Temporal Seizure Onset Research Articles

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.

Bilateral temporal lobe dysplasia and seizure onset associated with biallelic CNTNAP2 variants.

Biallelic CNTNAP2 variants have been associated with Pitt-Hopkins-like syndrome. We describe six novel and one previously reported patients from six independent families and review the literature including 64 patients carrying biallelic CNTNAP2 variants. Initial reports highlighted intractable focal seizures and the failure of epilepsy surgery in children, but subsequent reports did not expand on this aspect. In all our patients (n = 7), brain MRI showed bilateral temporal gray/white matter blurring with white matter high signal intensity, more obvious on the T2-FLAIR sequences, consistent with bilateral temporal lobe dysplasia. All patients had focal seizures with temporal lobe onset and semiology, which were recorded on EEG in five, showing bilateral independent temporal onset in four. Epilepsy was responsive to anti-seizure medications in two patients (2/7, 28.5%), and pharmaco-resistant in five (5/7, 71.5%). Splice-site variants identified in five patients (5/7, 71.5%) were the most common mutational finding. Our observation expands the phenotypic and genetic spectrum of biallelic CNTNAP2 alterations focusing on the neuroimaging features and provides evidence for an elective bilateral anatomoelectroclinical involvement of the temporal lobes in the associated epilepsy, with relevant implications on clinical management.

33 Pre-Surgical Evaluation of Bilingual Epilepsy Patients; A Case Study Demonstrating the Importance of Bilingual Assessment

Objective:In the US, >20% of individuals aged 5 years and older speak a language other than English at home, with rates of bi- and multilingualism increasing. Providing linguistically- and culturally- competent care to increasingly diverse populations is a necessary task for neuropsychologists. The need for close attention to bilingualism is even more glaring in the context of neurosurgical interventions, such as in intractable epilepsy. Pre-surgical epilepsy evaluations serve as a baseline for post-surgical change, inform lateralization and localization, and help determine cognitive risks associated with surgery. The importance of evaluating bilingual status and assessing cognitive abilities in both languages, if needed, in presurgical epilepsy evaluations is examined. We present the neuropsychological profile of a 10-year-old bilingual male with intractable epilepsy participating in a pre-surgical epilepsy evaluation.Participants and Methods:This right-handed male is a sequential language learner, exposed to Spanish at birth and English when he began kindergarten. His parent reported he was primarily English speaking. Developmental milestones were met within expected timeframes. Seizures began at age 5. He is prescribed Vimpat and Lamictal. vEEG during admission revealed right temporal-onset seizures. Neuropsychological assessment was conducted in English based on parent report; however, expressive language testing revealed significantly higher performance in Spanish (average) compared to English (exceptionally low). Subsequently, a bilingual provider was consulted, and supplemental Spanish verbal reasoning and verbal memory measures were administered.Results:The patient’s neuropsychological profile captured a significant difference between English and Spanish verbal abilities. WISC-V Similarities scaled scores (ss) were 5 and 11 in English and Spanish, respectively. Vocabulary scaled scores were 8 and 15 in English and Spanish, respectively. Regarding verbal memory, list learning was below average in English (ss = 5), but low average in Spanish (ss = 6). Contextual verbal memory was only administered in Spanish; scores were average (ss = 10). Verbal Fluency administered in English was low (phonemic fluency ss = 5, categorical fluency ss = 6). fMRI verbal tasks were performed in English and revealed left-sided language lateralization.Conclusions:In pre-surgical epilepsy evaluations of bilingual children, consideration of language is essential. Assessment of language dominance is a minimum requirement in bilingual families, followed by full bilingual evaluation if necessary. In this case, starkly different conclusions regarding lateralization and localization may have been made if the child had not been evaluated in both languages. In English, a significant split between verbal and non-verbal cognition was apparent, possibly suggesting involvement of the dominant left hemisphere. With Spanish testing, this split disappeared, with high average verbal skills. While a growing proportion of children in the US are bilingual, bilingual assessments are not commonly conducted in pre-surgical epilepsy evaluations. In fact, very little work has been done examining language functioning in bilingual epilepsy patients, particularly in children. With both epilepsy-and language-related factors at play in a developing brain, we encourage closer attention to these issues, particularly in the context of neurosurgical procedures.

High-rate leading spikes in propagating spike sequences predict seizure outcome in surgical patients with temporal lobe epilepsy.

