Seizure Onset Zone Research Articles

Characterizing Depth Electrode Coverage in Stereoelectroencephalography on Seizure Onset Zone Localization and Seizure Outcomes

Introduction: The number of intracranial depth electrodes implanted in stereoelectroencephalography (SEEG) investigations is primarily driven by the preimplantation hypothesis about SOZ location. Targeting is not standardized and highly variable between centers. Whether some of these electrodes may prove redundant, or target low-yield areas too frequently, is uncertain. Methods: We identified a retrospective multi-institutional cohort implanted with depth electrodes for iEEG monitoring between 2003 and 2022. We collected preoperative clinical features and iEEG investigation parameters, including the number of depth electrodes and contacts implanted. We built a propensity-matched cohort with respect to these covariates and evaluated outcomes, which included (1) the likelihood of SOZ localization, (2) complications, and (3) seizure-free outcomes as a function of electrode contact coverage. In addition, we aimed to identify brain regions commonly explored in conjunction with each other and identify the likelihood of a region being implicated in initial electroclinical seizure onset. Results: One hundred and sixty-seven patients were followed for a median of 3.8 (range 2, 18) years after SEEG. Propensity-matched cohorts demonstrated that a higher number of implanted contacts were associated with a greater likelihood of proceeding to treatment, but were not associated with SOZ localization, seizure freedom (Engel I), favorable seizure outcomes (Engel I/II), or complications, per Bayes factor analysis. Lateral orbitofrontal, supramarginal, posterior cingulate, inferior parietal, and inferior temporal areas were least likely to be implicated in initial electrographic onset, whereas hippocampus, caudal middle frontal, pericalcarine, and parahippocampal areas were most likely when controlling for electrode coverage. Conclusions: SEEG effectively localizes the SOZ in both lesional and non-lesional etiologies, and clinicians are generally optimizing the electrode coverage for hypothetical SOZ localization, leading to further therapeutic surgeries that may confer seizure freedom. Nevertheless, several areas are possibly being explored despite low likelihood (<2.5%) of participation within the SOZ.

Simulated resections and responsive neurostimulator placement can optimize postoperative seizure outcomes when guided by fast ripple networks.

In medication-resistant epilepsy, the goal of epilepsy surgery is to make a patient seizure free with a resection/ablation that is as small as possible to minimize morbidity. The standard of care in planning the margins of epilepsy surgery involves electroclinical delineation of the seizure-onset zone and incorporation of neuroimaging findings from MRI, PET, single-photon emission CT and magnetoencephalography modalities. Resecting cortical tissue generating high-frequency oscillations has been investigated as a more efficacious alternative to targeting the seizure-onset zone. In this study, we used a support vector machine (SVM), with four distinct fast ripple (FR: 350-600 Hz on oscillations, 200-600 Hz on spikes) metrics as factors. These metrics included the FR resection ratio, a spatial FR network measure and two temporal FR network measures. The SVM was trained by the value of these four factors with respect to the actual resection boundaries and actual seizure-free labels of 18 patients with medically refractory focal epilepsy. Leave-one-out cross-validation of the trained SVM in this training set had an accuracy of 0.78. We next used a simulated iterative virtual resection targeting the FR sites that were of highest rate and showed most temporal autonomy. The trained SVM utilized the four virtual FR metrics to predict virtual seizure freedom. In all but one of the nine patients who were seizure free after surgery, we found that the virtual resections sufficient for virtual seizure freedom were larger in volume (P < 0.05). In nine patients who were not seizure free, a larger virtual resection made five virtually seizure free. We also examined 10 medically refractory focal epilepsy patients implanted with the responsive neurostimulator system and virtually targeted the responsive neurostimulator system stimulation contacts proximal to sites generating FR at highest rates to determine if the simulated value of the stimulated seizure-onset zone and stimulated FR metrics would trend towards those patients with a better seizure outcome. Our results suggest the following: (i) FR measures can accurately predict whether a resection, defined by the standard of care, will result in seizure freedom; (ii) utilizing FR alone for planning an efficacious surgery can be associated with larger resections; (iii) when FR metrics predict the standard-of-care resection will fail, amending the boundaries of the planned resection with certain FR-generating sites may improve outcome and (iv) more work is required to determine whether targeting responsive neurostimulator system stimulation contact proximal to FR generating sites will improve seizure outcome.

