Irritative Zone Research Articles

Electroencephalographic source imaging of spikes with concurrent high-frequency oscillations is concordant with the clinical ground truth.

Epilepsy raises critical challenges to accurately localize the epileptogenic zone (EZ) to guide presurgical planning. Previous research has suggested that interictal spikes overlapping with high-frequency oscillations, referred to here as pSpikes, serve as a reliable biomarker for EZ estimation, but there remains a question as to whether and to how pSpikes perform as compared to other types of epileptic spikes. This study aims to address this question by investigating the source imaging capabilities of pSpikes alongside other spike types. A total of 2819 interictal spikes from 76-channel scalp electroencephalography (EEG) were analyzed in a cohort of 24 drug-resistant focal epilepsy patients. All patients received surgical resection, and 16 were declared seizure-free based on at least 1 year of postoperative follow-up. A recently developed electrophysiological source imaging algorithm-fast spatiotemporal iteratively reweighted edge sparsity (FAST-IRES)-was used for source imaging of the detected interictal spikes. The performance of 217 pSpikes was compared with 772 nSpikes (spikes with irregular high-frequency activations), 1830 rSpikes (spikes with no high-frequency activity), and all 2819 aSpikes (all interictal spikes). The localization and extent estimation using pSpikes are concordant with the clinical ground truth; using pSpikes yields the best performance compared with nSpikes, rSpikes, and conventional spike imaging (aSpikes). For multiple spike type seizure-free patients, the mean localization error for pSpike imaging was 6.8 mm, compared with 15.0 mm for aSpikes. The sensitivity, precision, and specificity were .41, .67, and .93 for pSpikes compared with .32, .48, and .93 for aSpikes. These results demonstrate the merits of noninvasive EEG source localization, and that (1) pSpike is a superior biomarker, outperforming conventional spike imaging for the localization of epileptic sources, and especially those with multiple irritative zones; and (2) FAST-IRES provides accurate source estimation that is highly concordant with clinical ground truth, even insituations of single spike analysis with low signal-to-noise ratio.

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).

Transcranial magnetic stimulation and magnetoencephalography are feasible alternatives to invasive methods in optimizing responsive neurostimulation device placement

Responsive neurostimulation (RNS) is a treatment option for patients with refractory epilepsy when surgical resection is not possible due to overlap of the irritative zone and eloquent cortex. Presurgical evaluations for RNS placement typically rely on invasive methods. This study investigated the potential of transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) to provide key presurgical information non-invasively. We hypothesized that these non-invasive methods may assist in optimizing RNS placement by providing useful information for seizure localization by MEG and eloquent cortex mapping by TMS. A retrospective chart review identified nine patients who underwent RNS placement (mean age = 20.4 years [SD = 5.6], two-thirds were female). Characterization of the irritative zone using MEG was successful in eight of nine patients. Non-invasive mapping of relevant eloquent cortex was attempted in all patients. TMS was successful in eight of nine patients, and MEG was successful in two of six patients. Importantly, patients mapped with non-invasive modalities experienced an average seizure reduction of 77 % at their most recent clinic visit, compared to 75 % seizure reduction in those with invasive evaluations, indicating appropriate RNS placement. These data demonstrate that TMS and MEG can provide key information for RNS and may be feasible alternatives to invasive methods for assisting in decision making regarding RNS placement. Non-invasive methods for determining RNS placement have a high rate of success when data from multiple non-invasive modalities converge and can inform more accurate placement of intracranial electrodes prior to RNS placement or mitigate their need.

Thermosensitive/thermochromic silicone and infrared thermography mapping in 60 consecutive cases of epilepsy surgery.

