Epileptogenic Zone In Patients Research Articles

Effects of the spatial resolution of the Virtual Epileptic Patient on the identification of epileptogenic networks

Abstract Digital twins play an increasing role in clinical decision making. This study evaluates a digital brain twin approach in presurgical evaluation, the Virtual Epileptic Patient (VEP), which estimates the epileptogenic zone in patients with drug-resistant epilepsy. We built the personalized digital brain twins of 14 patients and a series of synthetic dataset by considering different spatial configurations of the epileptogenic and/or propagation zone networks (EZN and PZN, respectively). Brain source signals were simulated with a high spatial resolution neural field model (NFM) composed of 81942 nodes, embedding both long-range (between brain regions) and short-range (within brain regions) coupling. Brain signals were then projected to stereotactic electroencephalographic (SEEG) contacts with an accurate forward solution. An inversion procedure based on a low spatial resolution neural mass model (NMM) composed of 162 nodes was applied to estimate the excitability of each region in each simulation. The ensuing estimated EZN/PZN was compared to the simulated ground truth by means of classification metrics. Overall, we observed correct but degraded performance when using an NMM to estimate the EZN from data simulated with an NFM, which was significant for the simplest spatial configurations. We quantified the reduced performance and demonstrated that the oversimplification of the forward problem is its principal cause. We showed that the absence of local coupling in the NMM affects the inversion process by an overestimation of the excitability, representing a significant clinical impact when using this procedure in the context of presurgical planning. In conclusion, this study highlighted the importance to shift from an NMM towards a full NFM modeling approach for the estimation of EZN, with a particularly relevant need when considering the most complex clinical cases.

Interictal EEG source connectivity to localize the epileptogenic zone in patients with drug-resistant epilepsy: A machine learning approach.

To deconstruct the epileptogenic networks of patients with drug-resistant epilepsy (DRE) using source functional connectivity (FC) analysis; unveil the FC biomarkers of the epileptogenic zone (EZ); and develop machine learning (ML) models to estimate the EZ using brief interictal electroencephalography (EEG) data. We analyzed scalp EEG from 50 patients with DRE who had surgery. We reconstructed the activity (electrical source imaging [ESI]) of virtual sensors (VSs) across the whole cortex and computed FC separately for epileptiform and non-epileptiform EEG epochs (with or without spikes). In patients with good outcome (Engel 1a), four cortical regions were defined: EZ (resection) and three non-epileptogenic zones (NEZs) in the same and opposite hemispheres. Region-specific FC features in six frequency bands and three spatial ranges (long, short, inner) were compared between regions (Wilcoxon sign-rank). We developed ML classifiers to identify the VSs in the EZ using VS-specific FC features. Cross-validation was performed using good outcome data. Performance was compared with poor outcomes and interictal spike localization. FC differed between EZ and NEZs (p < .05) during non-epileptiform and epileptiform epochs, showing higher FC in the EZ than its homotopic contralateral NEZ. During epileptiform epochs, the NEZ in the epileptogenic hemisphere showed higher FC than its contralateral NEZ. In good outcome patients, the ML classifiers reached 75% accuracy to the resection (91% sensitivity; 74% specificity; distance from EZ: 38 mm) using epileptiform epochs (gamma and beta frequency bands) and 62% accuracy using broadband non-epileptiform epochs, both outperforming spike localization (accuracy = 47%; p < .05; distance from EZ: 57 mm). Lower performance was seen in poor outcomes. We present an FC approach to extract EZ biomarkers from brief EEG data. Increased FC in various frequencies characterized the EZ during epileptiform and non-epileptiform epochs. FC-based ML models identified the resection better in good than poor outcome patients, demonstrating their potential for presurgical use in pediatric DRE.

