Circadian changes in aperiodic activity are correlated with seizure reduction in patients with mesial temporal lobe epilepsy treated with responsive neurostimulation.

OBJECTIVES: Responsive neurostimulation (RNS) is an established therapy for drug-resistant epilepsy that delivers direct electrical brain stimulation in response to detected epileptiform activity. However, despite an overall reduction in seizure frequency, clinical outcomes are variable, and few patients become seizure-free. The aim of this retrospective study was to evaluate aperiodic electrophysiological activity, associated with excitation/inhibition balance, as a novel electrographic biomarker of seizure reduction to aid early prognostication of the clinical response to RNS. METHODS: We identified patients with intractable mesial temporal lobe epilepsy who were implanted with the RNS System between 2015 and 2021 at the University of Utah. We parameterized the neural power spectra from intracranial RNS System recordings during the first 3 months following implantation into aperiodic and periodic components. We then correlated circadian changes in aperiodic and periodic parameters of baseline neural recordings with seizure reduction at the most recent follow-up. RESULTS: Seizure reduction was correlated significantly with a patient's average change in the day/night aperiodic exponent (r = .50, p = .016, n = 23 patients) and oscillatory alpha power (r = .45, p = .042, n = 23 patients) across patients for baseline neural recordings. The aperiodic exponent reached its maximum during nighttime hours (12 a.m. to 6 a.m.) for most responders (i.e., patients with at least a 50% reduction in seizures). SIGNIFICANCE: These findings suggest that circadian modulation of baseline broadband activity is a biomarker of response to RNS early during therapy. This marker has the potential to identify patients who are likely to respond to mesial temporal RNS. Furthermore, we propose that less day/night modulation of the aperiodic exponent may be related to dysfunction in excitation/inhibition balance and its interconnected role in epilepsy, sleep, and memory.

Delays in the diagnosis and surgical treatment of drug-resistant epilepsy: A cohort study.

OBJECTIVE: Delay in referral for epilepsy surgery of patients with drug-resistant epilepsy (DRE) is associated with decreased quality of life, worse surgical outcomes, and increased risk of sudden unexplained death in epilepsy (SUDEP). Understanding the potential causes of delays in referral and treatment is crucial for optimizing the referral and treatment process. We evaluated the treatment intervals, demographics, and clinical characteristics of patients referred for surgical evaluation at our level 4 epilepsy center in the U.S. Intermountain West. METHODS: We retrospectively reviewed the records of patients who underwent surgery for DRE between 2012 and 2022. Data collected included patient demographics, DRE diagnosis date, clinical characteristics, insurance status, distance from epilepsy center, date of surgical evaluation, surgical procedure, and intervals between different stages of evaluation. RESULTS: Within our cohort of 185 patients with epilepsy (99 female, 53.5%), the mean ± standard deviation (SD) age at surgery was 38.4 ± 11.9 years. In this cohort, 95.7% of patients had received definitive epilepsy surgery (most frequently neuromodulation procedures) and 4.3% had participated in phase 2 intracranial monitoring but had not yet received definitive surgery. The median (1st-3rd quartile) intervals observed were 10.1 (3.8-21.5) years from epilepsy diagnosis to DRE diagnosis, 16.7 (6.5-28.4) years from epilepsy diagnosis to surgery, and 1.4 (0.6-4.0) years from DRE diagnosis to surgery. We observed significantly shorter median times from epilepsy diagnosis to DRE diagnosis (p < .01) and epilepsy diagnosis to surgery (p < .05) in patients who traveled further for treatment. Patients with public health insurance had a significantly longer time from DRE diagnosis to surgery (p < .001). SIGNIFICANCE: Both shorter distance traveled to our epilepsy center and public health insurance were predictive of delays in diagnosis and treatment intervals. Timely referral of patients with DRE to specialized epilepsy centers for surgery evaluation is crucial, and identifying key factors that may delay referral is paramount to optimizing surgical outcomes.

Uric Acid Nephropathy Secondary to Generalized Tonic-Clonic Seizures.

