emerging from the hippocampus: a fast one (maximal amplitude at ∼250 ms) that could not be directly identified from raw recordings and a latter one, peaking at ∼400 ms. The former component presented different amplitudes between old and new items in 6 out of 10 patients. The latter component had different delays for each condition, with a faster activation (∼290 ms after stimulus onset) for recognized items. We hypothesize that both sources represent two steps of hippocampal recognition memory, the faster reflecting the input from other structures and the latter the hippocampal internal processing. Recognized images evoking early activations would facilitate neural computation in the hippocampus, accelerating memory retrieval of complementary information. Overall, our results suggest that the hippocampal activity is composed of several sources with an early activation related to recognition memory., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 López-Madrona et al.)

Epilepsy surgery in genetic drug-resistant epilepsy is a debated subject as more histological and molecular data are available. We retrospectively collected data from focal drug-resistant epilepsy patients that underwent stereoelectroencephalography (SEEG) invasive recordings. Patients with nonlesional brain imaging or in whom a first epilepsy surgery failed to control seizures were selected. We computed and displayed the intracranial ictal onset activity pattern on structural imaging. Patients underwent epilepsy gene panel testing, next generation sequencing-NGS. Of 113 patients, 13 underwent genetic testing, and in 6 patients, a mechanistic target of rapamycin pathway gene germline mutation (mTOR) was identified. Brain imaging was nonlesional except for one patient in whom two abnormalities suggestive of focal cortical dysplasia (FCD) were found. Patients underwent tailored brain surgery based on SEEG data, tissue analysis revealed FCD and postsurgical outcome was favorable. Our findings are similar to previous case series suggesting that epilepsy surgery can be a treatment option in patients with mTOR pathway mutation. In patients with mTOR pathway mutation, the postsurgical outcome is favorable if complete resection of the epileptogenic zone is performed. Electrophysiological seizure onset patterns in FCDs associated with mTOR pathway mutations display low-voltage fast activity as previously described., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Summary: The cingulate cortex is a paired brain region located on the medial wall of each hemisphere. This review explores the anatomy as well as the structural and functional connectivity of the cingulate cortex underlying essential roles this region plays in emotion, autonomic, cognitive, motor control, visual-spatial processing, and memory., Competing Interests: The work was funded by the Romanian UEFISCDI PN-III-P4-ID-PCE-2020-0935. The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 by the American Clinical Neurophysiology Society.)

Investigating cognitive brain functions using non-invasive electrophysiology can be challenging due to the particularities of the task-related EEG activity, the depth of the activated brain areas, and the extent of the networks involved. Stereoelectroencephalographic (SEEG) investigations in patients with drug-resistant epilepsy offer an extraordinary opportunity to validate information derived from non-invasive recordings at macro-scales. The SEEG approach can provide brain activity with high spatial specificity during tasks that target specific cognitive processes (e.g., memory). Full validation is possible only when performing simultaneous scalp SEEG recordings, which allows recording signals in the exact same brain state. This is the approach we have taken in 12 subjects performing a visual memory task that requires the recognition of previously viewed objects. The intracranial signals on 965 contact pairs have been compared to 391 simultaneously recorded scalp signals at a regional and whole-brain level, using multivariate pattern analysis. The results show that the task conditions are best captured by intracranial sensors, despite the limited spatial coverage of SEEG electrodes, compared to the whole-brain non-invasive recordings. Applying beamformer source reconstruction or independent component analysis does not result in an improvement of the multivariate task decoding performance using surface sensor data. By analyzing a joint scalp and SEEG dataset, we investigated whether the two types of signals carry complementary information that might improve the machine-learning classifier performance. This joint analysis revealed that the results are driven by the modality exhibiting best individual performance, namely SEEG., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Barborica, Mindruta, López-Madrona, Alario, Trébuchon, Donos, Oane, Pistol, Mihai and Bénar.)

This article provides recommendations on the minimum standards for recording routine ("standard") and sleep electroencephalography (EEG). The joint working group of the International Federation of Clinical Neurophysiology (IFCN) and the International League Against Epilepsy (ILAE) developed the standards according to the methodology suggested for epilepsy-related clinical practice guidelines by the Epilepsy Guidelines Working Group. We reviewed the published evidence using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The quality of evidence for sleep induction methods was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. A tool for Quality Assessment of Diagnostic Studies (QUADAS-2) was used to assess the risk of bias in technical and methodological studies. Where high-quality published evidence was lacking, we used modified Delphi technique to reach expert consensus. The GRADE system was used to formulate the recommendations. The quality of evidence was low or moderate. We formulated 16 consensus-based recommendations for minimum standards for recording routine and sleep EEG. The recommendations comprise the following aspects: indications, technical standards, recording duration, sleep induction, and provocative methods., (© 2023 International Federation of Clinical Neurophysiology, Inc. and International League Against Epilepsy. Published by Wiley Periodicals LLC.)

