Localization Of Seizure Onset Research Articles

Laser interstitial thermal therapy of a single nodule in a complex epileptic network with multiple periventricular nodular heterotopias.

Surgical management of drug-resistant epilepsy (DRE) in patients with multiple periventricular nodular heterotopias (PVNHs) is challenging. Identifying the location of seizure onset within these complex epileptic networks is difficult, and open resection carries risks of injury to surrounding functional white matter tracts such as optic radiations (ORs). The authors demonstrate tractography-assisted laser ablation of a single nodule in a patient with DRE and multiple PVNHs. Following surgery, visual fields were intact, highlighting the benefits of OR tractographic reconstruction. At 12 months postoperatively, the patient remained seizure free, suggesting the potential efficacy of targeting a single heterotopia within complex networks in well-selected cases. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2417.

Determinants of successful ictal SPECT injection in phase 1 epilepsy presurgical evaluation: Findings from the pediatric epilepsy research consortium surgery database project.

The main goal of presurgical evaluation in drug-resistant focal epilepsy is to identify a seizure onset zone (SOZ). Of the noninvasive, yet resource-intensive tests available, ictal single-photon emission computed tomography (SPECT) aids SOZ localization by measuring focal increases in blood flow within the SOZ via intravenous peri-ictal radionuclide administration. Recent studies indicate that geographic and center-specific factors impact utilization of these diagnostic procedures. Our study analyzed successful ictal SPECT acquisition (defined as peri-ictal injection during inpatient admission) using surgery-related data from the Pediatric Epilepsy Research Consortium (PERC) surgery database. We hypothesized that a high seizure burden, longer duration of video EEG monitoring (VEEG), and more center-specific hours of SPECT availability would increase the likelihood of successful ictal SPECT. We identified study participants (≤18 years of age) who underwent SPECT as part of their phase 1 VEEG from January 2018 to June 2022. We assessed association between ictal SPECT outcomes (success vs. failure) and variables including patient demographics, epilepsy history, and center-specific SPECT practices. Phase 1 VEEG monitoring with ictal SPECT injection was planned in 297 participants and successful in 255 participants (85.86%). On multivariable analysis, the likelihood of a successful SPECT injection was higher in patients of non-Hispanic ethnicity (p = 0.040), shorter duration VEEG (p = 0.004), and higher hours of available SPECT services (p < 0.001). Higher seizure frequency (p = 0.033) was significant only in bivariate analysis. Patients treated at centers with more operational hours were more likely to experience pre-admission protocols prior to VEEG (p = 0.002). There is inter-center variability in protocols and SPECT acquisition capabilities. Shorter duration of EEG monitoring, non-Hispanic ethnicity (when on private insurance), extended operational hours of nuclear medicine as noted on multivariate analysis and higher seizure frequency in bivariate analysis are strongly associated with successful ictal SPECT injection. In pediatric patients with drug-resistant epilepsy, single-photon emission computed tomography (SPECT) scans can be helpful in localizing seizure onset zone. However, due to many logistical challenges described below, which include not only the half-life of the technetium isotope used to inject intravenously during a seizure (called the ictal SPECT scan) but also available nuclear scanner time in addition to the unpredictability of seizures, obtaining an ictal SPECT during a planned elective inpatient hospital stay is not guaranteed. Thus, as healthcare costs increase, planning a prolonged hospital stay during which an ictal SPECT scan is not feasible is not optimal. We leveraged our prospective surgery database to look at center-specific factors and patient-specific factors associated with an ictal SPECT injection in the first, pediatric-focussed, large-scale, multicenter, prospective, SPECT feasibility study. We found that longer availability of the scanner is the most important center-specific factor in assuring ictal SPECT injection. Although seizure frequency is an important patient-specific factor on bivariate analysis, this factor lost statistical significance when other factors like patient insurance status and video EEG duration were also considered in our multivariable logistical model.

