The interictal suppression hypothesis is the dominant differentiator of seizure onset zones in focal epilepsy.

Successful surgical treatment of drug-resistant epilepsy traditionally relies on the identification of seizure onset zones (SOZs). Connectome-based analyses of electrographic data from stereo electroencephalography (SEEG) may empower improved detection of SOZs. Specifically, connectome-based analyses based on the Interictal Suppression Hypothesis (ISH) posit that when the patient is not having a seizure, SOZs are inhibited by non-SOZs through high inward connectivity and low outward connectivity. However, it is not clear whether there are other motifs that can better identify potential SOZs. Thus, we sought to use unsupervised machine learning to identify network motifs that elucidate SOZs and investigate if there is another motif that outperforms the ISH. Resting-state SEEG data from 81 patients with drug-resistant epilepsy undergoing a pre-surgical evaluation at Vanderbilt University Medical Center were collected. Directed connectivity matrices were computed using the alpha band (8-12Hz). Principal component analysis (PCA) was performed on each patient's connectivity matrix. Each patient's components were analyzed qualitatively to identify common patterns across patients. A quantitative definition was then used to identify the component that most closely matched the observed pattern in each patient. A motif characteristic of the Interictal Suppression Hypothesis (high-inward and low-outward connectivity) was present in all individuals and found to be the most robust motif for identification of SOZs in 64/81 (79%) patients. This principal component demonstrated significant differences in SOZs compared to non-SOZs. While other motifs for identifying SOZs were present in other patients, they differed for each patient, suggesting that seizure networks are patient specific, but the ISH is present in nearly all networks. We discovered that a potentially suppressive motif based on the Interictal Suppression Hypothesis was present in all patients, and it was the most robust motif for SOZs in 79% of patients. Each patient had additional motifs that further characterized SOZs, but these motifs were not common across all patients. This work has the potential to augment clinical identification of SOZs to improve epilepsy treatment.

Psychiatric complications following SEEG-guided radiofrequency thermocoagulations in patients with drug-resistant epilepsy.

SEEG-guided radiofrequency thermocoagulation (RF-TC) in the epileptogenic regions is a therapeutic option for patients with drug-resistant focal epilepsy who may have or not indication for epilepsy surgery. The most common adverse events of RF-TC are seizures, headaches, somatic pain, and sensory-motor deficits. If RF-TC could lead to psychiatric complications is unknown. In the present study, seven out of 164 patients (4.2 %) experienced psychiatric decompensation with or without memory deterioration after RF-TC of bilateral or unilateral amygdala and hippocampus. The appearance of symptoms was either acute, subacute, or chronic and the symptoms were either transient or lasted for several months. Common features among these patients were female sex, mesial temporal epilepsy, and a pre-existing history of psychological distress and memory dysfunction. Our study highlights the possibility of neuropsychiatric deterioration in specific patients following SEEG-guided RF-TC, despite its rarity.

Stereoelectroencephalography-guided radiofrequency thermocoagulation of the epileptogenic zone: a potential treatment and prognostic indicator for subsequent excision surgery.

PURPOSE: To evaluate the safety and efficacy of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC) for drug-resistant focal epilepsy and investigate the relationship between post-RFTC remission duration and delayed excision surgery effectiveness. METHODS: We conducted a retrospective analysis of 43 patients with drug-resistant focal epilepsy who underwent RFTC via SEEG electrodes. After excluding three, the remaining 40 were classified into subgroups based on procedures and outcomes. Twenty-four patients (60%) underwent a secondary excision surgery. We determined the predictive value of RFTC outcome upon subsequent surgical outcome by categorizing the delayed secondary surgery outcome as success (Engel I/II) versus failure (Engel III/IV). Demographic information, epilepsy characteristics, and the duration of seizure freedom after RFTC were assessed. RESULTS: Among 40 patients, 20% achieved Engel class I with RFTC alone, while 24 underwent delayed secondary excision surgery. Overall, 41.7% attained Engel class I, with a 66.7% success rate combining RFTC with delayed surgery. Seizure freedom duration was significantly longer in the success group (mean 4.9 months, SD = 2.7) versus the failure group (mean 1.9 months, SD = 1.1; P = 0.007). A higher proportion of RFTC-only and delayed surgical success group patients had preoperative lesional findings (p = 0.01), correlating with a longer time to seizure recurrence (p < 0.05). Transient postoperative complications occurred in 10%, resolving within a year. CONCLUSION: This study demonstrates that SEEG-guided RFTC is a safe and potential treatment option for patients with drug-resistant focal epilepsy. A prolonged duration of seizure freedom following RFTC may serve as a predictive marker for the success of subsequent excision surgery.

