A Learned Map for Places and Concepts in the Human Medial Temporal Lobe.

Distinct lines of research in both humans and animals point to a specific role of the hippocampus in both spatial and episodic memory function. The discovery of concept cells in the hippocampus and surrounding medial temporal lobe (MTL) regions suggests that the MTL maps physical and semantic spaces with a similar neural architecture. Here, we studied the emergence of such maps using MTL microwire recordings from 20 patients (9 female, 11 male) navigating a virtual environment featuring salient landmarks with established semantic meaning. We present several key findings. The array of local field potentials in the MTL contains sufficient information for above-chance decoding of subjects' instantaneous location in the environment. Closer examination revealed that as subjects gain experience with the environment the field potentials come to represent both the subjects' locations in virtual space and in high-dimensional semantic space. Similarly, we observe a learning effect on temporal sequence coding. Over time, field potentials come to represent future locations, even after controlling for spatial proximity. This predictive coding of future states, more so than the strength of spatial representations per se, is linked to variability in subjects' navigation performance. Our results thus support the conceptualization of the MTL as a memory space, representing both spatial- and nonspatial information to plan future actions and predict their outcomes.SIGNIFICANCE STATEMENT Using rare microwire recordings, we studied the representation of spatial, semantic, and temporal information in the human MTL. Our findings demonstrate that subjects acquire a cognitive map that simultaneously represents the spatial and semantic relations between landmarks. We further show that the same learned representation is used to predict future states, implicating MTL cell assemblies as the building blocks of prospective memory functions.

Add-on treatment with cenobamate is already effective at low doses in refractory focal epilepsy: A prospective observational study.

OBJECTIVE: Cenobamate, a novel antiseizure medication with a dual mechanism of action, has been shown in pivotal trials to significantly improve seizure control in treatment-resistant focal epilepsy. We aimed to evaluate whether these promising results could be confirmed in a real-world setting with a follow-up period of up to 12 months. METHODS: Patients from a tertiary epilepsy center who received cenobamate add-on between June 2021 and October 2023 were followed up prospectively at 3, 6, and 12 months after treatment initiation for assessment of seizure outcomes and treatment-related adverse events. RESULTS: The clinical cohort included 112 adult patients with 30% nonlesional cases and a wide spectrum of epileptogenic lesions underlying refractory focal epilepsy. We observed a significant reduction in monthly seizure frequency of all seizure types already after 3 months of treatment at a median cenobamate dose of 100 mg/day. Forty-six percent of patients were responders with a ≥50% seizure reduction, 26% had a ≥75% seizure reduction, and 9% became seizure-free. Among the 74 patients with available follow-up of 12 months, the responder rates reached 55%, 35%, and 19% for ≥50%, ≥75%, and 100% seizure reduction, respectively. After 3 months of treatment, 38% of patients reported adverse effects, mainly (84%) mild to moderate in intensity. Adjustment of comedication allowed successful management of adverse effects in 32% of patients. At a group level, there was no correlation between the cenobamate daily dose and the incidence of adverse events. SIGNIFICANCE: We found a clinically relevant response to cenobamate already at a low daily dose of 100 mg also in a patient cohort with a higher degree of drug resistance than in pivotal trials. Our prospectively collected data provide real-world evidence for high efficacy and good tolerability of the drug, although no standardized treatment protocol or comparison with a control group was applied.

Home recording of 3-Hz spike-wave discharges in adults with absence epilepsy using the wearable Sensor Dot.