This article provides recommendations on the minimum standards for recording routine ("standard") and sleep electroencephalography (EEG). The joint working group of the International Federation of Clinical Neurophysiology (IFCN) and the International League Against Epilepsy (ILAE) developed the standards according to the methodology suggested for epilepsy-related clinical practice guidelines by the Epilepsy Guidelines Working Group. We reviewed the published evidence using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The quality of evidence for sleep induction methods was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. A tool for Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the risk of bias in technical and methodological studies. Where high-quality published evidence was lacking, we used modified Delphi technique to reach expert consensus. The GRADE system was used to formulate the recommendations. The quality of evidence was low or moderate. We formulated 16 consensus-based recommendations for minimum standards for recording routine and sleep EEG. The recommendations comprise the following aspects: indications, technical standards, recording duration, sleep induction, and provocative methods., (Copyright © 2023 International Federation of Clinical Neurophysiology, Inc, International League Against Epilepsy. Published by Elsevier B.V. All rights reserved.)

Objectives: Parietal lobe epilepsy is one of the rarest types and patients with this form of epilepsy report multiple subjective symptoms during ictal manifestation. Specific facial coupling of emotion and motor symptoms may take various forms, such as pouting and disgust or smiling. We aimed to highlight brain structures and the network involved during ictal grimacing in parietal lobe seizures., Methods: In this study, we report two patients with drug-resistant epilepsy, with seizure onset located in the inferior parietal lobule and a semiology characterized by ictal grimacing. Patients were explored with intracranial electrodes using the stereo-electroencephalographic method. Time-frequency and functional connectivity (a non-linear regression method based on the h² correlation coefficient) signal analyses were performed time-locked to ictal grimace. For both patients, using spectral analysis, we were able to confirm that the bipolar channels, localized at the level of the inferior parietal lobule, were involved in the seizure onset zone, exhibiting a high frequency discharge., Results: The first patient presented with ictal pouting and disgust and the second with smiling/laughter. Connectivity analysis highlighted two different networks responsible for seizure semiology, consisting of grimacing with different emotional expression. The inferior parietal lobule, connected mainly to the anterior insula, dorsal-lateral prefrontal cortex and frontal operculum were responsible for the typical grimace associated with disgust. Furthermore, the inferior parietal lobule, basal temporal structures, superior temporal gyrus, orbitofrontal cortex and temporal pole were involved in smiling and laughter., Significance: It is of great significance for epileptologists to know that the same seizure onset zone in the inferior parietal lobule can generate contrasting facial expressions, smiling/laughter and pouting/disgust, by engaging different epileptogenic networks; the temporo-basal-orbitofrontal and insulo-opercular networks, respectively.

Cognitive tasks are commonly used to identify brain networks involved in the underlying cognitive process. However, inferring the brain networks from intracranial EEG data presents several challenges related to the sparse spatial sampling of the brain and the high variability of the EEG trace due to concurrent brain processes. In this manuscript, we use a well-known facial emotion recognition task to compare three different ways of analyzing the contrasts between task conditions: permutation cluster tests, machine learning (ML) classifiers, and a searchlight implementation of multivariate pattern analysis (MVPA) for intracranial sparse data recorded from 13 patients undergoing presurgical evaluation for drug-resistant epilepsy. Using all three methods, we aim at highlighting the brain structures with significant contrast between conditions. In the absence of ground truth, we use the scientific literature to validate our results. The comparison of the three methods' results shows moderate agreement, measured by the Jaccard coefficient, between the permutation cluster tests and the machine learning [0.33 and 0.52 for the left (LH) and right (RH) hemispheres], and 0.44 and 0.37 for the LH and RH between the permutation cluster tests and MVPA. The agreement between ML and MVPA is higher: 0.65 for the LH and 0.62 for the RH. To put these results in context, we performed a brief review of the literature and we discuss how each brain structure's involvement in the facial emotion recognition task., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Donos, Blidarescu, Pistol, Oane, Mindruta and Barborica.)