Ocular motility as a measure of cerebral dysfunction in adults with focal epilepsy.

OBJECTIVE: Using objective oculomotor measures, we aimed to: (1) compare oculomotor performance in patients with drug-resistant focal epilepsy to healthy controls, and (2) investigate the differential impact of epileptogenic focus laterality and location on oculomotor performance. METHODS: We recruited 51 adults with drug-resistant focal epilepsy from the Comprehensive Epilepsy Programs of two tertiary hospitals and 31 healthy controls to perform prosaccade and antisaccade tasks. Oculomotor variables of interest were latency, visuospatial accuracy, and antisaccade error rate. Linear mixed models were performed to compare interactions between groups (epilepsy, control) and oculomotor tasks, and between epilepsy subgroups and oculomotor tasks for each oculomotor variable. RESULTS: Compared to healthy controls, patients with drug-resistant focal epilepsy exhibited longer antisaccade latencies (mean difference = 42.8 ms, P = 0.001), poorer spatial accuracy for both prosaccade (mean difference = 0.4°, P = 0.002), and antisaccade tasks (mean difference = 2.1°, P < 0.001), and more antisaccade errors (mean difference = 12.6%, P < 0.001). In the epilepsy subgroup analysis, left-hemispheric epilepsy patients exhibited longer antisaccade latencies compared to controls (mean difference = 52.2 ms, P = 0.003), while right-hemispheric epilepsy was the most spatially inaccurate compared to controls (mean difference = 2.5°, P = 0.003). The temporal lobe epilepsy subgroup displayed longer antisaccade latencies compared to controls (mean difference = 47.6 ms, P = 0.005). SIGNIFICANCE: Patients with drug-resistant focal epilepsy exhibit poor inhibitory control as evidenced by a high percentage of antisaccade errors, slower cognitive processing speed, and impaired visuospatial accuracy on oculomotor tasks. Patients with left-hemispheric epilepsy and temporal lobe epilepsy have markedly impaired processing speed. Overall, oculomotor tasks can be a useful tool to objectively quantify cerebral dysfunction in drug-resistant focal epilepsy.

Outcomes of stereoelectroencephalography exploration at an epilepsy surgery center.

OBJECTIVES: Epilepsy surgery is offered in resistant focal epilepsy. Non-invasive investigations like scalp video EEG monitoring (SVEM) help delineate epileptogenic zone. Complex cases may require intracranial video EEG monitoring (IVEM). Stereoelectroencephalography (SEEG)-based intracerebral electrode implantation has better spatial resolution, lower morbidity, better tolerance, and superiority in sampling deep structures. Our objectives were to assess IVEM using SEEG with regard to reasoning behind implantation, course, surgical interventions, and outcomes. MATERIALS AND METHODS: Seventy-two admissions for SEEG from January 2014 to December 2018 were included in the study. Demographic and clinical data were retrospectively collected. RESULTS: The cohort comprised of 69 adults of which 34 (47%) had lesional MRI. Reasons for SEEG considering all cases included non-localizing ictal onset (76%), ictal-interictal discordance (21%), discordant semiology (17%), proximity to eloquent cortex (33%), nuclear imaging discordance (34%), and discordance with neuropsychology (19%). Among lesional cases, additional reasons included SVEM discordance (68%) and dual or multiple pathology (47%). Forty-eight patients (67%) were offered resective surgery, and 41 underwent it. Twenty-three (56%) had at least one year post-surgical follow-up of which 14 (61%) had Engels class I outcome. Of the remaining 23 who were continued on medical management, 4 (17%) became seizure-free and 12 (51%) had reduction in seizure frequency. CONCLUSION: SEEG monitoring is an important and safe tool for presurgical evaluation with good surgical and non-surgical outcomes. Whether seizure freedom following non-surgical management could be related to SEEG implantation, medication change, or natural course needs to be determined.

Stereoelectroencephalography: retrospective analysis of 742 procedures in a single centre.

