Factors Associated With Failed Focal Neocortical Epilepsy Surgery

Abstract Background: Seizure outcomes after focal neocortical epilepsy (FNE) surgery are less favorable than after temporal lobectomy, and the reasons for surgical failure are incompletely understood. Few groups have performed an in-depth examination of seizure recurrences to identify possible reasons for failure. Objective: To elucidate factors contributing to FNE surgery failures. Methods: We reviewed resections for drug-resistant FNE performed at our institution between 1998 and 2011. We performed a quantitative analysis of seizure outcome predictors and a detailed qualitative review of failed surgical cases. Results: Of 138 resections in 125 FNE patients, 91 (66%) resulted in freedom from disabling seizures (Engel I outcome). Mean ± SEM patient age was 20.0 ± 1.2 years; mean follow-up was 3.8 years (range, 1–17 years); and 57% of patients were male. Less favorable (Engel II–IV) seizure outcome was predicted by higher preoperative seizure frequency (odds ratio = 0.85; 95% confidence interval, 0.78–0.93), a history of generalized tonic-clonic seizures (odds ratio = 0.42; 95% confidence interval, 0.18–0.97), and normal magnetic resonance imaging (odds ratio = 0.30; 95% confidence interval, 0.09–1.02). Among 36 surgical failures examined, 26 (72%) were related to extent of resection, with residual epileptic focus at the resection margins, whereas 10 (28%) involved location of resection, with an additional epileptogenic zone distant from the resection. Of 16 patients who received reoperation after seizure recurrence, 10 (63%) achieved seizure freedom. Conclusion: Insufficient extent of resection is the most common reason for recurrent seizures after FNE surgery, although some patients harbor a remote epileptic focus. Many patients with incomplete seizure control are candidates for reoperation.

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Multiple Subpial Transections for Medically Refractory Epilepsy: A Disaggregated Review of Patient-Level Data

Neurosurgery ◽

10.1093/neuros/nyx311 ◽

2017 ◽

Vol 82 (5) ◽

pp. 613-620 ◽

Cited By ~ 10

Author(s):

John D Rolston ◽

Hansen Deng ◽

Doris D Wang ◽

Dario J Englot ◽

Edward F Chang

Keyword(s):

Confidence Interval ◽

Odds Ratio ◽

Refractory Epilepsy ◽

Seizure Type ◽

Seizure Outcome ◽

Seizure Freedom ◽

Patient Level Data ◽

Patient Demographics ◽

Patient Level ◽

Level Data

Abstract BACKGROUND Multiple subpial transections (MST) are a treatment for seizure foci in nonresectable eloquent areas. OBJECTIVE To systematically review patient-level data regarding MST. METHODS Studies describing patient-level data for MST procedures were extracted from the Medline and PubMed databases, yielding a synthetic cohort of 212 patients from 34 studies. Data regarding seizure outcome, patient demographics, seizure type, surgery type, and complications were extracted and analyzed. RESULTS Seizure freedom was achieved in 55.2% of patients undergoing MST combined with resection, and 23.9% of patients undergoing MST alone. Significant predictors for seizure freedom were a temporal lobe focus (odds ratio 4.9; 95% confidence interval 1.71, 14.3) and resection of portions of the focus, when feasible (odds ratio 3.88; 95% confidence interval 2.02, 7.45). Complications were frequent, with transient mono- or hemiparesis affecting 19.8% of patients, transient dysphasia 12.3%, and permanent paresis or dysphasia in 6.6% and 1.9% of patients, respectively. CONCLUSION MST is an effective treatment for refractory epilepsy in eloquent cortex, with greater chances of seizure freedom when portions of the focus are resected in tandem with MST. The reported rates of seizure freedom with MST are higher than those of existing neuromodulatory therapies, such as vagus nerve stimulation, deep brain stimulation, and responsive neurostimulation, though these latter therapies are supported by randomized-controlled trials, while MST is not. The reported complication rate of MST is higher than that of resection and neuromodulatory therapies. MST remains a viable option for the treatment of eloquent foci, provided a careful risk-benefit analysis is conducted.