Inter-ictal spikes aid in the diagnosis of epilepsy and in planning surgery of medication-resistant epilepsy. However, the localizing information from spikes can be unreliable because spikes can propagate, and the burden of spikes, often assessed as a rate, does not always correlate with the seizure onset zone or seizure outcome. Recent work indicates identifying where spikes regularly emerge and spread could localize the seizure network. Thus, the current study sought to better understand where and how rates of single and coupled spikes, and especially brain regions with high-rate and leading spike of a propagating sequence, informs the extent of the seizure network. In 37 patients with medication-resistant temporal lobe seizures, who had surgery to treat their seizure disorder, an algorithm detected spikes in the pre-surgical depth inter-ictal EEG. A separate algorithm detected spike propagation sequences and identified the location of leading and downstream spikes in each sequence. We analysed the rate and power of single spikes on each electrode and coupled spikes between pairs of electrodes, and the proportion of sites with high-rate, leading spikes in relation to the seizure onset zone of patients seizure free (n = 19) and those with continuing seizures (n = 18). We found increased rates of single spikes in mesial temporal seizure onset zone (ANOVA, P < 0.001, η2 = 0.138), and increased rates of coupled spikes within, but not between, mesial-, lateral- and extra-temporal seizure onset zone of patients with continuing seizures (P < 0.001; η2 = 0.195, 0.113 and 0.102, respectively). In these same patients, there was a higher proportion of brain regions with high-rate leaders, and each sequence contained a greater number of spikes that propagated with a higher efficiency over a longer distance outside the seizure onset zone than patients seizure free (Wilcoxon, P = 0.0172). The proportion of high-rate leaders in and outside the seizure onset zone could predict seizure outcome with area under curve = 0.699, but not rates of single or coupled spikes (0.514 and 0.566). Rates of coupled spikes to a greater extent than single spikes localize the seizure onset zone and provide evidence for inter-ictal functional segregation, which could be an adaptation to avert seizures. Spike rates, however, have little value in predicting seizure outcome. High-rate spike sites leading propagation could represent sources of spikes that are important components of an efficient seizure network beyond the clinical seizure onset zone, and like the seizure onset zone these, too, need to be removed, disconnected or stimulated to increase the likelihood for seizure control.

Comparison of the effectiveness of anterior thalamic stimulation in a European registry and a phase III study—English version

Besides the data of the phase III study (SANTE), the results of the MORE registry on the use of anterior thalamic deep brain stimulation (ANT-DBS) have recently become available. In which aspects do the phase III study and the MORE registry differ? A literature-based comparison was performed for the 2‑year outcomes of the prospective, randomized-controlled SANTE trial which included 110 patients and the prospective (nonrandomized, nonstandardized) MORE registry of 170 patients. The data analysis was focused on patient selection, surgical management, stimulation setting, therapeutic effects, and safety aspects. The median 2‑year seizure frequency reduction rate in the MORE registry remained clearly behind that of the SANTE trial (33% vs. 56%). Also in the subgroup of temporal lobe epilepsies, the seizure frequency reduction was not higher than 33%. Patients with cognitive impairment tended to have a poorer outcome compared to patients without cognitive impairment (26% vs. 36% median seizure frequency reduction rate). The MORE registry and the SANTE trial differed in several methodological aspects and patient selection: The SANTE trial included a higher percentage of patients with unifocal epilepsy (p = 0.007), temporal seizure onset (p = 0.0005), more frequent focal to bilateral tonic–clonic seizures (p = 0.02), and excluded patients with cognitive impairment (p < 0.0001). In the MORE registry, not only the trans- but also an extraventricular implantation approach was used and the achieved therapeutic effects were associated with the treating center’s level of expertise. The stimulation parameters and observed side-effects in the two studies were comparable. The registry data confirm the safe and effective use of ANT-DBS in drug-resistant epilepsy. They reflect the clinical routine use of the ANT-DBS therapy. While the results remained behind the outcomes of the phase III trial, they are within the effectiveness range of other neurostimulation therapies for epilepsy. The observed differences might be mainly due to differences in the cohort characteristics and differences in the implantation techniques.

