Semiology in spontaneous versus cortical stimulation-induced seizures during SEEG: A within-patient comparison study.

F152. Localization of the epileptogenic zone using direct cortical stimulation during stereo-EEG investigation

The value of stimulation-induced seizures for multimodal determination of the epileptogenic zone in preoperative epilepsy diagnostics has not yet been sufficiently investigated. Patients with focal pharmacorefractory epilepsy who underwent invasive electroencephalography with cortical 50 Hz stimulation at the Epilepsy Center Erlangen between 2018 and 2023, had at least one stimulation-induced seizure, underwent resective epilepsy surgery, and had a postoperative follow-up ≥ 1 year were analyzed. 20 patients were included, 11 (55.0%) with temporal, 7 (35.0%) with frontal and 2 (10.0%) with parietal lobe epilepsy. 12 patients (60.0%) had a good Engel outcome (Engel 1A). Associated with a good vs. poor (Engel 1B-4) surgical outcome were not only the percentage of resected electrode contacts of the spontaneous seizure onset zone, SOZ (p = 0.005), but also the stimulation SOZ (p = 0.022), as well as stimulation-induced seizure with a typical seizure semiology (p = 0.033), the electrodes inducing a stimulation-induced seizure (p = 0.014), electrodes with an identical seizure onset pattern (p = 0.035), and the occurrence of low voltage fast seizure onset pattern, LVFA (p = 0.015). ROC analyses showed that the AUC for the predictors of the spontaneous SOZ were greatest for the stimulation SOZ (AUC 0.876) and stimulation-induced seizures with LVFA (0.860). Analysis of combined predictors showed higher odds of predicting SOZ for combinations including LVFA. Electroclinical stimulation seizures have prognostic value in determining the epileptogenic zone. Characteristics such as the seizure onset zone, seizure pattern and stimulation seizure semiology predict seizure freedom in case of resection of electrode contacts. Electrodes should be resected where both stimulation seizures have been induced or the seizure pattern has been localized and low voltage fast seizure pattern has occurred.

The nature, frequency and value of stimulation induced seizures during extraoperative cortical stimulation for functional mapping

Automated seizure detection and localization from intracranial EEG requires validated benchmark datasets with expert annotations, yet existing open datasets lack multi-expert consensus annotations and exclude stimulation-induced seizures. We present stereotactic EEG recordings from 83 seizures (46 spontaneous, 37 stimulation-induced) across 32 patients (19 from the University of Pennsylvania, 13 from the Children's Hospital of Philadelphia) with drug-resistant epilepsy. Three board-certified epileptologists independently annotated each seizure for onset time, onset channels, and channels seizing at 10 seconds post-onset using a standardized protocol. Consensus annotations were determined through majority voting. Inter-rater agreement was κ = 0.64 for onset channels and κ = 0.62 for spread channels. Individual rater agreement with consensus was κ = 0.81 for onset and κ = 0.80 for spread. Agreement metrics did not differ between spontaneous and stimulation-induced seizures. All data follow Brain Imaging Data Structure (BIDS) standards and include electrode localizations, patient demographics, and clinical outcomes. This dataset enables the validation of seizure onset and spread detection and localization against human expert performance and supports comparative analysis of seizure networks across spontaneous and stimulation-induced seizures.

Cortical stimulation is used during presurgical epilepsy evaluation for functional mapping and for defining the cortical area responsible for seizure generation. Despite wide use of cortical stimulation, the association between cortical stimulation-induced seizures and surgical outcome remains unknown. To assess whether removal of the seizure-onset zone resulting from cortical stimulation is associated with a good surgical outcome. This cohort study used data from 2 tertiary epilepsy centers: Montreal Neurological Institute in Montreal, Quebec, Canada, and Grenoble-Alpes University Hospital in Grenoble, France. Participants included consecutive patients (n = 103) with focal drug-resistant epilepsy who underwent stereoelectroencephalography between January 1, 2007, and January 1, 2017. Participant selection criteria were cortical stimulation during implantation, subsequent open surgical procedure with a follow-up of 1 or more years, and complete neuroimaging data sets for superimposition between intracranial electrodes and the resection. Cortical stimulation-induced typical electroclinical seizures, the volume of the surgical resection, and the percentage of resected electrode contacts inducing a seizure or encompassing the cortical stimulation-informed and spontaneous seizure-onset zones were identified. These measures were correlated with good (Engel class I) and poor (Engel classes II-IV) surgical outcomes. Electroclinical characteristics associated with cortical stimulation-induced seizures were analyzed. In total, 103 patients were included, of whom 54 (52.4%) were female, and the mean (SD) age was 31 (11) years. Fifty-nine patients (57.3%) had cortical stimulation-induced seizures. The percentage of patients with cortical stimulation-induced electroclinical seizures was higher in the good outcome group than in the poor outcome group (31 of 44 [70.5%] vs 28 of 59 [47.5%]; P = .02). The percentage of the resected contacts encompassing the cortical stimulation-informed seizure-onset zone correlated with surgical outcome (median [range] percentage in good vs poor outcome: 63.2% [0%-100%] vs 33.3% [0%-84.6%]; Spearman ρ = 0.38; P = .003). A similar result was observed for spontaneous seizures (median [range] percentage in good vs poor outcome: 57.1% [0%-100%] vs 32.7% [0%-100%]; Spearman ρ = 0.32; P = .002). Longer elapsed time since the most recent seizure was associated with a higher likelihood of inducing seizures (>24 hours: 64.7% vs <24 hours: 27.3%; P = .04). Seizure induction by cortical stimulation appears to identify the epileptic generator as reliably as spontaneous seizures do; this finding might lead to a more time-efficient intracranial presurgical investigation of focal epilepsy as the need to record spontaneous seizures is reduced.

