Angela Peters

Objective: The optimal pre‐implantation evaluation and surgical targeting strategies for responsive neurostimulation (RNS) in patients with unresectable, drug‐resistant focal epilepsy continue to be debated. Although stereo‐electroencephalography (sEEG) is central to characterizing the seizure‐onset zone, its role in preoperative testing for neuromodulation remains undefined. We examined whether sEEG‐guided targeting for RNS implantation confers seizure‐reduction benefit compared with RNS implantation without sEEG. Methods: We retrospectively reviewed patients who underwent RNS implantation at our institution in 2015–2024. Patients were propensity score–matched based on demographics and epilepsy characteristics to create balanced groups of patients with and without prior sEEG. The primary outcome measure was seizure reduction as a percent change from baseline frequency, determined using linear regression. Results: Of 99 patients (median ± standard error [SE] follow‐up 45.3 ± 2.9 months), 78 (79%) underwent sEEG monitoring before RNS implantation and 21 (21%) did not. Most patients (62%) had no prior interventions for epilepsy and had non‐lesional epilepsy (75%). Mean seizure reduction at last follow‐up was 72.4% ± 29.3%. There were 21 patients in each propensity‐matched group. The use of preoperative sEEG was not associated with greater seizure reduction in the original ( p = .835) and propensity score–matched cohorts ( p = .914). In the unmatched cohort, female sex ( β = 16.7, p = .006,) older age ( β = .55, p = .027), thalamic RNS stimulation ( β = 18.0, p = .030), and follow‐up duration ( β = .2, p = .029) were associated with greater seizure reduction on linear regression. Subgroup analyses among epilepsy subtypes (bitemporal, temporal, or extratemporal) found no statistically significant differences in seizure reduction. Significance: In a climate of growing delays in epilepsy care, we did not observe differences in RNS efficacy with or without prior sEEG monitoring in patients with unilateral or bilateral temporal lobe epilepsy, temporal‐plus epilepsy, and extratemporal epilepsy. Although prospective data are needed to investigate the relative benefit of preoperative sEEG use, these findings may help guide patient selection and optimize definitive surgical planning.

Background and ObjectivesNeuromodulation therapies are approved for the treatment of focal epilepsy based on data from randomized controlled trials (RCTs). After approval of a responsive direct bra...

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.

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.

We describe an electrical "running down" phenomenon and also a consistent spectral change (in the aperiodic component of the power spectrum) derived from chronic interictal electrocorticography (ECoG) after surgery in a patient with drug‐resistant epilepsy. These data were recorded using a closed‐loop neurostimulation system that was implanted after resection. The patient has been seizure‐free for 2.5 years since resection without requiring the neurostimulator to be turned on to stimulate. Concurrently, there was an exponential decrease in the number of epileptiform electrographic detections recorded by the device, particularly over the first 26 weeks, indicative of an electrical running down phenomenon as the brain adapted to an extended period of seizure freedom. We also find that the aperiodic exponent of the power spectrum gradually decreases over time. The aperiodic component of intracranial ECoG may represent a novel marker of epileptogenicity, independent of seizures.

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.

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