NLP-based tools for localization of the epileptogenic zone in patients with drug-resistant focal epilepsy

Epilepsy surgery is an option for people with focal onset drug-resistant (DR) seizures but a delayed or incorrect diagnosis of epileptogenic zone (EZ) location limits its efficacy. Seizure semiological manifestations and their chronological appearance contain valuable information on the putative EZ location but their interpretation relies on extensive experience. The aim of our work is to support the localization of EZ in DR patients automatically analyzing the semiological description of seizures contained in video-EEG reports. Our sample is composed of 536 descriptions of seizures extracted from Electronic Medical Records of 122 patients. We devised numerical representations of anamnestic records and seizures descriptions, exploiting Natural Language Processing (NLP) techniques, and used them to feed Machine Learning (ML) models. We performed three binary classification tasks: localizing the EZ in the right or left hemisphere, temporal or extra-temporal, and frontal or posterior regions. Our computational pipeline reached performances above 70% in all tasks. These results show that NLP-based numerical representation combined with ML-based classification models may help in localizing the origin of the seizures relying only on seizures-related semiological text data alone. Accurate early recognition of EZ could enable a more appropriate patient management and a faster access to epilepsy surgery to potential candidates.

Simultaneous high-resolution whole-brain MR spectroscopy and [18F]FDG PET for temporal lobe epilepsy.

Precise lateralizing the epileptogenic zone in patients with drug-resistant mesial temporal lobe epilepsy (mTLE) remains challenging, particularly when routine MRI scans are inconclusive (MRI-negative). This study aimed to investigate the synergy of fast, high-resolution, whole-brain MRSI in conjunction with simultaneous [18F]FDG PET for the lateralization of mTLE. Forty-eight drug-resistant mTLE patients (M/F 31/17, age 12-58) underwent MRSI and [18F]FDG PET on a hybrid PET/MR scanner. Lateralization of mTLE was evaluated by visual inspection and statistical classifiers of metabolic mappings against routine MRI. Additionally, this study explored how disease status influences the associations between altered N-acetyl aspartate (NAA) and FDG uptake using hierarchical moderated multiple regression. The high-resolution whole-brain MRSI data offers metabolite maps at comparable resolution to [18F]FDG PET. Visual examinations of combined MRSI and [18F]FDG PET showed an mTLE lateralization accuracy rate of 91.7% in a 48-patient cohort, surpassing routine MRI (52.1%). Notably, out of 23 MRI-negative mTLE, combined MRSI and [18F]FDG PET helped detect 19 cases. Logistical regression models combining hippocampal NAA level and FDG uptake improved lateralization performance (AUC=0.856), while further incorporating extrahippocampal regions such as amygdala, thalamus, and superior temporal gyrus increased the AUC to 0.939. Concurrent MRSI/PET revealed a moderating influence of disease duration and hippocampal atrophy on the association between hippocampal NAA and glucose uptake, providing significant new insights into the disease's trajectory. This paper reports the first metabolic imaging study using simultaneous high-resolution MRSI and [18F]FDG PET, which help visualize MRI-unidentifiable lesions and may thus advance diagnostic tools and management strategies for drug-resistant mTLE.

Relative entropy is an easy-to-use invasive electroencephalographic biomarker of the epileptogenic zone.

High-frequency oscillations are considered among the most promising interictal biomarkers of the epileptogenic zone in patients suffering from pharmacoresistant focal epilepsy. However, there is no clear definition of pathological high-frequency oscillations, and the existing detectors vary in methodology, performance, and computational costs. This study proposes relative entropy as an easy-to-use novel interictal biomarker of the epileptic tissue. We evaluated relative entropy and high-frequency oscillation biomarkers on intracranial electroencephalographic data from 39 patients with seizure-free postoperative outcome (Engel Ia) from three institutions. We tested their capability to localize the epileptogenic zone, defined as resected contacts located in the seizure onset zone. The performance was compared using areas under the receiver operating curves (AUROCs) and precision-recall curves. Then we tested whether a universal threshold can be used to delineate the epileptogenic zone across patients from different institutions. Relative entropy in the ripple band (80-250 Hz) achieved an average AUROC of .85. The normalized high-frequency oscillation rate in the ripple band showed an identical AUROC of .85. In contrast to high-frequency oscillations, relative entropy did not require any patient-level normalization and was easy and fast to calculate due to its clear and straightforward definition. One threshold could be set across different patients and institutions, because relative entropy is independent of signal amplitude and sampling frequency. Although both relative entropy and high-frequency oscillations have a similar performance, relative entropy has significant advantages such as straightforward definition, computational speed, and universal interpatient threshold, making it an easy-to-use promising biomarker of the epileptogenic zone.