Exploration of epileptic networks in temporal lobe encephaloceles with stereotactic EEG: Electroclinical characteristics and surgical outcomes.

Temporal lobe encephaloceles (TLEN) have been implicated as a cause of temporal lobe epilepsy (TLE), the treatment which is primarily surgical; however, there is no clear consensus on the optimal surgical approach, because it is unclear whether TLE related to TLEN can be addressed by a restricted encephalocele resection or if a more extensive resection is required. The aim of the current article is to report the clinical and electrophysiological profile of patients with TLE secondary to TLEN who underwent stereotactic electroencephalography (SEEG) implantation to identify the epileptogenic network. A retrospective review was performed of patients with TLE related to TLEN who underwent SEEG implantation. Medical charts were reviewed for demographic data, the results of noninvasive and invasive investigations, and operative details. Surgical outcomes were based on Engel classification with at least 6 months follow-up. Nine patients were identified. The mean age at epilepsy onset was 28 years (range, 15-41 years), and 7/9 patients were female. Scalp EEG revealed interictal epileptiform activity most often maximum in the frontotemporal and/or temporal regions. A discrete TLEN was often not identified on initial imaging, but was identified during re-review or at the time of surgery. Seizure onset zones during SEEG were localized to the mesial temporal structures, the temporal pole, or both. One patient became seizure-free following SEEG and another refused further surgery. Of the 7 patients who underwent epilepsy surgery, 5/7 underwent an anterior temporal lobectomy-surgical outcomes were favorable, with 5/7 achieving Engel I outcomes. Invasive SEEG monitoring demonstrated ictal onsets may not be restricted to the TLEN, and often the temporal pole and mesial structures are involved at seizure onset. Ictal propagation patterns vary significantly, which may be related to the underlying pathology and explain the variability in semiology. These findings may inform surgical treatment options. Temporal lobe encephaloceles can cause intractable epilepsy, although their presence may be missed on routine imaging. The management of encephaloceles is primarily surgical; however, the optimal surgical approach can be unclear. Invasive monitoring with SEEG may help characterize the epileptogenic network and result in more optimal surgical outcomes.

Explaining slow seizure propagation with white matter tractography.

Epileptic seizures recorded with stereo-EEG can take a fraction of a second or several seconds to propagate from one region to another. What explains such propagation patterns? We combine tractography and stereo-EEG to determine the relationship between seizure propagation and the white matter architecture and to describe seizure propagation mechanisms. Patient-specific spatiotemporal seizure propagation maps were combined with tractography from diffusion imaging of matched subjects from the Human Connectome Project. The onset of seizure activity was marked on a channel-by-channel basis by two board-certified neurologists for all channels involved in the seizure. We measured the tract connectivity (number of tracts) between regions-of-interest pairs among the seizure onset zone, regions of seizure spread and non-involved regions. We also investigated how tract-connected the seizure onset zone is to regions of early seizure spread compared with regions of late spread. Comparisons were made after correcting for differences in distance. Sixty-nine seizures were marked across 26 patients with drug-resistant epilepsy; 11 were seizure free after surgery (Engel IA) and 15 were not (Engel IB-Engel IV). The seizure onset zone was more tract-connected to regions of seizure spread than to non-involved regions (P < 0.0001); however, regions of seizure spread were not differentially tract-connected to other regions of seizure spread compared with non-involved regions. In seizure-free patients only, regions of seizure spread were more tract-connected to the seizure onset zone than to other regions of spread (P < 0.0001). Over the temporal evolution of a seizure, the seizure onset zone was significantly more tract-connected to regions of early spread compared with regions of late spread in seizure-free patients only (P < 0.0001). By integrating information on structure, we demonstrate that seizure propagation is likely to be mediated by white matter tracts. The pattern of connectivity between seizure onset zone, regions of spread and non-involved regions demonstrates that the onset zone might be largely responsible for seizures propagating throughout the brain, rather than seizures propagating to intermediate points, from which further propagation takes place. Our findings also suggest that seizure propagation over seconds might be the result of a continuous bombardment of action potentials from the seizure onset zone to regions of spread. In non-seizure-free patients, the paucity of tracts from the presumed seizure onset zone to regions of spread suggests that the onset zone was missed. Fully understanding the structure-propagation relationship might eventually provide insight into selecting the correct targets for epilepsy surgery.