OBJECTIVE: Home monitoring of 3-Hz spike-wave discharges (SWDs) in patients with refractory absence epilepsy could improve clinical care by replacing the inaccurate seizure diary with objective counts. We investigated the use and performance of the Sensor Dot (Byteflies) wearable in persons with absence epilepsy in their home environment. METHODS: Thirteen participants (median age = 22 years, 11 female) were enrolled at the university hospitals of Leuven and Freiburg. At home, participants had to attach the Sensor Dot and behind-the-ear electrodes to record two-channel electroencephalogram (EEG), accelerometry, and gyroscope data. Ground truth annotations were created during a visual review of the full Sensor Dot recording. Generalized SWDs were annotated if they were 3 Hz and at least 3 s on EEG. Potential 3-Hz SWDs were flagged by an automated seizure detection algorithm, (1) using only EEG and (2) with an additional postprocessing step using accelerometer and gyroscope to discard motion artifacts. Afterward, two readers (W.V.P. and L.S.) reviewed algorithm-labeled segments and annotated true positive detections. Sensitivity, precision, and F1 score were calculated. Patients had to keep a seizure diary and complete questionnaires about their experiences. RESULTS: Total recording time was 394 h 42 min. Overall, 234 SWDs were captured in 11 of 13 participants. Review of the unimodal algorithm-labeled recordings resulted in a mean sensitivity of .84, precision of .93, and F1 score of .89. Visual review of the multimodal algorithm-labeled segments resulted in a similar F1 score and shorter review time due to fewer false positive labels. Participants reported that the device was comfortable and that they would be willing to wear it on demand of their neurologist, for a maximum of 1 week or with intermediate breaks. SIGNIFICANCE: The Sensor Dot improved seizure documentation at home, relative to patient self-reporting. Additional benefits were the short review time and the patients' device acceptance due to user-friendliness and comfortability.

Semiautomated electric source imaging determines epileptogenicity of encephaloceles in temporal lobe epilepsy.

OBJECTIVE: We aimed to assess the ability of semiautomated electric source imaging (ESI) from long-term video-electroencephalographic (EEG) monitoring (LTM) to determine the epileptogenicity of temporopolar encephaloceles (TEs) in patients with temporal lobe epilepsy. METHODS: We conducted a retrospective study involving 32 temporal lobe epilepsy patients with TEs as potentially epileptogenic lesions in structural magnetic resonance imaging scans. Findings were validated through invasive intracerebral stereo-EEG in six of 32 patients and postsurgical outcome after tailored resection of the TE in 17 of 32 patients. LTM (mean duration = 6 days) was performed using the 10/20 system with additional T1/T2 for all patients and sphenoidal electrodes in 23 of 32 patients. Semiautomated detection and clustering of interictal epileptiform discharges (IEDs) were carried out to create IED types. ESI was performed on the averages of the two most frequent IED types per patient, utilizing individual head models, and two independent inverse methods (sLORETA [standardized low-resolution brain electromagnetic tomography], MUSIC [multiple signal classification]). ESI maxima concordance and propagation in spatial relation to TEs were quantified for sources with good signal quality (signal-to-noise ratio > 2, explained signal > 60%). RESULTS: ESI maxima correctly colocalized with a TE in 20 of 32 patients (62.5%) either at the onset or half-rising flank of at least one IED type per patient. ESI maxima showed propagation from the temporal pole to other temporal or extratemporal regions in 14 of 32 patients (44%), confirming propagation originating in the area of the TE. The findings from both inverse methods validated each other in 14 of 20 patients (70%), and sphenoidal electrodes exhibited the highest signal amplitudes in 17 of 23 patients (74%). The concordance of ESI with the TE predicted a seizure-free postsurgical outcome (Engel I vs. >I) with a diagnostic odds ratio of 2.1. SIGNIFICANCE: Semiautomated ESI from LTM often successfully identifies the epileptogenicity of TEs and the IED onset zone within the area of the TEs. Additionally, it shows potential predictive power for postsurgical outcomes in these patients.

Minimum clinical utility standards for wearable seizure detectors: A simulation study.