INTRODUCTION: Acute kidney injury is a well-known complication of generalized tonic-clonic seizures, most commonly due to rhabdomyolysis. Elevated serum uric acid resulting in uric acid nephropathy is an overlooked cause of acute kidney injury in these patients, with only a few published case reports. CASE REPORT: In the first case, a 23-year-old male was admitted with status epilepticus. His kidney function worsened and he developed anuria. He had a serum uric acid level of 20.7 mg/dL and required multiple sessions of hemodialysis. In the second case, a 32-year-old male was admitted with acute kidney injury after experiencing a breakthrough seizure. He had a serum uric acid level of 20.4 mg/dL and was treated with rasburicase with recovery of renal function. In the third case, a 29-year-old male was admitted with status epilepticus. His renal function deteriorated. His serum uric acid level was 19.5 mg/dL. He required hemodialysis and rasburicase. CONCLUSION: Uric acid nephropathy is a rare complication of generalized tonic-clonic seizures, which is poorly recognized by healthcare providers. We advocate for Nephrology consultation early in a patient's hospitalization to discuss the use of rasburicase to avoid the associated morbidity of renal replacement therapies.

Responsive neurostimulation as a treatment for super-refractory focal status epilepticus: a systematic review and case series.

OBJECTIVE: Super-refractory status epilepticus (SRSE) has high rates of morbidity and mortality. Few published studies have investigated neurostimulation treatment options in the setting of SRSE. This systematic literature review and series of 10 cases investigated the safety and efficacy of implanting and activating the responsive neurostimulation (RNS) system acutely during SRSE and discusses the rationale for lead placement and selection of stimulation parameters. METHODS: Through a literature search (of databases and American Epilepsy Society abstracts that were last searched on March 1, 2023) and direct contact with the manufacturer of the RNS system, 10 total cases were identified that utilized RNS acutely during SE (9 SRSE cases and 1 case of refractory SE [RSE]). Nine centers obtained IRB approval for retrospective chart review and completed data collection forms. A tenth case had published data from a case report that were referenced in this study. Data from the collection forms and the published case report were compiled in Excel. RESULTS: All 10 cases presented with focal SE: 9 with SRSE and 1 with RSE. Etiology varied from known lesion (focal cortical dysplasia in 7 cases and recurrent meningioma in 1) to unknown (2 cases, with 1 presenting with new-onset refractory focal SE [NORSE]). Seven of 10 cases exited SRSE after RNS placement and activation, with a time frame ranging from 1 to 27 days. Two patients died of complications due to ongoing SRSE. Another patient's SE never resolved but was subclinical. One of 10 cases had a device-related significant adverse event (trace hemorrhage), which did not require intervention. There was 1 reported recurrence of SE after discharge among the cases in which SRSE resolved up to the defined endpoint. CONCLUSIONS: This case series offers preliminary evidence that RNS is a safe and potentially effective treatment option for SRSE in patients with 1-2 well-defined seizure-onset zone(s) who meet the eligibility criteria for RNS. The unique features of RNS offer multiple benefits in the SRSE setting, including real-time electrocorticography to supplement scalp EEG for monitoring SRSE progress and response to treatment, as well as numerous stimulation options. Further research is indicated to investigate the optimal stimulation settings in this unique clinical scenario.

Closed-loop stimulation in periods with less epileptiform activity drives improved epilepsy outcomes.

