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Periventricular nodular heterotopia (PVNH) is a neuronal migration disorder often associated with drug-resistant epilepsy. The epileptogenic zone network (EZN) in PVNH is generally large, contraindicating surgery. Stereoelectroencephalography (SEEG) can be proposed to map the EZN and perform radiofrequency thermocoagulation (THC) with an efficacy rate of approximately 65%. There are genetic forms of PVNH, particularly with mutations in the filamin A gene (FLNA). However, data on SEEG-guided THC in these patients still have not been described. We report four patients with FLNA-positive PVNH who underwent SEEG-guided THC. All were women with several types of seizures and psychiatric comorbidities. EZN was extensive and often bilateral, including a part of the heterotopias. The outcomes of SEEG-guided THC varied; two patients experienced significant seizure reduction and improvement in psychiatric symptoms (Engel class I-II), one showed partial improvement (Engel class III), and one had no significant benefit (Engel class IV). Psychiatric comorbidities, including posttraumatic stress disorder, depression, and anxiety, were present in all cases, with some patients showing symptom improvement alongside seizure reduction. Despite genetic origin, SEEG-guided THC can be proposed in FLNA-positive PVNH-related epilepsy, although outcomes vary. The presence of FLNA mutations should not contraindicate surgical intervention but may influence the therapeutic response. Further research is needed to understand the impact of genetic variants on epilepsy outcome., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Nodular heterotopia (NH)-related drug-resistant epilepsy is challenging due to the deep location of the NH and the complexity of the underlying epileptogenic network. Using ictal stereo-electroencephalography (SEEG) and functional connectivity (FC) analyses in 14 patients with NH-related drug-resistant epilepsy, we aimed to determine the leading structure during seizures. For this purpose, we compared node IN and OUT strength between bipolar channels inside the heterotopia and inside gray matter, at the group level and at the individual level. At seizure onset, the channels within NH belonging to the epileptogenic and/or propagation network showed higher node OUT-strength than the channels within the gray matter (p = .03), with higher node OUT-strength than node IN-strength (p = .03). These results are in favor of a "leading" role of NH during seizure onset when involved in the epileptogenic- or propagation-zone network (50% of patients). However, when looking at the individual level, no significant difference between NH and gray matter was found, except for one patient (in two of three seizures). This result confirms the heterogeneity and the complexity of the epileptogenic network organization in NH and the need for SEEG exploration to characterize more precisely patient-specific epileptogenic network organization., (© 2024 International League Against Epilepsy.)

Objective: Quantification of the epileptogenic zone network (EZN) most frequently implies analysis of seizure onset. However, important information can also be obtained from the postictal period, characterized by prominent changes in the EZN. We used permutation entropy (PE), a measure of signal complexity, to analyze the peri-ictal stereoelectroencephalography (SEEG) signal changes with emphasis on the postictal state. We sought to determine the best PE-derived parameter (PEDP) for identifying the EZN., Methods: Several PEDPs were computed retrospectively on SEEG-recorded seizures of 86 patients operated on for drug-resistant epilepsy: mean baseline preictal entropy, minimum ictal entropy, maximum postictal entropy, the ratio between the maximum postictal and the minimum ictal entropy, and the ratio between the maximum postictal and the baseline preictal entropy. The performance of each biomarker was assessed by comparing the identified epileptogenic contacts or brain regions against the EZN defined by clinical analysis incorporating the Epileptogenicity Index and the connectivity epileptogenicity index methods (EZNc), using the receiver-operating characteristic and precision-recall., Results: The ratio between the maximum postictal and the minimum ictal entropy (defined as the Permutation Entropy Index [PEI]) proved to be the best-performing PEDP to identify the EZN C . It demonstrated the highest area under the curve (AUC) and F1 score at the contact level (AUC 0.72; F1 0.39) and at the region level (AUC 0.78; F1 0.47). PEI values gradually decreased between the EZN, the propagation network, and the non-involved regions. PEI showed higher performance in patients with slow seizure-onset patterns than in those with fast seizure-onset patterns. The percentage of resected epileptogenic regions defined by PEI was significantly correlated with surgical outcome., Significance: PEI is a promising tool to improve the delineation of the EZN. PEI combines ease and robustness in a routine clinical setting with high sensitivity for seizures without fast activity at seizure onset., (© 2023 International League Against Epilepsy.)