OBJECTIVE: Epilepsy management employs self-reported seizure diaries, despite evidence of seizure underreporting. Wearable and implantable seizure detection devices are now becoming more widely available. There are no clear guidelines about what levels of accuracy are sufficient. This study aimed to simulate clinical use cases and identify the necessary level of accuracy for each. METHODS: Using a realistic seizure simulator (CHOCOLATES), a ground truth was produced, which was then sampled to generate signals from simulated seizure detectors of various capabilities. Five use cases were evaluated: (1) randomized clinical trials (RCTs), (2) medication adjustment in clinic, (3) injury prevention, (4) sudden unexpected death in epilepsy (SUDEP) prevention, and (5) treatment of seizure clusters. We considered sensitivity (0%-100%), false alarm rate (FAR; 0-2/day), and device type (external wearable vs. implant) in each scenario. RESULTS: The RCT case was efficient for a wide range of wearable parameters, though implantable devices were preferred. Lower accuracy wearables resulted in subtle changes in the distribution of patients enrolled in RCTs, and therefore higher sensitivity and lower FAR values were preferred. In the clinic case, a wide range of sensitivity, FAR, and device type yielded similar results. For injury prevention, SUDEP prevention, and seizure cluster treatment, each scenario required high sensitivity and yet was minimally influenced by FAR. SIGNIFICANCE: The choice of use case is paramount in determining acceptable accuracy levels for a wearable seizure detection device. We offer simulation results for determining and verifying utility for specific use case and specific wearable parameters.

Grading system for assessing the confidence in the epileptogenic zone reported in published studies: A Delphi consensus study.

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.

Multimodal mapping of regional brain vulnerability to focal cortical dysplasia.

Focal cortical dysplasia (FCD) type II is a highly epileptogenic developmental malformation and a common cause of surgically treated drug-resistant epilepsy. While clinical observations suggest frequent occurrence in the frontal lobe, mechanisms for such propensity remain unexplored. Here, we hypothesized that cortex-wide spatial associations of FCD distribution with cortical cytoarchitecture, gene expression and organizational axes may offer complementary insights into processes that predispose given cortical regions to harbour FCD. We mapped the cortex-wide MRI distribution of FCDs in 337 patients collected from 13 sites worldwide. We then determined its associations with (i) cytoarchitectural features using histological atlases by Von Economo and Koskinas and BigBrain; (ii) whole-brain gene expression and spatiotemporal dynamics from prenatal to adulthood stages using the Allen Human Brain Atlas and PsychENCODE BrainSpan; and (iii) macroscale developmental axes of cortical organization. FCD lesions were preferentially located in the prefrontal and fronto-limbic cortices typified by low neuron density, large soma and thick grey matter. Transcriptomic associations with FCD distribution uncovered a prenatal component related to neuroglial proliferation and differentiation, likely accounting for the dysplastic makeup, and a postnatal component related to synaptogenesis and circuit organization, possibly contributing to circuit-level hyperexcitability. FCD distribution showed a strong association with the anterior region of the antero-posterior axis derived from heritability analysis of interregional structural covariance of cortical thickness, but not with structural and functional hierarchical axes. Reliability of all results was confirmed through resampling techniques. Multimodal associations with cytoarchitecture, gene expression and axes of cortical organization indicate that prenatal neurogenesis and postnatal synaptogenesis may be key points of developmental vulnerability of the frontal lobe to FCD. Concordant with a causal role of atypical neuroglial proliferation and growth, our results indicate that FCD-vulnerable cortices display properties indicative of earlier termination of neurogenesis and initiation of cell growth. They also suggest a potential contribution of aberrant postnatal synaptogenesis and circuit development to FCD epileptogenicity.

Technical note: preliminary surgical experience with a new implantable epicranial stimulation device for chronic focal cortex stimulation in drug-resistant epilepsy.

