Focal ictal direct current shifts by a time constant of 2 seconds were clinically useful for resective epilepsy surgery.

OBJECTIVE: Ictal direct current shifts (icDCs) and ictal high-frequency oscillations (icHFOs) have been reported as surrogate markers for better surgical outcomes in epilepsy surgery. icDCs have been classified into two types: rapid and slow development. icDCs have been investigated with a time constant of 10 s (TC10s); however, many institutes use electroencephalography with a time constant of 2 s (TC2s). This study aimed to evaluate whether icDCs can be observed adequately with TC2s; moreover, it examined the relationship between the resected core area of icDCs or icHFOs and surgical outcomes, occurrence rate of each type of icDCs, and relationship between each type of icDCs and pathology. METHODS: Twenty-five patients with intractable focal epilepsy were analyzed retrospectively. icDCs and icHFOs were defined according to common metrics. The amplitude of icDCs was defined at >200 µV and even <200 µV. The two electrodes producing the most prominent icDCs and icHFOs were defined as core electrodes. The correlation between the resected core electrode area and degree of seizure control after surgery was analyzed. icDCs were classified into two types based on a peak latency value cutoff of 8.9 s, and the occurrence rates of both patterns were investigated. RESULTS: icDCs (142/147 seizures [96.6%]) and icHFOs (135/147 seizures [91.8%]) occurred in all patients (100%). Compared with the amplitude of icDCs with TC10s reported in previous studies, the amplitude of icDCs with TC2s was attenuated in the current study. A significant positive correlation was observed between the resected core electrode area and degree of seizure control in both icDCs and icHFOs. A rapid development pattern was observed in 202 of 264 electrodes (76.5%). SIGNIFICANCE: Similar to icDCs with TC10s, those with TC2s were observed adequately. Furthermore, favorable outcomes are expected using TC2s, which is currently available worldwide.

Barriers to telemedicine among physicians in epilepsy care during the COVID-19 pandemic: A national-level cross-sectional survey in Japan.

OBJECTIVE: This study aimed to investigate the factors affecting the unwillingness of physicians involved in epilepsy care to continue telemedicine during the coronavirus disease 2019 (COVID-19) pandemic in Japan. METHOD: This was a national-level cross-sectional survey initiated by Japan Young Epilepsy Section (YES-Japan) which is a national chapter of The Young Epilepsy Section of the International League Against Epilepsy (ILAE-YES). We asked physicians who conducted telemedicine in patients with epilepsy (PWE) during the COVID-19 pandemic at four clinics and 21 hospitals specializing in epilepsy care in Japan from March 1 to April 30, 2021. The following data were collected: (1) participant profile, (2) characteristics of PWE treated by telemedicine, and (3) contents and environmental factors of telemedicine. Statistically significant variables (p < 0.05) in the univariate analysis were analyzed in a multivariate binary logistic regression model to detect the independently associated factors with the unwillingness to continue telemedicine. RESULT: Among the 115 respondents (response rate: 64%), 89 were included in the final analysis. Of them, 60 (67.4%) were willing to continue telemedicine, and 29 (32.6%) were unwilling. In the univariate binary logistic regression analysis, age (Odds ratio [OR] = 1.84, 95% confidence interval [CI] 1.10-3.09, p = 0.02), psychiatrist (OR = 5.88, 95% CI 2.15-16.08, p = 0.001), hospital (OR = 0.10, 95% CI 0.01-0.94, p = 0.04), the number of COVID-19 risk factors in the participant (OR = 2.88, 95% CI 1.46-5.69, p = 0.002), the number of COVID-19 risk factors in the cohabitants (OR = 2.52, 95% CI 1.05-6.01, p = 0.04), COVID-19 epidemic area (OR = 4.37, 95% CI 1.18-16.20, p = 0.03), consultation time during telemedicine (OR = 2.51, 95% CI 1.32-4.76, p = 0.005), workload due to telemedicine (OR = 4.17, 95% CI 2.11-8.24, p < 0.001) were statistically significant. In the multivariate binary logistic regression analysis, workload due to telemedicine (OR = 4.93, 95% CI 1.96-12.35) was independently associated with the unwillingness to continue telemedicine. CONCLUSION: This national-level cross-sectional survey found that workload due to telemedicine among physicians involved in epilepsy care was independently associated with the unwillingness to continue telemedicine.