PO-04-033 CARDIONEUROABLATION IN A WOMAN WITH ICTAL-INDUCED CARDIAC ASYSTOLE

Ictal-induced cardiac bradyarrhythmia and asystole is a rare phenomenon. The exact mechanism of ictal-induced cardiac bradyarrhythmia and asystole remains unclear. It was postulated that stimulation of central autonomic network during ictal episode may trigger an abrupt burst of hypervagotonia. Prolonged episode of cardiac bradyarrhythmia and asystole may result in syncope or death due to impairment of cerebral perfusion. The role of cardioneuroablation (CNA) in this condition has not been well-described in the literature. To describe a case of successful CNA in a patient with ictal-induced bradyarrhythmia and asystole. n/a A 47-year-old female has a 1.5-year history of intractable focal epilepsy and COVID-19 infection. She started having multiple episodes of seizures following a mild COVID-19 infection. Electroencephalogram (EEG) and brain MRI revealed right temporal onset seizures without structural lesions. Due to ongoing uncontrolled seizures with multiple semiologies despite multiple anti-epileptic drugs, she was admitted to Epilepsy Monitoring Unit for seizure classification. Her ictal EEGs (Figure 1) showed onset of ictal rhythm in the right temporal region with episodes of severe sinus bradycardia (15-30 bpm) and sinus pauses (15-16 seconds). Telemetry tracings demonstrated PP interval slowing with PR interval prolongation prior to the pauses consistent with a vagally-mediated mechanism. Cardiac electrophysiology team recommended CNA for treating the episodes of ictal-induced bradyarrhythmia and asystole. 3D anatomic maps of the right atrium (RA) and left atrium (LA) were created using CARTO system (Biosense Webster). Right superior ganglionated plexus (RSGP) was localized with fractionation mapping and intracardiac echocardiography guidance. RSGP was targeted from the RA using an irrigated radiofrequency catheter with power limit of 25 W. Post-ablations of RSGP, her heart rate increased from 60 - 99 bpm. Additional lesions were delivered from the LA site but no additional heart rate increase was not seen. An implantable loop recorder was implanted post-ablation procedure. During follow-up of 8 months, she had recurrent focal epilepsy, but no bradyarrhythmias or asystole was noted on her loop recorder. Resting heart rates at long-term follow up were between 70 - 100 bpm. This case highlights the utility of CNA in patient with ictal-induced cardiac bradyarrhythmia and asystole. CNA may be an approach to avoid permanent pacemakers in this population.

Missing Piece of Puzzle: Electro-Convulsive Therapy (ECT) in Patients with anti-NMDA Receptor Encephalitis (P5-5.012)

<h3>Objective:</h3> To emphasize the importance of early clinical recognition of catatonia and implementation of ECT as adjuvant therapy in patients with anti-NMDAR encephalitis. <h3>Background:</h3> Catatonia is a symptom of anti-NMDAR encephalitis which can evolve rapidly into malignant catatonia with autonomic instability and increased morbidity. Although early immunomodulatory therapy is important to treat the underlying autoimmune disorder, resistant catatonia may require adjuvant management with ECT. <h3>Design/Methods:</h3> Not applicable. <h3>Results:</h3> We describe the cases of three females aged 23.7 ± 2.5, who were diagnosed with anti-NMDAR encephalitis. They presented with neuropsychiatric symptoms and were promptly and empirically treated with IV solumedrol with oral prednisone taper, IVIG, +/− plasma exchange (case 3), preceding diagnostic confirmation via CSF NMDA antibody positivity. Ovarian teratomas were detected in all cases and resected shortly after hospitalization. Additionally, cases 1 and 2 received Rituximab while hospitalized, and cases 2 and 3 received anti-seizure medications for temporal onset seizures. In spite of this, all required escalating large doses of benzodiazepines, in conjunction with amantadine and bromocriptine, for refractory malignant catatonia with dysautonomia. ECT treatments were thus initiated (once to twice daily for first week, followed by three times weekly) with bilateral electrode placement. All cases tolerated ECT treatments well and were gradually noted to have marked clinical improvement as was measured by the Bush-Francis Catatonia Rating Scale (BFCRS) (initial assessment: 27.6 ± 8.3; last assessment 1.3 ± 1.5). <h3>Conclusions:</h3> This case series supports the growing body of evidence emphasizing the importance of clinical recognition of catatonia among patients with suspected or confirmed anti-NMDAR encephalitis, and the early implementation of ECT into treatment algorithms. The use of standardized assessment tools such as the BFCRS and cognitive impairment screening scales should be considered for monitoring of symptom response and tolerability. <b>Disclosure:</b> Dr. Wadi has nothing to disclose. Dr. Mandge has nothing to disclose.