In patients with drug-resistant epilepsy, electrical stimulation of the brain in response to epileptiform activity can make seizures less frequent and debilitating. This therapy, known as closed-loop responsive neurostimulation (RNS), aims to directly halt seizure activity via targeted stimulation of a burgeoning seizure. Rather than immediately stopping seizures as they start, many RNS implants produce slower, long-lasting changes in brain dynamics that better predict clinical outcomes. Here we hypothesize that stimulation during brain states with less epileptiform activity drives long-term changes that restore healthy brain networks. To test this, we quantified stimulation episodes during low- and high-risk brain states-that is, stimulation during periods with a lower or higher risk of generating epileptiform activity-in a cohort of 40 patients treated with RNS. More frequent stimulation in tonic low-risk states and out of rhythmic high-risk states predicted seizure reduction. Additionally, stimulation events were more likely to be phase-locked to prolonged episodes of abnormal activity for intermediate and poor responders when compared to super-responders, consistent with the hypothesis that improved outcomes are driven by stimulation during low-risk states. These results support the hypothesis that stimulation during low-risk periods might underlie the mechanisms of RNS, suggesting a relationship between temporal patterns of neuromodulation and plasticity that facilitates long-term seizure reduction.

Long-Term Intracranial EEG Lateralization of Epileptogenicity in Patients With Confirmed or Suspected Bilateral Mesial Temporal Lobe Onsets During Epilepsy Surgical Evaluation.

PURPOSE: The data resulting from epilepsy surgical evaluation are occasionally unclear in cases of mesial temporal lobe (MTL) epilepsy. Long-term intracranial EEG (iEEG) collected by the Responsive Neurostimulation (RNS) System may be an approach for capturing additional seizure data while treating patients with neurostimulation. We reviewed iEEG seizure lateralization and clinical outcomes in bilateral MTL patients at University of Utah. METHODS: Long-term RNS System iEEG seizure lateralization was compared with pre-RNS System lateralization obtained during surgical evaluation. Safety and clinical outcomes were extracted retrospectively from patient records. RESULTS: Twenty-six patients received an RNS System with bilateral MTL leads. Fifteen of the patients had adequate follow-up to report clinical outcomes (>1 year), and 25 patients had enough recorded data (>6 months) to perform iEEG analysis. Median percent reduction in clinical seizures at last follow-up was 58%, and 40% reported being seizure-free at last follow-up, for variable durations. The electrographic seizure lateralization (unilateral vs. bilateral) differed between surgical evaluation and long-term iEEG in 44% of our patients. In the subset of eight patients (32%) who had only unilateral seizures recorded during surgical evaluation, but were implanted with bilateral MTL leads based on bilateral interictal epileptiform discharges, 62% (5/8) had bilateral seizures recorded on long-term iEEG. Interestingly, in the 18 patients who had bilateral seizures recorded during surgical evaluation, 28% (5/18) were found to be unilateral on long-term iEEG. CONCLUSIONS: Our data suggest that RNS System implantation in suspected bilateral MTL cases may be an option to assess a patient's true seizure lateralization on long-term iEEG. Responsive neuromodulation should be considered before resection or ablation in cases that have evaluation data suggesting bilaterality.

Subsets of cortico-cortical evoked potentials propagate as traveling waves.

Emerging evidence suggests that the temporal dynamics of cortico-cortical evoked potentials (CCEPs) may be used to characterize the patterns of information flow between and within brain networks. At present, however, the spatiotemporal dynamics of CCEP propagation cortically and subcortically are incompletely understood. We hypothesized that CCEPs propagate as an evoked traveling wave emanating from the site of stimulation. To elicit CCEPs, we applied single-pulse stimulation to stereoelectroencephalography (SEEG) electrodes implanted in 21 adult patients with intractable epilepsy. For each robust CCEP, we measured the timing of the maximal descent in evoked local field potentials and broadband high-gamma power (70-150 Hz) envelopes relative to the distance between the recording and stimulation contacts using three different metrics (i.e., Euclidean distance, path length, geodesic distance), representing direct, subcortical, and transcortical propagation, respectively. Many evoked responses to single-pulse electrical stimulation appear to propagate as traveling waves (~17-30%), even in the sparsely sampled, three-dimensional SEEG space. These results provide new insights into the spatiotemporal dynamics of CCEP propagation.

Using chronic recordings from a closed-loop neurostimulation system to capture seizures across multiple thalamic nuclei.