This retrospective description of a surgical series is aimed at reporting on indications, methodology, results on seizures, outcome predictors and complications from a 20-year stereoelectroencephalography (SEEG) activity performed at a single epilepsy surgery centre. Prospectively collected data from a consecutive series of 742 SEEG procedures carried out on 713 patients were reviewed and described. Long-term seizure outcome of SEEG-guided resections was defined as a binomial variable: absence (ILAE classes 1-2) or recurrence (ILAE classes 3-6) of disabling seizures. Predictors of seizure outcome were analysed by preliminary uni/bivariate analyses followed by multivariate logistic regression. Furthermore, results on seizures of these subjects were compared with those obtained in 1128 patients operated on after only non-invasive evaluation. Survival analyses were also carried out, limited to patients with a minimum follow-up of 10 years. Resective surgery has been indicated for 570 patients (79.9%). Two-hundred and seventy-nine of 470 patients operated on (59.4%) were free of disabling seizures at least 2 years after resective surgery. Negative magnetic resonance and post-surgical lesion remnant were significant risk factors for seizure recurrence, while type II focal cortical dysplasia, balloon cells, glioneuronal tumours, hippocampal sclerosis, older age at epilepsy onset and periventricular nodular heterotopy were significantly associated with seizure freedom. Twenty-five of 153 patients who underwent radio-frequency thermal coagulation (16.3%) were optimal responders. Thirteen of 742 (1.8%) procedures were complicated by unexpected events, including three (0.4%) major complications and one fatality (0.1%). In conclusion, SEEG is a safe and efficient methodology for invasive definition of the epileptogenic zone in the most challenging patients. Despite the progressive increase of MRI-negative cases, the proportion of seizure-free patients did not decrease throughout the years.

Interictal psychiatric comorbidities of drug-resistant focal epilepsy: Prevalence and influence of the localization of the epilepsy.

Psychiatric comorbidities are 2 to 3 times more frequent in patients with epilepsy than in the general population. This study aimed to prospectively assess the following: (i) the prevalence of specific and nonspecific interictal psychiatric comorbidities in a population of patients with drug-resistant focal epilepsy and (ii) the influence of epilepsy lateralization and localization on these psychiatric comorbidities. In this prospective monocentric study, we collected demographic data, characteristics of the epilepsy, interictal psychiatric comorbidities, mood, anxiety, and alexithymia dimensions. We used criteria from Diagnostic and Statistical Manual of Mental Disorders IV ( DSM IV) (Mini International Mental Interview (MINI)), diagnosis criteria for specific comorbidities, and validated mood and anxiety scales (general and specific for epilepsy). Among the 87 enrolled patients (39 males, 48 females), 52.9% had at least one psychiatric comorbidity. The most common comorbidity was anxiety disorder (28.7% according to the MINI, and 38.4% screening by the Generalized Anxiety Disorder 7 (GAD 7)). Mood disorders were the second most frequent psychiatric comorbidity: 21.8% of our patients had interictal dysphoric disorders (IDDs), 16.1% presented major depressive disorders according to the MINI, and 17.2% screening by the Neurological Disorders Depression Inventory for Epilepsy (NDDIE). Patients with temporal lobe epilepsy had a higher prevalence of psychiatric comorbidities than patients with extratemporal lobe epilepsy (p = 0.002), which is probably related to a higher rate of anxiety disorders in this subgroup (p = 0.012). Prevalence of psychiatric disorders prior to epilepsy in patients was higher in right- than in left-sided epilepsy (p = 0.042). No difference was found according to limbic involvement at seizure onset. Overall, this article highlighted a very high proportion of anxiety disorders in these patients with drug-resistant focal epilepsy and the necessity to systematically detect them and thus lead to a specific treatment.

Radiofrequency thermocoagulation of the seizure-onset zone during stereoelectroencephalography.

OBJECTIVE: To assess long-term outcome and identify prognostic factors of radiofrequency thermocoagulation (RFTC) following stereoelectroencephalography (SEEG) explorations in particularly complex cases of focal epilepsy. METHODS: We retrospectively reviewed the medical charts, video-SEEG recordings, and outcomes for 23 patients (aged 6-53 years) treated with SEEG-guided RFTC, of whom 15 had negative magnetic resonance imaging (MRI) findings, and 10 were considered noneligible for resective surgery after SEEG. Two to 11 RFTCs per patient (mean 5) were produced by applying 40-50 V, 75-110 mA current for 10-60 s on SEEG electrode contacts within the epileptogenic region, which was very close to eloquent cortices in 12 cases. The general features, SEEG findings, and RFTC extent of the patients were analyzed to extract potential preoperative predictors of post-RFTC seizure outcomes. RESULTS: After a mean follow-up of 32 months (range 2-119 months), eight patients experienced a ≥50% decrease of seizure frequency after RFTC (R+, 34.8%), of whom one had a sustained seizure freedom and 15 patients did not benefit from RFTC (R-, 65.2%). The presence of an MRI lesion was the only significant predictor of a positive outcome, whereas location of epilepsy, extent of interictal epileptiform discharges (IEDs) and of the seizure onset zone, induction of seizures by electrical stimulation, as well as the ratio of the coagulated sites did not show a significant correlation to the RFTC response. However, (sub-)continuous IEDs were more frequently found in R+ than in R- patients, thus suggesting that this EEG marker of the epileptogenic tissue might predict a positive outcome even in patients without obvious MRI lesion. SIGNIFICANCE: Our study confirms that RFTC, although less effective than resective surgery, can be a reasonable therapeutic option in complex cases where anatomic constraints make impossible any cortical resection. Further prospective studies are needed to better define RFTC indications and to optimize its methodology.

