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Objective: We have developed a novel method for estimating brain tissue electrical conductivity using low-intensity pulse stereoelectroencephalography (SEEG) stimulation coupled with biophysical modeling. We evaluated the hypothesis that brain conductivity is correlated with the degree of epileptogenicity in patients with drug-resistant focal epilepsy., Methods: We used bipolar low-intensity biphasic pulse stimulation (.2 mA) followed by a postprocessing pipeline for estimating brain conductivity. This processing is based on biophysical modeling of the electrical potential induced in brain tissue between the stimulated contacts in response to pulse stimulation. We estimated the degree of epileptogenicity using a semi-automatic method quantifying the dynamic of fast discharge at seizure onset: the epileptogenicity index (EI). We also investigated how the location of stimulation within specific anatomical brain regions or within lesional tissue impacts brain conductivity., Results: We performed 1034 stimulations of 511 bipolar channels in 16 patients. We found that brain conductivity was lower in the epileptogenic zone (EZ; unpaired median difference = .064, p < .001) and inversely correlated with the epileptogenic index value (p < .001, Spearman rho = -.32). Conductivity values were also influenced by anatomical site, location within lesion, and delay between SEEG electrode implantation and stimulation, and had significant interpatient variability. Mixed model multivariate analysis showed that conductivity is significantly associated with EI (F = 13.45, p < .001), anatomical regions (F = 5.586, p < .001), delay since implantation (F = 14.71, p = .003), and age at SEEG (F = 6.591, p = .027), but not with the type of lesion (F = .372, p = .773) or the delay since last seizure (F = 1.592, p = .235)., Significance: We provide a novel model-based method for estimating brain conductivity from SEEG low-intensity pulse stimulations. The brain tissue conductivity is lower in EZ as compared to non-EZ. Conductivity also varies significantly across anatomical brain regions. Involved pathophysiological processes may include changes in the extracellular space (especially volume or tortuosity) in epileptic tissue., (© 2024 The Authors. 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: 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.)

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: In this study, we seek to analyze the determinants of the intracranial electroencephalography seizure onset pattern (SOP) and the impact of the SOP in predicting postsurgical seizure outcome., Methods: To this end, we analyzed 820 seizures from 252 consecutive patients explored by stereo-electroencephalography (total of 2148 electrodes), including various forms of focal refractory epilepsies. We used a reproducible method combining visual and time-frequency analyses., Results: We described eight SOPs: low-voltage fast activity (LVFA), preictal spiking followed by LVFA, burst of polyspikes followed by LVFA, slow wave/DC shift followed by LVFA, sharp theta/alpha waves, beta sharp waves, rhythmic spikes/spike-waves, and delta-brush. LVFA occurred in 79% of patients. The seizure onset pattern was significantly associated with (1) underlying etiology (burst of polyspikes followed by LVFA with the presence of a focal cortical dysplasia, LVFA with malformation of cortical development, postvascular and undetermined epilepsies), (2) spatial organization of the epileptogenic zone (EZ; burst of polyspikes followed by LVFA with focal organization, slow wave/DC shift followed by LVFA with network organization), and (3) postsurgical seizure outcome (better outcome when LVFA present)., Significance: This study demonstrates that the main determinants of the SOP are the underlying etiology and the spatial organization of the EZ. Concerning the postsurgical seizure outcome, the main determinant factor is the spatial organization of the EZ, but the SOP plays also a role, conferring better prognosis when LVFA is present., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Objective: Non-rapid eye movement (NREM) sleep is known to be a brain state associated with an activation of interictal epileptic activity. The goal of this work was to quantify topographic changes occurring during NREM sleep in comparison with wakefulness., Method: We studied intracerebral recordings of 20 patients who underwent stereo-electroencephalography (SEEG) during presurgical evaluation for pharmacoresistant focal epilepsy. We measured the number of interictal spikes (IS) and quantified the co-occurrence of IS between brain regions during 1 hour of NREM sleep and 1 hour of wakefulness. Co-occurrence is a method to estimate IS networks based on a temporal concordance between IS of different brain regions. Each studied region was labeled as "seizure-onset zone" (SOZ), "propagation zone" (PZ), or "not involved region" (NIR)., Results: During NREM sleep, the number of interictal spikes significantly increased in all regions (mean of 68%). This increase was higher in medial temporal regions than in other regions, whether involved in the SOZ. Spike co-occurrence increased significantly in all regions during NREM sleep in comparison with wakefulness but was greater in neocortical regions. Spike co-occurrence in medial temporal regions was not higher than in other regions, suggesting that the increase of the number of spikes in this region was in great part a local effect., Significance: This study demonstrated that medial temporal regions show a greater propensity to spike production or propagation during NREM sleep compared to other brain regions, even when the medial temporal lobe is not involved in the SOZ., (Wiley Periodicals, Inc. © 2017 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.)