We report the case of a patient with unilateral diffuse frontotemporal epilepsy in whom we implanted a responsive neurostimulation system with leads spanning the anterior and centromedian nucleus of the thalamus. During chronic recording, ictal activity in the centromedian nucleus consistently preceded the anterior nucleus, implying a temporally organized seizure network involving the thalamus. With stimulation, the patient had resolution of focal impaired awareness seizures and secondarily generalized seizures. This report describes chronic recordings of seizure activity from multiple thalamic nuclei within a hemisphere and demonstrates the potential efficacy of closed-loop neurostimulation of multiple thalamic nuclei to control seizures.

Evaluating the concordance of functional MRI-based language lateralization and Wada testing in epilepsy patients: A single-center analysis.

BACKGROUND: For patients with drug-resistant epilepsy, surgery may be effective in controlling their disease. Surgical evaluation may involve localization of the language areas using functional magnetic resonance imaging (fMRI) or Wada testing. We evaluated the accuracy of task-based fMRI versus Wada-based language lateralization in a cohort of our epilepsy patients. METHODS: In a single-center, retrospective analysis, we identified patients with medically intractable epilepsy who participated in presurgical language mapping (n = 35) with fMRI and Wada testing. Demographic variables and imaging metrics were obtained. We calculated the laterality index (LI) from task-evoked fMRI activation maps across language areas during auditory and reading tasks to determine lateralization. Possible scores for LI range from -1 (strongly left-hemisphere dominant) to 1 (strongly right-hemisphere dominant). Concordance between fMRI and Wada was estimated using Cohen's Kappa coefficient. Association between the LI scores from the auditory and reading tasks was tested using Spearman's rank correlation coefficient. RESULTS: The fMRI-based laterality indices were concordant with results from Wada testing in 91.4% of patients during the reading task (κ = .55) and 96.9% of patients during the auditory task (κ = .79). The mean LIs for the reading and auditory tasks were -0.52 ± 0.43 and -0.68 ± 0.42, respectively. The LI scores for the language and reading tasks were strongly correlated, r(30) = 0.57 (p = 0.001). CONCLUSION: Our findings suggest that fMRI is generally an accurate, low-risk alternative to Wada testing for language lateralization. However, when fMRI indicates atypical language lateralization (e.g., bilateral dominance), patients may benefit from subsequent Wada testing or intraoperative language mapping.

Neuropsychological evaluation in American Sign Language: A case study of a deaf patient with epilepsy.

In high-stake cases (e.g., evaluating surgical candidacy for epilepsy) where neuropsychological evaluation is essential to care, it is important to have culturally and linguistically appropriate and accessible neuropsychological instruments and procedures for use with deaf individuals who use American Sign Language (ASL). Faced with these ethical and professional issues, clinicians may be unable to provide equitable services without consulting with other psychologists and collaborating with the patient and interpreter. This is a case report describing a 43-year-old male with bilateral sensorineural deafness and a lifelong history of drug-resistant temporal lobe epilepsy who presented as a candidate for a comprehensive neurological workup to determine surgical candidacy. He was bilingual (ASL and written English). We describe all aspects of the evaluation, including functional magnetic resonance imaging (fMRI) and Wada testing, using an ASL interpreter. Results from the neuropsychological evaluation were not clearly lateralizing, but suggested greater compromise to the non-dominant right hemisphere. fMRI and Wada test results revealed language and verbal memory functions were lateralized to the left hemisphere. The patient was deemed to be an adequate candidate for surgical resection of portions of the right hemisphere. Comprehensive assessment of neuropsychological functioning in deaf persons who use ASL is feasible. This case report illustrates the important considerations relevant to neuropsychologists providing culturally and linguistically informed assessments to deaf ASL users with epilepsy. Additional research in this area will support future efforts to develop effective and efficient models that could be implemented across different settings. Moreover, clinical guidance is warranted to guide professionals interested in promoting access to high quality neuropsychological services.

Patient-specific structural connectivity informs outcomes of responsive neurostimulation for temporal lobe epilepsy.