Stereo electroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) in drug-resistant focal epilepsy: Results from a 10-year experience.

OBJECTIVE: Stereo electroencephalography (SEEG)-guided radiofrequency thermocoagulation (SEEG-guided RF-TC) has been proposed since 2004 as a possible treatment of some focal drug-resistant epilepsy. The aim of this study is to provide extensive data about efficacy and safety of SEEG-guided RF-TC. METHODS: Over a 10-year period, 162 patients with drug-resistant focal epilepsy were eligible for SEEG-guided RF-TG during phase II invasive investigation by SEEG. All follow-up and safety data were collected prospectively. The primary outcome was seizure freedom at 2 months and at 1 year after SEEG-guided RF-TC. Secondary outcomes were the responders' rate (patient with at least 50% decrease in seizure frequency) and their long-term follow-up. RESULTS: Twenty-five percent of patients were seizure-free at 2 months and 7% at 1 year. We reported 67% of responders at 2 months and 48% at 1 year; 58% of responders maintained their status during the long-term follow-up. The seizure outcome was significantly better when the SEEG-guided RF-TC involved the occipital region (p = 0.007). When surgery followed an SEEG-guided RF-TC, the positive predictive value of being a responder 2 months after an SEEG-guided RF-TC and to be Engel's class I or II after surgery was 93%. We reported 1.1% of permanent deficit and 2.4% of transient side effects. SIGNIFICANCE: Our results, gathered in a large population over a 10-year period, confirm that SEEG-guided RF-TC is a safe technique, being efficient in many cases. More than two thirds of patients showed a short-term improvement, and almost half of them were responders at 1-year follow-up. The technique appears to be especially interesting for limited epileptic zone inaccessible to surgery and when epilepsy is related to a large unilateral network (network disruption by multiple RF-TC). Furthermore, SEEG-guided RF-TC effect is a predictor of outcome after conventional cortectomy in patients eligible for surgery.

Drug-resistant focal epilepsy in women of childbearing age: Reproduction and the effect of epilepsy surgery.

OBJECTIVE: Women with epilepsy (WWE) have lower birth rates than expected. The reasons for this are multifactorial and involve a complex interaction between reproductive endocrine and psychosocial factors. The effect of epilepsy surgery on reproduction in women with drug-resistant focal epilepsy has not previously been studied. METHODS: Adult women of childbearing age (18-45years old) with drug-resistant focal epilepsy who had undergone a focal cortical resection between 1997 and 2008 at the Mayo Clinic in Rochester, MN were included in the study. Patients who had a history of hysterectomy or tubal ligation or who were menopausal at the time of surgery were excluded. Data on prior pregnancies and births, epilepsy history, surgical treatment, hormonal dysfunction, and socioeconomic status were obtained using a retrospective chart review. Associations between various clinical and demographic variables with changes in pregnancies and births from pre- to postsurgery were assessed using Chi-square or Fisher's exact test for categorical variables and Wilcoxon rank sum test for continuous variables. All tests were 2-sided, and p-values less than 0.05 were considered statistically significant. All analyses were performed using SAS software version 9.2 (SAS INC, Cary NC). RESULTS: One hundred and thirteen women (average age: 30.5years) were included in the study. Average length of follow-up was 5.7years (SD-3.90). Sixty-four patients (57.5%) were nulliparous at the time of surgery. Sixty-one patients (54%) had never been married. Average number of pregnancies per patient prior to surgery was 0.93, and average number of births prior to surgery was 0.73. After surgery, a total of 17 women had a total of 35 pregnancies and 25 births. The average number of pregnancies and births after surgery was 1.27 and 0.96, respectively. Infertility was reported in one patient postoperatively. Patients who were younger at the time of surgery experienced a greater change in the number of pregnancies and births after surgery (p=0.0036 and 0.0060, respectively). Patients who received fewer antiepileptic drug medication trials by the time of surgery also had a greater change in the number of births after surgery (p=0.0362). Seizure onset localization and lateralization, presurgical seizure frequency, age at seizure onset, duration of epilepsy, and postoperative seizure outcome were not statistically significant factors. CONCLUSION: The present retrospective observational study provides additional evidence for the importance of early surgical treatment in women with drug-resistant focal epilepsy. Patients who had received fewer medications prior to surgery were more likely to experience an increase in births following surgery. The significance of these findings requires further investigation but may support a role for earlier surgical intervention in the management of drug-resistant focal epilepsy.

Real-world anti-seizure treatment and adverse events among individuals living with drug-resistant focal epilepsy in the United States.