A Robust eLORETA Technique for Localization of Brain Sources in the Presence of Forward Model Uncertainties.

In this paper, we present a robust version of the well-known exact low-resolution electromagnetic tomography (eLORETA) technique, named ReLORETA, to localize brain sources in the presence of different forward model uncertainties. We first assume that the true lead field matrix is a transformation of the existing lead field matrix distorted by uncertainties and propose an iterative approach to estimate this transformation accurately. Major sources of the forward model uncertainties, including differences in geometry, conductivity, and source space resolution between the real and simulated head models, and misaligned electrode positions, are then simulated to test the proposed method. ReLORETA and eLORETA are applied to simulated focal sources in different regions of the brain and the presence of various noise levels as well as real data from a patient with focal epilepsy. The results show that ReLORETA is considerably more robust and accurate than eLORETA in all cases. Having successfully dealt with the forward model uncertainties, ReLORETA proved to be a promising method for real-world clinical applications. eLORETA is one of the localization techniques that could be used to study brain activity for medical applications such as determining the epileptogenic zone in patients with medically refractory epilepsy. However, the major limitation of eLORETA is sensitivity to the uncertainties in the forward model. Since this problem can substantially undermine its performance in real-world applications where the exact lead field matrix is unknown, developing a more robust method capable of dealing with these uncertainties is of significant interest.

Novel noninvasive identification of patient-specific epileptic networks in focal epilepsies: Linking single-photon emission computed tomography perfusion during seizures with resting-state magnetoencephalography dynamics.

Single-photon emission computed tomography (SPECT) during seizures and magnetoencephalography (MEG) during the interictal state are noninvasive modalities employed in the localization of the epileptogenic zone in patients with drug-resistant focal epilepsy (DRFE). The present study aims to investigate whether there exists a preferentially high MEG functional connectivity (FC) among those regions of the brain that exhibit hyperperfusion or hypoperfusion during seizures. We studied MEG and SPECT data in 30 consecutive DRFE patients who had resective epilepsy surgery. We parcellated each ictal perfusion map into 200 regions of interest (ROIs) and generated ROI time series using source modeling of MEG data. FC between ROIs was quantified using coherence and phase-locking value. We defined a generalized linear model to relate the connectivity of each ROI, ictal perfusion z score, and distance between ROIs. We compared the coefficients relating perfusion z score to FC of each ROI and estimated the connectivity within and between resected and unresected ROIs. We found that perfusion z scores were strongly correlated with the FC of hyper-, and separately, hypoperfused ROIs across patients. High interictal connectivity was observed between hyperperfused brain regions inside and outside the resected area. High connectivity was also observed between regions of ictal hypoperfusion. Importantly, the ictally hypoperfused regions had a low interictal connectivity to regions that became hyperperfused during seizures. We conclude that brain regions exhibiting hyperperfusion during seizures highlight a preferentially connected interictal network, whereas regions of ictal hypoperfusion highlight a separate, discrete and interconnected, interictal network.

Volume of hippocampal activation as a determining factor for the lateralisation of the epileptogenic zone in patients with drug-resistant mesial temporal lobe epilepsy

IntroductionApproximately 30% of patients with mesial temporal lobe epilepsy (MTLE) will develop drug resistance, which requires early surgical treatment. The success of the surgical procedure largely depends on the correct lateralisation of the epileptogenic zone, which can only be determined in 70% of patients with such conventional diagnostic tools as video electroencephalography and volumetric structural magnetic resonance imaging. We evaluated the performance of a memory functional magnetic resonance imaging (fMRI) paradigm in lateralising the epileptogenic zone in patients with drug-resistant MTLE. MethodsWe included 18 patients with MTLE attended at the Instituto Neurológico Colombiano in Medellin (Colombia) between 2018 and 2019. The volume of functional activation in both temporal lobes was determined with a memory fMRI paradigm. A concordance analysis was performed to compare the performance of fMRI against that of conventional tests. ResultsIn patients with left MTLE, lower total activation was found in the hemisphere ipsilateral to the epileptogenic zone as compared to the contralateral hemisphere (121.15 ± 16.48 voxels vs 170.23 ± 17.8 voxels [P < .001]), showing substantial concordance with conventional tests. Patients with right MTLE displayed lower hippocampal activation ipsilateral to the epileptogenic zone (18.5 ± 3.38 voxels vs 27.8 ± 3.77 voxels in the contralateral hippocampus [P = .048]), showing moderate concordance with conventional tests. ConclusionsThese findings suggest that lower functional activation as determined by a memory fMRI paradigm has a high level of concordance with conventional tests for lateralising the epileptogenic zone in patients with drug-resistant MTLE.