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., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Direct electrical stimulation (DES) is considered to be the gold standard for mapping cortical function. A careful mapping of the eloquent cortex is key to successful resective or ablative surgeries, with a minimal postoperative deficit, for treatment of drug-resistant epilepsy. There is accumulating evidence suggesting that not only local, but also remote activations play an equally important role in evoking clinical effects. By introducing a new intracranial stimulation paradigm and signal analysis methodology allowing to disambiguate EEG responses from stimulation artifacts we highlight the spatial extent of the networks associated with clinical effects. Our study includes 26 patients that underwent stereoelectroencephalographic investigations for drug-resistant epilepsy, having 337 depth electrodes with 4,351 contacts sampling most brain structures. The routine high-frequency electrical stimulation protocol for eloquent cortex mapping was altered in a subtle way, by alternating the polarity of the biphasic pulses in a train, causing the splitting the spectral lines of the artifactual components, exposing the underlying tissue response. By performing a frequency-domain analysis of the EEG responses during DES we were able to capture remote activations and highlight the effect's network. By using standard intersubject averaging and a fine granularity HCP-MMP parcellation, we were able to create local and distant connectivity maps for 614 stimulations evoking specific clinical effects. The clinical value of such maps is not only for a better understanding of the extent of the effects' networks guiding the invasive exploration, but also for understanding the spatial patterns of seizure propagation given the timeline of the seizure semiology., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Objective: The default mode network (DMN) is deactivated by stimulation. We aimed to assess the DMN reactivity impairment by routine EEG recordings in stroke patients with impaired consciousness., Methods: Binocular light flashes were delivered at 1 Hz in 1-minute epochs, following a 1-minute baseline (PRE). The EEG was decomposed in a series of binary oscillatory macrostates by topographic spectral clustering. The most deactivated macrostate was labeled the default EEG macrostate (DEM). Its reactivity (DER) was quantified as the decrease in DEM occurrence probability during stimulation. A normalized DER index (DERI) was calculated as DER/PRE. The measures were compared between 14 healthy controls and 32 comatose patients under EEG monitoring following an acute stroke., Results: The DEM was mapped to the posterior DMN hubs. In the patients, these DEM source dipoles were 3-4 times less frequent and were associated with an increased theta activity. Even in a reduced 6-channel montage, a DER below 6.26% corresponding to a DERI below 0.25 could discriminate the patients with sensitivity and specificity well above 80%., Conclusion: The method detected the DMN impairment in post-stroke coma patients., Significance: The DEM and its reactivity to stimulation could be useful to monitor the DMN function at bedside., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors working with Termobit Prod SRL RO during this project were disclosed in the affiliations. AB and CS are shareholders at Termobit Prod Srl. The research grant structure required that the private partner, Termobit Prod, partially fund their own activities. MM was PI and was funded only through grant funds awarded to Termobit, without having a commercial interest in the company. All other authors involved in this study, representing public institutions (AMR, IRM, JC, ACP, AMZ, LZ) were funded from grant funds and have no stock interest or consultancies with Termobit Prod or FHC, Inc. Authors have filed a patent proposal for the presented method., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Importance: Stereoelectroencephalography (SEEG) has become the criterion standard in case of inconclusive noninvasive presurgical epilepsy workup. However, up to 40% of patients are subsequently not offered surgery because the seizure-onset zone is less focal than expected or cannot be identified., Objective: To predict focality of the seizure-onset zone in SEEG, the 5-point 5-SENSE score was developed and validated., Design, Setting, and Participants: This was a monocentric cohort study for score development followed by multicenter validation with patient selection intervals between February 2002 to October 2018 and May 2002 to December 2019. The minimum follow-up period was 1 year. Patients with drug-resistant epilepsy undergoing SEEG at the Montreal Neurological Institute were analyzed to identify a focal seizure-onset zone. Selection criteria were 2 or more seizures in electroencephalography and availability of complete neuropsychological and neuroimaging data sets. For validation, patients from 9 epilepsy centers meeting these criteria were included. Analysis took place between May and July 2021., Main Outcomes and Measures: Based on SEEG, patients were grouped as focal and nonfocal seizure-onset zone. Demographic, clinical, electroencephalography, neuroimaging, and neuropsychology data were analyzed, and a multiple logistic regression model for developing a score to predict SEEG focality was created and validated in an independent sample., Results: A total of 128 patients (57 women [44.5%]; median [range] age, 31 [13-58] years) were analyzed for score development and 207 patients (97 women [46.9%]; median [range] age, 32 [16-70] years) were analyzed for validation. The score comprised the following 5 predictive variables: focal lesion on structural magnetic resonance imaging, absence of bilateral independent spikes in scalp electroencephalography, localizing neuropsychological deficit, strongly localizing semiology, and regional ictal scalp electroencephalography onset. The 5-SENSE score had an optimal mean (SD) probability cutoff for identifying a focal seizure-onset zone of 37.6 (3.5). Area under the curve, specificity, and sensitivity were 0.83, 76.3% (95% CI, 66.7-85.8), and 83.3% (95% CI, 72.30-94.1), respectively. Validation showed 76.0% (95% CI, 67.5-84.0) specificity and 52.3% (95% CI, 43.0-61.5) sensitivity., Conclusions and Relevance: High specificity in score development and validation confirms that the 5-SENSE score predicts patients where SEEG is unlikely to identify a focal seizure-onset zone. It is a simple and useful tool for assisting clinicians to reduce unnecessary invasive diagnostic burden on patients and overutilization of limited health care resources.

