Osman, Gamaleldin

Abstract To characterize invasive neuromodulation for insular drug‐resistant epilepsy, we retrospectively evaluated 22 patients treated with responsive neurostimulation (RNS; n = 14) or chronic subthreshold stimulation (CSS; n = 8). Stereoelectroencephalography was performed in 20 cases (91%). Median baseline seizure frequency was 10.5/month. Forty‐one percent had prior epilepsy surgery. At year 3, median seizure reduction (MSR) was 83% ( p = .01, Wilcoxon signed‐rank test), with a responder rate (RR) of 77%; MSR was 92% for CSS and 75% for RNS. There were no significant differences in MSR ( p ≥ .4) or RR ( p > .9) when comparing RNS versus CSS. Three patients achieved seizure freedom by year 3. Patients undergoing combined insular–thalamic stimulation ( n = 5) demonstrated an MSR of 84%, 86%, and 88% at 1, 2, and 3 years; seizure reduction in thalamocortical versus cortical‐only stimulation was not different ( p ≥ .1). Parasagittal lead trajectories achieved closer insular proximity than transopercular trajectories ( p < .0001, Mann–Whitney U ‐test). Median charge density at last follow‐up was 1.3 μC/cm 2 . There were no acute surgical complications and all stimulation‐related side effects resolved with programming adjustments. This study expands the limited literature on insular neuromodulation by demonstrating effectiveness of RNS and CSS, suggesting potential benefit from combined thalamocortical targeting, and defining parasagittal trajectories as a surgical approach for optimal lead proximity.

Abstract Objective Anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) is an effective therapy for frontotemporal and limbic drug‐resistant focal epilepsies. The pulvinar nucleus (PUL) is an emerging neuromodulation target for seizure networks involving the posterior quadrant and temporal lobe. This study evaluates the safety and effectiveness of combined bilateral ANT plus PUL DBS for posterior quadrant and temporal lobe epilepsies. Methods We conducted a single‐center retrospective cohort study of patients receiving combined ANT/PUL DBS between 2021 and 2025. Outcomes included median seizure rate reduction (MSR), responder rate (RR; >50% seizure frequency reduction), and stimulation‐related side effects, assessed across ANT, PUL, and concurrent ANT/PUL stimulation settings. Acute surgical complications were evaluated. Statistical significance was assessed using two‐sided Wilcoxon signed‐rank tests with Holm–Bonferroni correction. Results Nine patients with combined ANT/PUL DBS were identified, and eight patients had sufficient follow‐up for inclusion (median follow‐up = 20 months). Posterior predominant structural abnormalities were present in eight of nine patients. There were no acute surgical complications. Three instances of transient stimulation‐related side effects resolved with parameter adjustments, whereas one patient required rescue antiseizure medication in addition to programming changes. Eight patients received periods of ANT stimulation, six PUL stimulation, and seven combined ANT/PUL stimulation. Regarding overall outcome, at last follow‐up, there was a significant 80.8% MSR ( p = .0078) and 87.5% RR, with two patients receiving ANT and six ANT/PUL stimulation. Regarding target‐specific MSR, concurrent ANT/PUL DBS (68.8% MSR) showed a trend toward superior performance relative to ANT (43.3%) and PUL DBS (17.5%) alone, although subgroup analysis of target‐specific performance did not reach statistical significance. Significance Combined four‐lead ANT/PUL DBS appears safe and effective for patients with drug‐resistant posterior quadrant and temporal lobe epilepsies. Dual‐network neuromodulation may provide greater flexibility to individually optimize neuromodulation for complex seizure networks.

Abstract Objective Ceribell Inc.'s point‐of‐care electroencephalographic (EEG) system and artificial intelligence‐based Automated Seizure Burden Estimator (ASBE; ClarityPro) have US Food and Drug Administration clearance for diagnosing electrographic status epilepticus (ESE). The AccuRASE study using ASBE version 6 (V6) showed high negative predictive value (NPV) but limited sensitivity and positive predictive value (PPV) at certain thresholds. Version 8 (V8) is the updated algorithm trained with additional EEG samples. Methods We tested V8 on the previously used rapid‐response EEG test dataset (not used to train V8). Sensitivity, specificity, PPV, and NPV were compared against blinded expert annotations. ESE, ESE and possible ESE (ESE/pESE), electrographic seizures (ESz), and Esz with highly epileptiform patterns (Esz/HEPs) at burden thresholds of >1%, >10%, >20%, >50%, and >90% were analyzed. Additionally, we evaluated the built‐in ESE and ESE/pESE alerts (≥90% over 5 min, ≥20% over 1 h, or ≥10 continuous minutes of seizure). Results V8 showed 100% sensitivity at lower thresholds (>10%–20%) for ESE (V6 .86), without a specificity loss (V8 .9 vs. V6 .85), and retained NPV (V8 1.0 vs. V6 .99). Sensitivity at 50% threshold was .86 for ESE (V6 .71), and specificity was .94 (V6 .91); PPV for ESE was 30% for ESE and 80% for ESE/pESE. The specificity for ESE remained high for 90% burden (V8 .96, V6 .97) but the sensitivity dropped (.29 vs. V6 .43). Sensitivity was lower for ESz/HEPs (.54 → .44 at >10% threshold), although the algorithm is not designed to detect HEPs. Built‐in alert analysis showed significantly improved sensitivity for ESE (.57 → .86); specificity and NPV remained high (>.94). Significance ASBE V8 showed meaningful improvements in sensitivity, continued excellent NPV, and improved built‐in alert accuracy for ESE and ESE/pESE. The best seizure burden threshold for ruling out ESE now is 20% (vs. 10% with V6) and that for ruling in ESE/pESE with reasonable certainty is 50% (vs. 90% with V6).

