Seizure Onset Zone Research Articles

Comparison of Ictal SPECT with 99mTc-HMPAO versus MRI for the Epileptic Seizure Onset Zone Detection in Saudi Patients

Background: In the presurgical evaluation of patients with drug-resistant epilepsy, magnetic resonance imaging (MRI) and ictal brain perfusion SPECT with the chemical microspheres 99mTc-HMPAO are widely used for diagnosing the seizure onset zone (SOZ). For both modalities, there is theoretical controversy over favoring one over the other. This study aimed to compare the performance of 99mTc-HMPAO SPECT with MRI for SOZ identification in EEG-proved epileptic Saudi patients. Methods and Results: For this observational retrospective study, the database of the nuclear medicine departments at the Prince Sultan Military Medical City (PSMMC) and King Abdullah bin Abdulaziz University Hospital (KAAUH) were searched for male and female patients with suspected unifocal epilepsy in whom ictal brain perfusion SPECT and MRI had been performed for presurgical evaluation. A total of 14 adult epileptic patients above 18 years were included who have undergone SPECT scans using 99mTc-HMPAO and MRI between Jan 2014 and Dec 2021. 99mTc-HMPAO SPECT and MRI scans were performed simultaneously for each patient, and there was almost general agreement that 99mTc-HMPAO SPECT accurately localized and detected the SOZ in 12/14 patients (sensitivity 85.71%). It was superior to MRI, which detected and localized the SOZ in only 7/14 patients (sensitivity 50.0%). Unfortunately, the specificity of ictal brain perfusion SPECT, by using 99mTc-HMPAO in seizure localization in epileptic patients, was not detected due to the shortage of data that led to all the EEG findings being 100% positive. Conclusion: This study reported that ictal SPECT using 99mTc-HMPAO provides more valuable information about SOZ localization than MRI. However, future studies with a larger sample size are needed to assess the specificity of 99mTc-HMPAO SPECT in detecting the SOZ.

Comparative effectiveness of stereotactic, subdural, or hybrid intracranial EEG monitoring in epilepsy surgery.

Surgical intervention can be curative or palliative for drug-resistant focal epilepsy. However, if the seizure onset zone (SOZ) cannot be adequately localized via noninvasive tests, intracranial EEG (iEEG) recordings are often carried out to develop surgical plans in appropriate candidates. Stereotactic EEG (SEEG), subdural EEG (SDE), and SDE with depth electrodes (hybrid) are major tools used for investigation, but there is no class 1 or 2 evidence comparing the effectiveness of these modalities. The authors identified an institutional cohort of patients who underwent iEEG monitoring between 2001 and 2022. Demographic data, preoperative clinical features, iEEG intervention, and follow-up data were identified. Primary study endpoints included the following: 1) likelihood of SOZ localization; 2) likelihood of surgical treatment after iEEG; 3) seizure outcomes; and 4) complications. A total of 329 patients were identified (176 in the SEEG, 60 in the SDE, and 93 in the hybrid cohort) who were followed for a median of 5.4 (IQR 6.8) years. Baseline characteristics, including demographics, mean age at epilepsy diagnosis, mean age at iEEG investigation, number of preoperative antiseizure medications, and preoperative seizure frequency, were not statistically different across the 3 cohorts. Patients in the SEEG cohort were more likely to have their SOZ localized than were the patients in the SDE group (OR 2.3) and were less likely to undergo subsequent resection (OR 0.3) or to have complications (OR 0.4), although there was no statistical difference with respect to likelihood of undergoing any subsequent neurosurgical treatment, or with respect to favorable seizure outcomes. Patients in the hybrid cohort were more likely to have SOZ localized than were patients in the SDE group (OR 3.1), but were more likely to undergo resection (OR 4.9) or any neurosurgical treatment (OR 2.5) compared to patients in the SEEG group. Patients in the hybrid cohort had better seizure outcomes compared to the SDE (OR 2.3) but not to the SEEG group. Patients in the SEEG group were more likely to have their SOZ localized and patients in the SDE group were more likely to undergo resection, but they did not differ with respect to seizure outcomes.

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.