Periventricular nodular heterotopias (PVNH) are areas of neurons abnormally located in the white matter that might be involved in physiological cortical functions. Autoscopic hallucinations are changes in self-consciousness determined by a mismatch in integration of multiple sensory inputs. Our goal is to highlight the brain network involved in generation of autoscopic hallucination elicited by electrical stimulation of a PVNH in a drug resistant epilepsy patient. Our patient was explored using stereo-electroencephalography with electrodes covering the right posterior temporal PVNH and the adjacent cortex. Direct electrical high frequency stimulation of the PVNH elicited autoscopic hallucinations mainly involving the face and upper trunk. We then used multiple modalities to determine brain connectivity: single pulse electrical stimulation of the PVNH and stimulation-evoked potentials were used to highlight resting state effective connectivity. High-frequency stimulation using alternating polarity pulses enabled us to identify the network involved, time-locked to the clinical effect and to map symptom-related effective connectivity. Functional connectivity using a non-linear regression method was used to determine dependencies between different cortical regions following the stimulation. Finally, structural connectivity was highlighted using deterministic fiber tracking. Multi-modal connectivity analysis identified a network involving the PVNH, occipital and temporal neocortex, fusiform gyrus and parietal cortex., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The SEEG International Course, organised in 2017, focused on the investigation and surgery of insulo-perisylvian epilepsies. We present one representative complex case that was discussed. The patient had seizures displaying startle/reflex components. He was MRI negative, while other non-invasive investigations offered only partially concordant data. Initial SEEG exploration resulted in an incomplete definition of the epileptogenic zone. A second SEEG followed, which led to a thorough assessment of the seizure onset zone and the epileptic network, localised to the lateral inferior premotor cortex, explaining the incongruent data obtained beforehand. This was the basis of a tailored resection with a favourable outcome. The patient has been seizure-free for five years without any motor nor cognitive deficits, but with pharmacodependence to one AED. The electroclinical reasoning is presented, accompanied by relevant commentaries and recommendations from the tutors [Published with video sequences].