OBJECTIVE: Responsive neurostimulation is an effective therapy for patients with refractory mesial temporal lobe epilepsy. However, clinical outcomes are variable, few patients become seizure-free, and the optimal stimulation location is currently undefined. The aim of this study was to quantify responsive neurostimulation in the mesial temporal lobe, identify stimulation-dependent networks associated with seizure reduction, and determine if stimulation location or stimulation-dependent networks inform outcomes. METHODS: We modeled patient-specific volumes of tissue activated and created probabilistic stimulation maps of local regions of stimulation across a retrospective cohort of 22 patients with mesial temporal lobe epilepsy. We then mapped the network stimulation effects by seeding tractography from the volume of tissue activated with both patient-specific and normative diffusion-weighted imaging. We identified networks associated with seizure reduction across patients using the patient-specific tractography maps and then predicted seizure reduction across the cohort. RESULTS: Patient-specific stimulation-dependent connectivity was correlated with responsive neurostimulation effectiveness after cross-validation (p = .03); however, normative connectivity derived from healthy subjects was not (p = .44). Increased connectivity from the volume of tissue activated to the medial prefrontal cortex, cingulate cortex, and precuneus was associated with greater seizure reduction. SIGNIFICANCE: Overall, our results suggest that the therapeutic effect of responsive neurostimulation may be mediated by specific networks connected to the volume of tissue activated. In addition, patient-specific tractography was required to identify structural networks correlated with outcomes. It is therefore likely that altered connectivity in patients with epilepsy may be associated with the therapeutic effect and that utilizing patient-specific imaging could be important for future studies. The structural networks identified here may be utilized to target stimulation in the mesial temporal lobe and to improve seizure reduction for patients treated with responsive neurostimulation.

Concurrent brain-responsive and vagus nerve stimulation for treatment of drug-resistant focal epilepsy.

OBJECTIVE: Clinical trials of a brain-responsive neurostimulator, RNS® System (RNS), excluded patients with a vagus nerve stimulator, VNS® System (VNS). The goal of this study was to evaluate seizure outcomes and safety of concurrent RNS and VNS stimulation in adults with drug-resistant focal-onset seizures. METHODS: A retrospective multicenter chart review was performed on all patients with an active VNS and RNS who were treated for a minimum of 6 months with both systems concurrently. Frequency of disabling seizures at baseline before RNS, at 1 year after RNS placement, and at last follow-up were used to calculate the change in seizure frequency after treatment. Data on adverse events and complications related to each device were collected. RESULTS: Sixty-four patients from 10 epilepsy centers met inclusion criteria. All but one patient received RNS after VNS. The median follow-up time after RNS implantation was 28 months. Analysis of the entire population of patients with active VNS and RNS systems revealed a median reduction in seizure frequency at 1 year post-RNS placement of 43% with a responder rate of 49%, and at last follow-up a 64% median reduction with a 67% responder rate. No negative interactions were reported from the concurrent use of VNS and RNS. Stimulation-related side-effects were reported more frequently in association with VNS (30%) than with RNS (2%). SIGNIFICANCE: Our findings suggest that concurrent treatment with VNS and RNS is safe and that the addition of RNS to VNS can further reduce seizure frequency.

Probabilistic comparison of gray and white matter coverage between depth and surface intracranial electrodes in epilepsy.

In this study, we quantified the coverage of gray and white matter during intracranial electroencephalography in a cohort of epilepsy patients with surface and depth electrodes. We included 65 patients with strip electrodes (n = 12), strip and grid electrodes (n = 24), strip, grid, and depth electrodes (n = 7), or depth electrodes only (n = 22). Patient-specific imaging was used to generate probabilistic gray and white matter maps and atlas segmentations. Gray and white matter coverage was quantified using spherical volumes centered on electrode centroids, with radii ranging from 1 to 15 mm, along with detailed finite element models of local electric fields. Gray matter coverage was highly dependent on the chosen radius of influence (RoI). Using a 2.5 mm RoI, depth electrodes covered more gray matter than surface electrodes; however, surface electrodes covered more gray matter at RoI larger than 4 mm. White matter coverage and amygdala and hippocampal coverage was greatest for depth electrodes at all RoIs. This study provides the first probabilistic analysis to quantify coverage for different intracranial recording configurations. Depth electrodes offer increased coverage of gray matter over other recording strategies if the desired signals are local, while subdural grids and strips sample more gray matter if the desired signals are diffuse.