PURPOSE: This study is to report some preliminary surgical considerations and outcomes after the first implantations of a new and commercially available implantable epicranial stimulation device for focal epilepsy. METHODS: We retrospectively analyzed data from clinical notes. Outcome parameters were as follows: wound healing, surgery time, and adverse events. RESULTS: Five patients were included (17-52 y/o; 3 female). Epicranial systems were uneventfully implanted under neuronavigation guidance. Some minor adverse events occurred. Wound healing in primary intention was seen in all patients. Out of these surgeries, certain concepts were developed: Skin incisions had to be significantly larger than expected. S-shaped incisions appeared to be a good choice in typical locations behind the hairline. Preoperative discussions between neurologist and neurosurgeon are mandatory in order to allow for the optimal coverage of the epileptogenic zone with the electrode geometry. CONCLUSION: In this first small series, we were able to show safe implantation of this new epicranial stimulation device. The use of neuronavigation is strongly recommended. The procedure is simple but not trivial and ideally belongs in the hands of a neurosurgeon.

Seizure forecasting: Where do we stand?

A lot of mileage has been made recently on the long and winding road toward seizure forecasting. Here we briefly review some selected milestones passed along the way, which were discussed at the International Conference for Technology and Analysis of Seizures-ICTALS 2022-convened at the University of Bern, Switzerland. Major impetus was gained recently from wearable and implantable devices that record not only electroencephalography, but also data on motor behavior, acoustic signals, and various signals of the autonomic nervous system. This multimodal monitoring can be performed for ultralong timescales covering months or years. Accordingly, features and metrics extracted from these data now assess seizure dynamics with a greater degree of completeness. Most prominently, this has allowed the confirmation of the long-suspected cyclical nature of interictal epileptiform activity, seizure risk, and seizures. The timescales cover daily, multi-day, and yearly cycles. Progress has also been fueled by approaches originating from the interdisciplinary field of network science. Considering epilepsy as a large-scale network disorder yielded novel perspectives on the pre-ictal dynamics of the evolving epileptic brain. In addition to discrete predictions that a seizure will take place in a specified prediction horizon, the community broadened the scope to probabilistic forecasts of a seizure risk evolving continuously in time. This shift of gears triggered the incorporation of additional metrics to quantify the performance of forecasting algorithms, which should be compared to the chance performance of constrained stochastic null models. An imminent task of utmost importance is to find optimal ways to communicate the output of seizure-forecasting algorithms to patients, caretakers, and clinicians, so that they can have socioeconomic impact and improve patients' well-being.

Seizure occurrence is linked to multiday cycles in diverse physiological signals.

OBJECTIVE: The factors that influence seizure timing are poorly understood, and seizure unpredictability remains a major cause of disability. Work in chronobiology has shown that cyclical physiological phenomena are ubiquitous, with daily and multiday cycles evident in immune, endocrine, metabolic, neurological, and cardiovascular function. Additionally, work with chronic brain recordings has identified that seizure risk is linked to daily and multiday cycles in brain activity. Here, we provide the first characterization of the relationships between the cyclical modulation of a diverse set of physiological signals, brain activity, and seizure timing. METHODS: In this cohort study, 14 subjects underwent chronic ambulatory monitoring with a multimodal wrist-worn sensor (recording heart rate, accelerometry, electrodermal activity, and temperature) and an implanted responsive neurostimulation system (recording interictal epileptiform abnormalities and electrographic seizures). Wavelet and filter-Hilbert spectral analyses characterized circadian and multiday cycles in brain and wearable recordings. Circular statistics assessed electrographic seizure timing and cycles in physiology. RESULTS: Ten subjects met inclusion criteria. The mean recording duration was 232 days. Seven subjects had reliable electroencephalographic seizure detections (mean = 76 seizures). Multiday cycles were present in all wearable device signals across all subjects. Seizure timing was phase locked to multiday cycles in five (temperature), four (heart rate, phasic electrodermal activity), and three (accelerometry, heart rate variability, tonic electrodermal activity) subjects. Notably, after regression of behavioral covariates from heart rate, six of seven subjects had seizure phase locking to the residual heart rate signal. SIGNIFICANCE: Seizure timing is associated with daily and multiday cycles in multiple physiological processes. Chronic multimodal wearable device recordings can situate rare paroxysmal events, like seizures, within a broader chronobiology context of the individual. Wearable devices may advance the understanding of factors that influence seizure risk and enable personalized time-varying approaches to epilepsy care.