The success of stereoelectroencephalographic (SEEG) investigations depends crucially on the hypotheses on the putative location of the seizure onset zone. This information is derived from non-invasive data either based on visual analysis or advanced source localization algorithms. While source localization applied to interictal spikes recorded on scalp is the classical method, it does not provide unequivocal information regarding the seizure onset zone. Raw ictal activity contains a mixture of signals originating from several regions of the brain as well as EMG artifacts, hampering direct input to the source localization algorithms. We therefore introduce a methodology that disentangles the various sources contributing to the scalp ictal activity using independent component analysis and uses equivalent current dipole localization as putative locus of ictal sources. We validated the results of our analysis pipeline by performing long-term simultaneous scalp - intracerebral (SEEG) recordings in 14 patients and analyzing the wavelet coherence between the independent component encoding the ictal discharge and the SEEG signals in 8 patients passing the inclusion criteria. Our results show that invasively recorded ictal onset patterns, including low-voltage fast activity, can be captured by the independent component analysis of scalp EEG. The visibility of the ictal activity strongly depends on the depth of the sources. The equivalent current dipole localization can point to the seizure onset zone (SOZ) with an accuracy that can be as high as 10 mm for superficially located sources, that gradually decreases for deeper seizure generators, averaging at 47 mm in the 8 analyzed patients. Independent component analysis is therefore shown to have a promising SOZ localizing value, indicating whether the seizure onset zone is neocortical, and its approximate location, or located in mesial structures. That may contribute to a better crafting of the hypotheses used as basis of the stereo-EEG implantations., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The cingulate cortex is part of the limbic system. Its function and connectivity are organized in a rostro-caudal and ventral-dorsal manner which was addressed by various other studies using rather coarse cortical parcellations. In this study, we aim at describing its function and connectivity using invasive recordings from patients explored for focal drug-resistant epilepsy. We included patients that underwent stereo-electroencephalographic recordings using intracranial electrodes in the University Emergency Hospital Bucharest between 2012 and 2019. We reviewed all high frequency stimulations (50 ​Hz) performed for functional mapping of the cingulate cortex. We used two methods to characterize brain connectivity. Effective connectivity was inferred based on the analysis of cortico-cortical potentials (CCEPs) evoked by single pulse electrical stimulation (SPES) (15 ​s inter-pulse interval). Functional connectivity was estimated using the non-linear regression method applied to 60 ​s spontaneous electrical brain signal intervals. The effective (stimulation-evoked) and functional (non-evoked) connectivity analyses highlight brain networks in a different way. While non-evoked connectivity evidences areas having related activity, often in close proximity to each other, evoked connectivity highlights spatially extended networks. To highlight in a comprehensive way the cingulate cortex's network, we have performed a bi-modal connectivity analysis that combines the resting-state broadband h 2 non-linear correlation with cortico-cortical evoked potentials. We co-registered the patient's anatomy with the fsaverage FreeSurfer template to perform the automatic labeling based on HCP-MMP parcellation. At a group level, connectivity was estimated by averaging responses over stimulated/recorded or recorded sites in each pair of parcels. Finally, for multiple regions that evoked a clinical response during high frequency stimulation, we combined the connectivity of individual pairs using maximum intensity projection. Connectivity was assessed by applying SPES on 2094 contact pairs and recording CCEPs on 3580 contacts out of 8582 contacts of 660 electrodes implanted in 47 patients. Clinical responses elicited by high frequency stimulations in 107 sites (pairs of contacts) located in the cingulate cortex were divided in 10 groups: affective, motor behavior, motor elementary, versive, speech, vestibular, autonomic, somatosensory, visual and changes in body perception. Anterior cingulate cortex was shown to be connected to the mesial temporal, orbitofrontal and prefrontal cortex. In the middle cingulate cortex, we located affective, motor behavior in the anterior region, and elementary motor and somatosensory in the posterior part. This region is connected to the prefrontal, premotor and primary motor network. Finally, the posterior cingulate was shown to be connected with the visual areas, mesial and lateral parietal and temporal cortex., Competing Interests: Declaration of competing interest Andrei Barborica PhD is also Vice-President and Chief Technological Officer of FHC Inc, the manufacturer of the electrical stimulator and stereotactic fixture used in Bucharest. The other authors have nothing to disclose in relation to this work., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Low-grade epilepsy-associated neuroepithelial tumours (LEATs) encompass the broad spectrum of tumours associated with epilepsy. Since the postsurgical seizure outcome in LEATs is favourable, it is speculated that epileptological presurgical evaluation (EPE) might not be required for patients with LEATs. A multicentre study involving referring epilepsy and neurosurgery centres was performed, aimed at evaluating postsurgical epilepsy outcome in patients with LEATs, with and without EPE, including long-term video-EEG monitoring (vEEGM). In total, 149 surgically treated patients were enrolled (age: 31±14 years; age at surgery: 26.4±13.1 years; males; 55.7%) with histopathological confirmation of LEATs and follow-up of more than six months. All patients had undergone standard assessment: clinical, routine EEG and brain MRI. In addition to vEEGM, EPE included other additional investigations. Epileptologists did not assess patients treated in neurosurgical centres. The EPE was performed in 51% of patients. Histopathological diagnosis revealed ganglioglioma in 43.6%, DNET in 32.9%, pilocytic astrocytoma in 17.4%, and others in 6.1% of patients. The majority of patients were seizure-free (ILAE epilepsy surgery outcome Class 1; 71.1%). The median follow-up period was 36 months. Patients who were rendered seizure-free were younger (mean age: 24.2±12.2) than those who were not seizure-free (31.8±14.0) (p=0.001). No difference was identified between evaluated and non-evaluated patients with respect to seizure freedom (p=0.45). EPE patients had a longer epilepsy duration (median: 10 years) and a higher proportion of drug resistance (73.6%) compared to non-evaluated patients (median: two years; 26.4%) (p<0.001). Based on a significant difference in major clinical variables, that may well affect postoperative results, the similar postsurgical seizure outcome in groups with and without EPE observed in our study should be considered with caution, and conclusions as to whether there is value in formal presurgical evaluation in LEAT patients cannot be drawn. Our data strongly encourage the clear need for continued discussion around such patients at epilepsy management conferences.