Subject-based assessment of large-scale integration dynamics in epileptic brain networks: insights from the intrinsic ignition framework.

This study examined the dynamic properties of brain regions involved in the genesis and spread of seizures in 10 individuals diagnosed with pharmacoresistant focal epilepsy. The patients and 30 healthy controls underwent resting-state functional magnetic resonance imaging scans and the brain's functional network dynamics were analyzed using the intrinsic ignition framework. Comparative statistical analyses examined the differences in the integration and metastability measures in both groups in the whole brain and specific local brain regions. Invasive electroencephalography evaluations validated the findings of significant global and regional changes in the patient's brain network dynamics. There was a marked increase in global integration and metastability across the brain, reflecting substantial alterations in the overall connectivity and flexibility of the functional networks. Specific brain regions exhibited paradoxical dynamics within the seizure onset zone, with decreased intrinsic ignition and increased metastability. Increased intrinsic ignition was observed in remote brain regions, suggesting a reorganization of the brain network hubs and potential pathways for seizure propagation. Using the intrinsic ignition framework provided insights into dynamic alterations in the brain networks of patients with epilepsy. These have increased our understanding of the mechanisms underlying epileptic seizures and may guide the development of diagnostic biomarkers and targeted therapeutic interventions.

Classifying High-Frequency Oscillations by Morphologic Contrast to Background, With Surgical Outcome Correlates.

Ictal high-frequency oscillations (HFOs) are a reliable indicator of a seizure onset zone for intracranial EEG recordings. Interictal HFOs often are also observed and may be a useful biomarker to supplement ictal data, but distinguishing pathologic from physiologic HFOs continues to be a challenging task. We present a method of classifying HFOs based on morphologic contrast to the background. We retrospectively screened 31 consecutive patients who underwent intracranial recordings for epilepsy at Stanford Medical Center during a 2-year period, and 13 patients met the criteria for inclusion. Interictal EEG data were analyzed using an automated event detector followed by morphologic feature extraction and k-means clustering. Instead of only using event features, the algorithm also incorporated features of the background adjacent to the events. High-frequency oscillations with higher morphologic contrast to the background were labeled as pathologic, and "hotspots" with the most active pathologic HFOs were identified and compared with clinically determined seizure onset zones. Clustering with contrast features produced groups with better separation and more consistent boundaries. Eleven of the 13 patients proceeded to surgery, and patients whose hotspots matched seizure onset zones had better outcomes, with 4 out of 5 "match" patients having no disabling seizures at 1+ year postoperatively (Engel I or International League Against Epilepsy Class 1-2), while all "mismatch" patients continued to have disabling seizures (Fisher exact test P-value = 0.015). High-frequency oscillations with higher contrast to background more likely represent paroxysmal bursts of pathologic activity. Patients with HFO hotspots outside of identified seizure onset zones may not respond as well to surgery.

Chronobiological Spatial Clusters of Cortical Regions in the Human Brain.

We demonstrate that different regions of the cerebral cortex have different diurnal rhythms of spontaneously occurring high-frequency oscillations (HFOs). High-frequency oscillations were assessed with standard-of-care stereotactic electroencephalography in patients with drug-resistant epilepsy. To ensure generalizability of our findings beyond patients with drug-resistant epilepsy, we excluded stereotactic electroencephalography electrode contacts lying within seizure-onset zones, epileptogenic lesions, having frequent epileptiform activity, and excessive artifact. For each patient, we evaluated twenty-four 5-minute stereotactic electroencephalography epochs, sampled hourly throughout the day, and obtained the HFO rate (number of HFOs/minute) in every stereotactic electroencephalography channel. We analyzed diurnal rhythms of the HFO rates with the cosinor model and clustered neuroanatomic parcels in a standard brain space based on similarity of their cosinor parameters. Finally, we compared overlap among resting-state networks, described in the neuroimaging literature, and chronobiological spatial clusters discovered by us. We found five clusters that localized predominantly or exclusively to the left perisylvian, left perirolandic and left temporal, right perisylvian and right parietal, right frontal, and right insular-opercular cortices, respectively. These clusters were characterized by similarity of the HFO rates according to the time of the day. Also, these chronobiological spatial clusters preferentially overlapped with specific resting-state networks, particularly default mode network (clusters 1 and 3), frontoparietal network (cluster 1), visual network (cluster 1), and mesial temporal network (cluster 2). This is probably the first human study to report clusters of cortical regions with similar diurnal rhythms of electrographic activity. Overlap with resting-state networks attests to their functional significance and has implications for understanding cognitive functions and epilepsy-related mortality.