1139 Retrospective Review of Stereotactic Electroencephalogram Recordings in Temporal Lobectomy Patients Demonstrates the Predictive Value of Interictal Cross-frequency Correlations

INTRODUCTION: Positive correlations between low and high frequency spectra in invasive electroencephalogram (EEG) have been implicated in pathological brain activity interictally and have been used for ictal detection in both focal and network models. METHODS: We retrospectively analyzed interictal signals from 22 patients who underwent SEEG at our institution between 12/2/14 to 12/8/20. We then analyzed significant HG/Beta cross-frequency correlations using similar processing to our previous publication. These signals were then separated based on temporal and extra-temporal locations. We further evaluated any statistical differences between the seizure free (SF) and non-seizure free (NSF) groups, and mesial (M) versus mesial temporal-plus (M+) onset location. RESULTS: 1) Clinical recordings from SEEG electrodes can detect cross-frequency correlations between HG/Beta using our previous methodology. 2) Positive correlations are significantly increased in temporal versus other sampled areas. 3) Positive correlations are more predictive of seizure onset during asleep recordings. 4) NSF patients show a significantly higher proportion of positive electrodes in the resected temporal lobe than SF patients. 5) SF patients have a greater proportion of significant contacts in the mesial versus the lateral temporal lobe than NSF patients. 6) Significant HG/Beta correlations in the mesial versus lateral temporal lobe predict seizure freedom better than ictal SEEG localization of seizure onset to M or M+ locations. CONCLUSIONS: We present preliminary data that local HG/Beta correlations may be predictive for epilepsy focus and surgical outcome and may have utility as adjunct methods to conventional SEEG analysis. Further studies are needed to determine strategies for prospective studies and clinical use.

Systematic 1 Hz direct electrical stimulation for seizure induction: A reliable method for localizing seizure onset zone and predicting seizure freedom

ObjectiveTo prospectively investigate the utility of seizure induction using systematic 1 Hz stimulation by exploring its concordance with the spontaneous seizure onset zone (SOZ) and relation to surgical outcome; comparison with seizures induced by non-systematic 50 Hz stimulation was attempted as well. MethodsProspective cohort study from 2018 to 2021 with ≥ 1 y post-surgery follow up at Yale New Haven Hospital. With 1 Hz, all or most of the gray matter contacts were stimulated at 1, 5, and 10 mA for 30–60s. With 50 Hz, selected gray matter contacts outside of the medial temporal regions were stimulated at 1–5 mA for 0.5–3s. Stimulation was bipolar, biphasic with 0.3 ms pulse width. The Yale Brain Atlas was used for data visualization. Variables were analyzed using Fisher's exact, χ2, or Mann–Whitney test. ResultsForty-one consecutive patients with refractory epilepsy undergoing intracranial EEG for localization of SOZ were included. Fifty-six percent (23/41) of patients undergoing 1 Hz stimulation had seizures induced, 83% (19/23) habitual (clinically and electrographically). Eighty two percent (23/28) of patients undergoing 50 Hz stimulation had seizures, 65% (15/23) habitual. Stimulation of medial temporal or insular regions with 1 Hz was more likely to induce seizures compared to other regions [15/32 (47%) vs. 2/41 (5%), p < 0.001]. Sixteen patients underwent resection; 11/16 were seizure free at one year and all 11 had habitual seizures induced by 1 Hz; 5/16 were not seizure free at one year and none of those 5 had seizures with 1 Hz (11/11 vs 0/5, p < 0.0001). No patients had convulsions with 1 Hz stimulation, but four did with 50 Hz (0/41 vs. 4/28, p = 0.02). SignificanceInduction of habitual seizures with 1 Hz stimulation can reliably identify the SOZ, correlates with excellent surgical outcome if that area is resected, and may be superior (and safer) than 50 Hz for this purpose. However, seizure induction with 1 Hz was infrequent outside of the medial temporal and insular regions in this study.

Stereotactic Electroencephalogram Recordings in Temporal Lobectomy Patients Demonstrates the Predictive Value of Interictal Cross-Frequency Correlations: A Retrospective Study.