Intracranial electroencephalographic (IEEG) recording, using subdural electrodes (SDEs) and stereoelectroencephalography (SEEG), plays a pivotal role in localizing the epileptogenic zone (EZ). SDEs, employed for superficial cortical seizure foci localization, provide information on two-dimensional seizure onset and propagation. In contrast, SEEG, with its three-dimensional sampling, allows exploration of deep brain structures, sulcal folds, and bihemispheric networks. SEEG offers the advantages of fewer complications, better tolerability, and coverage of sulci. Although both modalities allow electrical stimulation, SDE mapping can tessellate cortical gyri, providing the opportunity for a tailored resection. With SEEG, both superficial gyri and deep sulci can be stimulated, and there is a lower risk of afterdischarges and stimulation-induced seizures. Most systematic reviews and meta-analyses have addressed the comparative effectiveness of SDEs and SEEG in localizing the EZ and achieving seizure freedom, although discrepancies persist in the literature. The combination of SDEs and SEEG could potentially overcome the limitations inherent to each technique individually, better delineating seizure foci. This review describes the strengths and limitations of SDE and SEEG recordings, highlighting their unique indications in seizure localization, as evidenced by recent publications. Addressing controversies in the perceived usefulness of the two techniques offers insights that can aid in selecting the most suitable IEEG in clinical practice.

This study reports our center's initial experience with the use of low-frequency stimulation in provoking stimulation-induced seizures (SIS) in children with drug-resistant epilepsy undergoing stereo-EEG evaluations. This retrospective study enrolled children aged 2 to 18 years with drug-resistant focal epilepsy who underwent stereo-EEG evaluation and extraoperative direct electrical cortical stimulation to elicit seizures. The low-frequency stimulation parameters consisted of biphasic square waveforms at frequency of 1 Hz, pulse width 1 millisecond, current 1 to 3 mA, and train duration of 20 seconds. Various epilepsy-related, imaging, neurophysiology, and surgery-related variables were collected and summarized. Fourteen children (mean age 13 years; 57.1% girls) were included, 10 of whom had unilateral stereo-EEG coverage. Cortical stimulation for provoking seizures was performed after a median of 5 days after electrode implantation. The median number of electrode-contacts stimulated per patient was 42. Four patients (28.6%) experienced habitual SIS (all extratemporal). The etiology in three patients was focal cortical dysplasia. Interictal high-frequency oscillations at electrode-contacts provoking SIS were observed in three cases (75%). Two of these individuals (50%) had class 1 International League Against Epilepsy seizure outcome at last follow-up, after the resection of the brain regions generating SIS. Low-frequency (1-Hz) stimulation could provoke habitual SIS in nearly one-fourth of children with focal epilepsy undergoing stereo-EEG monitoring. This study provides a limited pediatric experience with the low-frequency cortical stimulation and SIS.

Background: Mapping of neurological function by cortical stimulation is an essential step in the evaluation of epilepsy patients undergoing invasive EEG for epilepsy surgery. Yet, controversy still exists regarding its role as a tool for delineating epileptogenic cortex. Objective: To evaluate the impact of electroclinical patterns of cortico-stimulation induced seizures (CIS) in stereo-electroencephalography (SEEG) and removal of CIS electrodes in seizure freedom. Methods: We reviewed all 230 consecutive patients who underwent SEEG and cortical stimulation from 2013 to 2016. CIS were induced in 79 (30.4%) patients, of whom 49 (21.2%) underwent surgical resection and entered the final analysis. Demographic, epilepsy and pathological data were collected. In addition, a detailed analysis of cortical stimulation and Stereo-EEG was performed. For the purpose of our study, we created a simple way to classify CIS based on semiological (complete, partial and atypical patterns), and EEG similarity to spontaneous seizures. Seizure freedom was used to calculate the predictive value of CIS with complete semiology and identical EEG (complete electroclinical picture). Results: Seventy-one (45.8%) patients were seizure-free with a mean follow up of 1.42±0.9 years. Twenty-six (52%) patients in the CIS group were seizure-free compared to 45 (42.9%) non-CIS patients (p=0.286). Complete seizure semiology was obtained in 22 (42.9%) patients and resection of electrodes involved in CIS led to seizure freedom in 73.7% compared to 45.9% of the stimulation cohort (p=0.021). Conversely, resection of electrodes involved in partial seizure semiology provided a rate of seizure-freedom of only 20% (p=0.021). Resection of electrodes involved in CIS identical to spontaneous seizures (both semiology and EEG) were significantly associated with seizure-freedom (80% x 42.4%; p=0.006, OR 5.4, 95% CI 1.46-20.0) and largely represented by FCD type 2 (42.9%; Fisher’s exact test, p=0.006). Complete electroclinical correlation of CIS displayed sensitivity of 16.9% (95% CI, 9.05-27.66%), specificity of 96.4% (95% CI, 89.8-99.25%) and positive predictive value of 80% (95% CI, 54.03-93.16%) for accurate localization of epileptogenic zone. Conclusion: Electroclinical characteristics of CIS are a valuable tool to localize the epileptogenic zone and craft a successful surgical strategy in SEEG. Moreover, it may represent a marker of underlying FCD type II.