OBJECTIVE: This study aimed to understand how people living with drug-resistant focal epilepsy (DRE) navigate through lines of antiseizure medications (ASM) and experience adverse events (AEs) in the real-world setting in the United States. METHODS: A retrospective study was conducted with medical chart data from clinical practices in the United States. Eligible adults had a confirmed diagnosis of DRE and initiated a third-line ASM therapy between January 2013 and January 2020 (i.e., the index date). Subjects must have medical history data available for ≥1 year prior to (the baseline) and ≥2 years after the index date (the follow-up). Treatment patterns were captured from first to fourth lines. After the emergence of drug resistance, time to ASM discontinuation, reasons for discontinuation, AE experience and AE management were reported separately during third and fourth lines of treatment and beyond. RESULTS: The study included a total of 345 individuals, with an average (standard deviation) age of 23.9 (11.9) years at first diagnosis. All individuals had at least three lines of ASMs with first and second lines during baseline, and third line during follow-up. The first line for most individuals was monotherapy. As individuals progressed through additional lines of ASM therapy, they were more likely to receive polytherapy. The regimens were more individualized after meeting drug resistance criteria. The top reasons for discontinuing were uncontrolled seizure and/or intolerance/AEs for both third and subsequent lines. More than a third of individuals experienced at least one AE. Among those with at least one AE, many individuals had to manage these AEs with dose adjustment (39.4%), discontinuation of offending ASM (37.9%), de novo pharmacotherapy (25.8%), emergency room visit (13.6%), and hospitalization (12.1%). SIGNIFICANCE: This study demonstrated that individuals living with DRE experience significant AEs, and many of these AEs lead to treatment disruption and significant healthcare resource utilization. PLAIN LANGUAGE SUMMARY: This study examined how individuals with focal epilepsy are treated across various clinics in United States and reported the adverse events these individuals experienced during treatment, along with the consequence associated with these adverse events. We found that as individuals progressed through additional treatments, they were more and more likely to receive more than one antiseizure medication, and a significant portion of individuals experienced at least one adverse event, often manifested as headache, somnolence, dizziness, and fatigue.

Effective connectivity relates seizure outcome to electrode placement in responsive neurostimulation.

Responsive neurostimulation is a closed-loop neuromodulation therapy for drug resistant focal epilepsy. Responsive neurostimulation electrodes are placed near ictal onset zones so as to enable detection of epileptiform activity and deliver electrical stimulation. There is no standard approach for determining the optimal placement of responsive neurostimulation electrodes. Clinicians make this determination based on presurgical tests, such as MRI, EEG, magnetoencephalography, ictal single-photon emission computed tomography and intracranial EEG. Currently functional connectivity measures are not being used in determining the placement of responsive neurostimulation electrodes. Cortico-cortical evoked potentials are a measure of effective functional connectivity. Cortico-cortical evoked potentials are generated by direct single-pulse electrical stimulation and can be used to investigate cortico-cortical connections in vivo. We hypothesized that the presence of high amplitude cortico-cortical evoked potentials, recorded during intracranial EEG monitoring, near the eventual responsive neurostimulation contact sites is predictive of better outcomes from its therapy. We retrospectively reviewed 12 patients in whom cortico-cortical evoked potentials were obtained during stereoelectroencephalography evaluation and subsequently underwent responsive neurostimulation therapy. We studied the relationship between cortico-cortical evoked potentials, the eventual responsive neurostimulation electrode locations and seizure reduction. Directional connectivity indicated by cortico-cortical evoked potentials can categorize stereoelectroencephalography electrodes as either receiver nodes/in-degree (an area of greater inward connectivity) or projection nodes/out-degree (greater outward connectivity). The follow-up period for seizure reduction ranged from 1.3-4.8 years (median 2.7) after responsive neurostimulation therapy started. Stereoelectroencephalography electrodes closest to the eventual responsive neurostimulation contact site tended to show larger in-degree cortico-cortical evoked potentials, especially for the early latency cortico-cortical evoked potentials period (10-60 ms period) in six out of 12 patients. Stereoelectroencephalography electrodes closest to the responsive neurostimulation contacts (≤5 mm) also had greater significant out-degree in the early cortico-cortical evoked potentials latency period than those further away (≥10 mm) (P < 0.05). Additionally, significant correlation was noted between in-degree cortico-cortical evoked potentials and greater seizure reduction with responsive neurostimulation therapy at its most effective period (P < 0.05). These findings suggest that functional connectivity determined by cortico-cortical evoked potentials may provide additional information that could help guide the optimal placement of responsive neurostimulation electrodes.

Integration of interictal EEG source localization in presurgical epilepsy evaluation - A single-center prospective study.