Positive correlations between low- and high-frequency spectra from stereotactic electroencephalogram (SEEG) recordings have been implicated in pathological brain activity interictally and have been used for ictal detection in both focal and network models. We evaluated SEEG signals in patients who ultimately underwent temporal lobectomy to evaluate their utility in seizure localization and prediction of seizure freedom post-resection. We retrospectively analyzed cross-frequency correlations between beta and high gamma (HG) interictal SEEG signals from 22 patients. We compared signals based on temporal versus extra-temporal locations, seizure-free (SF) versus non-seizure-free (NSF) outcomes, and mesial (M) versus mesial temporal-plus (M+) onset. Positive cross-correlations were increased in temporal areas. NSF patients showed a higher proportion of positive electrodes in temporal areas. SF patients had a greater proportion of significant channels in mesial versus lateral temporal areas. HG/Beta correlations in mesial versus lateral temporal areas predicted seizure freedom better than ictal SEEG seizure onset localization to M or M+ locations. We present preliminary data that local HG/Beta correlations may predict epilepsy focus and surgical outcome and may have utility as adjunct methods to conventional SEEG analysis. Further studies are needed to determine strategies for prospective studies and clinical use.

Localizing seizure onset zone by a cortico-cortical evoked potentials-based machine learning approach in focal epilepsy

ObjectiveWe aimed to develop a new approach for identifying the localization of the seizure onset zone (SOZ) based on corticocortical evoked potentials (CCEPs) and to compare the connectivity patterns in patients with different clinical phenotypes. MethodsFifty patients who underwent stereoelectroencephalography and CCEP procedures were included. Logistic regression was used in the model, and six CCEP metrics were input as features: root mean square of the first peak (N1RMS) and second peak (N2RMS), peak latency, onset latency, width duration, and area. ResultsThe area under the curve (AUC) for localizing the SOZ ranged from 0.88 to 0.93. The N1RMS values in the hippocampus sclerosis (HS) group were greater than that of the focal cortical dysplasia (FCD) IIa group (p < 0.001), independent of the distance between the recorded and stimulated sites. The sensitivity of localization was higher in the seizure-free group than in the non-seizure-free group (p = 0.036). ConclusionsThis new method can be used to predict the SOZ localization in various focal epilepsy phenotypes. SignificanceThis study proposed a machine-learning approach for localizing the SOZ. Moreover, we examined how clinical phenotypes impact large-scale abnormality of the epileptogenic networks.

Combined Depth and Subdural Electrodes for Lateralization of the Ictal Onset Zone in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

(1) Objective: This study aimed to explore the efficacy of conventional invasive techniques in confirming unilateral seizure onset localization in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to investigate the association between electrode type and intracranial electroencephalography (EEG) pattern. (2) Methods: This retrospective study encompasses patients diagnosed with MTLE-HS who underwent an invasive study prior to an anterior temporal lobectomy (ATL). Intracranial EEG features were assessed for 99 seizure events from 25 selected patients who achieved seizure remission with ATL after an invasive study using bilateral combined depth and subdural electrodes. Their findings were compared to those of 21 seizure events in eight patients who exhibited suboptimal seizure outcomes. (3) Results: For the distribution of electrodes that recorded the ictal onset, hippocampal depth electrodes recorded 96% of all seizure events, while subdural electrodes recorded 52%. Among the seizures recorded in subdural electrodes, 49% were localized in medial electrodes, with only 8% occurring in lateral electrodes. The initiation of seizures exclusively detected in hippocampal depth electrodes was associated with successful seizure remission, whereas those solely recorded in the lateral strip electrodes were often linked to refractory seizures after ATL. (4) Conclusions: These findings emphasize the importance of employing a combination of depth and subdural electrodes in invasive studies for patients with MTLE-HS to enhance the accuracy of lateralization. This also cautions against sole reliance on subdural electrodes without depth electrodes, which could lead to inaccurate localization.

Clinical outcomes following responsive neurostimulation implantation: a single center experience.