Expert Knowledge Driven Human-AI Collaboration for Medical Imaging: A Study on Epileptic Seizure Onset Zone Identification

Expert Knowledge Driven Human-AI Collaboration for Medical Imaging: A Study on Epileptic Seizure Onset Zone Identification

Quantifying hubness to predict surgical outcomes in epilepsy: Assessing resection-hub alignment in interictal intracranial EEG networks.

Intracranial EEG can identify epilepsy-related networks in patients with focal epilepsy; however, the association between network organization and post-surgical seizure outcomes remains unclear. Hubness serves as a critical metric to assess network organization by identifying brain regions that are highly influential to other regions. In this study, we tested the hypothesis that favorable post-operative seizure outcomes are associated with the surgical removal of interictal network hubs, measured by the novel metric "Resection-Hub Alignment Degree (RHAD)." We analyzed Phase II interictal intracranial EEG from 69 patients with epilepsy who were seizure-free (n = 45) and non-seizure-free (n = 24) 1 year post-operatively. Connectivity matrices were constructed from intracranial EEG recordings using imaginary coherence in various frequency bands, and centrality metrics were applied to identify network hubs. The RHAD metric quantified the congruence between hubs and resected/ablated areas. We used a logistic regression model, incorporating other clinical factors, and evaluated the association of this alignment regarding post-surgical seizure outcomes. There was a significant difference in RHAD in fast gamma (80-200 Hz) interictal network between patients with favorable and unfavorable surgical outcomes (p = .025). This finding remained similar across network definitions (i.e., channel-based or region-based network) and centrality measurements (Eigenvector, Closeness, and PageRank). The alignment between surgically removed areas and other commonly used clinical quantitative measures (seizure-onset zone, irritative zone, high-frequency oscillations zone) did not reveal significant differences in post-operative outcomes. This finding suggests that the hubness measurement may offer better predictive performance and finer-grained network analysis. In addition, the RHAD metric showed explanatory validity both alone (area under the curve [AUC] = .66) and in combination with surgical therapy type (resection vs ablation, AUC = .71). Our findings underscore the role of network hub surgical removal, measured through the RHAD metric of interictal intracranial EEG high gamma networks, in enhancing our understanding of seizure outcomes in epilepsy surgery.

Electromagnetic Source Imaging in Presurgical Evaluation of Children with Drug-Resistant Epilepsy.

For children with drug-resistant epilepsy (DRE), seizure freedom relies on the delineation and resection (or ablation/disconnection) of the epileptogenic zone (EZ) while preserving the eloquent brain areas. The development of a reliable and noninvasive localization method that provides clinically useful information for the localization of the EZ is, therefore, crucial to achieving successful surgical outcomes. Electric and magnetic source imaging (ESI and MSI) have been increasingly utilized in the presurgical evaluation of these patients showing promising findings in the delineation of epileptogenic as well as eloquent brain areas. Moreover, the combination of ESI and MSI into a single solution, namely electromagnetic source imaging (EMSI), performed on simultaneous high-density electroencephalography (HD-EEG) and magnetoencephalography (MEG) recordings has shown higher source localization accuracy than either modality alone. Despite these encouraging findings, such techniques are performed in only a few tertiary epilepsy centers, are rarely recorded simultaneously, and are underutilized in pediatric cohorts. This study illustrates the experimental setup for recording simultaneous MEG and HD-EEG data as well as the methodological framework for analyzing these data aiming to localize the irritative zone, the seizure onset zone, and eloquent brain areas in children with DRE. More specifically, the experimental setups are presented for (i) recording and localizing interictal and ictal epileptiform activity during sleep and (ii) recording visual-, motor-, auditory-, and somatosensory-evoked responses and mapping relevant eloquent brain areas (i.e., visual, motor, auditory, and somatosensory) during visuomotor task, as well as auditory and somatosensory stimulations. Detailed steps of the data analysis pipeline are further presented for performing EMSI as well as individual ESI and MSI using equivalent current dipole (ECD) and dynamic statistical parametric mapping (dSPM).

