Gregg, Nick

Thalamic neuromodulation has re-emerged as a central strategy for the treatment of drug-resistant epilepsy, driven by advances in stereo-electroencephalography, network neuroscience, and signal processing. This perspective paper summarizes and integrates the key scientific, technical, and clinical insights presented during the American Epilepsy Society (AES) 2025—Epilepsy Surgery Symposium on Advances in Thalamic Neuromodulation for Epilepsy: From Mechanisms of Action to Clinical Application . Beyond a summary of the individual presentations, this manuscript reflects the collective opinions of the panel regarding current evidence, unresolved controversies, and future directions. An unifying theme emerged: effective thalamic neuromodulation requires a shift from empiric, one-size-fits-all targeting toward patient-specific, hodology-informed strategies grounded in in situ electrophysiology and network-level biomarkers.

OBJECTIVE Deep brain stimulation (DBS) is emerging as an additional surgical option for refractory, multifocal epilepsy. Four-lead DBS systems can be used when seizure onset is poorly localized, generalized, or involves multiple targetable circuits. The goal of this study was to assess preliminary outcomes and complication rates in 4-lead DBS systems for treating epilepsy. METHODS A consecutive series of 32 patients with 4-lead DBS implants who had at least 6 months of follow-up was reviewed, and demographics, outcomes, and complications were abstracted. RESULTS Thirty-two patients implanted with 4 DBS leads (including off-label use) were included. The median age at surgery was 28.5 years, the median age at epilepsy diagnosis was 7.5 years, and 18 patients (56%) were women. The median epilepsy duration prior to implantation was 21 years. The most common seizure localization was frontotemporal (53%), followed by generalized (28%) and parietoccipital (13%). Prior vagus nerve stimulation had been trialed in 20 patients (63%), and an invasive stereotactic EEG recording was performed in 17 patients (59%). Eight patients had prior epilepsy surgery (25%). DBS targets included the anterior thalamic nucleus in combination with the centromedian thalamic nucleus, hippocampus, pulvinar nucleus, cingulate, insula, and globus pallidus. The median surgical duration was 5 hours 22 minutes, with a median operating room time of 8 hours 21 minutes. The median postoperative follow-up was 27 (interquartile range 17–41) months. Three patients experienced transient neurological deficits and 2 patients required intraoperative lead repositioning. There were no infections or hemorrhages. Most patients benefited from stimulation (22% Engel class I, 22% class II, 28% class III, and 28% class IV). The median patient-reported seizure reduction rate was 70%, with a responder rate of 72%. One patient elected to have the system explanted. CONCLUSIONS Four-lead DBS is safe and can achieve meaningful improvement in challenging cases of multifocal epilepsy with a low complication rate.

BACKGROUND AND OBJECTIVES: A typical workflow for deep brain stimulation (DBS) surgery consists of head frame placement, followed by stereotactic computed tomography (CT) or MRI before surgical implantation of the hardware. At some institutions, this workflow is prolonged when the imaging scanner is located far away from the operating room, thereby increasing workflow times by the addition of transport times. Recently, the intraoperative O-arm has been shown to provide accurate image fusion with preoperative CT or MR imaging, suggesting the possibility of obtaining an intraoperative localization scan and postoperative confirmation. In this article, we aim to evaluate the compatibility of the stereotactic frame system with the intraoperative O-arm system regarding lead accuracy and surgical flow. METHODS: A total of 17 patients undergoing DBS surgery for movement disorders were evaluated. One patient underwent both the stereotactic CT and O-arm localization, while 16 patients underwent only intraoperative O-arm localization. Following lead placement, intraoperative O-arm imaging was obtained to evaluate the accuracy of the lead placement. Accuracy was defined as the error measured as the distance from the center of the planned trajectory to the cannula. RESULTS: Less than 0.1 mm difference was found between the O-arm imaging technique and CT image localization of the NaviNetics stereotactic head frame in DBS surgery. Of the 16 patients who underwent the intraoperative O-arm imaging alone, the targets included bilateral ventral intermediate nucleus (16 leads), bilateral globus pallidus internus (4 leads), and subthalamic nucleus (12 leads). The mean ± SD radial error in the probe's eye view was 0.71 ± 0.33 mm for n = 32 leads. No tract hemorrhage was observed. CONCLUSION: Intraoperative O-arm imaging can be used safely and effectively for stereotactic registration and lead placement confirmation with the stereotactic system in both awake and asleep DBS surgery.