Preoperative Simulation in Epilepsy Surgery

In patients with intractable epilepsy, seizure focus resection can yield favorable seizure outcomes. First, the localization of the seizure focus is estimated by noninvasive methods such as magnetic resonance imaging(MRI), video-electroencephalography(EEG)monitoring, nuclear medicine examinations, magnetoencephalography, and neuropsychological tests. A subgroup of patients may require additional information obtained from the intracranial EEG. There are two major methods for intracranial EEG: intracranial EEG with subdural grid electrodes(SDG)and stereotactic electroencephalography. If the estimated seizure focus overlaps with the eloquent area in noninvasive studies, the margin and extent of the resection are determined by the results of intracranial EEG and functional mapping by electrical cortical stimulation. Herein, we present a case of lobe epilepsy with subtle MRI lesions in the superior temporal sulcus of the language-dominant hemisphere. The results of the SDG and functional mapping showed that the seizure onset zone overlapped with the language area. Resection of the middle and inferior temporal gyri and multiple transections of the language area resulted in Engel IIB seizure outcomes. In such cases, a thorough preoperative simulation is required to determine the best resection margin for seizure control and functional preservation.

Ictal Central Apnea Is Predictive of Mesial Temporal Seizure Onset: An Intracranial Investigation.

Ictal central apnea (ICA) is a semiological sign of focal epilepsy, associated with temporal and frontal lobe seizures. In this study, using qualitative and quantitative approaches, we aimed to assess the localizational value of ICA. We also aimed to compare ICA clinical utility in relation to other seizure semiological features of focal epilepsy. We analyzed seizures in patients with medically refractory focal epilepsy undergoing intracranial stereotactic electroencephalographic (SEEG) evaluations with simultaneous multimodal cardiorespiratory monitoring. A total of 179 seizures in 72 patients with reliable artifact-free respiratory signal were analyzed. ICA was seen in 55 of 179 (30.7%) seizures. Presence of ICA predicted a mesial temporal seizure onset compared to those without ICA (odds ratio = 3.8, 95% confidence interval = 1.3-11.6, p = 0.01). ICA specificity was 0.82. ICA onset was correlated with increased high-frequency broadband gamma (60-150Hz) activity in specific mesial or basal temporal regions, including amygdala, hippocampus, and fusiform and lingual gyri. Based on our results, ICA has an almost 4-fold greater association with mesial temporal seizure onset zones compared to those without ICA and is highly specific for mesial temporal seizure onset zones. As evidence of symptomatogenic areas, onset-synchronous increase in high gamma activity in mesial or basal temporal structures was seen in early onset ICA, likely representing anatomical substrates for ICA generation. ICA recognition may help anatomoelectroclinical localization of clinical seizure onset to specific mesial and basal temporal brain regions, and the inclusion of these regions in SEEG evaluations may help accurately pinpoint seizure onset zones for resection. ANN NEUROL 2024;95:998-1008.

EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy

Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epilepsy is the most frequent form of epilepsy. In patients with drug-resistant focal epilepsy, epilepsy surgery is a treatment option depending on the localisation of the seizure focus for seizure relief or seizure freedom with consecutive improvement in quality of life. Beside examinations such as scalp video/electroencephalography (EEG) telemetry, structural, and functional magnetic resonance imaging (MRI), which are primary standard tools for the diagnostic work-up and therapy management of epilepsy patients, molecular neuroimaging using different radiopharmaceuticals with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) influences and impacts on therapy decisions. To date, there are no literature-based praxis recommendations for the use of Nuclear Medicine (NM) imaging procedures in epilepsy. The aims of these guidelines are to assist in understanding the role and challenges of radiotracer imaging for epilepsy; to provide practical information for performing different molecular imaging procedures for epilepsy; and to provide an algorithm for selecting the most appropriate imaging procedures in specific clinical situations based on current literature. These guidelines are written and authorized by the European Association of Nuclear Medicine (EANM) to promote optimal epilepsy imaging, especially in the presurgical setting in children, adolescents, and adults with focal epilepsy. They will assist NM healthcare professionals and also specialists such as Neurologists, Neurophysiologists, Neurosurgeons, Psychiatrists, Psychologists, and others involved in epilepsy management in the detection and interpretation of epileptic seizure onset zone (SOZ) for further treatment decision. The information provided should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals and imaging modalities.

