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Adeel Ilyas, Emilia Toth, Diana Pizarro, Kristen O. Riley, and Sandipan Pati

The putative mechanism of vagus nerve stimulation (VNS) for medically refractory epilepsy is desynchronization of hippocampal and thalamocortical circuitry; however, the nature of the dose-response relationship and temporal dynamics is poorly understood. For greater elucidation, a study in a nonepileptic rat model was previously conducted and showed that rapid-cycle (RC) VNS achieved superior desynchrony compared to standard-cycle (SC) VNS. Here, the authors report on the first in-human analysis of the neuromodulatory dose-response effects of VNS in a patient with posttraumatic, independent, bilateral mesial temporal lobe epilepsy refractory to medications and SC-VNS who was referred as a potential candidate for a responsive neurostimulation device. During stereotactic electroencephalography (SEEG) recordings, the VNS device was initially turned off, then changed to SC-VNS and then RC-VNS settings. Spectral analysis revealed a global reduction of power in the theta (4–8 Hz) and alpha (8–15 Hz) bands with both SC- and RC-VNS compared to the stimulation off setting (p < 0.001). Furthermore, in the alpha band, both SC- and RC-VNS were associated with greater global desynchrony compared to the off setting (p < 0.001); and, specifically, in the bilateral epileptogenic hippocampi, RC-VNS further reduced spectral power compared to SC-VNS (p < 0.001). The dose-response and temporal effects suggest that VNS modulates regional and global dynamics differently.

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Lauren E. Rotman, T. Brooks Vaughan, James R. Hackney, and Kristen O. Riley

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Jacob R. Lepard, Esther Dupépé, Matthew Davis, Jennifer DeWolfe, Bonita Agee, J. Nicole Bentley, and Kristen Riley


Invasive monitoring has long been utilized in the evaluation of patients for epilepsy surgery, providing localizing information to guide resection. Stereoelectroencephalography (SEEG) was introduced at the authors’ level 4 epilepsy surgery program in 2013, with responsive neurostimulation (RNS) becoming available the following year. The authors sought to characterize patient demographics and epilepsy-related variables before and after SEEG introduction to understand whether differences emerged in their patient population. This information will be useful in understanding how SEEG, possibly in conjunction with RNS availability, may have changed practice patterns over time.


This is a retrospective cohort study of consecutive patients who underwent surgery for epilepsy from 2006 to 2018, comprising 7 years before and 5 years after the introduction of SEEG. The authors performed univariate analyses of patient characteristics and outcomes and used generalized estimating equations logistic regression for predictive analysis.


A total of 178 patients were analyzed, with 109 patients in the pre-SEEG cohort and 69 patients in the post-SEEG cohort. In the post-SEEG cohort, more patients underwent invasive monitoring for suspected bilateral seizure onsets (40.6% vs 22.0%, p = 0.01) and extratemporal seizure onsets (68.1% vs 8.3%, p < 0.0001). The post-SEEG cohort had a higher proportion of patients with seizures arising from eloquent cortex (14.5% vs 0.9%, p < 0.001). Twelve patients underwent RNS insertion in the post-SEEG group versus none in the pre-SEEG group. Fewer patients underwent resection in the post-SEEG group (55.1% vs 96.3%, p < 0.0001), but there was no significant difference in rates of seizure freedom between cohorts for those patients having undergone a follow-up resection (53.1% vs 59.8%, p = 0.44).


These findings demonstrate that more patients with suspected bilateral, eloquent, or extratemporal epilepsy underwent invasive monitoring after adoption of SEEG. This shift occurred coincident with the adoption of RNS, both of which likely contributed to increased patient complexity. The authors conclude that their practice now considers invasive monitoring for patients who likely would not previously have been candidates for surgical investigation and subsequent intervention.

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Jeffrey P. Blount, Jason Cormier, Hyunmi Kim, Pongkiat Kankirawatana, Kristen O. Riley, and Robert C. Knowlton

Intracranial monitoring using electroencephalography (IC-EEG) continues to play a critical role in the assessment of patients with medically intractable localization-related epilepsy. There has been minimal change in grid or electrode design in the last 15–20 years, and the surgical approaches for implantation are unchanged. Intracranial monitoring using EEG allows detailed definition of the region of ictal onset and defines the epileptogenic zone, particularly with regard to adjacent potentially eloquent tissue. Recent developments of IC-EEG include the coregistration of functional imaging data such as magnetoencephalography to the frameless navigation systems. Despite significant inherent limitations that are often overlooked, IC-EEG remains the gold standard for localization of the epileptogenic cortex. Intracranial electrodes take a variety of different forms and may be placed either in the subdural (subdural strips and grids, depth electrodes) or extradural spaces (sphenoidal, peg, and epidural electrodes). Each form has its own advantages and shortcomings but extensive subdural implantation of electrodes is most common and is most comprehensively discussed. The indications for intracranial electrodes are reviewed.