Epilepsy surgery represents a therapeutic opportunity for those patients who do not respond to drug therapy. However, an important challenge is the precise identification of the epileptogenic area during surgery. Since it can be hard to delineate, it makes it necessary to use auxiliary tools as a guide during the surgical procedure. Electrocorticography (ECoG), despite having shown favorable results in terms of reducing post-surgical seizures, have certain limitations. Brain mapping using infrared thermography mapping and a new thermosensitive/thermochromic silicone (TTS) in epilepsy surgery has introduced a new resource of noninvasive and real-time devices that allow the localization of irritative zones. Sixty consecutive patients with drug-resistant epilepsy with surgical indications who decided to participate voluntarily in the study were included in the study. We measured brain temperature using two quantitative methods and a qualitative method: the TTS sheet. In all cases, we used ECoG as the gold standard to identify irritative areas, and all brain tissue samples obtained were sent to pathology for diagnosis. In the subgroup in which the ECoG detected irritative areas (n = 51), adding the results in which there was a correlation with the different methods, the efficiency obtained to detect irritative areas is 94.11% (n = 48/51, P ≤ 0.0001) while the infrared thermography mapping method independently has an efficiency of 91.66% (P ≤ 0.0001). The TTS has a sensitivity of 95.71% and a specificity of 97.9% (P ≤ 0.0001) to detect hypothermic areas that correlate with the irritative zones detected by ECoG. No postoperative infections or wound dehiscence were documented, so the different methodologies used do not represent an additional risk for the surgical proceedings. We consider that the infrared thermography mapping using high-resolution infrared thermography cameras and the TTS are both accurate and safe methods to identify irritative areas in epilepsy surgeries.

Widespread slow oscillations support interictal epileptiform discharge networks in focal epilepsy

Interictal epileptiform discharges (IEDs) often co-occur across spatially-separated cortical regions, forming IED networks. However, the factors prompting IED propagation remain unelucidated. We hypothesized that slow oscillations (SOs) might facilitate IED propagation. Here, the amplitude and phase synchronization of SOs preceding propagating and non-propagating IEDs were compared in 22 patients with focal epilepsy undergoing intracranial electroencephalography (EEG) evaluation. Intracranial channels were categorized into the irritative zone (IZ) and normal zone (NOZ) regarding the presence of IEDs. During wakefulness, we found that pre-IED SOs within the IZ exhibited higher amplitudes for propagating IEDs than non-propagating IEDs (delta band: p = 0.001, theta band: p < 0.001). This increase in SOs was also concurrently observed in the NOZ (delta band: p = 0.04). Similarly, the inter-channel phase synchronization of SOs prior to propagating IEDs was higher than those preceding non-propagating IEDs in the IZ (delta band: p = 0.04). Through sliding window analysis, we observed that SOs preceding propagating IEDs progressively increased in amplitude and phase synchronization, while those preceding non-propagating IEDs remained relatively stable. Significant differences in amplitude occurred approximately 1150 ms before IEDs. During non-rapid eye movement (NREM) sleep, SOs on scalp recordings also showed higher amplitudes before intracranial propagating IEDs than before non-propagating IEDs (delta band: p = 0.006). Furthermore, the analysis of IED density around sleep SOs revealed that only high-amplitude sleep SOs demonstrated correlation with IED propagation. Overall, our study highlights that transient but widely distributed SOs are associated with IED propagation as well as generation in focal epilepsy during sleep and wakefulness, providing new insight into the EEG substrate supporting IED networks.

Sleep Spindle Generation Before and After Epilepsy Surgery: A Source Imaging Study in Children with Drug-Resistant Epilepsy.

Literature lacks studies investigating the cortical generation of sleep spindles in drug-resistant epilepsy (DRE) and how they evolve after resection of the epileptogenic zone (EZ). Here, we examined sleep EEGs of children with focal DRE who became seizure-free after focal epilepsy surgery, and aimed to investigate the changes in the spindle generation before and after the surgery using low-density scalp EEG and electrical source imaging (ESI). We analyzed N2-sleep EEGs from 19 children with DRE before and after surgery. We identified slow (8-12Hz) and fast spindles (13-16Hz), computed their spectral features and cortical generators through ESI and computed their distance from the EZ and irritative zone (IZ). We performed two-way ANOVA testing the effect of spindle type (slow vs. fast) and surgical phase (pre-surgery vs. post-surgery) on each feature. Power, frequency and cortical activation of slow spindles increased after surgery (p < 0.005), while this was not seen for fast spindles. Before surgery, the cortical generators of slow spindles were closer to the EZ (57.3 vs. 66.2mm, p = 0.007) and IZ (41.3 vs. 55.5mm, p = 0.02) than fast spindle generators. Our data indicate alterations in the EEG slow spindles after resective epilepsy surgery. Fast spindle generation on the contrary did not change after surgery. Although the study is limited by its retrospective nature, lack of healthy controls, and reduced cortical spatial sampling, our findings suggest a spatial relationship between the slow spindles and the epileptogenic generators.

Stereo-Electroencephalography-Recorded Interictal Epileptiform Discharges: Activation Pattern and Its Relationship With Surgical Outcome.