Negative MRI and a seizure onset zone close to eloquent areas in FCD type II: Application of MRg-LiTT after a SEEG re-evaluation in pediatric patients with a previous failed surgery

ObjectiveNegative MRI and an epileptogenic zone (EZ) adjacent to eloquent areas are two main issues that can be encountered during pre-surgical evaluation for epilepsy surgery. Focal Cortical Dysplasia type II (FCD type II) is the most common aetiology underlying a negative MRI.The objective of this study is to present three cases of pediatric patients exhibiting negative MRI and a seizure onset zone close to eloquent areas, who previously underwent traditional open surgery or SEEG-guided radiofrequency thermocoagulations (RF-TC). After seizure seizure recrudescence, pre-surgical SEEG was re-evaluated and Magnetic Resonance-guided laser interstitial thermal therapy (MRg-LiTT) was performed.We discuss the SEEG patterns, the planning of laser probes trajectories and the outcomes one year after the procedure. MethodsPediatric patients who underwent SEEG followed by MRg-LiTT for drug-resistant epilepsy associated with FCD type II at our Centre were included. Pre-surgical videoEEG (vEEG), stereoEEG (sEEG), and MRI were reviewed. Post-procedure clinical outcome (measured by Engel score) and complications rates were evaluated. ResultsThree patients underwent 3 MRg-LiTT procedures from January 2022 to June 2022. Epileptogenic zone was previously studied via SEEG in all the patients. All the three patients pre-surgical MRI was deemed negative. Mean age at seizure onset was 47 months (21–96 months), mean age at MRg-LiTT was 12 years (10 years 10 months – 12 years 9 months). Engel class Ia outcome was achieved in patients #2 and #3, Engel class Ib in patient #1. Mean follow-up length was of 17 months (13 months – 20 months). Complications occurred in one patient (patient #2, extradural hematoma). ConclusionsThe combined use of SEEG and MRg-LiTT in complex cases can lead to good outcomes both as a rescue therapy after failed surgery, but also as an alternative to open surgery after a successful SEEG-guided Radiofrequency Thermocoagulation (RF-TC). Specific SEEG patterns and a previous good outcome from RF-TC can be predictors of a favourable outcome.

Effects of midazolam on high-frequency oscillations in amygdala and hippocampus of epilepsy patients.

High-frequency oscillations (HFOs) are associated with normal brain function, but are also increasingly recognized as potential biomarkers of epileptogenic tissue. Considering the important role of interneuron activity in physiological HFO generation, we studied their modulation by midazolam (MDZ), an agonist of γ-aminobutyric acid type A (GABAA)-benzodiazepine receptors. Here, we analyzed 80 intracranial electrode contacts in amygdala and hippocampus of 13 patients with drug-refractory focal epilepsy who had received MDZ for seizure termination during presurgical monitoring. Ripples (80-250 Hz) and fast ripples (FRs; 250-400 Hz) were compared before and after seizures with MDZ application, and according to their origin either within or outside the individual seizure onset zone (SOZ). We found that MDZ distinctly suppressed all HFOs (ripples and FRs), whereas the reduction of ripples was significantly less pronounced inside the SOZ compared to non-SOZ contacts. The rate of FRs inside the SOZ was less affected, especially in hippocampal contacts. In a few cases, even a marked increase of FRs following MDZ administration was seen. Our results demonstrate, for the first time, a significant HFO modulation in amygdala and hippocampus by MDZ, thus giving insights into the malfunction of GABA-mediated inhibition within epileptogenic areas and its role in HFO generation.

Utilizing Excitatory and Inhibitory Activity Derived from Interictal Intracranial Electroencephalography as Potential Biomarkers for Epileptogenicity.