Responsive neurostimulation (RNS) is an implantable device for persons with medically refractory focal-onset epilepsy. We report a single-center experience for RNS outcomes with special focus on stereoelectroencephalography (sEEG) for seizure onset localization. We performed retrospective review of patients with drug resistant focal epilepsy implanted with the RNS System for a minimum of six months between July 2014 and July 2019. Records were reviewed for demographic data, epilepsy duration, seizure frequency, number of prior antiepileptic drugs (AEDs), number of AEDs at RNS System implantation, prior epilepsy surgery or device use, previous seizure localization with sEEG, and RNS system information. Clinical response was defined as a 50% reduction in seizures. Differing response rates were calculated using Fisher Exact test. 30 patients met inclusion criteria. Seventeen (57%) underwent previous sEEG. Average clinical follow up was 3.0 years. Overall response rate was 70%. Median seizure reduction was 74.5%. Response rate was 82.3% for patients with sEEG compared to 53.8% without (p = 0.08); 37.5% for prior epilepsy surgery compared to 81.8% without (p = 0.02); 70% for mesial temporal onset; 50% for previous vagal nerve stimulator compared to 77.3% without (p = 0.13). Our response rates match or surpass outcome metrics of previous studies. Although limited by small study size, subpopulation analyses show positive response rates in patients with previous sEEG versus no sEEG and in temporal versus extratemporal pathology. Additional research is needed to evaluate efficacy of RNS in patients with previous epilepsy surgery, and utility of sEEG in this population.

Using pre-surgical suspicion to guide insula implantation strategy

RationaleInsular epilepsy can be a challenging diagnosis due to overlapping semiology and scalp EEG findings with frontal, temporal, and parietal lobe epilepsies. Stereotactic electroencephalography (sEEG) provides an opportunity to better localize seizure onset. The possibility of improved localization is balanced by implantation risk in this vascularly rich anatomic region. We review both safety and pre-implantation factors involved in insular electrode placement across four years at an academic medical center. MethodsPresurgical data, operative reports, and invasive EEG summaries were retrospectively reviewed for patients undergoing invasive epilepsy monitoring on the insula from 2016 through 2019. EEG reports were reviewed to record the presence of insula ictal and interictal involvement. We recorded which presurgical findings suggested insular involvement (insula lesion on MRI, insula changes on PET/SPECT/scalp EEG, characteristic semiology, or history of failed anterior temporal lobectomy). The likelihood of pre-sEEG insular onset was categorized as low suspicion if no presurgical findings were present (“rule out”), moderate suspicion if one finding was present, and high suspicion if two or more findings were present. Results76 patients received 189 insular electrodes as part of their implantation strategy for 79 surgical cases. Seven patients (8.9%) had insular ictal onset. One clinically significant complication (left hemiparesis) occurred in a patient with moderate suspicion for insular onset. There were 38 low suspicion cases, 36 moderate suspicion cases, and 5 high suspicion cases for pre-sEEG insula ictal onset. Two low suspicion (5.3%), three moderate suspicion (8.6%), and two high suspicion (40%) cases had insular ictal onset. ConclusionsThe insula can safely receive sEEG. Having two or more presurgical factors indicating insular onset is a strong, albeit incomplete, predictor of insular seizure onset. Using pre-implantation clinical findings can offer clinicians predictive value for targeting the insula during invasive EEG monitoring.

External Validation of Novel Method of Seizure Onset Zone Localization Based on Neural Resonance (P2-1.006)

<h3>Objective:</h3> We aimed to validate a recently published technique that used neural resonance to localize seizure onset zones (SOZ) with a retrospective dataset collected at an external institution. Further, we critically examined the need for a larger, tailored prospective validation study. <h3>Background:</h3> Accurate localization of the SOZ could improve surgical outcomes in medically refractory epilepsy patients. A recent study successfully used a novel metric of neural resonance to retrospectively identify SOZ regions and predict surgical success. The technique leverages distinct electrophysiological features of evoked responses during single pulse electrode stimulation (SPES) and incorporates them into a dynamical model. We aimed to validate these findings with a retrospective cohort of six patients to assess whether neural resonance predicted surgical outcomes. <h3>Design/Methods:</h3> We collected intracranial electroencephalographic (iEEG) data from six patients that underwent intracranial monitoring, single-pulse electrical stimulation protocol, and resection surgery between June 2020 and May 2021. Four out of six patients were stimulated in both SOZ regions and non-SOZ regions and thus were tested using the logistic regression model trained on the original dataset at the primary study institution. <h3>Results:</h3> Three of the four patients had successful surgical outcomes. Of the four patients tested with the logistic regression model, only one out of four was predicted correctly; the model predicted success for one true success and the failure patient. <h3>Conclusions:</h3> We hypothesize that the non-reproducibility of the original findings are resultant of differences in a research-driven SPES protocol and a clinically driven stimulation protocol. The external validation dataset stimulated a fewer number of sites, used a different clinical EEG and stimulation system, and varied stimulation parameters in a different subspace. However, this work highlights the need for a large, prospective validation dataset that is multi-center and encompasses a wide range of parameters; the gathering of this dataset is currently underway. <b>Disclosure:</b> Mr. Barnagian has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Kang has nothing to disclose. Mark Hays has nothing to disclose. Dr. Gonzalez has nothing to disclose. Dr. Sarma has stock in Neurologic Solutions, Inc.. Dr. Barot has nothing to disclose.