A brain atlas of axonal and synaptic delays based on modelling of cortico-cortical evoked potentials.

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.

Listening to anxiety in persons with epilepsy. Development of an integrative assessment model based on qualitative interviews.

OBJECTIVE: The differentiation and assessment of anxiety in persons with epilepsy is the subject of current research. There is no consensus on which forms of anxiety are epilepsy-specific, what pathological significance they have, and how they should be conceptually systematized. The aim of this study was to detect formal landmarks that organize and further distinguish the clinical multitude of epilepsy-related anxiety, thereby establishing a basis on which an integrative assessment of epilepsy-specific fears can be developed. METHOD: Twenty-six patients with epilepsy-related fears were recruited for qualitative interviews at the Epilepsy Center of Freiburg in Germany. Prevalent types of anxiety included both periictal and interictal anxiety. Patients reported how living with epilepsy is associated with anxiety and to what extent. After an open interview, semi-structured questions were asked concerning epilepsy-specific anxiety, referring to established concepts and items. The contents of the interviews relating to anxiety were transcribed. RESULTS: The reported fears associated with epilepsy reflect the individual "pathography" of each patient. The potentially anxiety-inducing events within this pathography include the first seizure(s), especially in cases involving the amygdalae; the process of diagnostic procedures; therapy, including side effects of antiseizure medication, surgery as a therapeutic option, or a difficult physician-patient relationship; and the further course of the disease, including the fear of disease progression with brain damage, cognitive deterioration, or professional and social disintegration. The integrative assessment model derived from the pathography of the interviewed patients thus reflects the dynamics and quality of epilepsy-specific fears, especially in relation to the healthcare system, without instantly pathologizing them. It highlights that anxiety, to a variable degree, is perceived as an adequate and comprehensible emotion and might be a problem long before the diagnosis is made in the case of ictal fear. Furthermore, anxiety symptoms may (re-)emerge, consolidate, modulate, diminish, or even aggravate during the course of the disease. The integrative assessment model maps crucial events inherent to the healthcare system that may become relevant as objects of prevention, intervention, and therapy. CONCLUSION: The integrative assessment model can serve as a heuristic framework from which an integrative self-report questionnaire of epilepsy-specific anxiety might be designed. On the one hand, this would help to better understand the interrelation between epilepsy and anxiety in terms of their temporal occurrence and interdependence scientifically. On the other hand, it would allow for the enhancement of individual preventive and therapeutic measures for affected patients.

"What is this strange sensation?" A qualitative exploration of metaphors used to verbalise hard-to-describe experiences by people with epilepsy.

Mental health comorbidities are frequent in epilepsy. Consequently, psychotherapy is becoming increasingly important. To address the psychological needs of people with epilepsy (PwE) it is essential to understand the subjective experiences of seizures better. There is little research on how people report seizures, and which psychological representations they have. We conducted a thematic analysis based on 42 (micro-phenomenological) interviews with 15 participants on their experiences of seizures. In these interviews, we identified three categories of seizure descriptions: (1) phenomena related to the body and emotions; (2) the moments that are difficult to describe; and (3) the use of figurative language and metaphors. Paroxysmal physical and psychological sensations were often reported spontaneously by the participants. The moments that were difficult to describe were expressed, among other things, through the use of paradoxes or the report of a 'strange' feeling and led participants to use figurative language. As these metaphors can reveal important information about people's subjective experiences, they were analyzed in detail. We identified the three main types of metaphors that the participants used most frequently: (1) perception, (2) nature, and (3) battle. The theme of battle was most frequently used in different forms and was closely related to the metaphors from the fields of perception and nature, thus representing a key point in the personal experience of seizures. These findings can contribute to developing psychotherapeutic approaches for the treatment of seizure disorders.

Have attitudes toward epilepsy improved in Germany over the last 50 years?