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., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Sleep is an active process with an important role in memory. Epilepsy patients often display a disturbed sleep architecture, with consequences on cognition. We aimed to investigate the effect of sleep on cortical networks' organization., Methods: We analyzed cortico-cortical evoked responses elicited by single pulse electrical stimulation (SPES) using intracranial depth electrodes in 25 patients with drug-resistant focal epilepsy explored using stereo-EEG. We applied the SPES protocol during wakefulness and NREM - N2 sleep. We analyzed 31,710 significant responses elicited by 799 stimulations covering most brain structures, epileptogenic or non-epileptogenic. We analyzed effective connectivity between structures using a graph-theory approach., Results: Sleep increases excitability in the brain, regardless of epileptogenicity. Local and distant connections are differently modulated by sleep, depending on the tissue epileptogenicity. In non-epileptogenic areas, frontal lobe connectivity is enhanced during sleep. There is increased connectivity between the hippocampus and temporal neocortex, while perisylvian structures are disconnected from the temporal lobe. In epileptogenic areas, we found a clear interhemispheric difference, with decreased connectivity in the right hemisphere during sleep., Conclusions: Sleep modulates brain excitability and reconfigures functional brain networks, depending on tissue epileptogenicity., Significance: We found specific patterns of information flow during sleep in physiologic and pathologic structures, with possible implications for cognition., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: To profile European trends in pediatric epilepsy surgery (<16 years of age) between 2008 and 2015., Methods: We collected information on volumes and types of surgery, pathology, and seizure outcome from 20 recognized epilepsy surgery reference centers in 10 European countries., Results: We analyzed retrospective aggregate data on 1859 operations. The proportion of surgeries significantly increased over time (P < .0001). Engel class I outcome was achieved in 69.3% of children, with no significant improvement between 2008 and 2015. The proportion of histopathological findings consistent with glial scars significantly increased between the ages of 7 and 16 years (P for trend = .0033), whereas that of the remaining pathologies did not vary across ages. A significant increase in unilobar extratemporal surgeries (P for trend = .0047) and a significant decrease in unilobar temporal surgeries (P for trend = .0030) were observed between 2008 and 2015. Conversely, the proportion of multilobar surgeries and unrevealing magnetic resonance imaging cases remained unchanged. Invasive investigations significantly increased, especially stereo-electroencephalography. We found different trends comparing centers starting their activity in the 1990s to those whose programs were developed in the past decade. Multivariate analysis revealed a significant variability of the proportion of the different pathologies and surgical approaches across countries, centers, and age groups between 2008 and 2015., Significance: Between 2008 and 2015, we observed a significant increase in the volume of pediatric epilepsy surgeries, stability in the proportion of Engel class I outcomes, and a modest increment in complexity of the procedures., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Body awareness is the result of sensory integration in the posterior parietal cortex; however, other brain structures are part of this process. Our goal is to determine how the cingulate cortex is involved in the representation of our body. We retrospectively selected patients with drug-resistant epilepsy, explored by stereo-electroencephalography, that had the cingulate cortex sampled outside the epileptogenic zone. The clinical effects of high-frequency electrical stimulation were reviewed and only those sites that elicited changes related to body perception were included. Connectivity of the cingulate cortex and other cortical structures was assessed using the h 2 coefficient, following a nonlinear regression analysis of the broadband EEG signal. Poststimulation changes in connectivity were compared between two sets of stimulations eliciting or not eliciting symptoms related to body awareness (interest and control groups). We included 17 stimulations from 12 patients that reported different types of body perception changes such as sensation of being pushed toward right/left/up, one limb becoming heavier/lighter, illusory sensation of movement, sensation of pressure, sensation of floating or detachment of one hemi-body. High-frequency stimulation in the cingulate cortex (1 anterior, 15 middle, 1 posterior part) elicits body perception changes, associated with a decreased connectivity of the dominant posterior insula and increased coupling between other structures, located particularly in the nondominant hemisphere., (© 2019 Wiley Periodicals, Inc.)

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., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: We aimed to (1) assess the concordance between various polymicrogyria (PMG) types and the associated epileptogenic zone (EZ), as defined by stereoelectroencephalography (SEEG), and (2) determine the postsurgical seizure outcome in PMG-related drug-resistant epilepsy., Methods: We retrospectively analyzed 58 cases: 49 had SEEG and 39 corticectomy or hemispherotomy., Results: Mean age at SEEG or surgery was 28.3 years (range, 2-50). PMG was bilateral in 9 (16%) patients and unilateral in 49, including 17 (29%) unilobar, 12 (21%) multilobar, 15 (26%) perisylvian, and only 5 (9%) hemispheric. Twenty-eight (48%) patients additionally had schizencephaly, heterotopia, or focal cortical dysplasia. The SEEG-determined EZ was fully concordant with the PMG in only 8 (16%) cases, partially concordant in 74%, and discordant in 10%. The EZ included remote cortical areas in 21 (43%) cases and was primarily localized in those in 5 (10%), all related to the mesial temporal structures. All but 1 PMG patient with corticectomy or hemispherotomy had a unilateral PMG. At last follow-up (mean, 4.6 years; range, 1-16), 28 (72%) patients remained seizure free. Shorter epilepsy duration to surgery was an independent predictor of seizure freedom., Interpretation: PMG-related drug-resistant epilepsy warrants a comprehensive presurgical evaluation, including SEEG investigations in most cases, given that the EZ may only partially overlap with the PMG or include solely remote cortical areas. Seizure freedom is feasible in a large proportion of patients. PMG extent should not deter from exploring the possibility of epilepsy surgery. Our data support the early consideration of epilepsy surgery in this patient group. Ann Neurol 2017;82:781-794., (© 2017 American Neurological Association.)