Epilepsies associated with hypothalamic hamartomas (HHs) are frequently drug resistant with severe psychiatric and cognitive comorbidities. We performed a prospective trial to evaluate the safety and efficacy of Gamma Knife radiosurgery (GKS). Between October 1999 and October 2007, a total of 57 patients were investigated, included and treated by GKS in Timone University Hospital. Preoperative workup and 3-year postoperative evaluation consisted of seizure diary, neuropsychological, psychiatric, endocrinologic, visual field, and visual acuity examinations. Follow-up of >3 years was available for 48 patients. Topologic type was type I in 11 patients, type II in 15, type III in 17, type IV in one, type V in one, type VI in one, and mixed type in 2. The median marginal dose was 17 Gy (min 14 and max 25 Gy). The median target volume was 398 mm 3 (28-1,600 mm 3 ). Due to partial results, 28 patients (58.3%) required a second treatment. The median follow-up was 71 months (36-153 months). At last follow-up, the rate of Engel class I outcome was 39.6%, Engel class II was 29.2% (I+II 68.8%), and Engel class III was 20%. Global psychiatric comorbidity was considered cured in 28%, improved in 56%, stable in 8%, and continued to worsen in 8%. No permanent neurologic side effect was reported (in particular, no memory deficit). Nondisabling transient poikilothermia was observed in three patients (6.2%). A transient increase of seizure frequency was reported in 8 patients (16.6%) with a median duration of 30 days (9-90 days). Microsurgery was proposed because of insufficient efficacy of GKS in seven patients (14.5%) with a postoperative Engel class I-II in 28.6%. This prospective trial demonstrates very good long-term safety and efficacy of GKS for 2 patients. Beyond seizure reduction, the improvement of psychiatric and cognitive comorbidities along with better school performance and social functioning, being better socially integrated, having friends having a social life, working, participating to group activities turn out to be major benefits of GKS in this group of patients with frequently catastrophic epilepsy., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Gamma Knife radiosurgery (GK) is an effective treatment for hypothalamic hamartoma. No precise data are available on the risk of endocrine side effects of this treatment. In this study, 34 patients with hypothalamic hamartoma (HH) were followed prospectively at the Department of Endocrinology, La Timone Hospital, Marseille, France, for a mean follow-up of >2 years (mean ± standard deviation [SD] 3.6 ± 2 years). Initial pre- and post-GK radiosurgery evaluations were performed, including weight, body mass index (BMI), and a complete endocrinological workup. At diagnosis, eight patients presented with central precocious puberty at a mean age of 5.4 ± 2.4 years. At the time of GK (mean age 18.2 ± 11.1 years), two patients previously treated with surgery presented with luteinizing hormone/follicle-stimulating hormone (LH/FSH) deficiency. After GK, only one patient presented with a new thyrotropin-stimulating hormone (TSH) deficiency, 2 years after the procedure. The other pituitary axes remained normal in all but two patients (who had LH/FSH deficiency prior to GK). There was no significant difference between pre- and post-GK mean BMI (26.9 vs. 25.1 kg/m 2 , p = 0.59). To conclude, in this group of 34 patients, GK did not induce major endocrinologic side effects reported with all the other surgical techniques in the literature. It is, thus, a safe and effective procedure in the treatment of hypothalamic hamartoma., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Objectives: The study of intracerebral electroencephalography (EEG) seizure-onset patterns is crucial to accurately define the epileptogenic zone and guide successful surgical resection. It also raises