Wearable Reduced-Channel EEG System for Remote Seizure Monitoring.

Epitel has developed Epilog, a miniature, wireless, wearable electroencephalography (EEG) sensor. Four Epilog sensors are combined as part of Epitel's Remote EEG Monitoring platform (REMI) to create 10 channels of EEG for remote patient monitoring. REMI is designed to provide comprehensive spatial EEG recordings that can be administered by non-specialized medical personnel in any medical center. The purpose of this study was to determine how accurate epileptologists are at remotely reviewing Epilog sensor EEG in the 10-channel "REMI montage," with and without seizure detection support software. Three board certified epileptologists reviewed the REMI montage from 20 subjects who wore four Epilog sensors for up to 5 days alongside traditional video-EEG in the EMU, 10 of whom experienced a total of 24 focal-onset electrographic seizures and 10 of whom experienced no seizures or epileptiform activity. Epileptologists randomly reviewed the same datasets with and without clinical decision support annotations from an automated seizure detection algorithm tuned to be highly sensitive. Blinded consensus review of unannotated Epilog EEG in the REMI montage detected people who were experiencing electrographic seizure activity with 90% sensitivity and 90% specificity. Consensus detection of individual focal onset seizures resulted in a mean sensitivity of 61%, precision of 80%, and false detection rate (FDR) of 0.002 false positives per hour (FP/h) of data. With algorithm seizure detection annotations, the consensus review mean sensitivity improved to 68% with a slight increase in FDR (0.005 FP/h). As seizure detection software, the automated algorithm detected people who were experiencing electrographic seizure activity with 100% sensitivity and 70% specificity, and detected individual focal onset seizures with a mean sensitivity of 90% and mean false alarm rate of 0.087 FP/h. This is the first study showing epileptologists' ability to blindly review EEG from four Epilog sensors in the REMI montage, and the results demonstrate the clinical potential to accurately identify patients experiencing electrographic seizures. Additionally, the automated algorithm shows promise as clinical decision support software to detect discrete electrographic seizures in individual records as accurately as FDA-cleared predicates.

Comparative Effectiveness of Stereotactic Electroencephalography Versus Subdural Grids in Epilepsy Surgery.

OBJECTIVE: The aim was to compare the outcomes of subdural electrode (SDE) implantations versus stereotactic electroencephalography (SEEG), the 2 predominant methods of intracranial electroencephalography (iEEG) performed in difficult-to-localize drug-resistant focal epilepsy. METHODS: The Surgical Therapies Commission of the International League Against Epilepsy created an international registry of iEEG patients implanted between 2005 and 2019 with ≥1 year of follow-up. We used propensity score matching to control exposure selection bias and generate comparable cohorts. Study endpoints were: (1) likelihood of resection after iEEG; (2) seizure freedom at last follow-up; and (3) complications (composite of postoperative infection, symptomatic intracranial hemorrhage, or permanent neurological deficit). RESULTS: Ten study sites from 7 countries and 3 continents contributed 2,012 patients, including 1,468 (73%) eligible for analysis (526 SDE and 942 SEEG), of whom 988 (67%) underwent subsequent resection. Propensity score matching improved covariate balance between exposure groups for all analyses. Propensity-matched patients who underwent SDE had higher odds of subsequent resective surgery (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.05, 1.84) and higher odds of complications (OR = 2.24, 95% CI 1.34, 3.74; unadjusted: 9.6% after SDE vs 3.3% after SEEG). Odds of seizure freedom in propensity-matched resected patients were 1.66 times higher (95% CI 1.21, 2.26) for SEEG compared with SDE (unadjusted: 55% seizure free after SEEG-guided resections vs 41% after SDE). INTERPRETATION: In comparison to SEEG, SDE evaluations are more likely to lead to brain surgery in patients with drug-resistant epilepsy but have more surgical complications and lower probability of seizure freedom. This comparative-effectiveness study provides the highest feasible evidence level to guide decisions on iEEG. ANN NEUROL 2021;90:927-939.