Seizure onset patterns predict outcome after stereo-electroencephalography-guided laser amygdalohippocampotomy.

Stereotactic laser amygdalohippocampotomy (SLAH) is an appealing option for patients with temporal lobe epilepsy, who often require intracranial monitoring to confirm mesial temporal seizure onset. However, given limited spatial sampling, it is possible that stereotactic electroencephalography (stereo-EEG) may miss seizure onset elsewhere. We hypothesized that stereo-EEG seizure onset patterns (SOPs) may differentiate between primary onset and secondary spread and predict postoperative seizure control. In this study, we characterized the 2-year outcomes of patients who underwent single-fiber SLAH after stereo-EEG and evaluated whether stereo-EEG SOPs predict postoperative seizure freedom. This retrospective five-center study included patients with or without mesial temporal sclerosis (MTS) who underwent stereo-EEG followed by single-fiber SLAH between August 2014 and January 2022. Patients with causative hippocampal lesions apart from MTS or for whom the SLAH was considered palliative were excluded. An SOP catalogue was developed based on literature review. The dominant pattern for each patient was used for survival analysis. The primary outcome was 2-year Engel I classification or recurrent seizures before then, stratified by SOP category. Fifty-eight patients were included, with a mean follow-up duration of 39 ± 12 months after SLAH. Overall 1-, 2-, and 3-year Engel I seizure freedom probability was 54%, 36%, and 33%, respectively. Patients with SOPs, including low-voltage fast activity or low-frequency repetitive spiking, had a 46% 2-year seizure freedom probability, compared to 0% for patients with alpha or theta frequency repetitive spiking or theta or delta frequency rhythmic slowing (log-rank test, p = .00015). Patients who underwent SLAH after stereo-EEG had a low probability of seizure freedom at 2 years, but SOPs successfully predicted seizure recurrence in a subset of patients. This study provides proof of concept that SOPs distinguish between hippocampal seizure onset and spread and supports using SOPs to improve selection of SLAH candidates.

Are AI language models such as ChatGPT ready to improve the care of individuals with epilepsy?

Are AI language models such as ChatGPT ready to improve the care of individuals with epilepsy?

Post-ictal Rhythmic Thalamic Activity of the Centromedian Nucleus.

Deep brain stimulation of the centromedian nucleus of the thalamus (CMN) to treat drug-resistant epilepsy has been of interest for decades. However, little is known about the electrophysiological activity of the CMN during seizures. We describe a novel CMN EEG finding associated with seizure: post-ictal rhythmic thalamic activity. Five patients with drug-resistant epilepsy of unknown etiology with focal onset seizures underwent stereoelectroencephalography monitoring as part of evaluation for potential resective surgery or neuromodulation. Two patients had previously undergone complete corpus callosotomy and vagus nerve stimulation. A standardized plan for implantation included targets in the bilateral CMN. Each patient had frontal onset seizures, and two patients had additional insular, parietal, or mesial temporal onset seizures. Contacts of CMN were involved synchronously or rapidly after onset in most recorded seizures, particularly those with frontal onset. Focal onset hemiclonic and bilateral tonic-clonic seizures spread to involve cortical contacts with high-amplitude rhythmic spiking followed by abrupt offset with diffuse voltage attenuation. A post-ictal rhythmic 1.5 to 2.5 Hz delta frequency pattern, post-ictal rhythmic thalamic activity, emerged in CMN contacts amid the suppression of background activity in cortical contacts. In the two patients with corpus callosotomy, unilateral seizure spread and ipsilateral post-ictal rhythmic thalamic activity were observed. We observed post-ictal rhythmic thalamic activity in five patients with stereoelectroencephalography monitoring of the CMN with convulsive seizures. This rhythm appears late in ictal evolution and may signal an important role of the CMN in seizure termination. Furthermore, this rhythm may help identify CMN involvement in the epileptic network.

The diagnostic value of ictal SPECT-A retrospective, semiquantitative monocenter study.

