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Rei Enatsu, Jorge Gonzalez-Martinez, Juan Bulacio, John C. Mosher, Richard C. Burgess, Imad Najm, and Dileep R. Nair


The frontal and insular fiber network in humans remains largely unknown. This study investigated the connectivity of the frontal and anterior insular network in humans using cortico-cortical evoked potential (CCEP).


This retrospective analysis included 18 patients with medically intractable focal epilepsy who underwent stereoelectroencephalography and CCEP. Alternating 1-Hz electrical stimuli were delivered to parts of the frontal lobe and anterior insula (prefrontal cortex [PFC], ventrolateral and dorsolateral premotor area [vPM and dPM, respectively], presupplementary motor area [pre-SMA], SMA, frontal operculum, and anterior insula). A total of 40–60 stimuli were averaged in each trial to obtain CCEP responses. The distribution of CCEP was evaluated by calculating the root mean square of CCEP responses.


Stimulation of the PFC elicited prominent CCEP responses in the medial PFC and PMs over the ipsilateral hemisphere. Stimulation of the vPM and dPM induced CCEP responses in the ipsilateral frontoparietal areas. Stimulation of the pre-SMA induced CCEP responses in the ipsilateral medial and lateral frontal areas and contralateral pre-SMA, whereas stimulation of the SMA induced CCEP responses in the bilateral frontoparietal areas. Stimulation of the frontal operculum induced CCEP responses in the ipsilateral insula and temporal operculum. CCEPs were observed in the ipsilateral medial, lateral frontal, and frontotemporal operculum in the anterior insular stimulation. Stimulation of the vPM and SMA led to the network in the dominant hemisphere being more developed.


Various regions within the frontal lobe and anterior insula were linked to specific ipsilateral and contralateral regions, which may reflect distinct functional roles.

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Demitre Serletis, Juan Bulacio, William Bingaman, Imad Najm, and Jorge González-Martínez


Stereoelectroencephalography (SEEG) is a methodology that permits accurate 3D in vivo electroclinical recordings of epileptiform activity. Among other general indications for invasive intracranial electroencephalography (EEG) monitoring, its advantages include access to deep cortical structures, its ability to localize the epileptogenic zone when subdural grids have failed to do so, and its utility in the context of possible multifocal seizure onsets with the need for bihemispheric explorations. In this context, the authors present a brief historical overview of the technique and report on their experience with 2 SEEG techniques (conventional Leksell frame-based stereotaxy and frameless stereotaxy under robotic guidance) for the purpose of invasively monitoring difficult-to-localize refractory focal epilepsy.


Over a period of 4 years, the authors prospectively identified 200 patients with refractory epilepsy who collectively underwent 2663 tailored SEEG electrode implantations for invasive intracranial EEG monitoring and extraoperative mapping. The first 122 patients underwent conventional Leksell frame-based SEEG electrode placement; the remaining 78 patients underwent frameless stereotaxy under robotic guidance, following acquisition of a stereotactic ROSA robotic device at the authors' institution. Electrodes were placed according to a preimplantation hypothesis of the presumed epileptogenic zone, based on a standardized preoperative workup including video-EEG monitoring, MRI, PET, ictal SPECT, and neuropsychological assessment. Demographic features, seizure semiology, number and location of implanted SEEG electrodes, and location of the epileptogenic zone were recorded and analyzed for all patients. For patients undergoing subsequent craniotomy for resection, the type of resection and procedure-related complications were prospectively recorded. These results were analyzed and correlated with pathological diagnosis and postoperative seizure outcomes.


The epileptogenic zone was confirmed by SEEG in 154 patients (77%), of which 134 (87%) underwent subsequent craniotomy for epileptogenic zone resection. Within this cohort, 90 patients had a minimum follow-up of at least 12 months; therein, 61 patients (67.8%) remained seizure free, with an average follow-up period of 2.4 years. The most common pathological diagnosis was focal cortical dysplasia Type I (55 patients, 61.1%). Per electrode, the surgical complications included wound infection (0.08%), hemorrhagic complications (0.08%), and a transient neurological deficit (0.04%) in a total of 5 patients (2.5%). One patient (0.5%) ultimately died due to intracerebral hematoma directly ensuing from SEEG electrode placement.


Based on these results, SEEG methodology is safe, reliable, and effective. It is associated with minimal morbidity and mortality, and serves as a practical, minimally invasive approach to extraoperative localization of the epileptogenic zone in patients with refractory epilepsy.

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Juan C. Bulacio, James Bena, Piradee Suwanpakdee, Dileep Nair, Ajay Gupta, Andreas Alexopoulos, William Bingaman, and Imad Najm


The aim of this study was to investigate seizure outcomes after resective epilepsy surgery following stereoelectroencephalography (SEEG), including group characteristics, comparing surgical and nonsurgical groups and assess predictors of time to seizure recurrence.


Clinical and EEG data of 536 consecutive patients who underwent SEEG at Cleveland Clinic Epilepsy Center between 2009 and 2017 were reviewed. The primary outcome was defined as complete seizure freedom since the resective surgery, discounting any auras or seizures that occurred within the 1st postoperative week. In addition, the rate of seizure freedom based on Engel classification was determined in patients with follow-up of ≥ 1 year. Presumably significant outcome variables were first identified using univariate analysis, and Cox proportional hazards modeling was used to identify outcome predictors.


Of 527 patients satisfying study criteria, 341 underwent resective surgery. Complete and continuous seizure freedom after surgery was achieved in 55.5% of patients at 1 year postoperatively, 44% of patients at 3 years, and 39% of patients at 5 years. As a secondary outcome point, 58% of patients achieved Engel class I seizure outcome for at least 1 year at last follow-up. Among surgical outcome predictors, in multivariate model analysis, the seizure recurrence rate by type of resection (p = 0.039) remained statistically significant, with the lowest risk of recurrence occurring after frontal and temporal lobe resections compared with multilobar and posterior quadrant surgeries. Patients with a history of previous resection (p = 0.006) and bilateral implantations (p = 0.023) were more likely to have seizure recurrence. The absence of an MRI abnormality prior to resective surgery did not significantly affect seizure outcome in this cohort.


This large, single-center series shows that resective surgery leads to continuous seizure freedom in a group of patients with complex and severe pharmacoresistant epilepsy after SEEG evaluation. In addition, up to 58% of patients achieved seizure freedom at last follow-up. The authors’ results suggest that SEEG is equally effective in patients with frontal and temporal lobe epilepsy with or without MRI identified lesions.