Laser Ablation of Periventricular Nodular Heterotopia for Medically Refractory Epilepsy

ObjectivePeriventricular nodular heterotopia (PVNH) is the most common neuronal heterotopia, frequently resulting in pharmaco‐resistant epilepsy. Here, we characterize variables that predict good epilepsy outcomes following surgical intervention using stereo‐electroencephalography (SEEG) ‐informed magnetic resonance‐guided laser interstitial thermal therapy (MRgLITT).MethodsA retrospective review of consecutive cases from a single high‐volume epilepsy referral center identified patients who underwent SEEG evaluation for PVNH to characterize the intervention and outcomes.ResultsThirty‐nine patients underwent SEEG‐guided MRgLITT of the seizure onset zone (SoZ) in PVNH and associated epileptic tissue. PVNH and polymicrogyria (PMG) were densely sampled with a mean of 16.5 (SD = 2)/209.4 (SD = 36.9) SEEG probes/recording contacts per patient. Ablation principally targeted just the PVNH and cortex that was abnormal on imaging was ablated (5 patients) only if implicated in the SoZ. Volumetric analyses revealed a high percentage of PVNH SoZ ablation (96.6%, SD = 5.3%) in unilateral and bilateral (92.9%, SD = 7.2%) cases. Mean follow‐up duration was 31.4 months (SD = 20.9). Seizure freedom (ILAE 1) was excellent: unilateral PVNH without other imaging abnormalities, 80%; PVNH with mesial temporal sclerosis (MTS) or PMG, 63%; bilateral PVNH, 50%. SoZ ablation percentage significantly impacted surgical outcomes (p &lt; 0.001).InterpretationPVNH plays a central role in seizure genesis as revealed by dense recordings and selective targeting by LITT. MRgLITT represents a transformative technological advance in PVNH‐associated epilepsy with seizure control outcomes consistent with those seen in focal lesional epilepsies. In localized unilateral cases and otherwise normal imaging, PVNH ablation without invasive recordings may be considered, and this approach deserves to be explored further. ANN NEUROL 2024

Brain perfusion SPECT in the presurgical evaluation of epilepsy: is additional ictal SPECT required in case of high-confidence lateralization of the seizure onset zone by interictal SPECT and vice versa?

BackgroundIctal brain perfusion SPECT provides higher sensitivity for the identification of the epileptic seizure onset zone (SOZ) than interictal SPECT. However, ictal SPECT is demanding due to the unpredictable waiting period for the next seizure to allow for ictal tracer injection. Thus, starting with an interictal scan and skipping the ictal scan if the interictal scan provides a SOZ candidate with high confidence could be an efficient approach. The current study estimated the rate of high-confidence SOZ candidates and the false lateralization rate among them for interictal and ictal SPECT.Methods177 patients (48% females, median age 38y, interquartile range 27–48y) with ictal and interictal SPECT acquired with 99mTc-HMPAO (n = 141) or -ECD (n = 36) were included retrospectively. The vast majority of the patients was suspected to have temporal lobe epilepsy. Visual interpretation of the SPECT data was performed independently by 3 readers in 3 settings: “interictal only” (interictal SPECT and statistical hypoperfusion map), “ictal only” (ictal SPECT and hyperperfusion map), and “full” setting (side-by-side interpretation of ictal and interictal SPECT including statistical maps and SISCOM analysis). The readers lateralized the SOZ (right, left, none) and characterized their confidence using a 5-score. A case was considered "lateralizing with high confidence” if all readers lateralized to the same hemisphere with at least 4 of 5 confidence points. Lateralization of the SOZ in the “full” setting was used as reference standard.ResultsThe proportion of “lateralizing with high confidence” cases was 4.5/31.6/38.4% in the “interictal only”/“ictal only”/“full” setting. One (12.5%) of the 8 cases that were “lateralizing with high confidence” in the “interictal only” setting lateralized to the wrong hemisphere. Among the 56 cases that were “lateralizing with high confidence” in the “ictal only” setting, 54 (96.4%) were also lateralizing in the “full” setting, all to the same hemisphere.ConclusionsStarting brain perfusion SPECT in the presurgical evaluation of epilepsy with an interictal scan to skip the ictal scan in case of a high-confidence interictal SOZ candidate is not a useful approach. In contrast, starting with an ictal scan to skip the interictal scan in case of a high-confidence ictal SOZ candidate can be recommended.