Objective: We studied the rate dynamics of interictal events occurring over fast-ultradian time scales, as commonly examined in clinics to guide surgical planning in epilepsy., Methods: Stereo-electroencephalography (SEEG) traces of 35 patients with good surgical outcome (Engel I) were analyzed. For this we developed a general data mining method aimed at clustering the plethora of transient waveform shapes including interictal epileptiform discharges (IEDs) and assessed the temporal fluctuations in the capability of mapping the epileptogenic zone (EZ) of each type of event., Results: We found that the fast-ultradian dynamics of the IED rate may effectively impair the precision of EZ identification, and appear to occur spontaneously, that is, not triggered by or exclusively associated with a particular cognitive task, wakefulness, sleep, seizure occurrence, post-ictal state, or antiepileptic drug withdrawal. Propagation of IEDs from the EZ to the propagation zone (PZ) could explain the observed fast-ultradian fluctuations in a reduced fraction of the analyzed patients, suggesting that other factors like the excitability of the epileptogenic tissue could play a more relevant role. A novel link was found between the fast-ultradian dynamics of the overall rate of polymorphic events and the rate of specific IEDs subtypes. We exploited this feature to estimate in each patient the 5 min interictal epoch for near-optimal EZ and resected-zone (RZ) localization. This approach produces at the population level a better EZ/RZ classification when compared to both (1) the whole time series available in each patient (p = .084 for EZ, p < .001 for RZ, Wilcoxon signed-rank test) and (2) 5 min epochs sampled randomly from the interictal recordings of each patient (p < .05 for EZ, p < .001 for RZ, 10 5 random samplings)., Significance: Our results highlight the relevance of the fast-ultradian IED dynamics in mapping the EZ, and show how this dynamics can be estimated prospectively to inform surgical planning in epilepsy., (© 2023 International League Against Epilepsy.)

Objective: Stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) aims to reduce seizure frequency by modifying epileptogenic networks through local thermocoagulative lesions. Although RF-TC is hypothesized to functionally modify brain networks, reports of changes in functional connectivity (FC) following the procedure are missing. We evaluated, by means of SEEG recordings, whether variation in brain activity after RF-TC is related to clinical outcome., Methods: Interictal SEEG recordings from 33 patients with drug-resistant epilepsy (DRE) were analyzed. Therapeutic response was defined as a >50% reduction in seizure frequency for at least 1 month following RF-TC. Local (power spectral density [PSD]) and FC changes were evaluated in 3-min segments recorded shortly before (baseline), shortly after, and 15 min after RF-TC. The PSD and FC strength values after thermocoagulation were compared with baseline as well as between the responder and nonresponder groups., Results: In responders, we found a significant reduction in PSD after RF-TC in channels that were thermocoagulated for all frequency bands (p = .007 for broad, delta and theta, p <.001 for alpha and beta bands). However, we did not observe such PSD decrease in nonresponders. At the network level, nonresponders displayed a significant FC increase in all frequency bands except theta (broad, delta, beta band: p <.001; alpha band: p <.01), although responders showed a significant FC decrease in delta (p <.001) and alpha bands (p <.05). Nonresponders showed stronger FC changes with respect to responders exclusively in TC channels (broad, alpha, theta, beta: p >.05; delta: p = .001)., Significance: Thermocoagulation induces both local and network-related (FC) changes in electrical brain activity of patients with DRE lasting for at least 15 min. This study demonstrates that the observed short-term modifications in brain network and local activity significantly differ between responders and nonresponders and opens new perspectives for studying the longer-lasting FC changes after RF-TC., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Nodular heterotopias (NHs) are malformations of cortical development associated with drug-resistant focal epilepsy with frequent poor surgical outcome. The epileptogenic network is complex and can involve the nodule, the overlying cortex, or both. Single-pulse electrical stimulation (SPES) during stereo-electroencephalography (SEEG) allows the investigation of functional connectivity between the stimulated and responsive cortices by eliciting cortico-cortical evoked potentials (CCEPs). We used SPES to analyze the NH connectome and its relation to the epileptogenic network organization., Methods: We retrospectively studied 12 patients with NH who underwent 1 Hz or 0.2 Hz SPES of NH during SEEG. Outbound connectivity (regions where CCEPs were elicited by NH stimulation) and inbound connectivity (regions where stimulation elicited CCEPs in the NH) were searched. SEEG channels were then classified as "heterotopic" (located within the NH), "connected" (located in normotopic cortex and showing connectivity with the NH), and "unconnected." We used the epileptogenicity index (EI) to quantify implication of channels in the seizure-onset zone and to classify seizures as heterotopic, normotopic, and normo-heterotopic., Results: One hundred thirty-five outbound and 72 inbound connections were found. Three patients showed connectivity between hippocampus and NH, and seven patients showed strong internodular connectivity. A total of 39 seizures were analyzed: 23 normo-heterotopic, 12 normotopic, and 4 heterotopic. Logistic regression found that "connected" channels were significantly (p = 8.4e-05) more likely to be epileptogenic than "unconnected" channels (odds ratio 4.71, 95% confidence interval (CI) [2.17, 10.21]) and heterotopic channels were also significantly (p = .024) more epileptogenic than "unconnected" channels (odds ratio 3.29, 95% CI [1.17, 9.23])., Significance: SPES reveals widespread connectivity between NH and normotopic regions. Those connected regions show higher epileptogenicity. SPES might be useful to assess NH epileptogenic network., (© 2022 International League Against Epilepsy.)