Volumen de activación hipocampal como factor determinante para la lateralización del foco epileptogénico en pacientes con epilepsia farmacorresistente del lóbulo temporal mesial

IntroductionApproximately 30% of patients with mesial temporal lobe epilepsy (MTLE) will develop drug resistance, which necessitates early surgical treatment. The success of the surgical procedure largely depends on the correct lateralisation of the epileptogenic zone, which can only be determined in 70% of patients with such conventional diagnostic tools as video electroencephalography and volumetric structural magnetic resonance imaging. We evaluated the performance of a memory functional magnetic resonance imaging (fMRI) paradigm in lateralising the epileptogenic zone in patients with drug-resistant MTLE. MethodsWe included 18 patients with MTLE attended at the Instituto Neurológico Colombiano in Medellin (Colombia) between 2018 and 2019. The volume of functional activation in both temporal lobes was determined with a memory fMRI paradigm. A concordance analysis was performed to compare the performance of fMRI against that of conventional tests. ResultsIn patients with left MTLE, lower total activation was found in the hemisphere ipsilateral to the epileptogenic zone as compared to the contralateral hemisphere (121.15±16.48 voxels vs 170.23±17.8 voxels [P<.001]), showing substantial concordance with conventional tests. Patients with right MTLE displayed lower hippocampal activation ipsilateral to the epileptogenic zone (18.5±3.38 voxels vs 27.8±3.77 voxels in the contralateral hippocampus [P=.048]), showing moderate concordance with conventional tests. ConclusionsThese findings suggest that lower functional activation as determined by a memory fMRI paradigm has a high level of concordance with conventional tests for lateralising the epileptogenic zone in patients with drug-resistant MTLE.

Stereotactic Electroencephalography in Patients with Drug-resistant Epilepsy

Stereotactic electroencephalography (SEEG) is an important method for invasive presurgical exploration of candidates for epilepsy surgery by means of stereotactic implantation of intracerebral electrodes without craniotomy. Implantations of intracerebral electrodes through craniotomy in drug-resistant epileptic patients have been performed in Bulgaria in the 1980s, but no further development of epilepsy surgery followed. The aim of our study is to present the first Bulgarian series of patients with drug-resistant epilepsy explored by SEEG. Our study included 53 patients with drug-resistant epilepsy explored by SEEG. Stereotactic Leksell frame, stereotactic software for avascular trajectory planning and depth electrodes with diameter of 0.8 mm and 8–18 contacts were used in all patients. Subsequently, long-term video-SEEG monitoring of various duration was performed and registered interictal and ictal EEG activity in order to evaluate the putative epileptogenic zone. Fifty-three patients were explored by 62 SEEGs because one patient underwent three SEEG procedures and seven patients – two SEEG procedures. We implanted 753 electrodes in these 62 SEEGs (mean: 12 electrodes per exploration; range: 5–20 electrodes). The mean age in our cohort was 23.6 years (4–60 years). The main indication for SEEG was MRI-negative epilepsy (20 patients). Focal cortical dysplasia was found in 17 cases, and hippocampal sclerosis in 8 cases. Surgical intervention was done in 48 patients (91%). Surgical resection of the epileptogenic zone (EZ) as defined by the SEEG was performed in 27 patients; radiofrequency stereotactic thermocoagulation (RFTC) on selected electrode contacts was applied in seven patients, and both procedures (i.e. RFTC followed by resective surgery) were performed on 14 patients. Full seizure control (Engel class I) was achieved in 28 patients (58.3%) and significant improvement – in 17 patients (35.4%). Three patients (6.2%) had no effect from surgery. No complications were observed in our series of 62 SEEGs. SEEG is a major tool for the determination of the EZ in patients with drug-resistant epilepsy who are candidates for epilepsy surgery, including MRI-negative cases or such without congruent data from the clinical, neurophysiological and neuroimaging perspectives. SEEG is a low-risk invasive diagnostic and even a therapeutic method when performed by experienced epilepsy surgery team.