Epileptogenic zones (EZs), where epileptic seizures cease after resection, are localized by assessing the seizure-onset zone using ictal electroencephalography (EEG). Owing to the difficulty in capturing unpredictable seizures, biomarkers capable of identifying EZs from interictal EEG are anticipated. Recent studies using intracranial EEG have identified several potential candidate biomarkers for epileptogenicity. High-frequency oscillation (HFO) was initially expected to be a robust biomarker of abnormal excitatory activity in the ictogenic region. However, HFO-guided resection failed to improve seizure prognosis. Meanwhile, the regularity of low-gamma oscillations (30-80 Hz) indicates inhibitory interneurons' hypersynchronization, which could be used to localize the EZ. Besides resting-state EEG assessments, evoked potentials elicited by single-pulse electrical stimulation, such as corticocortical evoked potentials (CCEP), became valuable tools for assessing epileptogenic regions. CCEP responses recorded in the cortex remote from the stimulation site indicate functional connectivity, revealing increased internal connectivity within the ictogenic region and elevated inhibitory input from the non-involved regions to the ictogenic region. Conversely, large responses close to the stimulation site reflect local excitability, manifesting as an increased N1 amplitude and overriding HFO. Further research is required to establish whether these novel electrophysiological methods, either individually or in combination, can function as robust biomarkers of epileptogenicity and hold promise for improving seizure prognosis.

Somatic Mosaicism in PIK3CA Variant Correlates With Stereoelectroencephalography-Derived Electrophysiology.

Brain-limited pathogenic somatic variants are associated with focal pediatric epilepsy, but reliance on resected brain tissue samples has limited our ability to correlate epileptiform activity with abnormal molecular pathology. We aimed to identify the pathogenic variant and map variant allele fractions (VAFs) across an abnormal region of epileptogenic brain in a patient who underwent stereoelectroencephalography (sEEG) and subsequent motor-sparing left frontal disconnection. We extracted genomic DNA from peripheral blood, brain tissue resected from peri-sEEG electrode regions, and microbulk brain tissue adherent to sEEG electrodes. Samples were mapped based on an anatomic relationship with the presumed seizure onset zone (SOZ). We performed deep panel sequencing of amplified and unamplified DNA to identify pathogenic variants with subsequent orthogonal validation. We detect a pathogenic somatic PIK3CA variant, c.1624G>A (p.E542K), in the brain tissue samples, with VAF inversely correlated with distance from the SOZ. In addition, we identify this variant in amplified electrode-derived samples, albeit with lower VAFs. We demonstrate regional mosaicism across epileptogenic tissue, suggesting a correlation between variant burden and SOZ. We also validate a pathogenic variant from individual amplified sEEG electrode-derived brain specimens, although further optimization of techniques is required.

Learn how to interpret and use intracranial EEG findings.

Epilepsy surgery is the therapy of choice for many patients with drug-resistant focal epilepsy. Recognizing and describing ictal and interictal patterns with intracranial electroencephalography (EEG) recordings is important in order to most efficiently leverage advantages of this technique to accurately delineate the seizure-onset zone before undergoing surgery. In this seminar in epileptology, we address learning objective "1.4.11 Recognize and describe ictal and interictal patterns with intracranial recordings" of the International League against Epilepsy curriculum for epileptologists. We will review principal considerations of the implantation planning, summarize the literature for the most relevant ictal and interictal EEG patterns within and beyond the Berger frequency spectrum, review invasive stimulation for seizure and functional mapping, discuss caveats in the interpretation of intracranial EEG findings, provide an overview on special considerations in children and in subdural grids/strips, and review available quantitative/signal analysis approaches. To be as practically oriented as possible, we will provide a mini atlas of the most frequent EEG patterns, highlight pearls for its not infrequently challenging interpretation, and conclude with two illustrative case examples. This article shall serve as a useful learning resource for trainees in clinical neurophysiology/epileptology by providing a basic understanding on the concepts of invasive intracranial EEG.

The value of additional electrodes when stereo-electroencephalography is inconclusive.