Background Patients with drug-resistant epilepsy commonly undergo stereo-electroencephalography (SEEG) intracranial monitoring for surgical evaluation. Our current practice of defining the epileptogenic zone relies heavily on recognizing the seizure onset zone (SOZ), but the clinical significance of interictal epileptiform discharges (IEDs) is not well established. Methodology We retrospectively identified adult patients who underwent SEEG between January 2019 and May 2022. To study IED activation patterns, we classified IEDs as leading spikes (involved within the SOZ) and distant spikes (outside the SOZ). We calculated each patient's total number of brain subregions generating distant spikes. We correlated them with epilepsy type, duration, and surgical outcome (Engel I:good outcome and Engel II-IV: poor outcome). Results A total of 22 patients were identified during the study period, and 16 underwent surgical intervention (ablation or resection) with one-year post-surgery follow-up. The most common IED morphology was a single spike or sharp followed by periodic spikes or sharps. We found that 87% (n = 19/22) of leading spikes were activated during the first 24 hours of SEEG monitoring, whereas no activation pattern was observed for distant spikes. We found that a higher number of subregions generating distant spikes were associated with poor surgical outcomes (p = 0.002). However, we did not find any significant association between the number of subregions generating distant spikes with epilepsy duration (p = 0.67), temporal or extratemporal-onset epilepsy (p = 0.58), or the presence of an MRI lesion (p = 0.62). Conclusions IEDs involved within the SOZ were found to be activated during the first 24 hours of SEEG monitoring, which could aid in recognizing the pathological spikes and targeted mapping of the irritative zone. We also observed that a higher number of brain subregions generating IEDs outside the SOZ were associated with poor surgical outcomes, but this observation needs to be further studied with larger sample size prospective studies.

Network metrics to localize the Seizure Onset Zone: A Directed Functional Connectivity Study Using MEG Data (P2-1.004)

<h3>Objective:</h3> We aimed to analyze ictal networks via magnetoencephalography-based (MEG) directed functional connectivity (FC), to better guide intracranial EEG (iEEG) studies. <h3>Background:</h3> Epilepsy is a network disorder. Thus, the importance of integrating connectivity-based approaches during epilepsy presurgical evaluation. Studies applying MEG non-directed FC evidenced a good correlation with post-surgical outcomes. Directed FC, such as Spectral Bivariate Granger Causality (SBGC), has the advantage of differentiating probable sinks from hubs in networks. <h3>Design/Methods:</h3> Ictal MEG and MRI data from eight drug-resistant epilepsy patients (four pediatric, six females) were included. Source space SBGC was performed and grouped in frequency bands. Nodes with higher influence in outgoing signals (hubs) and receiving signals (authority) were identified. The top 2 hub and authority nodes were selected and compared to clinical data. <h3>Results:</h3> Seven patients had iEEG, three of which had subsequent epilepsy surgery. Another patient underwent direct surgery. Two patients continued presenting seizures after resection. All others were seizure-free after 1-month and 18-month follow-ups. For all patients, the irritative zone (80%) or nearby regions (20%) were captured by one of the top two hub nodes in the highest power frequency band and the delta band. For the patients with seizure freedom, at least one of the top two hub nodes included the Seizure Onset Zone (SOZ). In the patient with an 18-month Engel 1A classification, both top hub nodes were included in the resection area. For an adult patient with multifocal SOZs, the highest authority node represented another less active SOZ. <h3>Conclusions:</h3> The regions identified by our connectivity metrics demonstrated overlap with regions identified with iEEG in the majority of the patients, and those patients in which resection included a hub node had favorable post-surgical outcomes. We contend that network metrics using SBGC and MEG data can be useful to better understand epilepsy dynamics and enhance epilepsy management in clinical practice. <b>Disclosure:</b> Dr. Cardoso Da Fonseca has nothing to disclose. Ms. Askari has nothing to disclose. Dr. Proskovec has nothing to disclose. Dr. Alick-Lindstrom has nothing to disclose. Dr. Lowden has nothing to disclose. Dr. Talai has nothing to disclose. The institution of Joseph Maldjian has received research support from NIH. Dr. Davenport has nothing to disclose.

Usefulness of Intraoperative Electrocorticography for the Localization of Epileptogenic Zones.