Stereotactic Electroencephalography Is Associated With Reduced Pain and Opioid Use When Compared with Subdural Grids: A Case Series.

BACKGROUND: Minimally invasive surgery (MIS) has been shown to decrease length of hospital stay and opioid use. OBJECTIVE: To identify whether surgery for epilepsy mapping via MIS stereotactically placed electroencephalography (SEEG) electrodes decreased overall opioid use when compared with craniotomy for EEG grid placement (ECoG). METHODS: Patients who underwent surgery for epilepsy mapping, either SEEG or ECoG, were identified through retrospective chart review from 2015 through 2018. The hospital stay was separated into specific time periods to distinguish opioid use immediately postoperatively, throughout the rest of the stay and at discharge. The total amount of opioids consumed during each period was calculated by transforming all types of opioids into their morphine equivalents (ME). Pain scores were also collected using a modification of the Clinically Aligned Pain Assessment (CAPA) scale. The 2 surgical groups were compared using appropriate statistical tests. RESULTS: The study identified 43 patients who met the inclusion criteria: 36 underwent SEEG placement and 17 underwent craniotomy grid placement. There was a statistically significant difference in median opioid consumption per hospital stay between the ECoG and the SEEG placement groups, 307.8 vs 71.5 ME, respectively (P = .0011). There was also a significant difference in CAPA scales between the 2 groups (P = .0117). CONCLUSION: Opioid use is significantly lower in patients who undergo MIS epilepsy mapping via SEEG compared with those who undergo the more invasive ECoG procedure. As part of efforts to decrease the overall opioid burden, these results should be considered by patients and surgeons when deciding on surgical methods.

A systematic exploration of parameters affecting evoked intracranial potentials in patients with epilepsy.

BACKGROUND: Brain activity is constrained by and evolves over a network of structural and functional connections. Corticocortical evoked potentials (CCEPs) have been used to measure this connectivity and to discern brain areas involved in both brain function and disease. However, how varying stimulation parameters influences the measured CCEP across brain areas has not been well characterized. OBJECTIVE: To better understand the factors that influence the amplitude of the CCEPs as well as evoked gamma-band power (70-150 Hz) resulting from single-pulse stimulation via cortical surface and depth electrodes. METHODS: CCEPs from 4370 stimulation-response channel pairs were recorded across a range of stimulation parameters and brain regions in 11 patients undergoing long-term monitoring for epilepsy. A generalized mixed-effects model was used to model cortical response amplitudes from 5 to 100 ms post-stimulation. RESULTS: Stimulation levels <5.5 mA generated variable CCEPs with low amplitude and reduced spatial spread. Stimulation at ≥5.5 mA yielded a reliable and maximal CCEP across stimulation-response pairs over all regions. These findings were similar when examining the evoked gamma-band power. The amplitude of both measures was inversely correlated with distance. CCEPs and evoked gamma power were largest when measured in the hippocampus compared with other areas. Larger CCEP size and evoked gamma power were measured within the seizure onset zone compared with outside this zone. CONCLUSION: These results will help guide future stimulation protocols directed at quantifying network connectivity across cognitive and disease states.

Rhythmic ictal nonclonic hand (RINCH) motions in general EMU patients with focal epilepsy.