Risk factors for psychological distress in electroencephalography technicians during the COVID-19 pandemic: A national-level cross-sectional survey in Japan.

OBJECTIVE: To identify the risk factors for psychological distress in electroencephalography (EEG) technicians during the coronavirus disease 2019 (COVID-19) pandemic. METHOD: In this national-level cross-sectional survey initiated by Japan Young Epilepsy Section (YES-Japan), which is a national chapter of The Young Epilepsy Section of the International League Against Epilepsy (ILAE-YES), a questionnaire was administered to 173 technicians engaged in EEG at four clinics specializing in epilepsy care and 20 hospitals accredited as (quasi-) epilepsy centers or epilepsy training facilities in Japan from March 1 to April 30, 2021. We collected data on participants' profiles, information about work, and psychological distress outcome measurements, such as the K-6 and Tokyo Metropolitan Distress Scale for Pandemic (TMDP). Linear regression analysis was used to identify the risk factors for psychological distress. Factors that were significantly associated with psychological distress in the univariate analysis were subjected to multivariate analysis. RESULTS: Among the 142 respondents (response rate: 82%), 128 were included in the final analysis. As many as 35.2% of EEG technicians have been under psychological distress. In multivariate linear regression analysis for K-6, female sex, examination for patients (suspected) with COVID-19, and change in salary or bonus were independent associated factors for psychological distress. Contrastingly, in multivariate linear regression analysis for TMDP, female sex, presence of cohabitants who had to be separated from the respondent due to this pandemic, and change in salary or bonus were independent associated factors for psychological distress. CONCLUSION: We successfully identified the risk factors associated with psychological distress in EEG technicians during the COVID-19 pandemic. Our results may help in understanding the psychological stress in EEG technicians during the COVID-19 pandemic and improving the work environment, which is necessary to maintain the mental health of EEG technicians.

Palinopsia Accompanied with Migraine Attack After Having Occipital Brain Abscess.

Palinopsia is defined as persistence of recurrent visual images after the stimulus has been removed. A 55-year-old male patient with long-standing migraine history developed brain abscess in the right occipital lobe. The patient developed episodes of palinopsia accompanied with migraine attack after healing of occipital lesion. The phenomenon cannot be sufficiently explained with single risk factor, although occipital lesion and migraine are both known to cause palinopsia. We speculated that migrainous brain is not always symptomatic but may drive cortex sensitive for second insult, such as occipital brain lesion. The predisposition may contribute to appearance of palinopsia.

Intraventricular hemorrhage volume and younger age at surgery may be risk factors for postoperative hydrocephalus after hemispherotomy in children.

OBJECTIVE: Hemispherotomy is an effective treatment for intractable hemispheric epilepsy; however, hydrocephalus remains a common complication of the procedure. The causes of hydrocephalus following hemispherotomy have not been fully elucidated; therefore, the purpose of this study was to identify the risk factors associated with the condition. METHODS: The authors investigated the records of all patients aged < 18 years who underwent hemispherotomy at their institution between 2003 and 2020 and were monitored for hydrocephalus for at least 1 year after the procedure. To identify the risk factors for hydrocephalus, the following information about each patient was collected: sex, corrected age at surgery, body weight at surgery, previous intracranial surgery, etiology of epilepsy, results of PET for hypermetabolism, side of surgery, type of operation (vertical or horizontal approach), operation time, blood loss during surgery, use of intraventricular drainage, occurrence of intraventricular hemorrhage (IVH) on the 1st postoperative day, duration of postoperative fever of > 38°C, and maximum C-reactive protein level after the operation. Multivariate logistic regression analyses were performed. RESULTS: This study included 51 children who underwent hemispherotomies for drug-resistant epilepsy at our hospital. Seven patients (13.7%) experienced hydrocephalus and were treated with ventricular or subdural peritoneal shunts or fenestration. Multivariate logistic analysis using the Bayesian information criterion revealed that 3 factors were associated with the occurrence of hydrocephalus: age at surgery, postoperative IVH volume, and duration of postoperative fever of > 38°C. CONCLUSIONS: This study showed that younger age at surgery, postoperative IVH volume, and duration of postoperative fever of > 38°C might be risk factors for hydrocephalus after hemispherotomy. The risk of hydrocephalus should be considered in cases of early surgical indication in children. Intraoperative hemostasis and postoperative use of anti-inflammatory measures may reduce the risk of hydrocephalus.

Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors.

PURPOSE: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Because majority of adult malignant brain tumors are gliomas and primary CNS lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. In addition, diffuse gliomas require molecular information on single-nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen-section (FS) diagnosis through incorporation of a qPCR-based genotyping assay. EXPERIMENTAL DESIGN: FS evaluation, including GFAP and CD20 rapid IHC, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy-number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined on the basis of the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability. RESULTS: After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) with PCNSL. CONCLUSIONS: The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.

Safety, Feasibility, and Efficacy of Additional Extraventricular Anterior Commissurotomy With Corpus Callosotomy.

BACKGROUND: Corpus callosotomy (CC) is a palliative neurosurgical procedure for patients with intractable epilepsy and without resectable focal epileptogenic lesions. Anterior commissurotomy (AC) has been historically performed with CC. However, the efficacy and safety of adding AC to CC remain unknown. OBJECTIVE: To describe the surgical technique of extraventricular AC and retrospectively investigate its clinical efficacy and safety by assessing patients who underwent CC with and without AC. METHODS: AC has been added to CC at our institution since 2018. Fifty-five consecutive patients who received total callosotomy from 2016 to 2020 were included and categorized into 2 groups: 26 patients with additional AC and 29 patients without additional AC. Seizure outcome 1 year after surgery were compared between groups for assessing the efficacy of adding AC. The perioperative factors were compared for assessing the safety and feasibility. RESULTS: Seizure reduction rate (50% and 60%; P = .60) and disappearance of drop attacks (42% and 58%; P = .25) were not significantly different between CC and CC + AC groups. No statistical group differences were found in intraoperative estimated blood loss, number of days to first oral intake, duration of postoperative intravenous hydration, and length of hospital stay. CONCLUSION: Disconnection of the anterior commissure is a feasible and relatively safe procedure. This study failed to show the significant efficacy of adding AC to CC. However, further investigation is needed to prove its efficacy in ameliorating epilepsy.

Drug-resistant temporal lobe epilepsy due to middle fossa meningoencephalocele in a child: A surgical case report.

BACKGROUND: Meningoencephalocele (ME) of the temporal lobe through a bone defect in the middle cranial fossa is a rare known cause of refractory temporal lobe epilepsy (TLE). ME-induced drug-resistant TLE has been described in adults; however, its incidence in children is very rare. CASE REPORT: A 7-year-old girl presented at our hospital with brief episodes of impaired consciousness and enuresis. Initial brain MRI results were interpreted as normal. Her seizures could not be controlled even with multiple anti-seizure medications. She was diagnosed with drug-resistant TLE, which presented with prolonged impaired awareness seizures for 30-60 s and secondary bilateral tonic seizures. At 9 years of age, brain MRI revealed a left temporal anteroinferior ME with a congenital bone defect in the left middle cranial fossa. She was referred for presurgical epilepsy evaluation. Long-term video electroencephalography (EEG) failed to reveal regional abnormality in the left temporal lobe; invasive evaluation using stereoelectroencephalography (SEEG) was thus indicated. Ictal onset SEEG was identified in the temporal pole near the ME which was rapidly propagated to the mesial temporal structures and other cortical regions. The left temporal pole including the ME was micro-surgically disconnected while preserving the hippocampus and amygdala. The patient's seizures have been completely controlled for 1 year and 6 months post-operatively. CONCLUSION: SEEG revealed rapid propagation of ictal activity in this patient's case, confirming that the ME was epileptogenic. Since the majority of patients with refractory epilepsy caused by ME have favorable postoperative seizure outcomes, it is important to carefully check for ME in drug-resistant TLE patients with apparently normal MRI.

Arteries Around the Superior Limiting Sulcus: Motor Complication Avoidance in Insular and Insulo-Opercular Surgery.