Insulo-opercular stereoelectroencephalography exploration in children and young adults: Indications, techniques, and safety.

Sampling the insulo-opercular region with invasive recordings is crucial given the importance of this region in epileptic networks and a variety of electroclinical presentations. However, implantation of the insulo-opercular region via stereoelectroencephalography (sEEG) is considered technically challenging given complex vascular and gray matter relationships in this region. We investigated the safety of insulo-opercular sEEG exploration in children and young adults using standard sEEG approaches: (1) orthogonal insulo-opercular (including the pseudo-orthogonal insulo-opercular approach) and (2) medial-lateral insular oblique approach. We performed a retrospective cohort study of 30 consecutive patients who underwent 33 sEEG implantations. All patients had drug-resistant focal epilepsy, were between the ages of 4 and 21, and were operated at one institution between January 2019 and March 2021. Medical records and neuroimaging were reviewed. Hemorrhage, infection, and other complications were considered as outcome variables. A total of 519 electrodes were placed. Eighty-one were placed orthogonally into the temporal operculum, 53 orthogonally into the frontal operculum, and 19 obliquely into the insula. sEEG electrodes localized seizure onset to the insulo-opercular region in eight patients, leading to a resection three times, an ablation four times, and one peri-insular hemispherectomy. Of the 519 electrodes placed, none of them exhibited hemorrhage or serious complications. Of the 153 electrodes placed into the insula, none had any permanent deficits or complications and one had minor bleeding due to the electrode breaking. These results demonstrate that the orthogonal (including pseudo-orthogonal) and medial approaches to sampling the insula are safe.

Stereoelectroencephalography before 2 years of age.

Stereoelectroencephalography (SEEG) is a widely used technique for localizing seizure onset zones prior to resection. However, its use has traditionally been avoided in children under 2 years of age because of concerns regarding pin fixation in the immature skull, intraoperative and postoperative electrode bolt security, and stereotactic registration accuracy. In this retrospective study, the authors describe their experience using SEEG in patients younger than 2 years of age, with a focus on the procedure's safety, feasibility, and accuracy as well as surgical outcomes. A retrospective review of children under 2 years of age who had undergone SEEG while at Children's Hospital of Philadelphia between November 2017 and July 2021 was performed. Data on clinical characteristics, surgical procedure, imaging results, electrode accuracy measurements, and postoperative outcomes were examined. Five patients younger than 2 years of age underwent SEEG during the study period (median age 20 months, range 17-23 months). The mean age at seizure onset was 9 months. Developmental delay was present in all patients, and epilepsy-associated genetic diagnoses included tuberous sclerosis (n = 1), KAT6B (n = 1), and NPRL3 (n = 1). Cortical lesions included tubers from tuberous sclerosis (n = 1), mesial temporal sclerosis (n = 1), and cortical dysplasia (n = 3). The mean number of placed electrodes was 11 (range 6-20 electrodes). Bilateral electrodes were placed in 1 patient. Seizure onset zones were identified in all cases. There were no SEEG-related complications, including skull fracture, electrode misplacement, hemorrhage, infection, cerebrospinal fluid leakage, electrode pullout, neurological deficit, or death. The mean target point error for all electrodes was 1.0 mm. All patients proceeded to resective surgery, with a mean follow-up of 21 months (range 8-53 months). All patients attained a favorable epilepsy outcome, including Engel class IA (n = 2), IC (n = 1), ID (n = 1), and IIA (n = 1). SEEG can be safely, accurately, and effectively utilized in children under age 2 with good postoperative outcomes using standard SEEG equipment. With minimal modification, this procedure is feasible in those with immature skulls and guides the epilepsy team's decision-making for early and optimal treatment of refractory epilepsy through effective localization of seizure onset zones.