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Seizure outcome in temporal glioblastoma surgery: lobectomy as a supratotal resection regime outclasses conventional gross-total resection

Journal of Neuro-Oncology ◽

10.1007/s11060-021-03705-x ◽

2021 ◽

Author(s):

Valeri Borger ◽

Motaz Hamed ◽

Inja Ilic ◽

Anna-Laura Potthoff ◽

Attila Racz ◽

...

Keyword(s):

Tumor Resection ◽

Temporal Lobectomy ◽

Secondary Outcome ◽

Seizure Outcome ◽

Seizure Freedom ◽

Secondary Outcome Measure ◽

Total Resection ◽

Class 1 ◽

Postoperative Seizure ◽

The Impact

Abstract Introduction The postoperative seizure freedom represents an important secondary outcome measure in glioblastoma surgery. Recently, supra-total glioblastoma resection in terms of anterior temporal lobectomy (ATL) has gained growing attention with regard to superior long-term disease control for temporal-located glioblastoma compared to conventional gross-total resections (GTR). However, the impact of ATL on seizure outcome in these patients is unknown. We therefore analyzed ATL and GTR as differing extents of resection in regard of postoperative seizure control in patients with temporal glioblastoma and preoperative symptomatic seizures. Methods Between 2012 and 2018, 33 patients with preoperative seizures underwent GTR or ATL for temporal glioblastoma at the authors’ institution. Seizure outcome was assessed postoperatively and 6 months after tumor resection according to the International League Against Epilepsy (ILAE) classification and stratified into favorable (ILAE class 1) versus unfavorable (ILAE class 2–6). Results Overall, 23 out of 33 patients (70%) with preoperative seizures achieved favorable seizure outcome following resection of temporal located glioblastoma. For the ATL group, postoperative seizure freedom was present in 13 out of 13 patients (100%). In comparison, respective rates for the GTR group were 10 out of 20 patients (50%) (p = 0.002; OR 27; 95% CI 1.4–515.9). Conclusions ATL in terms of a supra-total resection strategy was associated with superior favorable seizure outcome following temporal glioblastoma resection compared to GTR. Regarding above mentioned survival benefit following ATL compared to GTR, ATL as an aggressive supra-total resection regime might constitute the surgical modality of choice for temporal-located glioblastoma.

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Extent of Mesiobasal Resection Determines Outcome after Temporal Lobectomy for Intractable Complex Partial Seizures

Neurosurgery ◽

10.1227/00006123-199107000-00009 ◽

1991 ◽

Vol 29 (1) ◽

pp. 55-61 ◽

Cited By ~ 72

Author(s):

Mohamed H. Nayel ◽

Issam A. Awad ◽

Hans Luders

Keyword(s):

Temporal Lobe ◽

Seizure Frequency ◽

Compartment Model ◽

Extent Of Resection ◽

Temporal Lobectomy ◽

Seizure Outcome ◽

Partial Seizures ◽

Complex Partial Seizures ◽

Lateral Structures

Abstract The extent of resection was assessed in 94 patients who underwent temporal lobectomy for medically intractable complex partial seizures originating from a unilateral seizure focus in the anteromesial temporal lobe. Postoperative magnetic resonance imaging in the coronal plane was used to quantify the extent of resection of lateral and mesiobasal structures according to a 20-compartment model of the temporal lobe. Successful seizure outcome (≥90% reduction in seizure frequency) was accomplished in 83% of the patients (all followed up for more than 1 year; mean duration of follow-up, 25.2 months) and correlated significantly (P<0.05) with the extent of mesiobasal resection, regardless of the extent of resection of lateral structures. Successful seizure outcome was accomplished in 81% of the patients with no structural lesions, and also correlated significantly (P<0.05) with the extent of mesiobasal resection regardless of the extent of lateral resection. A successful seizure outcome was accomplished in 90% of the 21 patients with structural lesions documented by neuroimaging studies. Two patients who underwent extensive lobectomy without resection of the structural lesion had no reduction in seizure frequency postoperatively. We conclude that the most important factor in determining the outcome of temporal lobectomy in patients with unilateral anteromesial temporal lobe epileptogenicity is the extent of resection of structures in the mesiobasal temporal lobe. In patients with structural lesions, lesion resection may be an added contributor to successful seizure outcome. (Neurosurgery 29:55-61, 1991)

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Stereoelectroencephalography in Children and Adolescents With Difficult-to-Localize Refractory Focal Epilepsy

Neurosurgery ◽

10.1227/neu.0000000000000453 ◽

2014 ◽

Vol 75 (3) ◽

pp. 258-268 ◽

Cited By ~ 50

Author(s):

Jorge Gonzalez-Martinez ◽

Jeffrey Mullin ◽

Juan Bulacio ◽

Ajay Gupta ◽

Rei Enatsu ◽

...