OBJECTIVE: In Germany, six previous representative surveys on attitudes toward epilepsy (AE) have been conducted between 1967 and 2008 using the four original Caveness questions (CQs) from 1949 to 1980. The aims of this study were (1) to investigate changes in AE over the time span of 50 years, including the current survey in 2018 (2) to investigate the first-time emotional reactions measured with the Scales of Attitudes toward People with Epilepsy (SAPE) (3) to identify predictors of AE. METHODS: A representative face-to-face survey with CQ, in addition with the SAPE scales of Social Distance, Stereotypes, Personal Concerns, and Emotional Reactions was carried out in Germany in 2018. One thousand and twenty-six persons who ever had heard of epilepsy participated. Respondents who answered "don't know" in the CQs were subsequently asked to answer only yes/no. The analysis of trends from 1967 to 2018 was based on the pooled data of the surveys. The four CQs in the 2018 survey were included in the SAPE item pool and an exploratory principal axis factor analysis was performed. General linear models were performed to identify predictors. RESULTS: For all four CQs, the trend of improved AE was significant over the past 50 years. In the 2018 survey, excluding the "don't know" answer option increased the proportion of negative responses for contact of one's own children with a person with epilepsy (PWE) from 6.9% to 11.4% and for the marriage of one's own children with a PWE from 13.9% to 23.8%. When encountering a PWE, 30.1% would feel insecure or uncomfortable and nearly 60% were concerned that the PWE might be injured in case of a seizure. Knowing what to do in case of a seizure, knowing that seizures can be treated successfully, personal contact with a PWE along with younger age, and higher education were found to be the strongest predictors for positive AE identified by multivariate analyses. Exploratory principal axis factor analysis revealed that three of the four CQs items loaded > 0.30 at the factors of Social Distance and Stereotypes of SAPE but none on the factors measuring emotional reactions. SIGNIFICANCE: AE measured by CQs have markedly improved in Germany over the last 50 years. Germany is to our knowledge the only country with such a long-term trend investigation in AE. Negative AE may be underestimated by survey questions with "don't know" answer option. Emotional aspects of attitudes are underexposed resp. neglected in the CQs, which are used worldwide for measuring AE. Additional tools like SAPE can close this gap. The identified predictors may help to derive interventions against negative AE.

Seizures as a Struggle between Life and Death: An Existential Approach to the Psychosocial Impact of Seizures in Candidates for Epilepsy Surgery.

INTRODUCTION: Mental health comorbidities such as depression and anxiety are common in epilepsy, especially among people with pharmacoresistant epilepsy who are candidates for epilepsy surgery. The Psychology Task Force of the International League Against Epilepsy advised that psychological interventions should be integrated into comprehensive epilepsy care. METHODS: To better understand the psychological impact of epilepsy and epileptic seizures in epilepsy surgery candidates, we analysed interviews with this subgroup of patients using Karl Jaspers' concept of limit situations, which are characterised by a confrontation with the limits and challenges of life. These are especially chance, randomness, and unpredictability, death and finitude of life, struggle and self-assertion, guilt, failure, and falling short of one's aspirations. RESULTS: In 43 interviews conducted with 15 people with drug-resistant epilepsy who were candidates for epilepsy surgery, we found that these themes are recurrent and have a large psychosocial impact, which can result in depression and anxiety. For some people, epileptic seizures appear to meet the criteria for traumatic events. CONCLUSION: Understanding epilepsy and seizures as existential challenges complements the neurobiological explanations for psychological comorbidities and can help tailor psychological interventions to the specific needs of people with epilepsy, especially those who are candidates for surgical treatment.

Differentiation of subclinical and clinical electrographic events in long-term electroencephalographic recordings.