Objective: Stereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) aims at modifying epileptogenic networks to reduce seizure frequency. High-frequency oscillations (HFOs), spikes, and cross-rate are quantifiable epileptogenic biomarkers. In this study, we sought to evaluate, using SEEG signals recorded before and after thermocoagulation, whether a variation in these markers is related to the therapeutic effect of this procedure and to the outcome of surgery., Methods: Interictal segments of SEEG signals were analyzed in 38 patients during presurgical evaluation. We used an automatized method to quantify the rate of spikes, rate of HFOs, and cross-rate (a measure combining spikes and HFOs) before and after thermocoagulation. We analyzed the differences both at an individual level with a surrogate approach and at a group level with analysis of variance. We then evaluated the correlation between these variations and the clinical response to RF-TC and to subsequent resective surgery., Results: After thermocoagulation, 19 patients showed a clinical improvement. At the individual level, clinically improved patients more frequently had a reduction in spikes and cross-rate in the epileptogenic zone than patients without clinical improvement (p = .002, p = .02). At a group level, there was a greater decrease of HFOs in epileptogenic and thermocoagulated zones in patients with clinical improvement (p < .05) compared to those with no clinical benefit. Eventually, a significant decrease of all the markers after RF-TC was found in patients with a favorable outcome of resective surgery (spikes, p = .026; HFOs, p = .03; cross-rate, p = .03)., Significance: Quantified changes in the rate of spikes, rate of HFOs, and cross-rate can be observed after thermocoagulation, and the reduction of these markers correlates with a favorable clinical outcome after RF-TC and with successful resective surgery. This may suggest that interictal biomarker modifications after RF-TC can be clinically used to predict the effectiveness of the thermocoagulation procedure and the outcome of resective surgery., (© 2021 International League Against Epilepsy.)

Accelerated long-term forgetting (ALF) is a particular form of amnesia mostly encountered in focal epilepsy, particularly in temporal lobe epilepsy. This type of memory loss is characterized by an impairment of long-term consolidation of declarative memory, and its mechanisms remain poorly understood. In particular, the respective contribution of lesion, seizures, interictal epileptic discharges, and sleep is still debated. Here, we provide an overview of the relationships intertwining epilepsy, sleep, and memory consolidation and, based on recent findings from intracranial electroencephalographic recordings, we propose a model of ALF pathophysiology that integrates the differential role of interictal spikes during wakefulness and sleep. This model provides a framework to account for the different timescales at which ALF may occur., (© 2021 International League Against Epilepsy.)