Keyword(s):

Children And Adolescents ◽

Pediatric Patients ◽

Focal Epilepsy ◽

Early Experience ◽

Morbidity Rate ◽

Seizure Outcome ◽

Seizure Freedom ◽

Epileptogenic Zone ◽

Eloquent Cortex

Abstract BACKGROUND: Although stereoelectroencephalography (SEEG) has been shown to be a valuable tool for preoperative decision making in focal epilepsy, there are few reports addressing the utility and safety of SEEG methodology applied to children and adolescents. OBJECTIVE: To present the results of our early experience using SEEG in pediatric patients with difficult-to-localize epilepsy who were not considered candidates for subdural grid evaluation. METHODS: Thirty children and adolescents with the diagnosis of medically refractory focal epilepsy (not considered ideal candidates for subdural grids and strip placement) underwent SEEG implantation. Demographics, electrophysiological localization of the hypothetical epileptogenic zone, complications, and seizure outcome after resections were analyzed. RESULTS: Eighteen patients (60%) underwent resections after SEEG implantations. In patients who did not undergo resections (12 patients), reasons included failure to localize the epileptogenic zone (4 patients); multifocal epileptogenic zone (4 patients); epileptogenic zone located in eloquent cortex, preventing resection (3 patients); and improvement in seizures after the implantation (1 patient). In patients who subsequently underwent resections, 10 patients (55.5%) were seizure free (Engel class I) and 5 patients (27.7%) experienced seizure improvement (Engel class II or III) at the end of the follow-up period (mean, 25.9 months; range, 12 to 47 months). The complication rate in SEEG implantations was 3%. CONCLUSION: The SEEG methodology is safe and should be considered in children/adolescents with difficult-to-localize epilepsy. When applied to highly complex and difficult-to-localize pediatric patients, SEEG may provide an additional opportunity for seizure freedom in association with a low morbidity rate.

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Drug-resistant temporal lobe epilepsy due to cavernous malformations

Neurosurgical FOCUS ◽

10.3171/foc.2006.21.1.9 ◽

2006 ◽

Vol 21 (1) ◽

pp. 1-5 ◽

Cited By ~ 16

Author(s):

Sergio Paolini ◽

Roberta Morace ◽

Giancarlo Di Gennaro ◽

Angelo Picardi ◽

Liliana G. Grammaldo ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Psychosocial Functioning ◽

Temporal Lobectomy ◽

Surgical Removal ◽

Seizure Outcome ◽

Epileptogenic Zone ◽

Drug Resistant ◽

Cavernous Malformations ◽

Number Of Patients

Object Supratentorial cavernous angiomas may be associated with drug-resistant focal epilepsy. Surgical removal of the malformation may result in seizure control in a number of patients, although in most studies a long history and high frequency of attacks have been recognized as indicators of unfavorable seizure outcome. In the literature, there are no clear indications regarding the optimal diagnostic presurgical workup and the surgical strategy for this particular subgroup of patients with symptomatic epilepsy. In this paper the authors focus on the preoperative workup and the surgical management of the disease in eight consecutive patients undergoing surgery for drug-resistant temporal lobe epilepsy (TLE) due to cavernous malformations (CMs), and the relevant literature on this issue is also reviewed. Methods Preoperatively, all patients were assessed using a noninvasive protocol aimed at localizing the epileptogenic zone on the basis of anatomical, electrical, and clinical criteria. The presurgical assessment yielded an indication for lesionectomy in two cases, lesionectomy plus anteromesial temporal lobectomy in four cases, and lesionectomy plus extended temporal lobectomy in two cases. At follow-up examinations, seizure, neuropsychological, and psychiatric outcomes were all evaluated. Seven patients were categorized in Engel Class IA (seizure free), and one was categorized in Engel Class IB (occasional auras only). No adverse effects on neuropsychological or psychosocial functioning were observed. Conclusions Epilepsy surgery can be performed with excellent results in patients with intractable TLE caused by CMs. Noninvasive presurgical evaluation of these patients may enable a tailored approach, providing complete seizure relief in most cases.