AGR – 2 The Multi-Dimensional Role of Neuropsychology in Diagnostically Complex Epilepsy Patients: Refining the Surgical Plan and Post-Operative Expectations

Abstract Objective We present a case highlighting the importance of neuropsychological involvement at all phases of a pre-surgical epilepsy work-up, including clinical interview, neuropsychological evaluation, Wada testing, extra-operative electrical stimulation mapping (ESM), and psychoeducation. Method A 24-year-old, right-handed, Caucasian female presented with non-lesional, intractable left-hemisphere localization-related epilepsy characterized by frequent experiences of déjà vu and autonomic sensations. Results Neuropsychological evaluation revealed weaknesses in processing speed and verbal memory implicating left hippocampal involvement. Wada testing suggested minimal contralateral memory support, indicating poor candidacy for resective surgery. The patient underwent prolonged sEEG monitoring to refine a plan for device implantation (i.e., responsive neurostimulation; RNS). No typical events were captured during extended study. Episodic somatosensory changes were captured, which had no electrographic correlate and were presumed to be non-epileptic. ESM evoked the patient’s classic semiology, elucidating nuanced information about her seizure onset zone and network. Barriers to extended monitoring and consistent, reliable engagement during ESM included depression, anxiety, and trauma; considerable neuropsychologist-led emotional support was required. Typical seizure semiology was elicited during stimulation of entorhinal cortices, posterior and anterior hippocampi, amygdala, cingulate and insula. RNS placement included a depth electrode targeting the medial structures (via a posterior approach) with a sub-temporal strip. Conclusions Involvement of neocortical and mesial temporal structures, coupled with a clear neuropsychiatric component, were believed to be poly-etiological factors to the patient’s presentation. Neuropsychological input at all phases of pre-surgical assessment was instrumental in systematically identifying and addressing her complex needs. Psychotherapeutic intervention was suggested to be equally as important to clinical, long-term patient outcome.

SEEG4D: a tool for 4D visualization of stereoelectroencephalography data.

Epilepsy is a prevalent and serious neurological condition which impacts millions of people worldwide. Stereoelectroencephalography (sEEG) is used in cases of drug resistant epilepsy to aid in surgical resection planning due to its high spatial resolution and ability to visualize seizure onset zones. For accurate localization of the seizure focus, sEEG studies combine pre-implantation magnetic resonance imaging, post-implant computed tomography to visualize electrodes, and temporally recorded sEEG electrophysiological data. Many tools exist to assist in merging multimodal spatial information; however, few allow for an integrated spatiotemporal view of the electrical activity. In the current work, we present SEEG4D, an automated tool to merge spatial and temporal data into a complete, four-dimensional virtual reality (VR) object with temporal electrophysiology that enables the simultaneous viewing of anatomy and seizure activity for seizure localization and presurgical planning. We developed an automated, containerized pipeline to segment tissues and electrode contacts. Contacts are aligned with electrical activity and then animated based on relative power. SEEG4D generates models which can be loaded into VR platforms for viewing and planning with the surgical team. Automated contact segmentation locations are within 1 mm of trained raters and models generated show signal propagation along electrodes. Critically, spatial-temporal information communicated through our models in a VR space have potential to enhance sEEG pre-surgical planning.