Stereo-electroencephalography (SEEG) is the preferred method for intracranial localization of the seizure-onset zone (SOZ) in drug-resistant focal epilepsy. Occasionally SEEG evaluation fails to confirm the pre-implantation hypothesis. This leads to a decision tree regarding whether the addition of SEEG electrodes (two-step SEEG - 2sSEEG) or placement of subdural electrodes (SDEs) after SEEG (SEEG2SDE) would help. There is a dearth of literature encompassing this scenario, and here we aimed to characterize outcomes following unplanned two-step intracranial EEG (iEEG). All 225 adult SEEG cases over 8 years at our institution were reviewed to extract patient data and outcomes following a two-step evaluation. Three raters independently quantified benefits of additional intracranial electrodes. The relationship between two-step iEEG benefit and clinical outcome was then analyzed. Fourteen patients underwent 2sSEEG and nine underwent SEEG2SDE. In the former cohort, the second SEEG procedure was performed for these reasons-precise localization of the SOZ (36%); defining margins of eloquent cortex (21%); and broadening coverage in the setting of non-localizable seizure onsets (43% of cases). Sixty-four percent of 2sSEEG cases were consistently deemed beneficial (Light's κ = 0.80). 2sSEEG performed for the first two indications was much more beneficial than when onsets were not localizable (100% vs 17%, p = .02). In the SEEG2SDE cohort, SDEs identified the SOZ and enabled delineation of margins relative to eloquent cortex in all cases. The two-step iEEG is useful if the initial evaluation is broadly concordant with the original electroclinical hypothesis, where it can clarify onset zones or delineate safe surgical margins; however, it provides minimal benefit when the implantation hypothesis is erroneous, and we recommend that 2sSEEG not be generally utilized in such cases. SDE implantation after SEEG minimizes the need for SDEs and is helpful in delineating surgical boundaries relative to ictal-onset zones and eloquent cortex.

The expert's knowledge combined with AI outperforms AI alone in seizure onset zone localization using resting state fMRI.

We evaluated whether integration of expert guidance on seizure onset zone (SOZ) identification from resting state functional MRI (rs-fMRI) connectomics combined with deep learning (DL) techniques enhances the SOZ delineation in patients with refractory epilepsy (RE), compared to utilizing DL alone. Rs-fMRI was collected from 52 children with RE who had subsequently undergone ic-EEG and then, if indicated, surgery for seizure control (n = 25). The resting state functional connectomics data were previously independently classified by two expert epileptologists, as indicative of measurement noise, typical resting state network connectivity, or SOZ. An expert knowledge integrated deep network was trained on functional connectomics data to identify SOZ. Expert knowledge integrated with DL showed a SOZ localization accuracy of 84.8 ± 4.5% and F1 score, harmonic mean of positive predictive value and sensitivity, of 91.7 ± 2.6%. Conversely, a DL only model yielded an accuracy of <50% (F1 score 63%). Activations that initiate in gray matter, extend through white matter, and end in vascular regions are seen as the most discriminative expert-identified SOZ characteristics. Integration of expert knowledge of functional connectomics can not only enhance the performance of DL in localizing SOZ in RE but also lead toward potentially useful explanations of prevalent co-activation patterns in SOZ. RE with surgical outcomes and preoperative rs-fMRI studies can yield expert knowledge most salient for SOZ identification.

The longitudinal effects of cannabidiol on brain temperature in patients with treatment-resistant epilepsy

Neuroinflammation (NI) is a key pathophysiological contributor to treatment-resistant epilepsy (TRE) that remains challenging to observe in vivo. Magnetic resonance spectroscopic imaging and thermometry (MRSI-t) is an emerging technique that can be used to non-invasively map brain temperature, whereby brain temperature elevations serve as a surrogate for the cellular and biochemical processes associated with NI. In a previous multimodal imaging study of focal epilepsy patients, we observed MRSI-t-based brain temperature elevations ipsilateral to the seizure onset zone (SOZ) that were concordant with evidence of edema (Sharma et al., 2023). Despite its potential as tool, it is unclear if MRSI-t can monitor changes in brain temperature in response to treatment. We imaged 25 participants approximately 12-weeks apart. Eight patients with TRE were imaged before receiving highly-purified pharmaceutical grade cannabidiol (CBD; pre-CBD) and after 12-weeks of CBD (on-CBD) therapy. Seventeen healthy controls (HCs) were also imaged twice. Repeated measures t-tests computed changes in TRE patients’ seizure symptoms, mood, and brain temperature within their respective SOZs. Repeated measures ANOVAs tested Group*Time changes in imaging data. Participants with TRE had abnormally high peak brain temperatures within their SOZs that decreased after CBD initiation (p < 0.0001). Seizure severity scores also improved after CBD initiation (p < 0.001). These findings provide insights into the possible neural effects of CBD, and further demonstrate MRSI-t’s potential as a tool for delineating SOZ. Further investigations into MRSI-t as a longitudinal measure of therapy-induced changes in NI are warranted.