Animal models with spontaneous epileptic seizures may be useful in the discovery of new antiepileptic drugs (AEDs). The purpose of the present study was to evaluate the efficacy of carisbamate on spontaneous motor seizures in rats with kainate-induced epilepsy. Repeated, low-dose (5 mg/kg), intraperitoneal injections of kainate were administered every hour until each male Sprague-Dawley rat had experienced convulsive status epilepticus for at least 3 h. Five 1-month trials (n = 8-10 rats) assessed the effects of 0.3, 1, 3, 10, and 30 mg/kg carisbamate on spontaneous seizures. Each trial involved six AED-versus-vehicle tests comprised of carisbamate or 10% solutol-HS-15 treatments administered as intraperitoneal injections on alternate days with a recovery day between each treatment day. Carisbamate significantly reduced motor seizure frequency at doses of 10 and 30 mg/kg, and caused complete seizure cessation during the 6-h postdrug epoch in seven of the eight animals at 30 mg/kg. The effects of carisbamate (0.3-30 mg/kg) on spontaneous motor seizures appeared dose dependent. These data support the hypothesis that a repeated-measures, crossover protocol in animal models with spontaneous seizures is an effective method for testing AEDs. Carisbamate reduced the frequency of spontaneous motor seizures in a dose-dependent manner, and was more effective than topiramate at reducing seizures in rats with kainate-induced epilepsy.

Early onset motor semiology in seizures triggered by cortical stimulation during SEEG

Editor's evaluation: Disease-modifying effects of sodium selenate in a model of drug-resistant, temporal lobe epilepsy

Seizure outcomes after cortical stimulation-induced seizures: A systematic review and meta-analysis.

Musicogenic epilepsy: A Stereo-electroencephalography study

Spontaneous seizures preferentially injure interneurons in the pilocarpine model of chronic spontaneous seizures.

Objective To observe the expressions of multidrug resistance-associated protein(MRP)1 in the hippocampus of the rat models with chronic epilepsy, and to explore whether antiepileptic drug oxcarbazepine(OXC) affects the expression of MRP1. Methods One hundred rats of 14 days old were randomly divided into model group(n=52) and the control group(n=48). The model group received intraperitoneal injection of kainic acid(KA) 1 mg/kg(0.5 g/L) to induce seizures, and the control group rats were injected the same dose of 9 g/L chloride.According to Lado standard classification of seizures, the young rats whose seizure degree was beyond 5 and became status epilepticus after intraperitoneal injection used as successful seizure models if they caught the spontaneous seizures after 2 weeks.When spontaneous seizures were developed, 48 surviving KA rats were divided into KA group and KA+ OXC group.Rats in the control group were divided into NS group and NS+ OXC group.After spontaneous recurrent seizures, the treatment groups began to take drugs.Each group started to be sacrificed from the beginning of drug perfusion at diffe-rent times and they were divided into the 4th week group, the 6th week group and the 8th week group.The expression of MRP1 in hippocampus(CA3 area) was detected by immunohistochemistry methods. Results 1.Epileptic performance: all rats injected with NS had no epileptic performance.In the chronic epilepsy, Ⅰ-Ⅴ Racine grade of spontaneous recurrent seizures were found in all rats with KA.The rats in KA group had higher epilepsy seizure frequency than those in KA+ OXC group(P 0.05). The trend of expression in KA group and KA+ OXC group gradually increased.The MRP1 positive cells in KA+ OXC group compared with those in the KA group was significantly different in the 8th week(P 0.05). And there was a significant difference in the positive cells in KA group compared with those of KA group(P<0.05). The expression of MRP1 positive cells in KA+ OXC group increased significantly compared with those in NA+ OXC group(all P<0.05). Conclusions MRP1 plays an important role in resistance mechanisms of refractory epilepsy, while the expression of MRP1 can be induced by using OXC in a long term. Key words: Oxcarbazepine; Multidrug resistance-associated protein; Chronic epilepsy