Ictal single photon emission computed tomography (SPECT) can be used as an advanced diagnostic modality to detect the seizure onset zone in the presurgical evaluation of people with epilepsy. In addition to visual assessment (VSA) of ictal and interictal SPECT images, postprocessing methods such as ictal-interictal SPECT analysis using SPM (ISAS) can visualize regional ictal blood flow differences. We aimed to evaluate and differentiate the diagnostic value of VSA and ISAS in the Bonn cohort. We included 161 people with epilepsy who underwent presurgical evaluation at the University Hospital Bonn between 2008 and 2020 and received ictal and interictal SPECT and ISAS. We retrospectively assigned SPECT findings to one of five categories according to their degree of concordance with the clinical focus hypothesis. Seizure onset zones could be identified more likely on a sublobar concordance level by ISAS than by VSA (31% vs. 19% of cases; OR=1.88; 95% Cl [1.04, 3.42]; P=0.03). Both VSA and ISAS more often localized a temporal seizure onset zone than an extratemporal one. Neither VSA nor ISAS findings were predicted by the latency between seizure onset and tracer injection (P=0.75). In people who underwent successful epilepsy surgery, VSA and ISAS indicated the correct resection site in 54% of individuals, while MRI and EEG showed the correct resection localization in 96% and 33% of individuals, respectively. It was more likely to become seizure-free after epilepsy surgery if ISAS or VSA had been successful. There was no MR-negative case with successful surgery, indicating that ictal SPECT is more useful for confirmation than for localization. The results of the most extensive clinical study of ictal SPECT to date allow an assessment of the diagnostic value of this elaborate examination and emphasize the importance of postprocessing routines.

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.

Face-induced gamma oscillations and event-related potentials in patients with epilepsy: an intracranial EEG study

BackgroundTo examine the pathological effect of a mesial temporal seizure onset zone (SOZ) on local and inter-regional response to faces in the amygdala and other structures of the temporal lobe.MethodsIntracranial EEG data was obtained from the amygdala, hippocampus, fusiform gyrus and parahippocampal gyrus of nine patients with drug-refractory epilepsy during visual stimulation with faces and mosaics. We analyzed event-related potentials (ERP), gamma frequency power, phase-amplitude coupling and phase-slope-index and compared the results between patients with versus without a mesial temporal SOZ.ResultsIn the amygdala and fusiform gyrus, faces triggered higher ERP amplitudes compared to mosaics in both patient groups and higher gamma power in patients without a mesial temporal SOZ. In the hippocampus, famous faces triggered higher gamma power for both groups combined but did not affect ERPs in either group. The differentiated ERP response to famous faces in the parahippocampal gyrus was more pronounced in patients without a mesial temporal SOZ. Phase-amplitude coupling and phase-slope-index results yielded bidirectional modulation between amygdala and fusiform gyrus, and predominately unidirectional modulation between parahippocampal gyrus and hippocampus.ConclusionsA mesial temporal SOZ was associated with an impaired response to faces in the amygdala, fusiform gyrus and parahippocampal gyrus in our patients. Compared to this, the response to faces in the hippocampus was impaired in patients with, as well as without, a mesial temporal SOZ. Our results support existing evidence for face processing deficits in patients with a mesial temporal SOZ and suggest the pathological effect of a mesial temporal SOZ on the amygdala to play a pivotal role in this matter in particular.

A simplified depth implantation approach in bitemporal lobe epilepsy

Background: Up to 73.0% of patients with bilateral temporal lobe epilepsy (BTLE) on scalp electroencephalogram (EEG) were found to have unilateral temporal seizure onset via invasive EEG monitoring (iEEG) and 58% of them achieved good surgical outcome. However, iEEG in resource- limited countries is limited by cost. We aimed to present the surgical outcome of a simplified and cost- effective 2-electrode bilateral hippocampal depth implantation strategy in 7 cases with bilateral temporal lobe epilepsy based on scalp EEG and unilateral mesial temporal sclerosis (MTS). Methods: Total 7 cases who underwent epilepsy surgery were reviewed. All patients underwent 2-stage evaluation of video-EEG monitoring followed by intracranial monitoring. A simplified 2-depth electrode implantation strategy was used, targeting the bilateral anterior hippocampus. Results: All 7 patients had interictal bilateral independent temporal epileptiform discharges. Four had bilateral temporal ictal onset on scalp EEG and 3 with ictal onset contralateral to the MTS. With iEEG, 4 patients (57.1%) were confirmed to be unilateral TLE, concordant with the MTS, and 3 patients (42.9%) had true BTLE. All 7 patients underwent anterior temporal lobectomy, ipsilateral to the side of MTS. Four patients (57.1%) achieved Engel I surgical outcome, of which 3/4 (75.0%) were patients with unilateral TLE. For those with true BTLE, 2/3 (66.7%) achieved favourable surgical outcome (Engel I and II). Conclusions: This simplified two-electrode implantation strategy is effective in lateralization of TLE in patients with BTLE and more affordable to those in resource-limited countries.