Objective: To investigate functional coupling between brain networks using spectral changes induced by single-pulse electric stimulation (SPES)., Method: We analyzed 20 patients with focal epilepsy, implanted with depth electrodes. SPES was applied to each pair of adjacent contacts, and responses were recorded from all other contacts. The mean response amplitude value was quantified in three time-periods after stimulation (10-60, 60-255, 255-500ms) for three frequency-ranges (Gamma, Ripples, Fast-Ripples), and compared to baseline. A total of 30,755 responses were analyzed, taking into consideration three dichotomous pairs: stimulating in primary sensory areas (S1-V1) vs. outside them, to test the interaction in physiologic networks; stimulating in seizure onset zone (SOZ) vs. non-SOZ, to test pathologic interactions; recording in default mode network (DMN) vs. non-DMN., Results: Overall, we observed an early excitation (10-60ms) and a delayed inhibition (60-500ms). More specifically, in the delayed period, stimulation in S1-V1 produced a higher gamma-inhibition in the DMN, while stimulation in the SOZ induced a higher inhibition in the epilepsy-related higher frequencies (Ripples and Fast-Ripples)., Conclusion: Physiologic and pathologic interactions can be assessed using spectral changes induced by SPES., Significance: This is a promising method for connectivity studies in patients with drug-resistant focal epilepsy., (Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Pre-surgical assessment and surgical management of frontal epilepsy with normal MRI is often challenging. We present a case of a 33-year-old, right-handed, educated male. During childhood, his seizures presented with mandibular myoclonus and no particular trigger. As a young adult, he developed seizures with a startle component, triggered by unexpected noises. During his ictal episodes, he felt fear and grimaced with sudden head flexion and tonic axial posturing. Similar seizures also occurred without startle. Neuropsychological assessment showed executive dysfunction and verbal memory deficit. The cerebral MRI was normal. Electro-clinical reasoning, investigations performed, the results obtained and follow-up are discussed in detail. [Published with video sequence].

Background: Based on a case report, the authors reviewed the data about involuntary emotional expression disorder (IEED). IEED includes the syndromes of pathological laughing and crying (PLC) and emotional lability (EL). PLC is a rare disorder of emotional expression characterized by relatively uncontrollable episodes of laughter and crying or both that do not have an apparent motivating stimulus., Case Presentation: Authors report the case of a 59-year-old man who presented with recurrent episodes of PLC of approximately 2 min duration, consisting of accelerated breathing, emission of guttural, snoring sounds, frowning of the eyebrows, followed by laughter accompanied by motor restlessness of all four limbs. PLC episodes preceded left carotid transient ischemic attacks (TIA's) manifested by reversible aphasia and right hemiparesis. Electroencephalography performed during PLC episodes revealed no spike-wave activity. Brain magnetic resonance imaging showed lacunar infarcts in the left lenticulo-capsulo-thalamic area and multiple round lesions in the cortical-subcortical and in the deep white matter of frontal-parietal-occipital lobes bilaterally, with T2 hyperintensity, T1 isointensity and no diffusion changes. The episodes were interpreted as transient ischemic attacks although gelastic seizures could not be excluded. The etiological investigations revealed unstable plaques on the left carotid artery bulb and the aortic arch and a degenerative mitral valve stenosis. The patient was treated first with antiplatelet therapy and antiepileptic drugs but PLC stopped only after anticoagulation was started. During follow-up the patient continued to have left carotid and vertebrobasilar TIA's being on oral anticoagulation. The patient became asymptomatic only after mitral valve replacement was performed., Conclusions: This case illustrates the difficulty distinguishing between gelastic epilepsy and TIA's in cases of PLC episodes and discuss the neuroanatomic bases and pathophysiology of this rare condition.