OBJECTIVE: With the advent of ultra-long-term recordings for monitoring of epilepsies, the interpretation of results of isolated electroencephalographic (EEG) recordings covering only selected brain regions attracts considerable interest. In this context, the question arises of whether detected ictal EEG patterns correspond to clinically manifest seizures or rather to purely electrographic events, that is, subclinical events. METHODS: EEG patterns from 268 clinical seizures and 252 subclinical electrographic events from 50 patients undergoing video-EEG monitoring were analyzed. Features extracted included predominant frequency band, duration, association with rhythmic muscle artifacts, spatial extent, and propagation patterns. Classification using logistic regression was performed based on data from the whole dataset of 10-20 system EEG recordings and from a subset of two temporal electrode contacts. RESULTS: Correct separation of clinically manifest and purely electrographic events based on 10-20 system EEG recordings was possible in up to 83.8% of events, depending on the combination of features included. Correct classification based on two-channel recordings was only slightly inferior, achieving 78.6% accuracy; 74.4% and 74.8%, respectively, of events could be correctly classified when using duration alone with either electrode set, although classification accuracies were lower for some subgroups of seizures, particularly focal aware seizures and epileptic arousals. SIGNIFICANCE: A correct classification of subclinical versus clinical EEG events was possible in 74%-83% of events based on full EEG recordings, and in 74%-78% when considering only a subset of two electrodes, matching the channel number available from new implantable diagnostic devices. This is a promising outcome, suggesting that ultra-long-term low-channel EEG recordings may provide sufficient information for objective seizure diaries. Intraindividual optimization using high numbers of ictal events may further improve separation, provided that supervised learning with external validation is feasible.

Practical considerations in epilepsy neurostimulation.

Neuromodulation is a key therapeutic tool for clinicians managing patients with drug-resistant epilepsy. Multiple devices are available with long-term follow-up and real-world experience. The aim of this review is to give a practical summary of available neuromodulation techniques to guide the selection of modalities, focusing on patient selection for devices, common approaches and techniques for initiation of programming, and outpatient management issues. Vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (DBS-ANT), and responsive neurostimulation (RNS) are all supported by randomized controlled trials that show safety and a significant impact on seizure reduction, as well as a suggestion of reduction in the risk of sudden unexplained death in epilepsy (SUDEP). Significant seizure reductions are observed after 3 months for DBS, RNS, and VNS in randomized controlled trials, and efficacy appears to improve with time out to 7 to 10 years of follow-up for all modalities, albeit in uncontrolled follow-up or retrospective studies. A significant number of patients experience seizure-free intervals of 6 months or more with all three modalities. Number and location of epileptogenic foci are important factors affecting efficacy, and together with comorbidities such as severe mood or sleep disorders, may influence the choice of modality. Programming has evolved-DBS is typically initiated at lower current/voltage than used in the pivotal trial, whereas target charge density is lower with RNS, however generalizable optimal parameters are yet to be defined. Noninvasive brain stimulation is an emerging stimulation modality, although it is currently not used widely. In summary, clinical practice has evolved from those established in pivotal trials. Guidance is now available for clinicians who wish to expand their approach, and choice of neuromodulation technique may be tailored to individual patients based on their epilepsy characteristics, risk tolerance, and preferences.

Fully automated detection of focal cortical dysplasia: Comparison of MPRAGE and MP2RAGE sequences.

OBJECTIVE: The detection of focal cortical dysplasia (FCD) in magnetic resonance imaging is challenging. Voxel-based morphometric analysis and automated FCD detection using an artificial neural network (ANN) integrated into the Morphometric Analysis Program (MAP18) have been shown to facilitate FCD detection. This study aimed to evaluate whether the detection of FCD can be further improved by feeding this approach with magnetization prepared two rapid acquisition gradient echoes (MP2RAGE) instead of magnetization-prepared rapid acquisition gradient echo (MPRAGE) datasets. METHODS: MPRAGE and MP2RAGE datasets were acquired in a consecutive sample of 32 patients with FCD and postprocessed using MAP18. Visual analysis and, if available, histopathology served as the gold standard for assessing the sensitivity and specificity of FCD detection. Out-of-sample specificity was evaluated in a cohort of 32 healthy controls. RESULTS: The sensitivity and specificity of FCD detection were 82.4% and 62.5% for the MPRAGE and 97.1% and 34.4% for the MP2RAGE sequences, respectively. Median volumes of true-positive voxel clusters were .16 ml for the MPRAGE and .52 ml for the MP2RAGE sequences compared to .08- and .04-ml volumes of false-positive clusters. With regard to cluster volumes, FCD detection was substantially improved for the MP2RAGE data when the estimated optimal threshold of .23 ml was applied (sensitivity = 72.9%, specificity = 83.0%). In contrast, the estimated optimal threshold of .37 ml for the MPRAGE data did not improve FCD lesion detection (sensitivity = 42.9%, specificity = 79.5%). SIGNIFICANCE: In this study, the sensitivity of FCD detection by morphometric analysis and an ANN integrated into MAP18 was higher for MP2RAGE than for MPRAGE sequences. Additional usage of cluster volume information helped to discriminate between true- and false-positive MP2RAGE results.