Intraoperative electrocorticography (iECoG) is widely performed to identify irritative zones in the cortex during brain surgery; however, several limitations (e.g., short recording times and the effects of general anesthesia) reduce its effectiveness. The present study aimed to evaluate the utility of iECoG for localizing epileptogenic zones. We compared the results of iECoG and chronic electrocorticography (cECoG) in 25 patients with refractory epilepsy. Subdural electrodes were implanted with iECoG under general anesthesia (2% sevoflurane). cECoG recordings were performed for 3-14 days. The distribution of iECoG spikes was compared with cECoG spike, seizure onset zone, and resection areas. The concordance patterns of each distribution were classified into four patterns: Group 1: No spike in iECoG, Group 2: concordant (2a: iECoG smaller, 2b: iECoG larger, Group 3: discordant >50%). The concordance rate of interictal spikes, seizure onset zones, and resection areas were 88.0% (Group 2a: 72.0%, Group 2b: 16.0%), 70.0% (Group 2a: 25.0%, Group 2b: 45.0%), and 81.0% (Group 2a: 42.9%, Group 2b: 38.1%), respectively. The resection of iECoG spike areas significantly correlated with good surgical outcomes. The indication and limitations of iECoG need to be realized, and the complementary use of iECoG and cECoG may enhance clinical utility.

The Potential of Bemegride as an Activation Agent in Electroencephalography in Dogs.

The present study investigated the potential of bemegride as a pharmacological activation agent that elicits epileptiform discharges (EDs) in interictal electroencephalogram (EEG) recordings in dogs. Four laboratory dogs with idiopathic epilepsy and four without epilepsy were included. The dogs were anesthetized using sevoflurane during EEG recordings. Bemegride was administered intravenously and repeatedly until EDs were enhanced or induced, or until the maximum dose (20 mg/kg) had been administered. Bemegride activated EDs in all dogs with epilepsy. These EDs predominantly occurred in each dog's spontaneous irritative zones, which were identified without the administration of bemegride. EDs occurred after the administration of bemegride in 50% of dogs without epilepsy. The dose required for activation was significantly lower in dogs with epilepsy (median; 7.3 mg/kg) than in those without (median; 19.7 mg/kg) (p = 0.0294). The only suspected adverse effect associated with the administration of bemegride was vomiting in two dogs after awakening from anesthesia. There were no other adverse effects, including seizures. The present results demonstrated the potential of bemegride as a safe and effective pharmacological activation agent of EDs in anesthetized dogs with epilepsy and provided more options for the diagnosis and therapeutic planning of epilepsy, including presurgical evaluations, in dogs.

SURG-18. VARIOUS APPLICATIONS OF INTRAOPERATIVE ELECTROCORTICOGRAPHY FOR EPILEPTOGENIC TISSUE MAPPING IN AWAKE GLIOMA SURGERY

Abstract New-onset epilepsy is a symptomatic expression of diffuse glioma and lowers the quality of life. Surgical resection could extend beyond the traditional lesionectomy and include the epileptic focus when permitted by neurological function. Intraoperative electrocorticography (ioECoG) is used during epilepsy surgery to estimate the epileptogenic tissue by mapping the irritative zone. We aimed to determine the added value of ioECoG for postoperative seizure control in patients with non-refractory, glioma-related seizures. We retrospectively included patients who underwent ioECoG-assisted (awake) tumor resection. The ioECoG tailoring strategy was based on electrographic seizures and interictal discharges (sporadic spikes, continuous spiking patterns, and sharp waves). The extent of resection (EOR) and the residual tumor volume (cm3) were quantified from pre- and postoperative magnetic resonance imaging. We used the Weibull regression model for multivariate time to event (seizure recurrence) analyses. Fifty patients underwent ioECoG-assisted surgery. IoECoG recorded eight (16%) spontaneous electrographic seizures. Seventeen patients had residual interictal discharges after tumor resection. Residual interictal discharges were significantly associated with shorter seizure-free period after surgery (HR = 3.1 [1.3 – 7.2], p-value = 0,01). This effect was especially prominent in primary high-grade glioma resections. Residual tumor volume and EOR did not associate with seizure outcome. We sampled 14 interictal spike-positive brain tissues (three inside and 11 outside the MRI abnormalities) for additional histopathological analyses. Tumor cells were found in all specimens. The overall sensitivity of interictal spikes for tumor infiltration was 78% (95%CI [56 – 93]) and the specificity was 100%. IoECoG could serve multiple purposes in brain tumor surgery. It can assist in intraoperative seizure detection. Complete resection of epileptic discharges may improve seizure outcome independently of rest tumor volume or EOR. IoECoG could help guide supramaximal resection to improve seizure control and assist patient counseling. Furthermore, interictal spikes might serve as markers for intraoperative tumor identification.