Localizing seizure onset zones in surgical epilepsy with neurostimulation deep learning.

In drug-resistant temporal lobe epilepsy, automated tools for seizure onset zone (SOZ) localization that use brief interictal recordings could supplement presurgical evaluations and improve care. Thus, the authors sought to localize SOZs by training a multichannel convolutional neural network on stereoelectroencephalography (SEEG) cortico-cortical evoked potentials. The authors performed single-pulse electrical stimulation in 10 drug-resistant temporal lobe epilepsy patients implanted with SEEG. Using 500,000 unique poststimulation SEEG epochs, the authors trained a multichannel 1-dimensional convolutional neural network to determine whether an SOZ had been stimulated. SOZs were classified with mean sensitivity of 78.1% and specificity of 74.6% according to leave-one-patient-out testing. To achieve maximum accuracy, the model required a 0- to 350-msec poststimulation time period. Post hoc analysis revealed that the model accurately classified unilateral versus bilateral mesial temporal lobe seizure onset, as well as neocortical SOZs. This was the first demonstration, to the authors' knowledge, that a deep learning framework can be used to accurately classify SOZs with single-pulse electrical stimulation-evoked responses. These findings suggest that accurate classification of SOZs relies on a complex temporal evolution of evoked responses within 350 msec of stimulation. Validation in a larger data set could provide a practical clinical tool for the presurgical evaluation of drug-resistant epilepsy.

Limited utility of structural MRI to identify the epileptogenic zone in young children with tuberous sclerosis.

The success of epilepsy surgery in children with tuberous sclerosis complex (TSC) hinges on identification of the epileptogenic zone (EZ). We studied structural MRI markers of epileptogenic lesions in young children with TSC. We included 26 children with TSC who underwent epilepsy surgery before the age of 3 years at five sites, with 12months or more follow-up. Two neuroradiologists, blinded to surgical outcome data, reviewed 10 candidate lesions on preoperative MRI for characteristics of the tuber (large affected area, calcification, cyst-like properties) and of focal cortical dysplasia (FCD) features (cortical malformation, gray-white matter junction blurring, transmantle sign). They selected lesions suspect for the EZ based on structural MRI, and reselected after unblinding to seizure onset location on electroencephalography (EEG). None of the tuber characteristics and FCD features were distinctive for the EZ, indicated by resected lesions in seizure-free children. With structural MRI alone, the EZ was identified out of 10 lesions in 31%, and with addition of EEG data, this increased to 48%. However, rates of identification of resected lesions in non-seizure-free children were similar. Across 251 lesions, interrater agreement was moderate for large size (κ=.60), and fair (κ=.24) for all other features. In young children with TSC, the utility of structural MRI features is limited in the identification of the epileptogenic tuber, but improves when combined with EEG data.