Epileptic discharges initiate from brain areas with elevated accumulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors.

Presurgical identification of the epileptogenic zone is a critical determinant of seizure control following surgical resection in epilepsy. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor is a major component of neurotransmission. Although elevated α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor levels are observed in surgically resected brain areas of patients with epilepsy, it remains unclear whether increased α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-mediated currents initiate epileptic discharges. We have recently developed the first PET tracer for α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, [11C]K-2, to visualize and quantify the density of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors in living human brains. Here, we detected elevated [11C]K-2 uptake in the epileptogenic temporal lobe of patients with mesial temporal lobe epilepsy. Brain areas with high [11C]K-2 uptake are closely colocalized with the location of equivalent current dipoles estimated by magnetoencephalography or with seizure onset zones detected by intracranial electroencephalogram. These results suggest that epileptic discharges initiate from brain areas with increased α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, providing a biological basis for epileptic discharges and an additional non-invasive option to identify the epileptogenic zone in patients with mesial temporal lobe epilepsy.

Electrode placement for SEEG: Combining stereotactic technique with latest generation planning software for intraoperative visualization and postoperative evaluation of accuracy and accuracy predictors

BackgroundIntracranial recordings with stereoelectroencephalography (SEEG) aims at defining the epileptogenic zone in patients with pharmacoresistant epilepsy. Currently used techniques for depth electrode implantation include stereotactic frame-based and navigated frameless applications, both either conventional or robot-assisted. Safety and diagnostic effectiveness depend on accuracy of implantation. ObjectiveTo evaluate the planning experience, accuracy of stereotactic electrode placement as well as accuracy predictors with the use of latest generation planning software. MethodsRetrospective study of 15 consecutive patients who received depth electrodes using the Leksell stereotactic frame, after planning with Elements (Brainlab, Munich, Germany). For each electrode, we calculated the entry point error (EPE) as lateral deviation and target point error (TPE) both as lateral deviation and distance to tip. Multivariate regression analysis and computation of 95% confidence intervals using the bootstrap method were applied for statistical analysis and evaluation of accuracy predictors. ResultsThe mean EPE, lateral deviation at TP and distance to tip at TP were 0.6 ±0.5 mm, 1.1 ±0.7 mm and 1.5 ±0.8 mm respectively. Order of implantation (1–6 vs. >6) is predictor for distance to tip at TP and length of electrode predictor for the lateral deviation at TP. Localization of electrode generally did not correlate to error, but insular electrodes were significantly less accurate than lobar ones. ConclusionCombination of frame-based stereotaxy with latest generation planning software may offer a better planning and implantation experience. Accuracy predictors should be analyzed and be considered for the improvement of accuracy and safety of SEEG implantation methods.

High density electric source imaging in childhood-onset epilepsy due to focal cortical dysplasia

ObjectiveThe goal of this study was to investigate the diagnostic utility of electric source imaging (ESI) in the presurgical evaluation of children with focal cortical dysplasia (FCD) and to compare it with other imaging techniques. MethodsTwenty patients with epilepsy onset before 18 years, surgically treated focal epilepsy with a minimal follow-up of 2 years, and histologically proven FCD were retrospectively selected. All patients underwent MRI, positron emission tomography (PET), and 16 patients also had ictal single-photon emission computed tomography (iSPECT). ESI, using EEG with 64 electrodes or more (HD-ESI), was performed in all 20 patients. We determined sensitivity, specificity and accuracy of ESI, and compared its yield to that of other imaging techniques. ResultsTwelve patients were seizure-free post-operatively (60%). Among all patients, highest localization accuracy (80%) was obtained with ESI, followed by PET and iSPECT (75%). When results from ESI and SPECT were concordant 100% of patients achieved Engel I outcome. If ESI and PET showed concordant localization, 90% of patients achieved postoperative seizure freedom. ConclusionsOur findings demonstrate that HD-ESI allows accurate localization of the epileptogenic zone in patients with FCD. SignificanceIn combination with other imaging modalities, ESI helps with planning a more accurate surgery and therefore, the chances of postoperative seizure control are higher. Since it is based on EEG recordings, it does not require sedation, which is particularly interesting in pediatric patients. ESI represents an important imaging tool in focal epilepsies due to cortical dysplasia, which might be difficult to detect on standard imaging.