Objective: Hyperkinetic epileptic seizures (HKS) are difficult to characterize and localize according to semiologic features. We propose a multicriteria scale to help visual analysis and report results of cerebral localization., Methods: We assessed seizures from 37 patients with HKS, explored with stereoelectroencephalography during presurgical evaluation. We used a multicriteria scale (hyperkinetic seizure scale [HSS]) with 10 semiologic features, scored independently by two neurologists. The item scores were used to group seizures using the k-means method. Semiologic features were correlated with the seizure onset zone (SOZ) localization (temporal, prefrontal dorsolateral, prefrontal ventromesial, parietal, insular)., Results: Fifty-five seizures were analyzed, and each item of the HSS was compared between the two examiners with good interrater agreement (85.3%). Dystonia, integrated behavior, and bilateral or unilateral hyperkinetic movements were statistically significant according to localization. Three clusters were identified according to the HSS and correlated with different patterns of anatomic localization of SOZ. Cluster 1 was characterized clinically by asymmetric hyperkinetic movements associated with marked dystonia and vocalization. It mainly included parietal seizures. Cluster 2 was characterized by bilateral and symmetrical stereotyped hyperkinetic movements without dystonia. It represented half of temporal seizures and one-third of prefrontal seizures (dorsolateral). Cluster 3 was characterized by seizures with strong emotionality and vocalization with bilateral and symmetrical hyperkinetic movements and integrated behavior. It involved half of temporal seizures and a majority of prefrontal (ventromesial) seizures., Significance: We propose a first attempt to quantify clinical patterns of HKS. The HSS may help to predict SOZ localization according to three main groups of hyperkinetic seizures., (© 2020 International League Against Epilepsy.)

We investigated the effect of electrical stimulation of the medial pulvinar (PuM) in terms of its effect on temporal lobe seizures. Eight patients with drug-resistant temporal lobe epilepsy undergoing stereoelectroencephalographic exploration were included. All had at least one electrode exploring the PuM. High-frequency (50 Hz) stimulations of the PuM were well tolerated in the majority of them. During diagnostic stimulation to confirm the epileptogenic zone, 19 seizures were triggered by stimulating the hippocampus. During some of these seizures, ipsilateral pulvinar stimulation was applied (130 Hz, pulse width = 450 microseconds, duration = 3-7 seconds, 1-2 mA). Compared to non-PuM-stimulated seizures, five of eight patients experienced clinically less severe seizures, particularly in terms of degree of alteration of consciousness. On the electrical level, seizures were more rapidly clonic with a shorter tonic phase. This proof of concept study is the first to suggest that PuM stimulation could be a well-tolerated and effective means of therapeutic deep brain stimulation in drug-resistant epilepsies., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Objective: Defining the roles of heterotopic and normotopic cortex in the epileptogenic networks in patients with nodular heterotopia is challenging. To elucidate this issue, we compared heterotopic and normotopic cortex using quantitative signal analysis on stereoelectroencephalography (SEEG) recordings., Methods: Clinically relevant biomarkers of epileptogenicity during ictal (epileptogenicity index; EI) and interictal recordings (high-frequency oscillation and spike) were evaluated in 19 patients undergoing SEEG. These biomarkers were then compared between heterotopic cortex and neocortical regions. Seizures were classified as normotopic, heterotopic, or normoheterotopic according to respective values of quantitative analysis (EI ≥0.3)., Results: A total of 1,246 contacts were analyzed: 259 in heterotopic tissue (heterotopic cortex), 873 in neocortex in the same lobe of the lesion (local neocortex), and 114 in neocortex distant from the lesion (distant neocortex). No significant difference in EI values, high-frequency oscillations, and spike rate was found comparing local neocortex and heterotopic cortex at a patient level, but local neocortex appears more epileptogenic (p < 0.001) than heterotopic cortex analyzing EI values at a seizure level. According to EI values, seizures were mostly normotopic (48.5%) or normoheterotopic (45.5%); only 6% were purely heterotopic. A good long-term treatment response was obtained in only two patients after thermocoagulation and surgical disconnection., Significance: This is the first quantitative SEEG study providing insight into the mechanisms generating seizures in nodular heterotopia. We demonstrate that both the heterotopic lesion and particularly the normotopic cortex are involved in the epileptogenic network. This could open new perspectives on multitarget treatments, other than resective surgery, aimed at modifying the epileptic network., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)