Diagnostic yield and limitations of in-hospital documentation in patients with epilepsy.

OBJECTIVE: To determine the diagnostic yield of in-hospital video-electroencephalography (EEG) monitoring to document seizures in patients with epilepsy. METHODS: Retrospective analysis of electronic seizure documentation at the University Hospital Freiburg (UKF) and at King's College London (KCL). Statistical assessment of the role of the duration of monitoring, and subanalyses on presurgical patient groups and patients undergoing reduction of antiseizure medication. RESULTS: Of more than 4800 patients with epilepsy undergoing in-hospital recordings at the two institutions since 2005, seizures with documented for 43% (KCL) and 73% (UKF).. Duration of monitoring was highly significantly associated with seizure recordings (p < .0001), and presurgical patients as well as patients with drug reduction had a significantly higher diagnostic yield (p < .0001). Recordings with a duration of >5 days lead to additional new seizure documentation in only less than 10% of patients. SIGNIFICANCE: There is a need for the development of new ambulatory monitoring strategies to document seizures for diagnostic and monitoring purposes for a relevant subgroup of patients with epilepsy in whom in-hospital monitoring fails to document seizures.

Detection of interictal epileptiform discharges in an extended scalp EEG array and high-density EEG-A prospective multicenter study.

OBJECTIVES: High counts of averaged interictal epileptiform discharges (IEDs) are key components of accurate interictal electric source imaging (ESI) in patients with focal epilepsy. Automated detections may be time-efficient, but they need to identify the correct IED types. Thus we compared semiautomated and automated detection of IED types in long-term video-EEG (electroencephalography) monitoring (LTM) using an extended scalp EEG array and short-term high-density EEG (hdEEG) with visual detection of IED types and the seizure-onset zone (SOZ). METHODS: We prospectively recruited consecutive patients from four epilepsy centers who underwent both LTM with 40-electrode scalp EEG and short-term hdEEG with 256 electrodes. Only patients with a single circumscribed SOZ in LTM were included. In LTM and hdEEG, IED types were identified visually, semiautomatically and automatically. Concordances of semiautomated and automated detections in LTM and hdEEG, as well as visual detections in hdEEG, were compared against visually detected IED types and the SOZ in LTM. RESULTS: Fifty-two of 62 patients with LTM and hdEEG were included. The most frequent IED types per patient, detected semiautomatically and automatically in LTM and visually in hdEEG, were significantly concordant with the most frequently visually identified IED type in LTM and the SOZ. Semiautomated and automated detections of IED types in hdEEG were significantly concordant with visually identified IED types in LTM, only when IED types with more than 50 detected single IEDs were selected. The threshold of 50 detected IED in hdEEG was reached in half of the patients. For all IED types per patient, agreement between visual and semiautomated detections in LTM was high. SIGNIFICANCE: Semiautomated and automated detections of IED types in LTM show significant agreement with visually detected IED types and the SOZ. In short-term hdEEG, semiautomated detections of IED types are concordant with visually detected IED types and the SOZ in LTM if high IED counts were detected.