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Seizure Types and Frequency in Patients Who “Fail” Temporal Lobectomy for Intractable Epilepsy

Neurosurgery ◽

10.1227/neu.0000000000000120 ◽

2013 ◽

Vol 73 (5) ◽

pp. 838-844 ◽

Cited By ~ 20

Author(s):

Dario J. Englot ◽

Anthony T. Lee ◽

Catherine Tsai ◽

Cathra Halabi ◽

Nicholas M. Barbaro ◽

...

Keyword(s):

Intractable Epilepsy ◽

Temporal Lobectomy ◽

Seizure Type ◽

Seizure Outcome ◽

Seizure Freedom ◽

Partial Seizures ◽

Complex Partial Seizures ◽

Generalized Seizures ◽

Number Of Patients ◽

Before And After

Abstract BACKGROUND: Temporal lobectomy can lead to favorable seizure outcomes in medically-refractory temporal lobe epilepsy (TLE). Although most studies focus on seizure freedom after temporal lobectomy, less is known about seizure semiology in patients who “fail” surgery. Morbidity differs between seizure types that impair or spare consciousness. Among TLE patients with seizures after surgery, how does temporal lobectomy influence seizure type and frequency? OBJECTIVE: To characterize seizure types and frequencies before and after temporal lobectomy for TLE, including consciousness-sparing or consciousness-impairing seizures. METHODS: We performed a retrospective longitudinal cohort study examining patients undergoing temporal lobectomy for epilepsy at our institution from January 1995 to August 2010. RESULTS: Among 241 TLE patients who received temporal lobectomy, 174 (72.2%) patients achieved Engel class I outcome (free of disabling seizures), including 141 (58.5%) with complete seizure freedom. Overall seizure frequency in patients with persistent postoperative seizures decreased by 70% (P < .01), with larger reductions in consciousness-impairing seizures. While the number of patients experiencing consciousness-sparing simple partial seizures decreased by only 19% after surgery, the number of individuals having consciousness-impairing complex partial seizures and generalized tonic-clonic seizures diminished by 70% and 68%, respectively (P < .001). Simple partial seizure was the predominant seizure type in 19.1% vs 37.0% of patients preoperatively and postoperatively, respectively (P < .001). Favorable seizure outcome was predicted by a lack of generalized seizures preoperatively (odds ratio 1.74, 95% confidence interval 1.06-2.86, P < .5). CONCLUSION: Given important clinical and mechanistic differences between seizures with or without impairment of consciousness, seizure type and frequency remain important considerations in epilepsy surgery.

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Resective Epilepsy Surgery for Tuberous Sclerosis in Children

Neurosurgery ◽

10.1227/neu.0000000000000875 ◽

2015 ◽

Vol 77 (4) ◽

pp. 517-524 ◽

Cited By ~ 43

Author(s):

Aria Fallah ◽

Shaun D. Rodgers ◽

Alexander G. Weil ◽

Sumeet Vadera ◽

Alireza Mansouri ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Epilepsy Surgery ◽

Medical Center ◽

Cleveland Clinic ◽

Intractable Epilepsy ◽

Seizure Outcome ◽

Seizure Freedom ◽

Epileptogenic Zone ◽

Children's Hospital ◽

Children’S Hospital

Abstract BACKGROUND: There are no established variables that predict the success of curative resective epilepsy surgery in children with tuberous sclerosis complex (TSC). OBJECTIVE: We performed a multicenter observational study to identify preoperative factors associated with seizure outcome in children with TSC undergoing resective epilepsy surgery. METHODS: A retrospective chart review was performed in eligible children at New York Medical Center, Miami Children's Hospital, Cleveland Clinic Foundation, BC Children's Hospital, Hospital for Sick Children, and Sainte-Justine Hospital between January 2005 and December 2013. A time-to-event analysis was performed. The “event” was defined as seizures after resective epilepsy surgery. RESULTS: Seventy-four patients (41 male) were included. The median age of the patients at the time of surgery was 120 months (range, 3-216 months). The median time to seizure recurrence was 24.0 ± 12.7 months. Engel Class I outcome was achieved in 48 (65%) and 37 (50%) patients at 1- and 2-year follow-up, respectively. On univariate analyses, younger age at seizure onset (hazard ratio [HR]: 2.03, 95% confidence interval [CI]: 1.03-4.00, P = .04), larger size of predominant tuber (HR: 1.03, 95% CI: 0.99-1.06, P = .12), and resection larger than a tuberectomy (HR: 1.86, 95% CI: 0.92-3.74, P = .084) were associated with a longer duration of seizure freedom. In multivariate analyses, resection larger than a tuberectomy (HR: 2.90, 95% CI: 1.17-7.18, P = .022) was independently associated with a longer duration of seizure freedom. CONCLUSION: In this large consecutive cohort of children with TSC and medically intractable epilepsy, a greater extent of resection (more than just the tuber) is associated with a greater probability of seizure freedom. This suggests that the epileptogenic zone may include the cortex surrounding the presumed offending tuber.