BACKGROUND AND OBJECTIVES: Insulo-opercular surgery can cause ischemic motor complications. A source of this is the arteries around the superior limiting sulcus (SLS), which reach the corona radiata, but the detailed anatomy remains unclear. To characterize arteries around the SLS including the long insular arteries (LIAs) and long medullary arteries, we classified them and examined their distribution in relation to the SLS, which helps reduce the risk of ischemia. METHODS: Twenty adult cadaveric hemispheres were studied. Coronal brain slices were created perpendicular to the SLS representing insular gyri (anterior short, middle short, posterior short, anterior long, and posterior long). The arteries within 10-mm proximity of the SLS that reached the corona radiata were excavated and classified by the entry point. RESULTS: A total of 122 arteries were identified. Sixty-three (52%), 20 (16%), and 39 (32%) arteries penetrated the insula (LIAs), peak of the SLS, and operculum (long medullary arteries), respectively. 100 and six (87%) arteries penetrated within 5 mm of the peak of the SLS. The arteries were distributed in the anterior short gyrus (19%), middle short gyrus (17%), posterior short gyrus (20%), anterior long gyrus (19%), and posterior long gyrus (25%). Seven arteries (5.7%) had anastomoses after they penetrated the parenchyma. CONCLUSION: Approximately 90% of the arteries that entered the parenchyma and reached the corona radiata were within a 5-mm radius of the SLS in both the insula and operculum side. This suggests that using the SLS as a landmark during insulo-opercular surgery can decrease the chance of ischemia.

Sevoflurane-induced high-frequency oscillations, effective connectivity and intraoperative classification of epileptic brain areas.

OBJECTIVE: To determine how sevoflurane anesthesia modulates intraoperative epilepsy biomarkers on electrocorticography, including high-frequency oscillation (HFO) effective connectivity (EC), and to investigate their relation to epileptogenicity and anatomical white matter. METHODS: We studied eight pediatric drug-resistant focal epilepsy patients who achieved seizure control after invasive monitoring and resective surgery. We visualized spatial distributions of the electrocorticography biomarkers at an oxygen baseline, three time-points while sevoflurane was increasing, and at a plateau of 2 minimum alveolar concentration (MAC) sevoflurane. HFO EC was combined with diffusion-weighted imaging, in dynamic tractography. RESULTS: Intraoperative HFO EC diffusely increased as a function of sevoflurane concentration, although most in epileptogenic sites (defined as those included in the resection); their ability to classify epileptogenicity was optimized at sevoflurane 2 MAC. HFO EC could be visualized on major white matter tracts, as a function of sevoflurane level. CONCLUSIONS: The results strengthened the hypothesis that sevoflurane-activated HFO biomarkers may help intraoperatively localize the epileptogenic zone. SIGNIFICANCE: Our results help characterize how HFOs at non-epileptogenic and epileptogenic networks respond to sevoflurane. It may be warranted to establish a normative HFO atlas incorporating the modifying effects of sevoflurane and major white matter pathways, as critical reference in epilepsy presurgical evaluation.

Dynamics of AMPA receptors regulate epileptogenesis in patients with epilepsy.

The excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) contribute to epileptogenesis. Thirty patients with epilepsy and 31 healthy controls are scanned using positron emission tomography with our recently developed radiotracer for AMPARs, [11C]K-2, which measures the density of cell-surface AMPARs. In patients with focal-onset seizures, an increase in AMPAR trafficking augments the amplitude of abnormal gamma activity detected by electroencephalography. In contrast, patients with generalized-onset seizures exhibit a decrease in AMPARs coupled with increased amplitude of abnormal gamma activity. Patients with epilepsy had reduced AMPAR levels compared with healthy controls, and AMPARs are reduced in larger areas of the cortex in patients with generalized-onset seizures compared with those with focal-onset seizures. Thus, epileptic brain function can be regulated by the enhanced trafficking of AMPAR due to Hebbian plasticity with increased simultaneous neuronal firing and compensational downregulation of cell-surface AMPARs by the synaptic scaling.

Low EEG Gamma Entropy and Glucose Hypometabolism After Corpus Callosotomy Predicts Seizure Outcome After Subsequent Surgery.