OBJECTIVE: To investigate cost in working hours for initial integration of interictal EEG source localization (ESL) into clinical practice of a tertiary epilepsy center, and to examine concordance of results obtained with three different ESL pipelines. METHODS: This prospective study covered the first year of using ESL in the Epilepsy-Center Berlin-Brandenburg. Patients aged ≥14 years with drug-resistant focal epilepsy referred for noninvasive presurgical evaluation were included. Interictal ESL was based on low-density EEG and individual head models. Source maxima were obtained from two freely available software packages and one commercial provider. One physician and computer scientist documented their working hours for setting up and processing ESL. Additionally, a survey was conducted among epilepsy centers in Germany to assess the current role of ESL in presurgical evaluation. RESULTS: Of 40 patients included, 22 (55%) had enough interictal spikes for ESL. The physician's working times decreased from median 4.7 hours [interquartile range 3.9-6.4] in the first third of cases to 2.0 hours [1.9-2.4] in the remaining two thirds; P < 0.01. In addition, computer scientist and physician spent a total of 35.5 and 33.0 working hours on setting up the digital infrastructure, and on training and testing. Sublobar agreement between all three pipelines was 20%, mean measurement of agreement (kappa) 0.13. Finally, the survey revealed that 53% of epilepsy centers in Germany currently use ESL for presurgical evaluation. SIGNIFICANCE: This study provides information regarding expected effort and costs for integration of ESL into an epilepsy surgery program. Low result agreement across different ESL pipelines calls for further standardization.

Stereo-electroencephalography-guided radiofrequency thermocoagulation in patients with MRI-negative focal epilepsy.

OBJECTIVE: Coupled with stereo-electroencephalography (SEEG), radiofrequency thermocoagulation (RFTC) has emerged as a therapeutic alternative for patients with refractory focal epilepsy, with proven safe but highly variable results across studies. The authors aimed to describe the outcomes and safety of SEEG-RFTC, focusing on patients with MRI-negative epilepsy. METHODS: A retrospective observational study was conducted on patients evaluated by SEEG in the authors' center. Of 84 total cases, 55 underwent RFTC, with 31 MRI-negative epilepsies that were ultimately included in the study. The primary outcome was freedom from disabling seizures at last follow-up. Secondary outcomes were reduction in seizure frequency (RFTC response = seizure frequency reduction > 50%), peri-interventional complications, and neuropsychological outcomes. Potential factors influencing post-RFTC outcome were considered by comparing different variables between responders and nonresponders. RESULTS: The mean follow-up period was 30.9 months (range 7.1-69.8 months). Three patients underwent subsequent resection/laser interstitial thermal therapy within the 1st year after RFTC failure. All other patients completed a minimum follow-up period of 1 year. Fourteen patients (45.2%) showed at least a 50% reduction in seizure frequency (responders), and 8 were seizure free (25.8% of the whole cohort). One case showed a permanent complication not directly related to thermolesions. Most patients (76%) showed no significant cognitive decline. Electrically elicited seizures (EESs) were observed in all seizure-free patients and were more frequent in responders (p = 0.038). All patients who were seizure free at the 6-month visit maintained their status during long-term follow-up. CONCLUSIONS: SEEG-RFTC is a safe procedure and leads to a good response in many cases of MRI-negative focal epilepsies. One-quarter of the patients were seizure free and almost one-half were responders at the last follow-up. Although these results are still far from those achieved through conventional resection, a nonnegligible proportion of patients may benefit from this one-stage and much less invasive approach. Factors associated with seizure outcome remain to be elucidated; however, responders were significantly more frequent among patients with EESs, and achieving 6 months of seizure freedom appears to predict a good long-term response. In addition, the positive predictive value of RFTC response may be a valuable factor in the decision to proceed to subsequent surgery.

Hippocampal resection in temporal lobe epilepsy: Do we need to resect the tail?