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Predictive Factors of Surgical Outcome in Frontal Lobe Epilepsy Explored with Stereoelectroencephalography

Neurosurgery ◽

10.1093/neuros/nyx342 ◽

2017 ◽

Vol 83 (2) ◽

pp. 217-225 ◽

Cited By ~ 16

Author(s):

Francesca Bonini ◽

Aileen McGonigal ◽

Didier Scavarda ◽

Romain Carron ◽

Jean Régis ◽

...

Keyword(s):

Frontal Lobe ◽

Surgical Resection ◽

Complete Resection ◽

Conditional Inference ◽

Prognostic Indicators ◽

Frontal Lobe Epilepsy ◽

Seizure Outcome ◽

Seizure Freedom ◽

Epileptogenic Zone

Abstract BACKGROUND Resective surgery established treatment for pharmacoresistant frontal lobe epilepsy (FLE), but seizure outcome and prognostic indicators are poorly characterized and vary between studies. OBJECTIVE To study long-term seizure outcome and identify prognostic factors. METHODS We retrospectively analyzed 42 FLE patients having undergone surgical resection, mostly preceded by invasive recordings with stereoelectroencephalography (SEEG). Postsurgical outcome up to 10-yr follow-up and prognostic indicators were analyzed using Kaplan–Meier analysis and multivariate and conditional inference procedures. RESULTS At the time of last follow-up, 57.1% of patients were seizure-free. The estimated chance of seizure freedom was 67% (95% confidence interval [CI]: 54-83) at 6 mo, 59% (95% CI: 46-76) at 1 yr, 53% (95% CI: 40-71) at 2 yr, and 46% (95% CI: 32-66) at 5 yr. Most relapses (83%) occurred within the first 12 mo. Multivariate analysis showed that completeness of resection of the epileptogenic zone (EZ) as defined by SEEG was the main predictor of seizure outcome. According to conditional inference trees, in patients with complete resection of the EZ, focal cortical dysplasia as etiology and focal EZ were positive prognostic indicators. No difference in outcome was found in patients with positive vs negative magnetic resonance imaging. CONCLUSION Surgical resection in drug-resistant FLE can be a successful therapeutic approach, even in the absence of neuroradiologically visible lesions. SEEG may be highly useful in both nonlesional and lesional FLE cases, because complete resection of the EZ as defined by SEEG is associated with better prognosis.

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Temporal plus epilepsy is a major determinant of temporal lobe surgery failures

Brain ◽

10.1093/brain/awv372 ◽

2015 ◽

Vol 139 (2) ◽

pp. 444-451 ◽

Cited By ~ 86

Author(s):

Carmen Barba ◽

Sylvain Rheims ◽

Lorella Minotti ◽

Marc Guénot ◽

Dominique Hoffmann ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Epilepsy Surgery ◽