important pathophysiologic issues concerning mechanisms of seizure generation. Until now, several seizure-onset patterns have been described using distinct recording methods (subdural, depth electrode), mostly in temporal lobe epilepsies or with heterogeneous neocortical lesions., Methods: We analyzed data from a cohort of 53 consecutive patients explored by stereoelectroencephalography (SEEG) and with pathologically confirmed malformation of cortical development (MCD; including focal cortical dysplasia [FCD] and neurodevelopmental tumors [NDTs])., Results: We identified six seizure-onset patterns using visual and time-frequency analysis: low-voltage fast activity (LVFA); preictal spiking followed by LVFA; burst of polyspikes followed by LVFA; slow wave/DC shift followed by LVFA; theta/alpha sharp waves; and rhythmic spikes/spike-waves. We found a high prevalence of patterns that included LVFA (83%), indicating nevertheless that LVFA is not a constant characteristic of seizure onset. An association between seizure-onset patterns and histologic types was found (p = 001). The more prevalent patterns were as follows: (1) in FCD type I LVFA (23.1%) and slow wave/baseline shift followed by LVFA (15.4%); (2) in FCD type II burst of polyspikes followed by LVFA (31%), LVFA (27.6%), and preictal spiking followed by LVFA (27.6%); (3) in NDT, LVFA (54.5%). We found that a seizure-onset pattern that included LVFA was associated with favorable postsurgical outcome, but the completeness of the EZ resection was the sole independent predictive variable., Significance: Six different seizure-onset patterns can be described in FCD and NDT. Better postsurgical outcome is associated with patterns that incorporate LVFA., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Objective: The objective of the study was to characterize interictal 18-fluorodeoxyglucose-positron emission tomography ((18) FDG-PET) whole-brain voxel-based metabolic patterns among distinct subtypes of temporal lobe epilepsy (TLE), as defined by stereo-electroencephalography (SEEG) and to determine predictive value of PET result on postoperative outcome., Methods: Fifty-four consecutive patients with pharmacoresistant TLE were enrolled retrospectively after a comprehensive presurgical evaluation. This evaluation defined: 7 lateral TLE, 17 mesial TLE, 14 "plus" TLE, and 16 bilateral TLE. Whole-brain voxel-based brain metabolism was studied in each group of patients, in comparison to 23 healthy subjects, and individual classification was evaluated by cross-validation using the found clusters. An (18) FDG-PET index was moreover calculated for each patient, based on the individual Z-score of the most significant cluster extracted on the comparison between patients' subgroup and healthy subjects. Logistic regression analysis was used to estimate factors associated with postoperative outcome (Engel's classes III-IV vs. I-II), including age, gender, disease duration, seizure frequency, as well as magnetic resonance imaging (MRI) and PET findings., Results: Different patterns of hypometabolism were found inside and outside the epileptogenic zone, among patients with distinct subgroups of TLE, in comparison to healthy subjects (p < 0.001, corrected for the cluster). At individual level, cross-validation showed satisfactory discrimination between the four groups with 71.4-88.2% overall accuracy. Multivariate analysis shows that (18) FDG-PET index was the only significant predictor of postoperative outcome to distinguish between Engel's classes I-II and III-IV (p = 0.037)., Significance: Overall, this whole-brain voxel-based analysis validates specific patterns of hypometabolism, inside and outside the EZ, in distinct subgroups of patients with TLE, as defined by SEEG gold standard, and in relation with postoperative outcome., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)