Magnetoencephalography: at the forefront of optimizing epilepsy surgery

Magnetoencephalography: at the forefront of optimizing epilepsy surgery

WS1.6. Focal-Onset Seizures: Surface Ictal EEG Recordings and Localization

Ictal EEG can be identified by sustained electrographic discharges showing onsets and offsets being clearly distinguished from background rhythm, consisting of rhythmic discharges of variable frequencies and morphology showing gradual variations in frequency and amplitude. Morphology of ictal onset patterns in focal epilepsies are quite diverse and varies even in a same patient. For localizing purposes, onset patterns of ictal EEG are most important than following ictal discharges and they are topographically divided into focal, regional, lateralized, and diffuse. From the electrophysiological point of view, scalp ictal EEG in focal epilepsy requires a source area of synchronized EEG activities spreading over at least 10 cm2, indicating that an ictal onset usually reflects already spreaded activities from the EZ, thus the localization of EZ should not be based upon ictal EEG onset alone but should require its correlation with other investigations. Considering that scalp EEG reflects electrical activities from the cortical surface, ictal discharges arising from the EZ locating in deep sulci or deep cortical structures are not readily picked up by scalp EEG until they spread a significant distance to the cortical surface under the recording electrodes. Another caveat of ictal EEG is that the degree of synchronization is difficult to recognize from the surface EEG. In cases of poor synchrony, scalp EEG may not detect any clear focal or regional discharges but showing widely spread arrhythmic activities, thus fail to carry any localizing information. The lateralizing value of ictal scalp EEG seem to be higher in temporal lobe epilepsy than extratemporal lobe epilepsy, which were reported 76% to 83% and 47% to 65%, respectively. The probability of false lateralization was around 1% to 7% with remaining proportion of ictal EEG being unhelpful due to contamination by severe artifacts or diffuse discharges without focal features. The source localization of ictal onset rhythm by high-density EEG is an emerging technique that seems to perform similarly well to the source localization of interictal spike, which has been proved in large patient cohorts to be accurate and clinically relevant, with positive and negative predictive values rivaling those of structural MRI, although there remain questions regarding the processing of signals for reliable results. A further promising development in seizure onset localization is the inclusion of directed connectivity analysis: thus, not only the most active source is taken into consideration when localizing the onset of a seizure, but also how strongly each source broadcasts its activity to other brain regions (the so-called outgoing connections). Such an approach was shown to be more accurate than merely considering the most active source.

Volumetric glutamate imaging (GluCEST) using 7T MRI can lateralize nonlesional temporal lobe epilepsy: A preliminary study.

IntroductionDrug‐resistant epilepsy patients show worse outcomes after resection when standard neuroimaging is nonlesional, which occurs in one‐third of patients. In prior work, we employed 2‐D glutamate imaging, Glutamate Chemical Exchange Saturation Transfer (GluCEST), to lateralize seizure onset in nonlesional temporal lobe epilepsy (TLE) based on increased ipsilateral GluCEST signal in the total hippocampus and hippocampal head. We present a significant advancement to single‐slice GluCEST imaging, allowing for three‐dimensional analysis of brain glutamate networks.MethodsThe study population consisted of four MRI‐negative, nonlesional TLE patients (two male, two female) with electrographically identified left temporal onset seizures. Imaging was conducted on a Siemens 7T MRI scanner using the CEST method for glutamate, while the advanced normalization tools (ANTs) pipeline and the Automated Segmentation of the Hippocampal Subfields (ASHS) method were employed for image analysis.ResultsVolumetric GluCEST imaging was validated in four nonlesional TLE patients showing increased glutamate lateralized to the hippocampus of seizure onset (p = .048, with a difference among ipsilateral to contralateral GluCEST signal percentage ranging from −0.05 to 1.37), as well as increased GluCEST signal in the ipsilateral subiculum (p = .034, with a difference among ipsilateral to contralateral GluCEST signal ranging from 0.13 to 1.57).ConclusionsThe ability of 3‐D, volumetric GluCEST to localize seizure onset down to the hippocampal subfield in nonlesional TLE is an improvement upon our previous 2‐D, single‐slice GluCEST method. Eventually, we hope to expand volumetric GluCEST to whole‐brain glutamate imaging, thus enabling noninvasive analysis of glutamate networks in epilepsy and potentially leading to improved clinical outcomes.

Imaging of focal seizures with Electrical Impedance Tomography and depth electrodes in real time

Intracranial EEG is the current gold standard technique for localizing seizures for surgery, but it can be insensitive to tangential dipole or distant sources. Electrical Impedance Tomography (EIT) offers a novel method to improve coverage and seizure onset localization. The feasibility of EIT has been previously assessed in a computer simulation, which revealed an improved accuracy of seizure detection with EIT compared to intracranial EEG. In this study, slow impedance changes, evoked by cell swelling occurring over seconds, were reconstructed in real time by frequency division multiplexing EIT using depth and subdural electrodes in a swine model of epilepsy. EIT allowed to generate repetitive images of ictal events at similar time course to fMRI but without its significant limitations. EIT was recorded with a system consisting of 32 parallel current sources and 64 voltage recorders. Seizures triggered with intracranial injection of benzylpenicillin (BPN) in five pigs caused a repetitive peak impedance increase of 3.4 ± 1.5 mV and 9.5 ± 3% (N =205 seizures); the impedance signal change was seen already after a single, first seizure. EIT enabled reconstruction of the seizure onset 9 ± 1.5 mm from the BPN cannula and 7.5 ± 1.1 mm from the closest SEEG contact (p<0.05, n =37 focal seizures in three pigs) and it could address problems with sampling error in intracranial EEG. The amplitude of the impedance change correlated with the spread of the seizure on the SEEG (p <<0.001, n =37). The results presented here suggest that combining a parallel EIT system with intracranial EEG monitoring has a potential to improve the diagnostic yield in epileptic patients and become a vital tool in improving our understanding of epilepsy.