Non-thermal Electroporation Ablation of Epileptogenic Zones Stops Seizures in Mice While Providing Reduced Vascular Damage and Accelerated Tissue Recovery.

In epilepsy, the most frequent surgical procedure is the resection of brain tissue in the temporal lobe, with seizure-free outcomes in approximately two-thirds of cases. However, consequences of surgery can vary strongly depending on the brain region targeted for removal, as surgical morbidity and collateral damage can lead to significant complications, particularly when bleeding and swelling are located near delicate functional cortical regions. Although focal thermal ablations are well-explored in epilepsy as a minimally invasive approach, hemorrhage and edema can be a consequence as the blood-brain barrier is still disrupted. Non-thermal irreversible electroporation (NTIRE), common in many other medical tissue ablations outside the brain, is a relatively unexplored method for the ablation of neural tissue, and has never been reported as a means for ablation of brain tissue in the context of epilepsy. Here, we present a detailed visualization of non-thermal ablation of neural tissue in mice and report that NTIRE successfully ablates epileptic foci in mice, resulting in seizure-freedom, while causing significantly less hemorrhage and edema compared to conventional thermal ablation. The NTIRE approach to ablation preserves the blood-brain barrier while pathological circuits in the same region are destroyed. Additionally, we see the reinnervation of fibers into ablated brain regions from neighboring areas as early as day 3 after ablation. Our evidence demonstrates that NTIRE could be utilized as a precise tool for the ablation of surgically challenging epileptogenic zones in patients where the risk of complications and hemorrhage is high, allowing not only reduced tissue damage but potentially accelerated recovery as vessels and extracellular matrix remain intact at the point of ablation.

Theoretical stereoelectroencephalography density on the brain convexity

IntroductionInvasive electroencephalography (EEG) remains the “gold standard” for diagnosing the epileptogenic zone in patients with drug-resistant epilepsy and discrepancies between seizure semiology, video-EEG and magnetic resonance imaging (MRI) findings. However, the possibilities of stereoelectroencephalography (SEEG) to explore the brain surface remain a matter of debate and subdural EEG (SDEEG) is still preferred in some centers for cases when the supposed epileptogenic zone is on the brain convexity. The aim of our study was to evaluate the theoretical safe SEEG coverage on the brain convexity and to compare the theoretical SEEG cortical density with the usual SDEEG density. Materials and methodsOur material included 10 hemispheres in 5 patients, who had been already investigated with SEEG for drug-resistant epilepsy. We translated our previously described technique in a theoretical model in an attempt to calculate the maximal number of avascular windows for each cerebral hemisphere. The distance between every entry point and the other entry points for each hemisphere was calculated using a mathematical formula. Subsequently, the theoretical SEEG coverage on the brain convexity was described using the maximal, minimal and average distances between each entry point and the closest 4 neighboring points. This type of measurement allows a direct comparison between SEEG and SDEEG in their ability to explore the brain convexity. ResultsTen hemispheres had 1328 safe entry points with a safety margin of 2.5 mm and a minimal distance of 2.5 mm between 2 entry points (average number of entry points: 132.8 (SD ± 5). The number of entry points in the explored 10 hemispheres varied from 104 to 156. The average distance between each entry point and its 4 neighbors was 11.47 mm. The maximal distance between two entry points in these 10 hemispheres was ranging from 20.28 to 27.23 mm (average: 24.67 mm). The closest entry points for the explored hemispheres were at an average distance of 4.67 mm (range: 2.82 – 5.96 mm). The average convexity surface was 223.68 cm2 (range: 204.63–238.77 cm2). The safe electrode density without electrode collision on the cortical surface was ranging from 0.46 to 0.69 electrodes per cm2 (average: 0.59 electrodes per cm2) (SD ± 0.023). ConclusionThe theoretical SEEG cortical density is comparable with the usual SDEEG density. These findings, combined with the better safety profile of SEEG and the possibilities to explore deep cortical structures, explain the progressive shift from SDEEG to SEEG during the last years.