Specific afterdischarge properties can enhance the clinical utility of electrical stimulation mapping during intracranial monitoring

ObjectiveExtraoperative electrical cortical stimulation (ECS) facilitates defining the seizure onset zone (SOZ) and eloquent cortex. The clinical relevance of stimulation-induced afterdischarges (ADs) is not well defined. MethodsFifty-five patients who underwent intracranial electroencephalogram evaluations with ECS were retrospectively identified. ADs were identified in these recordings and categorized by pattern, location, and association with stimulation-induced seizures. ResultsADs were generated in 1774/9285 (19%) trials. Rhythmic spikes and irregular ADs within the stimulated bipolar contact pair were predictive of location within the SOZ compared to non-epileptogenic/non-irritative cortex (rhythmic spikes OR 2.24, p = 0.0098; irregular OR 1.39; p = 0.013). ADs immediately preceding stimulated seizures occurred at lower stimulation intensity thresholds compared to other stimulations (mean 2.94 ± 0.28 mA vs. 4.16 ± 0.05 mA respectively; p = 0.0068). ConclusionsChanges in AD properties can provide clinically relevant data in extraoperative stimulation mapping. SignificanceAlthough not exclusive to the SOZ, the generation of rhythmic spikes may suggest that a stimulation location is within the SOZ, while decreased stimulation intensity thresholds eliciting ADs may alert clinicians to a heightened probability of seizure generation with subsequent stimulation.

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.

Connectivity of high-frequency bursts as SOZ localization biomarker.

For patients with refractory epilepsy, the seizure onset zone (SOZ) plays an essential role in determining the specific regions of the brain that will be surgically resected. High-frequency oscillations (HFOs) and connectivity-based approaches have been identified among the potential biomarkers to localize the SOZ. However, there is no consensus on how connectivity between HFO events should be estimated, nor on its subject-specific short-term reliability. Therefore, we propose the channel-level connectivity dispersion (CLCD) as a metric to quantify the variability in synchronization between individual electrodes and to identify clusters of electrodes with abnormal synchronization, which we hypothesize to be associated with the SOZ. In addition, we developed a specialized filtering method that reduces oscillatory components caused by filtering broadband artifacts, such as sharp transients, spikes, or direct current shifts. Our connectivity estimates are therefore robust to the presence of these waveforms. To calculate our metric, we start by creating binary signals indicating the presence of high-frequency bursts in each channel, from which we calculate the pairwise connectivity between channels. Then, the CLCD is calculated by combining the connectivity matrices and measuring the variability in each electrode's combined connectivity values. We test our method using two independent open-access datasets comprising intracranial electroencephalography signals from 89 to 15 patients with refractory epilepsy, respectively. Recordings in these datasets were sampled at approximately 1000Hz, and our proposed CLCDs were estimated in the ripple band (80-200Hz). Across all patients in the first dataset, the average ROC-AUC was 0.73, and the average Cohen's d was 1.05, while in the second dataset, the average ROC-AUC was 0.78 and Cohen's d was 1.07. On average, SOZ channels had lower CLCD values than non-SOZ channels. Furthermore, based on the second dataset, which includes surgical outcomes (Engel I-IV), our analysis suggested that higher CLCD interquartile (as a measure of CLCD distribution spread) is associated with favorable outcomes (Engel I). This suggests that CLCD could significantly assist in identifying SOZ clusters and, therefore, provide an additional tool in surgical planning for epilepsy patients.

Insights into epileptic aphasia: Intracranial recordings in a child with a left insular ganglioglioma

Intracranial EEG was recorded during a dialog-based task in a 16-year-old boy with a left insular ganglioglioma, medically intractable epilepsy, epileptic foci in auditory cortex on the lateral superior temporal gyrus (STG) and language deficiencies. Performance of the task was highly erratic, characterized by rapid cycling between providing correct answers, incorrect answers and failure to respond. There was no relationship between performance and the degree of concurrent epileptic activity in auditory cortex. High gamma activity in core auditory cortex (posterior medial Heschl’s gyrus, HGPM) was markedly diminished during listening and, with two exceptions, was less than activity from 17 control subjects. The two exceptions also had seizure onset zones in perisylvian cortex. Responses during listening were of smaller amplitude than those occurring during speaking, a pattern opposite that typically seen in the left HGPM. Within HGPM, lateral STG and pars opercularis of the inferior frontal gyrus, high gamma activity while listening was greatest when questions were correctly answered and least when the subject failed to respond. Alpha activity preceding utterances was lowest in pars opercularis when the subject failed to respond. Comparisons between resting state activity in another cohort of controls and the subject were most disparate in HGPM. Alpha activity during performance of the task was greatest in the mid-anterior cingulate when the subject failed to respond, suggesting dysfunction beyond the speech network and into the salience network. Multiple abnormalities noted in this patient paralleled those seen in epileptic aphasia and Rolandic epilepsy.