Background: Patients with generalized epilepsy who had lateralized EEG abnormalities after corpus callosotomy (CC) occasionally undergo subsequent surgeries to control intractable epilepsy. Objectives: This study evaluated retrospectively the combination of EEG multiscale entropy (MSE) and FDG-PET for identifying lateralization of the epileptogenic zone after CC. Methods: This study included 14 patients with pharmacoresistant epilepsy who underwent curative epilepsy surgery after CC. Interictal scalp EEG and FDG-PET obtained after CC were investigated to determine (1) whether the MSE calculated from the EEG and FDG-PET findings was lateralized to the surgical side, and (2) whether the lateralization was associated with seizure outcomes. Results: Seizure reduction rate was higher in patients with lateralized findings to the surgical side than those without (MSE: p < 0.05, FDG-PET: p < 0.05, both: p < 0.01). Seizure free rate was higher in patients with lateralized findings in both MSE and FDG-PET than in those without (p < 0.05). Conclusions: This study demonstrated that patients with lateralization of MSE and FDG-PET to the surgical side had better seizure outcomes. The combination of MSE and conventional FDG-PET may help to select surgical candidates for additional surgery after CC with good postoperative seizure outcomes.

Epileptic discharges initiate from brain areas with elevated accumulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors.

Presurgical identification of the epileptogenic zone is a critical determinant of seizure control following surgical resection in epilepsy. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor is a major component of neurotransmission. Although elevated α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor levels are observed in surgically resected brain areas of patients with epilepsy, it remains unclear whether increased α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-mediated currents initiate epileptic discharges. We have recently developed the first PET tracer for α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, [11C]K-2, to visualize and quantify the density of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors in living human brains. Here, we detected elevated [11C]K-2 uptake in the epileptogenic temporal lobe of patients with mesial temporal lobe epilepsy. Brain areas with high [11C]K-2 uptake are closely colocalized with the location of equivalent current dipoles estimated by magnetoencephalography or with seizure onset zones detected by intracranial electroencephalogram. These results suggest that epileptic discharges initiate from brain areas with increased α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors, providing a biological basis for epileptic discharges and an additional non-invasive option to identify the epileptogenic zone in patients with mesial temporal lobe epilepsy.

Predictors of Seizure Outcome after Repeat Pediatric Epilepsy Surgery: Reasons for Failure, Sex, Electrophysiology, and Temporal Lobe Surgery.

Considering that seizure freedom is one of the most important goals in the treatment of epilepsy, repeat epilepsy surgery could be considered for patients who continue to experience drug-resistant seizures after epilepsy surgery. However, the chance of seizure freedom is reported to be below 50% after reoperation for failed epilepsy surgery. This study aimed to elucidate the predictive factors for seizure outcomes after repeat pediatric epilepsy surgery. In all, 39 pediatric patients who underwent repeat curative epilepsy surgery between 2008 and 2020 at our institution were retrospectively studied. The relationship between preoperative clinical factors and postoperative seizure freedom at the last follow-up was statistically evaluated. The mean age at the first surgery was 5.5 years (0-16). The etiology of epilepsy was malformation of cortical development in 33 patients. The average time to seizure recurrence after the first surgery was 6.4 months (range, 0-26 months). In all, 16 patients (41.0%) achieved seizure freedom after the second surgery. Seven patients underwent a third surgery, and three (42.9%) achieved seizure freedom. Overall, 19 patients achieved seizure freedom after repeat epilepsy surgery (48.7%). Female sex, surgical failure due to technical limitations, congruent electroencephalography (EEG) findings, lesional magnetic resonance imaging (MRI) and Rt-sided surgery were predictive of seizure freedom, and surgery limited to the temporal lobe was predictive of residual seizures, as determined in the multivariate analysis. The reoperation of failed epilepsy surgery is challenging. Consideration of the above predictive factors can be helpful in deciding whether to reoperate on pediatric patients whose initial surgical intervention failed.

Volume-Based Radiofrequency Thermocoagulation for Pediatric Insulo-Opercular Epilepsy: A Feasibility Study.