Abstract Despite the growing interest in network-guided neuromodulation for epilepsy, uncertainty about the safety and long-term efficacy of thalamocortical stimulation persists. Our evaluation focused on the use of a four-lead open-loop implantable pulse generator for thalamocortical network neuromodulation. We retrospectively reviewed seven patients with diverse seizure networks—poorly localized, regional, or multifocal—undergoing thalamocortical neuromodulation. Employing a four-lead system, electrodes targeted both thalamic and cortical seizure network nodes. We assessed seizure severity, life satisfaction and sleep quality on a 10-point scale, and seizure frequency was assessed via telephone interviews and chart review. Outcomes were assessed by the Wilcoxon sign-rank test at the 0.05 significance level. Seven patients with a median age at implant of 22 years (range 14–42 years) had a median disabling seizure reduction of 93% (range 50–100%, P = 0.0156), with 100% responder rate (≥50% reduction in seizure frequency) after a median of 17 months post-implantation (range 13–60). The median improvement in seizure severity was 3.5 out of 10 points (P = 0.0312), life satisfaction 4.5 points (P = 0.0312) and quality of sleep 3 points (P = 0.062). No perioperative complications occurred. Transient seizure exacerbations (n = 2) and stimulation-related sensory/motor side-effects (n = 2) quickly resolved with parameter adjustments. One patient required surgical revision due to delayed infection. Six patients had permanent electrode placement refined by intracranial EEG trial stimulation; five patients had &gt;90% reduction in seizure frequency during trial stimulation. Thalamocortical network neuromodulation using a four-lead open-loop system is safe and associated with significant improvements in seizure control and patient quality of life. Trial stimulation during intracranial EEG shows promise for enhancing seizure network engagement and parameter optimization but requires further study. Prospective controlled trials are needed to further characterize and validate the efficacy and side-effect profile of thalamocortical network neuromodulation for epilepsy.

AbstractObjectiveThe effects of brain stimulation for diseases like epilepsy are delayed, making stimulation optimization difficult. The parameters for anterior thalamic nuclei (ANT) deep brain stimulation (DBS) for focal drug‐resistant epilepsy management are often restricted to those used in the SANTE landmark trial. There is little evidence regarding effective alternatives, and low‐frequency stimulation is typically neglected. We prospectively compare a widely differing stimulation parameter set to typical settings.MethodsThis randomized, modified crossover, open trial compares the efficacy and safety of an alternative set of parameters using continuous low‐frequency stimulation (cLFS) with a longer pulse width (7 Hz, 200 μs, continuous) compared to SANTE's intermittent high‐frequency stimulation (iHFS) with a short pulse width (145 Hz, 90 μs, cycling 1 min on/5 min off). After 3 months on a randomly assigned first set, patients are switched to the other settings, unless seizure‐free. Patients are re‐evaluated after 3 more months, which marks the completion of the trial. After that, they can either remain on the same settings or switch back.ResultsSixteen patients with a median baseline seizure frequency of 13.8 seizures/month (interquartile range [IQR] = 2.7–22.8) were included in the analysis. At trial completion (median follow‐up = 30 weeks, IQR = 26–35), ANT‐DBS significantly reduced median seizure frequency (62%, IQR = 18–81, Wilcoxon test statistic [W] = 99, p = .008). Both iHFS (33%, IQR = 0–65, W = 81, p = .02) and cLFS (73%, IQR = 30–79, W = 105, p = .001) significantly reduced median seizure frequency. cLFS showed improved median seizure frequency reduction compared to iHFS (W = 63, p = .03) and was not associated with any moderate or severe adverse effects.SignificanceResults support cLFS for ANT‐DBS as a safe and effective alternative to typical iHFS parameters. Stimulation with widely differing parameter sets may be as effective as or, in some situations, more effective than typical stimulation parameters.

Abstract There are limited treatment options for individuals with drug‐resistant idiopathic generalized epilepsy (IGE). Small, limited case series suggest that centromedian thalamus deep brain stimulation (CM‐DBS) may be an effective treatment option. The optimal CM‐DBS target for IGE is underexamined. Here, we present a retrospective analysis of CM‐DBS targeting and efficacy for five patients with drug‐resistant IGE. Volume of tissue activated (VTA) overlap with CM nucleus was performed using an open‐source toolbox. Median follow‐up time was 13 months. Median convulsive seizure frequency reduction was 66%. One patient had only absence seizures, with >99% reduction in absence seizure frequency. Four patients had electrode contacts positioned within the CM nucleus target, all of whom had >50% reduction in primary semiology seizure, with 85% median seizure reduction ( p = .004, paired‐sample t test). Volumetric “sweet‐spot” mapping revealed that best outcomes were correlated with stimulation of the middle ventral CM nucleus. Connectivity strength between the sweet‐spot region and central peri‐Rolandic cortex was increased significantly relative to other cortical regions ( p = 8.6 × 10 −4 , Mann–Whitney U test). Our findings indicate that CM‐DBS can be an effective treatment for patients with IGE, highlight the importance of accurate targeting and targeting analysis, and within the context of prior work, suggest that ideal CM‐DBS targets may be syndrome specific.