Thalamocortical network neuromodulation for epilepsy

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 >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.

Keywords: cortical stimulation; deep brain stimulation.

Graphical Abstract

Figure 1

Results from trial stimulation for six patients and example of automated interictal discharge detection. (A) Box and whisker plot showing results from trial stimulation; two-sided Wilcoxon signed-rank test, 0.05 significance level, N = 6, statistically significant results indicated by *. (B) Top two panels showing iEEG with 2 Hz stimulation artefact (blue arrows) in LY (medial anterior cingulum) and interictal discharges (IEDs) in LF (inferior frontal/gyrus rectus); the bottom panel shows output from automated IED detector on a single channel (LF 15, blue tracing; third-order 1D median filtering to remove stimulation artefact). Automated IED detections marked with ‘o’. (C) Sample intracranial recording during sleep from Patient 3, bipolar montage, top panel (pre-stimulation, showing seizure discharge from LY 4–5 and 6–7 causing frequent arousals) and bottom panel matching lead and sleep state post stimulation at 2 Hz (blue arrows stimulation artefact), 2 V, 200 μs, time base 15 mm/s, sensitivity 150 μV/mm (sensitivity reduced for stimulation channels (LY 4–6) for better visualization).

Figure 2

Thalamic and cortical lead localization in permanent implants. (A–G) represent Patients 1–7. For each patient, rendered thalamic leads (left panel for each patient; lead-DBS imaging package), and whole brain with cortical and thalamic leads (right panel for each patient; Curry imaging package). For thalamic reconstruction, anterior nuclei of the thalamus (blue), ventral anterior parvocellular (yellow), mediodorsal (white), ventral lateral posterior, dorsal division (orange, patient 2), centromedian (green), parafascicular (gold), and ventral intermediate nucleus (orange, Patient 7) are displayed. All nuclei are from Krauth–Morel atlas, except ventral intermediate nucleus from DISTAL atlas.^,

Figure 3

Outcomes related to seizure severity, life satisfaction and sleep quality. (A) Seizure frequency % change from baseline until the last follow-up. (B) Box whisker plots of chronic thalamocortical network neuromodulation outcomes; mean marked by ‘x’ and median by a horizontal line. Change in seizure severity, life satisfaction and quality of sleep were adjusted to a 100-point scale. No worsening from baseline noted. Two-sided Wilcoxon signed-rank test P-values: seizure/month 0.0156, seizure severity 0.0312, life satisfaction 0.0312 and quality of sleep 0.0625; Benjamini–Hochberg false discovery rate–adjusted q values: 0.0417, 0.0417, 0.0417 and 0.0625, respectively. Statistically significant results are indicated by ‘*’.