Assessment of localization accuracy and postsurgical prediction of simultaneous 18F-FDG PET/MRI in refractory epilepsy patients.

To evaluate the accuracies of simultaneous 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ([18F]-FDG PET/MRI) in preoperative localization and the postsurgical prediction. This retrospective study was performed on ninety-eight patients diagnosed with refractory epilepsy whose presurgical evaluation included [18F]-FDG PET/MRI, with 1-year post-surgery follow-up between August 2016 and December 2018. PET/MRI images were interpreted by two radiologists and a nuclear medicine physician to localize the EOZ using standard visual analysis and asymmetry index based on standard uptake value (SUV). The localization accuracy and predictive performance of simultaneous 18F-FDG PET/MRI based on the surgial pathology and postsurgical outcome were evaluated. A total of 41.8% (41/98) patients were found to have a definitely structural abnormality on the MR portion of PET/MRI; 93.9% (92/98) were shown hypometabolism on the PET portion of the hybrid PET/MRI. PET/MRI identified 18 cases with subtle structural abnormalities on MRI re-read. Six percent (6/98) of patients PET/MRI were negative. A total of 65.3% (64/98) patients showed seizure-free at 1-year follow-up after epilepsy surgery. The sensitivity, specificity, and accuracy of [18F]-FDG PET/MRI was 95.3%, 8.8%, and 65.3% for seizure onset localization based on surgical pathology and postsurgical outcome, respectively. Multivariate regression analysis indicated that concordant of EOZ localization between PET/MRI and surgical resection range, which was a good positive predictor of seizure freedom (Engel I) (OR = 14.741, 95% CI 3.934-55.033, p < 0.001). [18F]-FDG PET/MRI used as two combined modalities providing additional sensitivity when detecting possible epileptic foci and will probably improve the surgical outcome. • Sensitivity, specificity, and accuracy of [18F]-FDG PET/MRI were 95.3%, 8.8%, and 65.3% for seizure onset localization based on surgical pathology and postsurgical outcome, respectively. • Concordance of EOZ localization between PET/MRI and surgical resection range was a good positive predictor of seizure freedom; presurgical [18F]-FDG PET/MRI will probably improve the surgical outcome.

HFO Detection in Epilepsy: A Stacked Denoising Autoencoder and Sample Weight Adjusting Factors-Based Method.

High-frequency oscillations (HFOs) recorded by the intracranial electroencephalography (iEEG) are the promising biomarkers of epileptogenic zones. Accurate detection of HFOs is the key to pre-operative assessment for epilepsy. Due to the subjective bias caused by manual features and the class imbalance between HFOs and false HFOs, it is difficult to obtain satisfactory detection performance by the existing methods. To solve these problems, we put forward a novel method to accurately detect HFOs based on the stacked denoising autoencoder (SDAE) and the ensemble classifier with sample weight adjusting factors. First, the adjustable threshold of Hilbert envelopes is proposed to isolate the events of interest (EoIs) from background activities. Then, the SDAE network is utilized to automatically extract features of EoIs in the time-frequency domain. Finally, the AdaBoost-based support vector machine ensemble classifier with sample weight adjusting factors is devised to separate HFOs from EoIs by using the extracted features. These adjusting factors are used to solve the class imbalance problem by adjusting sample weights when learning the base classifiers. Our HFO detection method is evaluated by using clinical iEEG data recorded from 20 patients with medically refractory epilepsy. The experimental results show that our detection method outperforms some existing methods in terms of sensitivity and false discovery rate. In addition, the HFOs detected by our method are effective for localizing seizure onset zones.