Worrell, Gregory A.

Synchronization of local and distributed neuronal assemblies is thought to underlie fundamental brain processes such as perception, learning, and cognition. In neurological disease, neuronal synchrony can be altered and in epilepsy may play an important role in the generation of seizures. Linear cross-correlation and mean phase coherence of local field potentials (LFPs) are commonly used measures of neuronal synchrony and have been studied extensively in epileptic brain. Multiple studies have reported that epileptic brain is characterized by increased neuronal synchrony except possibly prior to seizure onset when synchrony may decrease. Previous studies using intracranial electroencephalography (EEG), however, have been limited to patients with epilepsy. Here we investigate neuronal synchrony in epileptic and control brain using intracranial EEG recordings from patients with medically resistant partial epilepsy and control subjects with intractable facial pain. For both epilepsy and control patients, average LFP synchrony decreases with increasing interelectrode distance. Results in epilepsy patients show lower LFP synchrony between seizure-generating brain and other brain regions. This relative isolation of seizure-generating brain underlies the paradoxical finding that control patients without epilepsy have greater average LFP synchrony than patients with epilepsy. In conclusion, we show that in patients with focal epilepsy, the region of epileptic brain generating seizures is functionally isolated from surrounding brain regions. We further speculate that this functional isolation may contribute to spontaneous seizure generation and may represent a clinically useful electrophysiological signature for mapping epileptic brain.

High-frequency oscillations (HFOs) have been observed in animal and human intracranial recordings during both normal and aberrant brain states. It has been proposed that the relationship between subclasses of these oscillations can be used to identify epileptic brain. Studies of HFOs in epilepsy have been hampered by selection bias arising primarily out of the need to reduce the volume of data so that clinicians can manually review it. In this study, we introduce an algorithm for detecting and classifying these signals automatically and demonstrate the tractability of analyzing a data set of unprecedented size, over 31,000 channel-hours of intracranial electroencephalographic (iEEG) recordings from micro- and macroelectrodes in humans. Using an unsupervised approach that does not presuppose a specific number of clusters in the data, we show direct evidence for the existence of distinct classes of transient oscillations within the 100- to 500-Hz frequency range in a population of nine neocortical epilepsy patients and two controls. The number of classes we find, four (three plus one putative artifact class), is consistent with prior studies that identify “ripple” and “fast ripple” oscillations using human-intensive methods and, additionally, identifies a less examined class of mixed-frequency events.

Object Microsurgical resection of supratentorial cavernomas associated with intractable epilepsy is performed frequently. Despite its common occurrence, little is known about patient perceptions of microsurgical resection for cavernomas. This survey study was performed to investigate patient perceived outcome after surgery for cavernomas associated with intractable epilepsy. Methods The authors' surgical database was searched for cavernoma resection performed between 1971 and July of 2006. Of the initial 173 patients identified, 102 met criteria for medically intractable seizures. These 102 patients were then mailed a survey to determine follow-up and patient satisfaction. Thirty-nine surveys were returned as undeliverable, and 30 (48%) of the remaining 63 patients responded. Results The average age at surgery for patients responding to this survey was 40 ± 16 years compared with 35 ± 15 years for all 102 patients. At prolonged follow-up, 87% of patients reported being seizure-free. Of those with seizures, 2 (7%) reported being nearly seizure-free (rare disabling seizures), 2 (7%) believed they had a worthwhile improvement in seizure frequency, and no patient (0%) in this series believed they did not have a worthwhile improvement in seizure frequency. Ninety percent of responders stated they definitely, and 10% probably, would have surgery again. No patient responded that they probably or definitely would not have epilepsy surgery. Mean clinical follow-up was 36 ± 8 months and survey follow-up was 97 ± 13 months for these 30 patients. Use of the mail-in survey increased follow-up length 2.7 times longer compared with clinical follow-up. Conclusions It is clear from this select group of survey responders that patients undergoing surgery for cavernomas associated with medically intractable epilepsy are happy they underwent surgery (100%) and had excellent surgical outcomes (87% seizure-free) at prolonged follow-up of 97 ± 13 months. These survey results support that microsurgical resection for cavernomas is highly effective and significantly improves these patients' quality of life.