Data-driven approach for the delineation of the irritative zone in epilepsy in MEG.

The reliable identification of the irritative zone (IZ) is a prerequisite for the correct clinical evaluation of medically refractory patients affected by epilepsy. Given the complexity of MEG data, visual analysis of epileptiform neurophysiological activity is highly time consuming and might leave clinically relevant information undetected. We recorded and analyzed the interictal activity from seven patients affected by epilepsy (Vectorview Neuromag), who successfully underwent epilepsy surgery (Engel > = II). We visually marked and localized characteristic epileptiform activity (VIS). We implemented a two-stage pipeline for the detection of interictal spikes and the delineation of the IZ. First, we detected candidate events from peaky ICA components, and then clustered events around spatio-temporal patterns identified by convolutional sparse coding. We used the average of clustered events to create IZ maps computed at the amplitude peak (PEAK), and at the 50% of the peak ascending slope (SLOPE). We validated our approach by computing the distance of the estimated IZ (VIS, SLOPE and PEAK) from the border of the surgically resected area (RA). We identified 25 spatiotemporal patterns mimicking the underlying interictal activity (3.6 clusters/patient). Each cluster was populated on average by 22.1 [15.0-31.0] spikes. The predicted IZ maps had an average distance from the resection margin of 8.4 ± 9.3 mm for visual analysis, 12.0 ± 16.5 mm for SLOPE and 22.7 ±. 16.4 mm for PEAK. The consideration of the source spread at the ascending slope provided an IZ closer to RA and resembled the analysis of an expert observer. We validated here the performance of a data-driven approach for the automated detection of interictal spikes and delineation of the IZ. This computational framework provides the basis for reproducible and bias-free analysis of MEG recordings in epilepsy.

WGCNA combined with GSVA to explore biomarkers of refractory neocortical epilepsy.

About two-thirds of epilepsy patients relapse within five years after surgery. It is significant to note that the limitations of current treatments stem from a lack of understanding of molecular mechanisms. In this study, Weighted Gene Co-expression Network Analysis (WGCNA) and Gene set variation analysis (GSVA) methods were used to analyze the total RNA data from 20 surgical removal samples (epileptogenic zone and irritative zone, EZ and IZ) of 10 Chinese patients with refractory neocortical epilepsy downloaded from the original microarray dataset (GSE31718) of the National Center for Biological Information -Gene Expression Omnibus database (NCBI-GEO). The late stages of the estrogen response pathway, the IL6-JAK-STAT3-signal pathway and G2 checkpoints are correlated with the EZ, whereas the early stages of the estrogen response pathway and TGF-β signal are more strongly expressed in the IZ. The allogeneic rejection, apical surface and the TGF-β signal are relevant to the high seizure frequency, the unfolded protein response and MYC-target are mostly expressed in patients with low-frequency seizures. Genes with high gene significance(GS) values that were correlated with seizure frequency include OSR2, CABP4, CAPSL, CYP4F8, and FRK in the pink module, and SH3GLB2, CHAC1 and DDX23 in the yellow module. The occurrence of EZ and IZ act on different biological mechanisms. The upregulated genes associated with seizure frequency include OSR2, CABP4, CAPSL, CYP4F8, and FRK, and the downregulated genes include SH3GLB2, CHAC1 and DDX23. The evidence of key genes and differential pathways obtained by WGCNA and GSVA may be biomarkers for novel preventive and pharmacological interventions in clinical practice.

WE-184. From “irritative zone” to “irritative network”: a novel interictal estimate of the epileptogenic zone using invasive EEG

WE-184. From “irritative zone” to “irritative network”: a novel interictal estimate of the epileptogenic zone using invasive EEG

Robot-Assisted Radiofrequency Ablation Combined with Thermodynamic Simulation for Epilepsy Reoperations.