Future of Neurology & Technology: Stereoelectroencephalography in Presurgical Epilepsy Evaluation.

Stereoelectroencephalography (SEEG) is not only a sophisticated and highly technological investigation but a new and better way to conceptualize the spatial and temporal dynamics of epileptic activity. The first intracranial investigations with SEEG were performed in France in the mid-twentieth century; however, its use in North America is much more recent. Given its significantly lower risk of complications and its ability to sample both superficial and deep structures and both hemispheres simultaneously, SEEG has become the preferred method to conduct intracranial EEG monitoring in most comprehensive epilepsy centers in North America. SEEG is an invasive neurophysiologic methodology used for advanced presurgical workup in the 20% of drug-resistant patients with more complex focal epilepsy in whom noninvasive investigations do not allow to decide on surgical candidacy. SEEG uses stereotactically implanted depth electrodes to map the origin and propagation of epileptic seizures by creating a 3-dimensional representation of the abnormal electrical activity in the brain. SEEG analysis takes into account the background, interictal, and ictal activity, as well as the results of cortical electrical stimulation procedures, to reliably delineate the epileptogenic network. By means of a clinical vignette, this article will walk general neurologists, but especially neurology trainees through the immense potential of this methodology. In summary, SEEG enables to accurately identify the epileptogenic zone in patients with drug-resistant focal epilepsy who otherwise would be not amenable to surgical treatment. In this patient population, SEEG is the best way to improve seizure control and achieve seizure freedom.

Transcriptomic profiling of high- and low-spiking regions reveals novel epileptogenic mechanisms in focal cortical dysplasia type II patients

Focal cortical dysplasia (FCD) is a malformation of the cerebral cortex with poorly-defined epileptogenic zones (EZs), and poor surgical outcome in FCD is associated with inaccurate localization of the EZ. Hence, identifying novel epileptogenic markers to aid in the localization of EZ in patients with FCD is very much needed. High-throughput gene expression studies of FCD samples have the potential to uncover molecular changes underlying the epileptogenic process and identify novel markers for delineating the EZ. For this purpose, we, for the first time performed RNA sequencing of surgically resected paired tissue samples obtained from electrocorticographically graded high (MAX) and low spiking (MIN) regions of FCD type II patients and autopsy controls. We identified significant changes in the MAX samples of the FCD type II patients when compared to non-epileptic controls, but not in the case of MIN samples. We found significant enrichment for myelination, oligodendrocyte development and differentiation, neuronal and axon ensheathment, phospholipid metabolism, cell adhesion and cytoskeleton, semaphorins, and ion channels in the MAX region. Through the integration of both MAX vs non-epileptic control and MAX vs MIN RNA sequencing (RNA Seq) data, PLP1, PLLP, UGT8, KLK6, SOX10, MOG, MAG, MOBP, ANLN, ERMN, SPP1, CLDN11, TNC, GPR37, SLC12A2, ABCA2, ABCA8, ASPA, P2RX7, CERS2, MAP4K4, TF, CTGF, Semaphorins, Opalin, FGFs, CALB2, and TNC were identified as potential key regulators of multiple pathways related to FCD type II pathology. We have identified novel epileptogenic marker elements that may contribute to epileptogenicity in patients with FCD and could be possible markers for the localization of EZ.

Stereoelectroencephalography in the preoperative assessment of patients with refractory focal epilepsy: experience at an epilepsy centre