The part and the whole: how single nodes contribute to large-scale phase-locking in functional EEG networks

ObjectiveThe application of signal analysis techniques to electroencephalographic (EEG) recordings from epilepsy patients shows that epilepsy involves not only altered neuronal synchronization but also the reorganization of functional EEG networks. This study aims to assess the large-scale phase-locking of such functional networks and how individual network nodes contribute to this collective dynamics. MethodsWe analyze the EEG recorded before, during and after seizures from sixteen patients with pharmacoresistant focal-onset epilepsy. The data is filtered to low (4–30 Hz) and high (80–150 Hz) frequencies. We define the multivariate phase-locking measure and the univariate phase-locking contribution measure. Surrogate signals are used to estimate baseline results expected under the null hypothesis that the EEG is a correlated linear stochastic process. ResultsOn average, nodes from inside and outside the seizure onset zone (SOZ) increase and decrease, respectively, the large-scale phase-locking. This difference becomes most evident in a joint analysis of low and high frequencies. ConclusionsNodes inside and outside the SOZ play opposite roles for the large-scale phase-locking in functional EEG network in epilepsy patients. SignificanceThe application of the phase-locking contribution measure to EEG recordings from epilepsy patients can potentially help in localizing the SOZ.

Integrating the 5-SENSE Score for Patient Selection in Vagus Nerve Stimulation for Drug-Resistant Epilepsy.

Addressing the challenge of drug-resistant epilepsy, our study offers a novel perspective by retrospectively applying the 5-SENSE score, initially created for stereoelectroencephalography (SEEG) planning, to evaluate its predictive value in patients undergoing vagus nerve stimulation (VNS) therapy. We conducted a comprehensive preoperative diagnostic work-up, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT (PET-CT), video-electroencephalogram (video-EEG), and clinical semiology. We then stratified 76 patients into three groups - low, moderate, and high focality - based on the focality of the seizure-onset zone. Such stratification was made to check the scoring ability in predictingVNStherapy seizure reduction. Our findings demonstrate an association between the extent of focality at the seizure-onset zone and the effectiveness of VNS, which may help to define the role of the 5-SENSE score in patient selection for VNS. This high dispersion of responses in the group with high focality reinforces the idea that outcome estimation is difficult and argues for an individualized strategy in the treatment of drug-resistant epilepsy. A study at the level of the 5-SENSE score indicates the importance of detailed preoperative assessments that may better optimize selection for VNS therapy and further improve clinical outcomes.

Prognostic value of the 5-SENSE Score to predict focality of the seizure-onset zone as assessed by stereoelectroencephalography: a prospective international multicentre validation study

IntroductionEpilepsy surgery is the only curative treatment for patients with drug-resistant focal epilepsy. Stereoelectroencephalography (SEEG) is the gold standard to delineate the seizure-onset zone (SOZ). However, up to 40% of...

Combined value of interictal markers and stimulated seizures to estimate the seizure onset zone in stereoelectroencephalography.

This study was undertaken to investigate the potential of interictal electroencephalographic (EEG) findings and electrically stimulated seizures during stereo-EEG (SEEG) as surrogate markers for the spontaneous seizure onset zone (spSOZ). We hypothesized that combining the localizing information of these markers would allow clinically meaningful estimation of the spSOZ. We included all patients (n = 63) who underwent SEEG between January 2013 and March 2020 at Helsinki University Hospital and had spontaneous seizures during the recording. We scored spikes, gamma activity, and background abnormality on each channel visually during a 12-h epoch containing waking state and sleep. Based on semiology, we classified stimulated seizures as typical or atypical/unclassifiable and estimated the stimulated SOZ (stimSOZ) for typical seizures. To assess which markers increased the odds of channel inclusion in the spSOZ, we fitted mixed effects logistic regression models. A combined regression model including the stimSOZ and interictal markers scored during sleep performed better in estimating which channels were part of the spSOZ than models based on stimSOZ (p < .001) or interictal markers (p < .001) alone. Of the individual markers, the effect sizes were greatest for inclusion of a channel in the stimSOZ (odds ratio [OR] = 60, 95% confidence interval [CI] = 37-97, p < .001) and for continuous (OR = 25, 95% CI = 12-55, p < .001) and subcontinuous (OR = 36, 95% CI = 21-64, p < .001) interictal spiking. At the individual level, the model's accuracy to predict spSOZ inclusion varied markedly (median accuracy = 85.7, range = 54.4-100), which was not explained by etiology (p > .05). Compared to either marker alone, combining visually rated interictal SEEG markers and stimulated seizures improved prediction of which SEEG channels belonged to the spSOZ. Inclusion in the stimSOZ and continuous or subcontinuous spikes increased the odds of spSOZ inclusion the most. Future studies should investigate whether suboptimal sampling of the true epileptogenic zone can explain the model's poor performance in certain patients.