BACKGROUND: Automatisms are frequently encountered during video-monitoring of patients with focal epilepsy in the EMU and generally thought to have a low lateralizing value in isolation. Rhythmic ictal nonclonic hand (RINCH) motions have been described in small series as a potentially lateralizing semiologic sign. We aimed to expand on prior work and determine the prevalence, characteristics, and lateralizing value of RINCH motions in general epilepsy monitoring unit (EMU) population with focal epilepsy. METHODS: All patients with recorded seizures in the EMU were included in our database search. Search was performed to identify seizures with reported RINCH motions. Both electroencephalography (EEG) and video of identified seizures were reviewed. RESULTS: We identified RINCH motions in 131 seizures in 71 patients. Overall seizure localization was temporal in 57 patients, frontotemporal in 3 patients, and extratemporal in 7 patients. We estimated RINCH motions to occur in 8.5% of EMU patients with recorded seizures. The most common RINCH motions in descending order were as follows: hand opening and closing, finger rubbing, milking motions, finger flexion/extension, and pill rolling. The mean RINCH motion latency from seizure onset was 34.48 s in temporal lobe epilepsy and 10.31 s in frontal lobe epilepsy. The RINCH motions were contralateral to seizure onset in 61 of 65 (93.8%) with lateralized seizure onset. Dystonic posturing was present in 43% of seizures with RINCH motions. CONCLUSION: The RINCH motions are a common sign in focal seizures and should be distinguished from other types of manual automatism as they carry a strong lateralizing value.

Localization value of ictal turning prone.

PURPOSE: Ictal semiology complements ictal EEG in identifying the likely epileptogenic zone. Ictal turning prone (ITP) with body turning of 90 ° or more can be seen with frontal lobe epilepsies. The aim of our study was to evaluate the localizing value of ITP in a general population of patients undergoing long term video-EEG monitoring. METHODS: We reviewed our epilepsy monitoring unit database for adult patients with recorded habitual seizures with ITP. All 16 patients identified had continuous video-EEG monitoring using standard scalp electrodes; eight patients also had intracranial EEG monitoring. We only included focal seizures without evolution to bilateral tonic-clonic activity. RESULTS: We identified 16 patients with ITP, mean age of 32.5 years (range 18-50). ITP was consistently seen in at least one focal impaired awareness seizure of all patients. Ictal onset zone on scalp EEG was left temporal in five, right temporal in three, left frontal convexity in two, right frontal convexity in two, probable right medial frontal in three and probable left medial frontal in one patient. Direction of ITP was uni-directional in 12 patients while 4 patients had ITP in opposite direction in different seizures. Nine patients underwent epilepsy surgery; five patients had Engel class I outcome and four patients had Engel class III outcome. CONCLUSIONS: Ictal turning prone does not have a consistent single localizing or lateralizing value and can be seen with various epileptogenic zones including medial frontal, lateral frontal or temporal. ITP direction can vary even with a single epileptogenic zone.

Interictal Epileptiform Discharge Detection in EEG in Different Practice Settings.

OBJECTIVE: The goal of the study was to measure the performance of academic and private practice (PP) neurologists in detecting interictal epileptiform discharges in routine scalp EEG recordings. METHODS: Thirty-five EEG scorers (EEGers) participated (19 academic and 16 PP) and marked the location of ETs in 200 30-second EEG segments using a web-based EEG annotation system. All participants provided board certification status, years of Epilepsy Fellowship Training (EFT), and years in practice. The Persyst P13 automated IED detection algorithm was also run on the EEG segments for comparison. RESULTS: Academic EEGers had an average of 1.66 years of EFT versus 0.50 years of EFT for PP EEGers (P < 0.0001) and had higher rates of board certification. Inter-rater agreement for the 35 EEGers was fair. There was higher performance for EEGers in academics, with at least 1.5 years of EFT, and with American Board of Clinical Neurophysiology and American Board of Psychiatry and Neurology-E specialty board certification. The Persyst P13 algorithm at its default setting (perception value = 0.4) did not perform as well at the EEGers, but at substantially higher perception value settings, the algorithm performed almost as well human experts. CONCLUSIONS: Inter-rater agreement among EEGers in both academic and PP settings varies considerably. Practice location, years of EFT, and board certification are associated with significantly higher performance for IED detection in routine scalp EEG. Continued medical education of PP neurologists and neurologists without EFT is needed to improve routine scalp EEG interpretation skills. The performance of automated detection algorithms is approaching that of human experts.