Object Intracranial monitoring for temporal lobe seizure localization to differentiate neocortical from mesial temporal onset seizures requires both neocortical subdural grids and hippocampal depth electrode implantation. There are 2 basic techniques for hippocampal depth electrode implantation. This first technique uses a stereotactically guided 8-contact depth electrode directed along the long axis of the hippocampus to the amygdala via an occipital bur hole. The second technique involves direct placement of 2 or 3 4-contact depth electrodes perpendicular to the temporal lobe through the middle temporal gyrus and overlying subdural grid. The purpose of this study was to determine whether one technique was superior to the other by examining monitoring success and complications. Methods Between 1997 and 2005, 41 patients underwent invasive seizure monitoring with both temporal subdural grids and depth electrodes placed in 2 ways. Patients in Group A underwent the first technique, and patients in Group B underwent the second technique. Results Group A consisted of 26 patients and Group B 15 patients. There were no statistically significant differences between Groups A and B regarding demographics, monitoring duration, seizure localization, or outcome (Engel classification). There was a statistically significant difference at the point in time at which these techniques were used: Group A represented more patients earlier in the series than Group B (p < 0.05). The complication rate attributable to the grids and depth electrodes was 0% in each group. It was more likely that the depth electrodes were placed through the grid if there was a prior resection and the patient was undergoing a new evaluation (p < 0.05). Furthermore, Group A procedures took significantly longer than Group B procedures. Conclusions In this patient series, there was no difference in efficacy of monitoring, complications, or outcome between hippocampal depth electrodes placed laterally through temporal grids or using an occipital bur hole stereotactic approach. Placement of the depth electrodes perpendicularly through the grids and middle temporal gyrus is technically more practical because multiple head positions and redraping are unnecessary, resulting in shorter operative times with comparable results.

Object Cavernous hemangiomas associated with epilepsy present an interesting surgical dilemma in terms of whether one should perform a pure lesionectomy or tailored resection, especially in the temporal lobe given the potential for cognitive damage. This decision is often guided by electrocorticography (ECoG), despite the lack of data regarding its value in cavernoma surgery. The purpose of the present study was several-fold: first, to determine the epilepsy outcome following resection of cavernomas in all brain regions; second, to evaluate the usefulness of ECoG in guiding surgical decision making; and third, to determine the optimum surgical approach for temporal lobe cavernomas. Methods The authors identified from their surgical database 173 patients who had undergone resection of cavernomas. One hundred two of these patients presented with epilepsy, and 61 harbored temporal lobe cavernomas. Preoperatively, all patients were initially evaluated by an epileptologist. The mean follow-up was 37 months. Results Regardless of the cavernoma location, surgery resulted in an excellent seizure control rate: Engel Class I outcome in 88% of patients at 2 years postoperatively. Of 61 patients with temporal lobe cavernomas, the mesial structures were involved in 35. Among the patients with temporal lobe cavernomas, those who underwent ECoG typically had a more extensive parenchymal resection rather than a lesionectomy (p < 0.0001). The use of ECoG in cases of temporal lobe cavernomas resulted in a superior seizure-free outcome: 79% (29 patients) versus 91% (23 patients) of patients at 6 months postresection, 77% (22 patients) versus 90% (20 patients) at 1 year, and 79% (14 patients) versus 83% (18 patients) at 2 years without ECoG versus with ECoG, respectively. Conclusions The surgical removal of cavernomas most often leads to an excellent epilepsy outcome. In cases of temporal lobe cavernomas, the more extensive the ECoG-guided resection, the better the seizure outcome. In addition to upholding the concept of kindling, the data in this study support the use of ECoG in temporal lobe cavernoma surgery in patients presenting with epilepsy.