Purpose: To investigate whether hyperventilation (HV) for 5min increases the diagnostic yield of electroencephalography (EEG) compared to 3min HV., Methods: data were evaluated from 1084 consecutive patients, from three European centres, referred to EEG on suspicion of epilepsy. Seizures and interictal EEG abnormalities precipitated during the first 3min and during the last 2min of the HV period (totally 5min) were determined., Results: Eight hundred seventy-seven patients (81%) completed 5min HV. Seizures were precipitated during the first 3min of HV in 21 patients, and during the last 2min in four more patients. Interictal EEG abnormalities were precipitated in the first 3min of HV in 16 patients, and during the last 2min in 7 more patients. Psychogenic nonepileptic seizures occurred in eight patients during the first 3min of HV and in two more patients during the last 2min. No adverse events occurred during the last 2min of HV, but eight patients (1%) stopped HV during the last 2min because they were not able to hyperventilate further., Conclusion: 16% of seizures and 30% of interictal EEG abnormalities triggered by HV occurred during the last 2min of HV, suggesting the clinical usefulness of prolonged hyperventilation for 5min. The vast majority of patients (99%) who are able to hyperventilate for 3min can complete 5min HV, without additional adverse events., (Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Magnetic resonance imaging (MRI)-negative epilepsy may be successfully solved with a multidisciplinary approach using invasive recordings, image and signal analysis. The whole methodology used by the epilepsy surgery team is systematically described based on an resistant epilepsy case with all steps and rationale of choosing different investigation methods from surface electroencephalography (EEG) to invasive recordings. Due to negative MRI and non-concordant ictal surface EEG with clinical semiology, the patient was investigated with stereo- EEG (SEEG), aiming to delimitate epileptogenic and eloquent cerebral areas. Implantation strategy, seizures recordings, stimulation, resection planning using quantitative EEG analysis, and the surgery plan are presented. The patient has been seizure-free for 14 months so far, with improved behavior and daily life quality. Post-operative examination revealed focal cortical dysplasia type II B.

Background: The stereoelectroencephalographic (SEEG) implantation procedures still represent a challenge due to the intrinsic complexity of the method and the number of depth electrodes required., Objectives: We aim at designing and evaluating the accuracy of a custom stereotactic fixture based on the StarFix™ technology (FHC Inc., Bowdoin, ME) that significantly simplifies and optimizes the implantation of depth electrodes used in presurgical evaluation of patients with drug-resistant epilepsy., Methods: Fiducial markers that also serve as anchors for the fixture are implanted into the patient's skull prior to surgery. A 3D fixture model is designed within the surgical planning software, with the planned trajectories incorporated in its design, aligned with the patient's anatomy. The stereotactic fixture is built using 3D laser sintering technology based on the computer-generated model. Bilateral rectangular grids of guide holes orthogonal to the midsagittal plane and centered on the midcommissural point are incorporated in the fixture design, allowing a wide selection of orthogonal trajectories. Up to two additional grids can be accommodated for targeting structures where oblique trajectories are required. The frame has no adjustable parts, this feature reducing the risk of inaccurate coordinate settings while simultaneously reducing procedure time significantly., Results: We have used the fixture for the implantation of depth electrodes for presurgical evaluation of 4 patients with drug-resistant focal epilepsy, with nearly 2-fold reduction in the duration of the implantation procedure. We have obtained a high accuracy with a submillimetric mean positioning error of 0.68 mm for the anchor bolts placed at the trajectory entry point and 1.64 mm at target., Conclusions: The custom stereotactic fixture design greatly simplifies the planning procedure and significantly reduces the time in the operating room, while maintaining a high accuracy., (© 2014 S. Karger AG, Basel.)

Purpose: The aim of this survey was to review and compare the current approaches to epilepsy management in central and eastern EU (CEEU) countries., Method: The questionnaire was sent to ten invited experts from Bulgaria, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, and Slovenia. It focused on the treatment of adults., Results: The number of neurologists and epilepsy reference centers is highly variable in CEEU countries. None of the analyzed states has a formal specialization in epileptology. No universal state-approved criteria for reference centers exist in Czech Republic, Estonia, Hungary, Latvia, and Slovenia. Generally, the protocols for epilepsy treatment in CEEU countries, including drug-resistant epilepsy, are in accordance with international guidelines; however, most countries have their own national standards of care and some have local clinical guidelines. Also, the reimbursement systems for antiepileptic drugs in CEEU countries are highly variable. Seven countries have epilepsy surgery centers. The costs of epilepsy surgeries are fully reimbursed, procedures performed abroad may also be covered. The length of time spent on waiting lists for surgery following the completion of preoperative investigations varies from two weeks to three years. The fraction of patients who qualified and were operated on within 12 months ranges from 20% to 100%., Conclusion: The lack of unified procedures pertaining to the evaluation and therapy of epilepsy is reflected by marked differences in access to treatment modalities for patients from CEEU countries., (Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)