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Ganne Chaitanya, Andrew K. Romeo, Adeel Ilyas, Auriana Irannejad, Emilia Toth, Galal Elsayed, J. Nicole Bentley, Kristen O. Riley, and Sandipan Pati


Despite numerous imaging studies highlighting the importance of the thalamus in a patient’s surgical prognosis, human electrophysiological studies involving the limbic thalamic nuclei are limited. The objective of this study was to evaluate the safety and accuracy of robot-assisted stereotactic electrode placement in the limbic thalamic nuclei of patients with suspected temporal lobe epilepsy (TLE).


After providing informed consent, 24 adults with drug-resistant, suspected TLE undergoing evaluation with stereoelectroencephalography (SEEG) were enrolled in the prospective study. The trajectory of one electrode planned for clinical sampling of the operculoinsular cortex was modified to extend it to the thalamus, thereby preventing the need for additional electrode placement for research. The anterior nucleus of the thalamus (ANT) (n = 13) and the medial group of thalamic nuclei (MED) (n = 11), including the mediodorsal and centromedian nuclei, were targeted. The postimplantation CT scan was coregistered to the preoperative MR image, and Morel’s thalamic atlas was used to confirm the accuracy of implantation.


Ten (77%) of 13 patients in the ANT group and 10 (91%) of 11 patients in the MED group had electrodes accurately placed in the thalamic nuclei. None of the patients had a thalamic hemorrhage. However, trace asymptomatic hemorrhages at the cortical-level entry site were noted in 20.8% of patients, who did not require additional surgical intervention. SEEG data from all the patients were interpretable and analyzable. The trajectories for the ANT implant differed slightly from those of the MED group at the entry point—i.e., the precentral gyrus in the former and the postcentral gyrus in the latter.


Using judiciously planned robot-assisted SEEG, the authors demonstrate the safety of electrophysiological sampling from various thalamic nuclei for research recordings, presenting a technique that avoids implanting additional depth electrodes or compromising clinical care. With these results, we propose that if patients are fully informed of the risks involved, there are potential benefits of gaining mechanistic insights to seizure genesis, which may help to develop neuromodulation therapies.

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Blake E. Pearson, James M. Markert, Winfield S. Fisher, Barton L. Guthrie, John B. Fiveash, Cheryl A. Palmer, and Kristen Riley


The World Health Organization (WHO) reclassified atypical meningiomas in 2000, creating a more clear and broadly accepted definition. In this paper, the authors evaluated the pathological and clinical transition period for atypical meningiomas according to the implementation of the new WHO grading system at their institution.


A total of 471 meningiomas occurring in 440 patients between 1994 and 2006 were retrospectively reviewed to determine changes in diagnostic rates, postoperative treatment trends, and early outcomes.


Between 1994 and 2000, the incidence of the atypical meningiomas ranged from 0 to 3/year, or 4.4% of the meningiomas detected during the entire period. After 2002, the annual percentage of atypical meningiomas rose over a 2-year period, leveling off at between 32.7 and 35.5% between 2004 and 2006. The authors also found a recent trend toward increased use of adjuvant radiation therapy for incompletely resected atypical meningiomas. Prior to 2003, 18.7% were treated with this therapy; after 2003, 34.4% of lesions received this treatment. Incompletely resected tumors were treated with some form of radiation 76% of the time. In cases of complete resection, most patients were not given adjuvant therapy but were expectantly managed by close monitoring using serial imaging and by receiving immediate treatment for tumor recurrence. The overall recurrence rate for expectantly managed tumors was 9% over 28.2 months, and 75% of recurrences responded to delayed radiation therapy.


The authors documented a significant change in the proportion of meningiomas designated as atypical during a transition period from 2002 to 2004, and propose a conservative strategy for the use of radiation therapy in atypical meningiomas.