Resting state connectivity biomarkers of seizure freedom after epilepsy surgery

Alterations in brain networks may cause the lowering of the seizure threshold and hypersynchronization that underlie the recurrence of unprovoked seizures in epilepsy. The aim of this work is to estimate functional network characteristics, which may help predicting outcome of epilepsy surgery.Twenty patients were studied (11 females, 9 males, mean age 33 years) with scalp-recorded HD-EEG in resting state (eyes closed, no interictal discharges) before intracranial evaluation, which allowed the precise determination of the epileptogenic zone. Dipole source time courses in the brain were estimated using Weighted Minimum Norm Estimate based on HD-EEG signals. Information inflow and outflow of atlas-based brain regions were computed using partial directed connectivity. A set of graph measures for pairwise connections in standard EEG frequency bands was calculated.After epilepsy surgery 10 patients were seizure-free (Engel 1a) and 10 patients continued suffering from seizures (Engel outcome worse than 1a). Inflow of the regions containing the epileptogenic zone in the beta and delta frequency bands was significantly lower in patients who achieved seizure-freedom after surgery, compared with patients who continued to have seizures (p = 0.012, and p = 0.026, respectively). Average path length in the beta frequency band was significantly higher in patients who achieved seizure freedom (p = 0.012). In the delta frequency band, local efficiency and clustering coefficient were significantly higher in patients who achieved seizure freedom (0.033, 0.046).In patients who achieved seizure freedom after surgery, the preoperative analysis of the epileptic network exhibited stronger separation of the region containing the seizure onset zone, with less inflow of information. In contrast, shorter paths within the epileptic network may facilitate hypersynchronous neuronal activity and thus the recurrence of seizures in non-seizure free patients. This study supports the hypothesis that epileptic network properties might help to define suitable candidates for epilepsy surgery.

Insular lobe epilepsy. Part 2: presurgical evaluation & surgical interventions with stereo-electroencephalography

Identification of insular lobe epilepsy (ILE) presents a major clinical challenge in the diagnosis and treatment of drug-resistant focal epilepsies. ILE has diverse clinical presentations due to the multifaceted functions of the insula. Surface EEG findings do not provide straightforward information to predict this deeply-situated origin of seizures; they are even misleading, masquerading as those of other focal epilepsies, such as temporal and frontal ones. Non-invasive imagings may disclose insular abnormalities, but extra-insular abnormalities can coexist or even stand out. Careful reading and a second-look guided by other clinical information are crucial in order not to miss subtle insulo-opercular abnormalities. Furthermore, a possible insular origin of seizures should be considered in MRI-negative frontal/temporal/parietal epilepsies. Therefore, exploration/exclusion of insular-origin seizures is necessary for a great majority of surgical candidates. As for the stereo-electroencephalography, considered as the gold standard method for intra-cranial EEG investigations with suspicion of ILE, planning of electrode positions/trajectories require sufficient knowledge of the functional localization and anatomo-functional connectivity of the insula. Dense sampling within the insula is required in patients with probable ILE, because the seizure-onset zone can be restricted to a single insular gyrus or even a part of it. It is also crucial to explore extra-insular regions on the basis of non-invasive investigation results while considering their anatomo-functional relationships with the insula. From a surgical perspective, differentiating seizures strictly confined to the insula from those extending to the opercula is of particular importance. Pure insular seizures can be treated with less invasive measures, such as radiofrequency thermocoagulation. To conclude, close attention must be paid to the possibility of ILE throughout the diagnostic workup. The precise identification/exclusion of ILE is a prerequisite to provide appropriate and effective surgical treatment in pharmaco-resistant focal epilepsies.