Repeat craniotomies to treat recurrent seizures may be difficult, and minimally invasive radiofrequency ablation is an alternative therapy. On the basis of this procedure, we aimed to develop a more reliable methodology which is helpful for institutions where real-time image monitoring or electrophysiologic guidance during ablation are not available. We used simulation combined with a robot-assisted radiofrequency ablation (S-RARFA) protocol to plan and execute brain epileptic tissue lesioning. Trajectories of electrodes were planned on the robot system, and time-dependent thermodynamics was simulated with radiofrequency parameters. Thermal gradient and margin were displayed on a computer to calculate ablation volume with a mathematic equation. Actual volume was measured on images after the ablation. This small series included one pediatric and two adult patients. The remnant hippocampus, corpus callosum, and irritative zone around arteriovenous malformation nidus were all treated with S-RARFA. The mean error percentage of the volume ablated between preoperative simulation and postoperative measurement was 2.4 ± 0.7%. No complications or newly developed neurologic deficits presented postoperatively, and the patients had little postoperative pain and short hospital stays. In this pilot study, we preliminarily verified the feasibility and safety of this novel protocol. As an alternative to traditional surgeries or real-time monitoring, S-RARFA served as successful seizure reoperation with high accuracy, minimal collateral damage, and good seizure control.

Clinical Yield of Electromagnetic Source Imaging and Hemodynamic Responses in Epilepsy: Validation With Intracerebral Data.

Accurate delineation of the seizure-onset zone (SOZ) in focal drug-resistant epilepsy often requires stereo-EEG (SEEG) recordings. Our aims were to propose a truly objective and quantitative comparison between EEG/magnetoencephalography (MEG) source imaging (EMSI), EEG/fMRI responses for similar spikes with primary irritative zone (PIZ) and SOZ defined by SEEG and to evaluate the value of EMSI and EEG/fMRI to predict postsurgical outcome. We identified patients with drug-resistant epilepsy who underwent EEG/MEG, EEG/fMRI, and subsequent SEEG at the Epilepsy Service from the Montreal Neurological Institute and Hospital. We quantified multimodal concordance within the SEEG channel space as spatial overlap with PIZ/SOZ and distances to the spike-onset, spike maximum amplitude and seizure core intracerebral channels by applying a new methodology consisting of converting EMSI results into SEEG electrical potentials (EMSIe-SEEG) and projecting the most significant fMRI response on the SEEG channels (fMRIp-SEEG). Spatial overlaps with PIZ/SOZ (AUCPIZ, AUCSOZ) were assessed by using the area under the receiver operating characteristic curve (AUC). Here, AUC represents the probability that a randomly picked active contact exhibited higher amplitude when located inside the spatial reference than outside. Seventeen patients were included. Mean spatial overlaps with the PIZ and SOZ were 0.71 and 0.65 for EMSIe-SEEG and 0.57 and 0.62 for fMRIp-SEEG. Good EMSIe-SEEG spatial overlap with the PIZ was associated with smaller distance from the maximum EMSIe-SEEG contact to the spike maximum amplitude channel (median distance 14 mm). Conversely, good fMRIp-SEEG spatial overlap with the SOZ was associated with smaller distances from the maximum fMRIp-SEEG contact to the spike-onset and seizure core channels (median distances 10 and 5 mm, respectively). Surgical outcomes were correctly predicted by EEG/MEG in 12 of 15 (80%) patients and EEG/fMRI in 6 of 11(54%) patients. With the use of a unique quantitative approach estimating EMSI and fMRI results in the reference SEEG channel space, EEG/MEG and EEG/fMRI accurately localized the SOZ and the PIZ. Precisely, EEG/MEG more accurately localized the PIZ, whereas EEG/fMRI was more sensitive to the SOZ. Both neuroimaging techniques provide complementary localization that can help guide SEEG implantation and select good candidates for surgery.