More Than Spikes: On the Added Value of Non-linear Intracranial EEG Analysis for Surgery Planning in Temporal Lobe Epilepsy.

Epilepsy surgery can be a very effective therapy in medication refractory patients. During patient evaluation intracranial EEG is analyzed by clinical experts to identify the brain tissue generating epileptiform events. Quantitative EEG analysis increasingly complements this approach in research settings, but not yet in clinical routine. We investigate the correspondence between epileptiform events and a specific quantitative EEG marker. We analyzed 99 preictal epochs of multichannel intracranial EEG of 40 patients with mixed etiologies. Time and channel of occurrence of epileptiform events (spikes, slow waves, sharp waves, fast oscillations) were annotated by a human expert and non-linear excess interrelations were calculated as a quantitative EEG marker. We assessed whether the visually identified preictal events predicted channels that belonged to the seizure onset zone, that were later resected or that showed strong non-linear interrelations. We also investigated whether the seizure onset zone or the resection were predicted by channels with strong non-linear interrelations. In patients with temporal lobe epilepsy (32 of 40), epileptic spikes and the seizure onset zone predicted the resected brain tissue much better in patients with favorable seizure control after surgery than in unfavorable outcomes. Beyond that, our analysis did not reveal any significant associations with epileptiform EEG events. Specifically, none of the epileptiform event types did predict non-linear interrelations. In contrast, channels with strong non-linear excess EEG interrelations predicted the resected channels better in patients with temporal lobe epilepsy and favorable outcome. Also in the small number of patients with seizure onset in the frontal and parietal lobes, no association between epileptiform events and channels with strong non-linear excess EEG interrelations was detectable. In contrast to patients with temporal seizure onset, EEG channels with strong non-linear excess interrelations did neither predict the seizure onset zone nor the resection of these patients or allow separation between patients with favorable and unfavorable seizure control. Our study indicates that non-linear excess EEG interrelations are not strictly associated with epileptiform events, which are one key concept of current clinical EEG assessment. Rather, they may provide information relevant for surgery planning in temporal lobe epilepsy. Our study suggests to incorporate quantitative EEG analysis in the workup of clinical cases. We make the EEG epochs and expert annotations publicly available in anonymized form to foster similar analyses for other quantitative EEG methods.

Beamforming Seizures from the Temporal Lobe Using Magnetoencephalography.

Surgical treatment of drug-resistant temporal lobe epilepsy (TLE) depends on proper identification of the seizure onset zone (SOZ) and differentiation of mesial, temporolimbic seizure onsets from temporal neocortical seizure onsets. Noninvasive source imaging using electroencephalography (EEG) and magnetoencephalography (MEG) can provide accurate information on interictal spike localization; however, EEG and MEG have low sensitivity for epileptiform activity restricted to deep temporolimbic structures. Moreover, in mesial temporal lobe epilepsy (MTLE), interictal spikes frequently arise in neocortical foci distant from the SOZ, rendering interictal spike localization potentially misleading for presurgical planning. In this study, we used two different beamformer techniques applied to the MEG signal of ictal events acquired during EEG-MEG recordings in six patients with TLE (three neocortical, three MTLE) in whom the ictal source localization results could be compared to ground truth SOZ localizations determined from intracranial EEG and/or clinical, neuroimaging, and postsurgical outcome evidence. Beamformer analysis proved to be highly accurate in all cases and was able to identify focal SOZs in mesial, temporolimbic structures. In three patients, interictal spikes were absent, too complex for dipole modeling, or localized to anterolateral temporal neocortex distant to a mesial temporal SOZ, and thus unhelpful in presurgical investigation. MEG beamformer source reconstruction is suitable for analysis of ictal events in TLE and can complement or supersede the traditional analysis of interictal spikes. The method outlined is applicable to any type of epileptiform event, expanding the information value of MEG and broadening its utility for presurgical recording in epilepsy.