INTRODUCTION: Anteromesial temporal lobe resection is the most common surgical technique used to treat drug-resistant mesial temporal lobe epilepsy, particularly when secondary to hippocampal sclerosis. Structural and functional imaging data suggest the importance of sparing the posterior hippocampus for minimising language and memory deficits. Recent work has challenged the view that maximal posterior hippocampal resection improves seizure outcome. This study was designed to assess whether resection of posterior hippocampal atrophy was associated with improved seizure outcome. METHODS: Retrospective analysis of a prospective database of all anteromesial temporal lobe resections performed in individuals with hippocampal sclerosis at our epilepsy surgery centre, 2013-2021. Pre- and post-operative MRI were reviewed by 2 neurosurgical fellows to assess whether the atrophic segment, displayed by automated hippocampal morphometry, was resected, and ILAE seizure outcomes were collected at 1 year and last clinical follow-up. Data analysis used univariate and binary logistic regression. RESULTS: Sixty consecutive eligible patients were identified of whom 70% were seizure free (ILAE Class 1 & 2) at one year. There was no statistically significant difference in seizure freedom outcomes in patients who had complete resection of atrophic posterior hippocampus or not (Fisher's Exact test statistic 0.69, not significant at p < .05) both at one year, and at last clinical follow-up. In the multivariate analysis only a history of status epilepticus (OR=0.2, 95%CI:0.042-0.955, p = .04) at one year, and pre-operative psychiatric disorder (OR=0.145, 95%CI:0.036-0.588, p = .007) at last clinical follow-up, were associated with a reduced chance of seizure freedom. SIGNIFICANCE: Our data suggest that seizure freedom is not associated with whether or not posterior hippocampal atrophy is resected. This challenges the traditional surgical dogma of maximal posterior hippocampal resection in anteromesial temporal lobe resections and is a step further optimising this surgical procedure to maximise seizure freedom and minimise associated language and memory deficits.

Common Ictal and Interictal Perfusion Patterns: A Window into the Epileptogenic Network and SUDEP Mechanism in Drug-Resistant Focal Epilepsy.

BACKGROUND: Focal epilepsies have been described as a network disease. Noninvasive investigative techniques have been used to characterize epileptogenic networks. OBJECTIVE: This study aimed to describe ictal and interictal cortical and subcortical perfusion patterns using single- photon emission computed tomography (SPECT) in patients with drug-resistant epilepsy (DRE). METHODS: Thirty-five interictal-ictal SPECT scans were obtained from 15 patients with DRE. A methodology was developed to get a relative perfusion index (PI) of 74 cortical and sub-cortical brain structures. K-means algorithm, together with modified v-fold cross-validation, was used to identify the two regions of interest (ROIs) that represent hypoperfused and hyperperfused areas. RESULTS: In common with the individual analysis, the statistical analysis evidenced that the hyperperfusion ROIs resulting from group analysis during interictal and ictal involved mainly the cingulate gyrus, cuneus, lingual gyrus, and gyrus rectus as well as the putamen. ROIs hypoperfused included the red nucleus, the substantia nigra, and the medulla. The medians of the group analysis of the hypoperfusion and hyperperfusion ROIs were 0.601-0.565 and 1.133-1.119 for the ictal and interictal states, correspondingly. A group of mostly cortical structures involved in the hyperperfused ROIs in both interictal and ictal states showed no change or negative change in the transition from interictal to ictal state (mean change of -0.002). On the other hand, the brain stem, basal ganglia, red nucleus, and thalamus revealed a mean global change of 0.19, indicating a mild increase in the PI. However, some of these structures (red nucleus, substantia nigra, and medulla oblongata) remained hypoperfused during the interictal to ictal transition. CONCLUSION: The methodology employed made it possible to identify common cortical and subcortical perfusion patterns not directly linked to epileptogenicity, for a better epileptogenic network and sudden unexpected death (SUDEP) mechanism in DRE.

Subclinical seizures on stereotactic EEG: characteristics and prognostic value.

OBJECTIVE: Although stereotactic EEG (sEEG) has become a widely used intracranial EEG technique, the significance of subclinical seizures (SCS) recorded on sEEG is unclear and studies examining this finding on sEEG are limited. We investigated (1) the prevalence of SCS in patients undergoing sEEG and clinical factors associated with their presence, (2) how often the subclinical seizure onset zone (SOZ) colocalizes with clinical SOZ, (3) the association of SCS and surgical outcomes, and (4) the influence of resection of the subclinical SOZ on surgical outcome. METHODS: We reviewed all patients who underwent intracranial monitoring with sEEG at our institution from 2015 through 2020 (n=169). Patient and seizure characteristics were recorded, as was concordance of subclinical and clinical seizures and post-surgical outcomes. RESULTS: SCS were observed during sEEG monitoring in 84 of 169 patients (50%). There was no difference in the prevalence of SCS based on imaging abnormalities, temporal vs extratemporal SOZ, number of electrodes, or pathology. SCS were more common in females than males (62% vs 40%, p=0.0054). SCS had complete concordance with clinical SOZ in 40% of patients, partial concordance in 29%, overlapping in 19%, and discordant in 12%. Eighty-three patients had surgery, 44 of whom had SCS. There was no difference in excellent outcome (ILAE 12 or 2) based on the presence of SCS or SCS concordance with clinical SOZ; however, there were improved outcomes in patients with complete resection of the subclinical SOZ compared with patients with incomplete resection (p =0.013). SIGNIFICANCE: These findings demonstrate that SCS are common during sEEG and colocalize with the clinical SOZ in most patients. Discordance with clinical SOZ does not necessarily predict poor surgical outcome; rather, complete surgical treatment of the subclinical SOZ correlates with excellent outcome. For unclear reasons, subclinical seizures occurred more commonly in females than males.