Hippocampal Sclerosis ◽

Cox Proportional Hazards Model ◽

Temporal Lobectomy ◽

Seizure Freedom ◽

Epileptogenic Zone ◽

Anterior Temporal Lobectomy

Abstract See Engel (doi:10.1093/awv374) for a scientific commentary on this article. Reasons for failed temporal lobe epilepsy surgery remain unclear. Temporal plus epilepsy, characterized by a primary temporal lobe epileptogenic zone extending to neighboured regions, might account for a yet unknown proportion of these failures. In this study all patients from two epilepsy surgery programmes who fulfilled the following criteria were included: (i) operated from an anterior temporal lobectomy or disconnection between January 1990 and December 2001; (ii) magnetic resonance imaging normal or showing signs of hippocampal sclerosis; and (iii) postoperative follow-up ≥ 24 months for seizure-free patients. Patients were classified as suffering from unilateral temporal lobe epilepsy, bitemporal epilepsy or temporal plus epilepsy based on available presurgical data. Kaplan-Meier survival analysis was used to calculate the probability of seizure freedom over time. Predictors of seizure recurrence were investigated using Cox proportional hazards model. Of 168 patients included, 108 (63.7%) underwent stereoelectroencephalography, 131 (78%) had hippocampal sclerosis, 149 suffered from unilateral temporal lobe epilepsy (88.7%), one from bitemporal epilepsy (0.6%) and 18 (10.7%) from temporal plus epilepsy. The probability of Engel class I outcome at 10 years of follow-up was 67.3% (95% CI: 63.4–71.2) for the entire cohort, 74.5% (95% CI: 70.6–78.4) for unilateral temporal lobe epilepsy, and 14.8% (95% CI: 5.9–23.7) for temporal plus epilepsy. Multivariate analyses demonstrated four predictors of seizure relapse: temporal plus epilepsy (P < 0.001), postoperative hippocampal remnant (P = 0.001), past history of traumatic or infectious brain insult (P = 0.022), and secondary generalized tonic-clonic seizures (P = 0.023). Risk of temporal lobe surgery failure was 5.06 (95% CI: 2.36–10.382) greater in patients with temporal plus epilepsy than in those with unilateral temporal lobe epilepsy. Temporal plus epilepsy represents a hitherto unrecognized prominent cause of temporal lobe surgery failures. In patients with temporal plus epilepsy, anterior temporal lobectomy appears very unlikely to control seizures and should not be advised. Whether larger resection of temporal plus epileptogenic zones offers greater chance of seizure freedom remains to be investigated.

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Technique, Results, and Complications Related to Robot-Assisted Stereoelectroencephalography

Neurosurgery ◽

10.1227/neu.0000000000001034 ◽

2015 ◽

Vol 78 (2) ◽

pp. 169-180 ◽

Cited By ~ 121

Author(s):

Jorge González-Martínez ◽

Juan Bulacio ◽

Susan Thompson ◽

John Gale ◽

Saksith Smithason ◽

...

Keyword(s):

Focal Epilepsy ◽

Interquartile Range ◽

Implantation Technique ◽

Target Point ◽

Seizure Outcome ◽

Seizure Freedom ◽

Epileptogenic Zone ◽

Robot Assisted ◽

Depth Electrodes

ABSTRACT BACKGROUND: Robot-assisted stereoelectroencephalography (SEEG) may represent a simplified, precise, and safe alternative to the more traditional SEEG techniques. OBJECTIVE: To report our clinical experience with robotic SEEG implantation and to define its utility in the management of patients with medically refractory epilepsy. METHODS: The prospective observational analyses included all patients with medically refractory focal epilepsy who underwent robot-assisted stereotactic placement of depth electrodes for extraoperative brain monitoring between November 2009 and May 2013. Technical nuances of the robotic implantation technique are presented, as well as an analysis of demographics, time of planning and procedure, seizure outcome, in vivo accuracy, and procedure-related complications. RESULTS: One hundred patients underwent 101 robot-assisted SEEG procedures. Their mean age was 33.2 years. In total, 1245 depth electrodes were implanted. On average, 12.5 electrodes were implanted per patient. The time of implantation planning was 30 minutes on average (range, 15-60 minutes). The average operative time was 130 minutes (range, 45-160 minutes). In vivo accuracy (calculated in 500 trajectories) demonstrated a median entry point error of 1.2 mm (interquartile range, 0.78-1.83 mm) and a median target point error of 1.7 mm (interquartile range, 1.20-2.30 mm). Of the group of patients who underwent resective surgery (68 patients), 45 (66.2%) gained seizure freedom status. Mean follow-up was 18 months. The total complication rate was 4%. CONCLUSION: The robotic SEEG technique and method were demonstrated to be safe, accurate, and efficient in anatomically defining the epileptogenic zone and subsequently promoting sustained seizure freedom status in patients with difficult-to-localize seizures.

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