SEEG in 3D: Interictal Source Localization From Intracerebral Recordings

BackgroundStereo-electroencephalography (SEEG) uses a three-dimensional configuration of depth electrodes to localize epileptiform activity, but traditional analysis of SEEG is spatially restricted to the point locations of the electrode contacts. Interpolation of brain activity between contacts might allow for three-dimensional representation of epileptiform activity and avoid pitfalls of SEEG interpretation.ObjectiveThe goal of this study was to validate SEEG-based interictal source localization and assess the ability of this technique to monitor far-field activity in non-implanted brain regions.MethodsInterictal epileptiform discharges were identified on SEEG in 26 patients who underwent resection, ablation, or disconnection of the suspected epileptogenic zone. Dipoles without (free) and with (scan) gray matter restriction, and current density (sLORETA and SWARM methods), were calculated using a finite element head model. Source localization results were compared to the conventional irritative zone (IZ) and the surgical treatment volumes (TV) of seizure-free vs. non-seizure-free patients.ResultsThe median distance from dipole solutions to the nearest contact in the conventional IZ was 7 mm (interquartile range 4–15 mm for free dipoles and 4–14 mm for scan dipoles). The IZ modeled with SWARM predicted contacts within the conventional IZ with 83% (75–100%) sensitivity and 94% (88–100%) specificity. The proportion of current within the TV was greater in seizure-free patients (P = 0.04) and predicted surgical outcome with 45% sensitivity and 93% specificity. Dipole solutions and sLORETA results did not correlate with seizure outcome. Addition of scalp EEG led to more superficial modeled sources (P = 0.03) and negated the ability to predict seizure outcome (P = 0.23). Removal of near-field data from contacts within the TV resulted in smearing of the current distribution (P = 0.007) and precluded prediction of seizure freedom (P = 0.20).ConclusionsSource localization accurately represented interictal discharges from SEEG. The proportion of current within the TV distinguished between seizure-free and non-seizure-free patients when near-field recordings were obtained from the surgical target. The high prevalence of deep sources in this cohort likely obscured any benefit of concurrent scalp EEG. SEEG-based interictal source localization is useful in illustrating and corroborating the epileptogenic zone. Additional techniques are needed to localize far-field epileptiform activity from non-implanted brain regions.

Localization of irritative zones in epilepsy with thermochromic silicone.

Background: During epilepsy surgery, the gold standard to identify irritative zones (IZ) is electrocorticography (ECoG); however, new techniques are being developed to detect IZ in epilepsy surgery and in neurosurgery in general, such as infrared thermography mapping (ITM), and the use of thermosensitive/thermochromic materials.Methods: In a cohort study of consecutive patients with focal drug-resistant epilepsy of the temporal lobe treated with surgery, we evaluated possible adverse effects to the transient placement of a thermochromic/thermosensitive silicone (TTS) on the cerebral cortex and their postoperative evolution. Furthermore, we compared the precision of TTS for detecting cortical IZ against the gold standard ECoG and with ITM, as proof of concept.Results: We included 10 consecutive patients, 6 women (60%) and 4 men (40%). Age ranges from 15 to 56 years, mean 33.2 years. All were treated with unilateral temporal functional lobectomy. The mean hospital stay was 4 days. There were no immediate or late complications associated with the use of any of the modalities described. In the 10 patients, we obtained consistency in locating the IZ with ECoG, ITM, and the TTS.Conclusion: The TTS demonstrated biosecurity in this series. The accuracy of the TTS to locate IZ was similar to that of ECoG and ITM in this study. More extensive studies are required to determine its sensitivity and specificity.

Low density electrical source imaging of the ictal onset zone in the surgical evaluation of children with epilepsy

PurposeTo investigate the utility of Low Density (LD) Electrical Source Imaging (ESI) to model the ictal onset zone (IOZ) for the surgical work up of children with medically refractory epilepsy. MethodsThis was a retrospective review of 12 patients from a district and regional pediatric epilepsy center, who underwent focal resections between 2014 and 2019. ESI was generated using the Curry 8 software, incorporating T1 Magnetic Resonance Imaging (MRI) scans and scalp electroencephalogram (EEG) recordings. Concordance of the ictal LD-ESI localizations to the epileptogenic zone was assessed by comparing the location of the ictal LD-ESI to the focal resection margins on neuroimaging and noting the post-operative outcomes at one year. Localizations determined by ictal LD-ESI were also compared to interictal LD-ESI, positron emission tomography (FDG-PET) and interictal magnetoencephalography (MEG). ResultsIctal ESI correctly localized the ictal onset zone in 4/6 patients, with all four being seizure free at one year. Similarly, interictal ESI localized the irritative zone in 7/9 patients with focal resections, with 6/7 being seizure free at one year. Additionally, we observed ictal ESI to be concordant to interictal ESI in 5/6 patients. Ictal ESI and interictal ESI were concordant to interictal MEG in 3/6 patients. Ictal ESI was concordant with FDG-PET in 6/7 cases. ConclusionIOZ source localization through LD-ESI is a promising complementary method of assessing the epileptogenic focus in children. These findings may support the inclusion of ictal LD-ESI within the pre-surgical evaluation of children to supplement current diagnostic tools.