ObjectiveStereoelectroencephalography (SEEG) is a technique for preoperative evaluation of patients with difficult-to-localise refractory focal epilepsy (DLRFE), enabling the study of deep cortical structures. The procedure, which is increasingly used in international epilepsy centres, has not been fully developed in Spain. We describe our experience with SEEG in the preoperative evaluation of DLRFE. Material and methodsIn the last 8 years, 71 patients with DLRFE were evaluated with SEEG in our epilepsy centre. We prospectively analysed our results in terms of localisation of the epileptogenic zone (EZ), surgical outcomes, and complications associated with the procedure. ResultsThe median age of the sample was 30 years (range, 4-59 years); 27 patients (38%) were women. Forty-five patients (63.4%) showed no abnormalities on brain MR images. A total of 627 electrodes were implanted (median, 9 electrodes per patient; range, 1-17), and 50% of implantations were multilobar. The EZ was identified in 64 patients (90.1%), and was extratemporal or temporal plus in 66% of the cases. Follow-up was over one year in 55 of the 61 patients undergoing surgery: in the last year of follow-up, 58.2% were seizure-free (Engel Epilepsy Surgery Outcome Scale class I) and 76.4% had good outcomes (Engel I-II). Three patients (4.2%) presented brain haemorrhages. ConclusionSEEG enables localisation of the EZ in patients in whom this was previously impossible, offering better surgical outcomes than other invasive techniques while having a relatively low rate of complications.

Performance of PET imaging for the localization of epileptogenic zone in patients with epilepsy: a meta-analysis.

The aim of this meta-analysis was to estimate the clinical use value of 11C-FMZ and 18F-FDG in PET for the localization of epileptogenic zone and to provide evidence for practitioners' clinical decision-making. We searched PubMed and Embase in a time frame from inception to May 31, 2020. Studies utilizing FMZ or FDG-PET or FDG-PET/MRI used in patients with epilepsy, with EEG or surgical outcomes as the gold standard and corresponding outcomes such as concordance rates of PET or PET/MRI scan compared with reference standard, absolute numbers of participants with true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) results in FDG or FMZ PET. Pooled concordance rates, overall sensitivity, and specificity of 11C-FMZ-PET and 18F-FDG-PET were calculated. In total, 44 studies met the inclusion criteria. The pooled concordance rates of FDG-PET, FMZ-PET, and FDG-PET/MRI coregistration compared with reference standard were 0.67 (95% CI: 0.60-0.73), 0.75 (95% CI: 0.57-0.93), and 0.93 (95% CI: 0.89-0.97), respectively. The concordance rate of 18F-FDG-PET in patients with temporal lobe epilepsy (TLE) was 0.79 (0.63; 0.92). The overall sensitivity and specificity of 18F-FDG-PET were 0.66 (95% CI: 0.58-0.73) and 0.71 (95% CI: 0.63-0.78), respectively. 11C-FMZ-PET displayed an overall sensitivity of 0.62 (95% CI: 0.49-0.73) and specificity of 0.73 (95% CI: 0.59-0.84). Both 11C-FMZ PET and 18F-FDG PET are the choice of modalities for the localization of epileptogenic zone, especially when coregistered with MRI. • 11C-FMZ-PET may be more helpful than 18F-FDG-PET in the localization of epilepsy foci. • Coregistration of FDG-PET and MRI is recommended in the localization of epileptogenic zone.

Seizure Freedom After Epilepsy Surgery and Higher Baseline Cognition May Be Associated With a Negatively Correlated Epilepsy Network in Temporal Lobe Epilepsy.

Background: Brain regions positively correlated with the epileptogenic zone in patients with temporal lobe epilepsy vary in spread across the brain and in the degree of correlation to the temporal lobes, thalamus, and limbic structures, and these parameters have been associated with pre-operative cognitive impairment and seizure freedom after epilepsy surgery, but negatively correlated regions have not been as well studied. We hypothesize that connectivity within a negatively correlated epilepsy network may predict which patients with temporal lobe epilepsy will respond best to surgery.Methods: Scalp EEG and resting state functional MRI (rsfMRI) were collected from 19 patients with temporal lobe epilepsy and used to estimate the irritative zone. Using patients’ rsfMRI, the negatively correlated epilepsy network was mapped by determining all the brain voxels that were negatively correlated with the voxels in the epileptogenic zone and the spread and average connectivity within the network was determined.Results: Pre-operatively, connectivity within the negatively correlated network was inversely related to the spread (diffuseness) of that network and positively associated with higher baseline verbal and logical memory. Pre-operative connectivity within the negatively correlated network was also significantly higher in patients who would go on to be seizure free.Conclusion: Patients with higher connectivity within brain regions negatively correlated with the epilepsy network had higher baseline memory function, narrower network spread, and were more likely to be seizure free after surgery.