Relation of Brain Perfusion Patterns to Sudden Unexpected Death Risk Stratification: A Study in Drug Resistant Focal Epilepsy.

To explore the role of the interictal and ictal SPECT to identity functional neuroimaging biomarkers for SUDEP risk stratification in patients with drug-resistant focal epilepsy (DRFE). Twenty-nine interictal-ictal Single photon emission computed tomography (SPECT) scans were obtained from nine DRFE patients. A methodology for the relative quantification of cerebral blood flow of 74 cortical and sub-cortical structures was employed. The optimal number of clusters (K) was estimated using a modified v-fold cross-validation for the use of K means algorithm. The two regions of interest (ROIs) that represent the hypoperfused and hyperperfused areas were identified. To select the structures related to the SUDEP-7 inventory score, a data mining method that computes an automatic feature selection was used. During the interictal and ictal state, the hyperperfused ROIs in the largest part of patients were the bilateral rectus gyrus, putamen as well as globus pallidus ipsilateral to the seizure onset zone. The hypoperfused ROIs included the red nucleus, substantia nigra, medulla, and entorhinal area. The findings indicated that the nearly invariability in the perfusion pattern during the interictal to ictal transition observed in the ipsi-lateral putamen F = 12.60, p = 0.03, entorhinal area F = 25.80, p = 0.01, and temporal middle gyrus F = 12.60, p = 0.03 is a potential biomarker of SUDEP risk. The results presented in this paper allowed identifying hypo- and hyperperfused brain regions during the ictal and interictal state potentially related to SUDEP risk stratification.

Previous, current, and future stereotactic EEG techniques for localising epileptic foci.

INTRODUCTION: Drug-resistant focal epilepsy presents a significant morbidity burden globally, and epilepsy surgery has been shown to be an effective treatment modality. Therefore, accurate identification of the epileptogenic zone for surgery is crucial, and in those with unclear noninvasive data, stereoencephalography is required. AREAS COVERED: This review covers the history and current practices in the field of intracranial EEG, particularly analyzing how stereotactic image-guidance, robot-assisted navigation, and improved imaging techniques have increased the accuracy, scope, and use of SEEG globally. EXPERT OPINION: We provide a perspective on the future directions in the field, reviewing improvements in predicting electrode bending, image acquisition, machine learning and artificial intelligence, advances in surgical planning and visualization software and hardware. We also see the development of EEG analysis tools based on machine learning algorithms that are likely to work synergistically with neurophysiology experts and improve the efficiency of EEG and SEEG analysis and 3D visualization. Improving computer-assisted planning to minimize manual input from the surgeon, and seamless integration into an ergonomic and adaptive operating theater, incorporating hybrid microscopes, virtual and augmented reality is likely to be a significant area of improvement in the near future.

Anticipatory anxiety of epileptic seizures: An overlooked dimension linked to trauma history.

OBJECTIVE: Fear of having a seizure called anticipatory anxiety of epileptic seizure (AAS), constitutes a daily life burden but has been rarely studied. Our aim was to assess the prevalence and the determining factors of AAS in patients with drug-resistant focal epilepsy, a dimension that has not been thoroughly investigated before. METHODS: We conducted an observational, prospective study enrolling patients with drug-resistant focal epilepsy. The psychiatric assessment aimed to evaluate psychiatric comorbidities, trauma history, and quality of life using hetero-evaluation and self-assessment tools. Dimensions of anxiety specifically related to epilepsy (peri-and-inter-ictal) were explored as exhaustively as possible. RESULTS: AAS was found in 53 % of the 87 patients. We compared the two groups of patients: with or without AAS. Patients with AAS had a significantly shorter duration of epilepsy (p = 0.04). There was no difference between groups with respect to psychiatric disorders, except for cannabis dependence, more frequent in patients with AAS (p = 0.02). Compared to patients without AAS, those with AAS presented more subjective ictal anxiety (p = 0.0003) and postictal anxiety (p = 0.02), were more likely to avoid outdoor social situations due to seizure fear (p = 0.001), and had a poorer quality of life (QOLIE emotional well-being; p = 0.03). Additionally, they had experienced more traumatic events in their lifetime (p = 0.005) and reported more frequently a feeling of being unsafe during their seizures (p = 0.00002). SIGNIFICANCE: AAS is a specific dimension of anxiety, possibly linked to trauma history. AAS is strongly linked to subjective ictal anxiety but not to the objective severity of seizures or frequency.