Deep Learning of Simultaneous Intracranial and Scalp EEG for Prediction, Detection, and Lateralization of Mesial Temporal Lobe Seizures.

In people with drug resistant epilepsy (DRE), seizures are unpredictable, often occurring with little or no warning. The unpredictability causes anxiety and much of the morbidity and mortality of seizures. In this work, 102 seizures of mesial temporal lobe onset were analyzed from 19 patients with DRE who had simultaneous intracranial EEG (iEEG) and scalp EEG as part of their surgical evaluation. The first aim of this paper was to develop machine learning models for seizure prediction and detection (i) using iEEG only, (ii) scalp EEG only and (iii) jointly analyzing both iEEG and scalp EEG. The second goal was to test if machine learning could detect a seizure on scalp EEG when that seizure was not detectable by the human eye (surface negative) but was seen in iEEG. The final question was to determine if the deep learning algorithm could correctly lateralize the seizure onset. The seizure detection and prediction problems were addressed jointly by training Deep Neural Networks (DNN) on 4 classes: non-seizure, pre-seizure, left mesial temporal onset seizure and right mesial temporal onset seizure. To address these aims, the classification accuracy was tested using two deep neural networks (DNN) against 3 different types of similarity graphs which used different time series of EEG data. The convolutional neural network (CNN) with the Waxman similarity graph yielded the highest accuracy across all EEG data (iEEG, scalp EEG and combined). Specifically, 1 second epochs of EEG were correctly assigned to their seizure, pre-seizure, or non-seizure category over 98% of the time. Importantly, the pre-seizure state was classified correctly in the vast majority of epochs (>97%). Detection from scalp EEG data alone of surface negative seizures and the seizures with the delayed scalp onset (the surface negative portion) was over 97%. In addition, the model accurately lateralized all of the seizures from scalp data, including the surface negative seizures. This work suggests that highly accurate seizure prediction and detection is feasible using either intracranial or scalp EEG data. Furthermore, surface negative seizures can be accurately predicted, detected and lateralized with machine learning even when they are not visible to the human eye.

Low frequency novel interictal EEG biomarker for localizing seizures and predicting outcomes.

Localizing hyperexcitable brain tissue to treat focal seizures remains challenging. We want to identify the seizure onset zone from interictal EEG biomarkers. We hypothesize that a combination of interictal EEG biomarkers, including a novel low frequency marker, can predict mesial temporal involvement and can assist in prognosis related to surgical resections. Interictal direct current wide bandwidth invasive EEG recordings from 83 patients implanted with 5111 electrodes were retrospectively studied. Logistic regression was used to classify electrodes and patient outcomes. A feed-forward neural network was implemented to understand putative mechanisms. Interictal infraslow frequency EEG activity was decreased for seizure onset zone electrodes while faster frequencies such as delta (2–4 Hz) and beta-gamma (20–50 Hz) activity were increased. These spectral changes comprised a novel interictal EEG biomarker that was significantly increased for mesial temporal seizure onset zone electrodes compared to non-seizure onset zone electrodes. Interictal EEG biomarkers correctly classified mesial temporal seizure onset zone electrodes with a specificity of 87% and positive predictive value of 80%. These interictal EEG biomarkers also correctly classified patient outcomes after surgical resection with a specificity of 91% and positive predictive value of 87%. Interictal infraslow EEG activity is decreased near the seizure onset zone while higher frequency power is increased, which may suggest distinct underlying physiologic mechanisms. Narrowband interictal EEG power bands provide information about the seizure onset zone and can help predict mesial temporal involvement in seizure onset. Narrowband interictal EEG power bands may be less useful for predictions related to non-mesial temporal electrodes. Together with interictal epileptiform discharges and high-frequency oscillations, these interictal biomarkers may provide prognostic information prior to surgical resection. Computational modelling suggests changes in neural adaptation may be related to the observed low frequency power changes.

Slow oscillations open susceptible time windows for epileptic discharges.