A comparative study between a power and a connectivity sEEG biomarker for seizure-onset zone identification in temporal lobe epilepsy

Background:Ictal stereo-encephalography (sEEG) biomarkers for seizure onset zone (SOZ) localization can be classified depending on whether they target abnormalities in signal power or functional connectivity between signals, and they may depend on the frequency band and time window at which they are estimated. New method:This work aimed to compare and optimize the performance of a power and a connectivity-based biomarker to identify SOZ contacts from ictal sEEG recordings. To do so, we used a previously introduced power-based measure, the normalized mean activation (nMA), which quantifies the ictal average power activation. Similarly, we defined the normalized mean strength (nMS), to quantify the ictal mean functional connectivity of every contact with the rest. The optimal frequency bands and time windows were selected based on optimizing AUC and F2-score. Results:The analysis was performed on a dataset of 67 seizures from 10 patients with pharmacoresistant temporal lobe epilepsy. Our results suggest that the power-based biomarker generally performs better for the detection of SOZ than the connectivity-based one. However, an equivalent performance level can be achieved when both biomarkers are independently optimized. Optimal performance was achieved in the beta and lower-gamma range for the power biomarker and in the lower- and higher-gamma range for connectivity, both using a 20 or 30 s period after seizure onset. Conclusions:The results of this study highlight the importance of this optimization step over frequency and time windows when comparing different SOZ discrimination biomarkers. This information should be considered when training SOZ classifiers on retrospective patients’ data for clinical applications.

Stereo-electroencephalography-guided radiofrequency thermocoagulation restricted to periventricular nodular heterotopias in patients with drug-resistant epilepsy: A single center experience

IntroductionPeriventricular nodular heterotopias (PVNH) are developmental abnormalities with neurons abnormally clustered around the cerebral ventricles. Patients frequently present with focal drug-resistant epilepsy (DRE). However, the relationship between PVNH and the seizure onset zone (SOZ) is complex.Stereo-electroencephalography (SEEG) is an invasive diagnostic procedure for patients with DRE. In selected patients, the SEEG may be converted into a therapeutic procedure, lesioning the probable (SOZ) with pulsed radiofrequency thermocoagulation (RFTC). The aim of our study was to evaluate the efficacy and safety of SEEG-RFTC in a series of DRE patients with PVNH. MethodsTwenty-four patients with focal DRE related to PVNH and treated with SEEG-guided-RFTC restricted to nodules were prospectively collected between 2016 and 2023 and retrospectively analyzed after a follow-up of at least 12 months. ResultsSeventeen patients (71 %) responded (ILAE class 1–4) after SEEG-guided RFTC of whom eleven (46 %) became seizure-free (class 1) at last follow up, nine (45 %) despite residual PVNH tissue on MRI. SEEG seizure onset was restricted to PVNH in eleven patients (class 1 in 45 %) and simultaneously in PVNH and other cortical areas in thirteen patients (class 1 in 46 %). Out of 31 SEEG-RFTC procedures in twenty-four patients, adverse events, related to RFTC, were recorded in eight (26 %), of which two patients (8 %) had predicted permanent visual complaints whilst the other five had transient complaints. SignificanceThis study demonstrates that a considerable percentage of patients, even with bilateral, multiple PVNH and involvement of adjacent cortical regions can be rendered seizure-free with SEEG-guided-RFTC restricted to the nodules. Furthermore, this study delivers evidence that the complete destruction of the entire nodule is not necessary to render a patient seizure free. This justifies the use of SEEG in patients with single, multiple or bilateral PVNHs to provide insight into the epileptogenic organization in and around these lesions.