BACKGROUND: Stereotactic ablation surgeries including radiofrequency thermocoagulation (RFTC) and laser interstitial thermal therapy are recent less invasive treatment methods for insular epilepsy. Volume-based RFTC after stereoelectroencephalography was first proposed by a French group as a more effective method for seizure relief in insular epilepsy patients than stereoelectroencephalography-guided RFTC. OBJECTIVE: To describe the feasibility and technical details about volume-based RFTC in patients with insulo-opercular epilepsy. METHODS: We successfully treated 3- and 6-year-old patients with medically refractory insulo-opercular epilepsy with volume-based RFTC, in which the target volume of coagulation was flexibly designed by combining multiple spherical models of 5-mm diameter which is smaller than reported previously. RESULTS: The insula was targeted by oblique trajectory from the frontoparietal area in one case, and the opercular cortex was targeted by perpendicular trajectories from the perisylvian cortex in the other case. The use of the small sphere model required more trajectories and manipulations but enabled more exhaustive coagulation of the epileptogenic zone, with 70% to 78% of the planned target volume coagulated without complications, and daily seizures disappeared after RFTC in both patients. CONCLUSION: Volume-based RFTC planned with small multiple sphere models may improve the completeness of lesioning for patients with insulo-opercular epilepsy. Careful planning is necessary to reduce the risks of vascular injuries.

Is Hippocampal Resection Necessary for Low-Grade Epilepsy-Associated Tumors in the Temporal Lobe?

Low-grade epilepsy-associated tumors (LEATs) are common in the temporal lobe and can cause drug-resistant epilepsy. Complete resection of LEATs is sufficient for seizure relief. However, hippocampal resection might result in postoperative cognitive impairment. This study aimed to clarify the necessity of hippocampal resection for seizure and cognitive outcomes in patients with temporal lobe LEATs and a normal hippocampus. The study included 32 patients with temporal lobe LEATs and without hippocampal abnormalities. All patients underwent gross total resection as treatment for drug-resistant epilepsy at our tertiary epilepsy center from 2005 to 2020, followed by at least a 12-month follow-up period. Seizure and cognitive outcomes were compared between patients who underwent additional hippocampal resection (Resected group) and those who did not (Preserved group). Among the participants, 14 underwent additional hippocampal resection and 28 (87.5%) achieved seizure freedom irrespective of hippocampal resection. The seizure-free periods were not different between the two groups. Additional hippocampal resection resulted in a significantly negative impact on the postoperative verbal index. In conclusion, additional hippocampal resection in patients with temporal lobe LEATs without hippocampal abnormalities is unnecessary because lesionectomy alone results in good seizure control. Additional hippocampal resection may instead adversely affect the postoperative language function.

Sevoflurane-based enhancement of phase-amplitude coupling and localization of the epileptogenic zone.

OBJECTIVE: Phase-amplitude coupling between high-frequency (≥150 Hz) and delta (3-4 Hz) oscillations - modulation index (MI) - is a promising, objective biomarker of epileptogenicity. We determined whether sevoflurane anesthesia preferentially enhances this metric within the epileptogenic zone. METHODS: This is an observational study of intraoperative electrocorticography data from 621 electrodes chronically implanted into eight patients with drug-resistant, focal epilepsy. All patients were anesthetized with sevoflurane during resective surgery, which subsequently resulted in seizure control. We classified 'removed' and 'retained' brain sites as epileptogenic and non-epileptogenic, respectively. Mixed model analysis determined which anesthetic stage optimized MI-based classification of epileptogenic sites. RESULTS: MI increased as a function of anesthetic stage, ranging from baseline (i.e., oxygen alone) to 2.0 minimum alveolar concentration (MAC) of sevoflurane, preferentially at sites showing higher initial MI values. This phenomenon was accentuated just prior to sevoflurane reaching 2.0 MAC, at which time, the odds of a site being classified as epileptogenic were enhanced by 86.6 times for every increase of 1.0 MI. CONCLUSIONS: Intraoperative MI best localized the epileptogenic zone immediately before sevoflurane reaching 2.0 MAC in this small cohort of patients. SIGNIFICANCE: Prospective, large cohort studies are warranted to determine whether sevoflurane anesthesia can reduce the need for extraoperative, invasive evaluation.