ObjectiveIn patients with epilepsy, interictal epileptic discharges are a diagnostic hallmark of epilepsy and represent abnormal, so‐called “irritative” activity that disrupts normal cognitive functions. Despite their clinical relevance, their mechanisms of generation remain poorly understood. It is assumed that brain activity switches abruptly, unpredictably, and supposedly randomly to these epileptic transients. We aim to study the period preceding these epileptic discharges, to extract potential proepileptogenic mechanisms supporting their expression.MethodsWe used multisite intracortical recordings from patients who underwent intracranial monitoring for refractory epilepsy, the majority of whom had a mesial temporal lobe seizure onset zone. Our objective was to evaluate the existence of proepileptogenic windows before interictal epileptic discharges. We tested whether the amplitude and phase synchronization of slow oscillations (.5–4 Hz and 4–7 Hz) increase before epileptic discharges and whether the latter are phase‐locked to slow oscillations. Then, we tested whether the phase‐locking of neuronal activity (assessed by high‐gamma activity, 60–160 Hz) to slow oscillations increases before epileptic discharges to provide a potential mechanism linking slow oscillations to interictal activities.ResultsChanges in widespread slow oscillations anticipate upcoming epileptic discharges. The network extends beyond the irritative zone, but the increase in amplitude and phase synchronization is rather specific to the irritative zone. In contrast, epileptic discharges are phase‐locked to widespread slow oscillations and the degree of phase‐locking tends to be higher outside the irritative zone. Then, within the irritative zone only, we observe an increased coupling between slow oscillations and neuronal discharges before epileptic discharges.SignificanceOur results show that epileptic discharges occur during vulnerable time windows set up by a specific phase of slow oscillations. The specificity of these permissive windows is further reinforced by the increased coupling of neuronal activity to slow oscillations. These findings contribute to our understanding of epilepsy as a distributed oscillopathy and open avenues for future neuromodulation strategies aiming at disrupting proepileptic mechanisms.

P3. Significance of intracranial EEG parameters in prediction of seizure freedom

Introduction. In patients with focal drug-resistant epilepsy (DRE), intracranial electroencephalography (iEEG) with subdural electrodes (SDE) is used to delineate the seizure onset zone (SOZ) and to distinguish eloquent cortex areals, if non-invasive diagnostics did not yield conclusive results. Previous studies have shown ambiguous findings on the significance of iEEG parameters with respect to prediction of seizure freedom after resective epilepsy surgery. Most studies focused on subgroups of patients, such as those with frontal or temporal lobe epilepsy, or on some iEEG parameters, only. To that end, we comprehensively analyzed the significance of several iEEG parameters in one set of consecutive patients with DRE. Methods. All patients who had undergone invasive monitoring with SDE between 2005 and 2015 at our tertiary epilepsy center were included in this study 1 . We retrospectively analyzed iEEG parameters including seizure onset pattern (SOP), size of SOZ, latency to EEG seizure propagation and latency from clinical to EEG seizure onset. Furthermore, we assessed associations with post-operative seizure freedom, histopathology und brain region of SOZ. Results. Eighty-one patients (34 female) with 324 seizures were assessed. Low-voltage fast activity (LVFA, 37%) and sharp activity < 13 Hz (30%) were the most frequent SOPs. Focal SOZ (≤2 cm) was the only iEEG parameter independently associated with 1-year post-operative seizure freedom (OR 4.1, 95% CI 1.433–11.679). While no SOP was linked to specific histopathologies, LVFA was associated with temporal neocortical SOZ ( p < 0.01). Median latencies to EEG seizure propagation were significantly longer ( p < 0.001) in seizures originating from temporo-mesial SOZ (median 16.0 s) compared with temporo-neocortical (median 8.0 s) and frontal seizure onset (median 5.5 s). Also, latencies from clinical to EEG seizure onset were significantly longer ( p < 0.001) in seizures from temporo-mesial SOZ (median −20.0 s) compared with temporo-neocortical (median −12.0 s) and frontal seizure onset (median −6.0 s). Discussion. A focal EEG seizure onset but no specific SOP predicted seizure freedom after surgery. Also, different SOPs could be generated by the same histopathology and vice versa, putting clinical significance of SOPs into question. LVFA was associated with temporal neocortical seizure onset, possibly indicating a close-by seizure generator. Longer latencies until seizure spread and clinical signs or symptoms in seizures originating from temporo-mesial SOZ may be explained by inhibitory circuits in the hippocampus. Reference 1. Steinbart D, Steinbrenner M, Oltmanns F, Holtkamp M. Prediction of seizure freedom after epilepsy surgery – critical reappraisal of significance of intracranial EEG parameters. Clin Neurophysiol. 2020;131(11):2682-2690. doi:https://doi.org/10.1016/j.clinph.2020.08.018