Object Patients with normal MR imaging (nonlesional) findings and medically refractory extratemporal epilepsy make up a disproportionate number of nonexcellent outcomes after epilepsy surgery. In this paper, the authors investigated the usefulness of intracranial electroencephalography (iEEG) in the identification of surgical candidates. Methods Between 1992 and 2002, 51 consecutive patients with normal MR imaging findings and extratemporal epilepsy underwent intracranial electrode monitoring. The implantation of intracranial electrodes was determined by seizure semiology, interictal and ictal scalp EEG, SPECT, and in some patients PET studies. The demographics of patients at the time of surgery, lobar localization of electrode implantation, duration of follow-up, and Engel outcome score were abstracted from the Mayo Rochester Epilepsy Surgery Database. A blinded independent review of the iEEG records was conducted for this study. Results Thirty-one (61%) of the 51 patients who underwent iEEG ultimately underwent resection for their epilepsy. For 28 (90.3%) of the 31 patients who had epilepsy surgery, adequate information regarding follow-up (> 1 year), seizure frequency, and iEEG recordings was available. Twenty-six (92.9%) of 28 patients had frontal lobe resections, and 2 had parietal lobe resections. The most common iEEG pattern at seizure onset in the surgically treated group was a focal high-frequency discharge (in 15 [53.6%] of 28 patients). Ten (35.7%) of the 28 surgically treated patients were seizure free. Fourteen (50%) had Engel Class I outcomes, and overall, 17 (60.7%) had significant improvement (Engel Class I and IIAB with ≥80% seizure reduction). Focal high-frequency oscillation at seizure onset was associated with Engel Class I surgical outcome (12 [85.7%] of 14 patients, p = 0.02), and it was uncommon in the nonexcellent outcome group (3 [21.4%] of 14 patients). Conclusions A focal high-frequency oscillation (> 20 Hz) at seizure onset on iEEG may identify patients with nonlesional extratemporal epilepsy who are likely to have an Engel Class I outcome after epilepsy surgery. The prospect of excellent outcome in nonlesional extratemporal lobe epilepsy prior to intracranial monitoring is poor (14 [27.5%] of 51 patients). However, iEEG can further stratify patients and help identify those with a greater likelihood of Engel Class I outcome after surgery.

Object Cerebral cortex electrophysiology is poorly sampled using standard, low spatial resolution clinical intracranial electrodes. Adding microelectrode arrays to the standard clinical macroelectrode arrays increases the spatial resolution and may ultimately improve the clinical utility of intracranial electroencephalography (iEEG). However, the safety of hybrid electrode systems containing standard clinical macroelectrode and microelectrode arrays is not yet known. The authors report on their preliminary experience in 24 patients who underwent implantation of hybrid electrodes. Methods In this study, 24 consecutive patients underwent long-term iEEG monitoring with implanted hybrid depth and subdural grid and strip electrodes; both clinical macroelectrodes and research microelectrodes were used. The patients included 18 women and 6 men with an average age of 35 ± 12 years (range 21–65). The mean hospital stay was 11 ± 4 days (range 5–20), with mean duration of implantation 7.0 ± 3.2 days (range 3–15). Data from the 198 consecutive craniotomies for standard clinical subdural grid insertion (prior to surgery in the 24 patients described here) were used for comparison to investigate the relative risk of complications. Results Focal seizure identification and subsequent resection was performed in 20 patients. One patient underwent a subsequent operation after neurological deterioration secondary to cerebral swelling and a 5-mm subdural hematoma. There were no infections. The overall complication rate was 4.2% (only 1 patient had a complication), which did not significantly differ from the complication rate previously reported by the authors of 6.6% when standard subdural and depth intracranial electrodes were used. There were no deaths or permanent neurological deficits related to electrode implantation. Conclusions The authors demonstrate the use of hybrid subdural strip and grid electrodes containing high-density microwire arrays and standard clinical macroelectrodes. Hybrid electrodes provide high spatial resolution electrophysiology of the neocortex that is impossible with standard clinical iEEG. In this initial study in 24 patients, the complication rate is acceptable, and there does not appear to be increased risk associated with the use of hybrid electrodes compared with standard subdural and depth iEEG electrodes. More research is required to show whether hybrid electrode recordings will improve localization of epileptic foci and tracking the generation of neocortical seizures.