Abstracts

Rationale: In the ongoing clinical trial evaluating thalamic responsive neurostimulation as a therapy for idiopathic generalized epilepsy (IGE, NCT05147571), depth leads are targeted at the centromedian nucleus of the thalamus (CM). High-frequency (HF, >100Hz), long burst ( >1000ms) stimulation is the preferred initial stimulation condition. However, some participants experience paresthesias at these settings and consequently their devices are programmed to deliver an alternative low-frequency (LF, 5-33.3Hz) stimulation protocol. Because the CM is a small target, at most two of the four electrodes on the depth lead can be in the target. The sensorimotor nuclei are lateral to CM, and stimulating these locations is likely to evoke somatosensory perception. In this study, we test the hypothesis that participants experiencing paresthesias with HF stimulation are more likely to have electrodes lateral to the CM. Further, we present the LF stimulation parameters that mitigate stimulation-related paresthesias and allow these participants to receive responsive neurostimulation therapy in the CM.

Methods: All participants are implanted with the RNS® System with two depth leads targeted at the bilateral CM. Stimulation testing is performed in clinic; if the participant experiences paresthesias with HF stimulation (125Hz, 1.0 µC/cm² , 5000ms), their device is programmed to deliver LF stimulation (11-18Hz, 5000ms). To identify the location of the electrodes, the Lead DBS (Horn et al, 2014) platform was used to coregister pre-implant MR images with post-implant CT images. The outcome of this procedure was morphed into MNI space and displayed on the MNI template brain. The electrodes were visually compared to the location of the CM in MNI space. Each electrode was classified as inferior, superior, medial, lateral or in the target depending on where the majority of the electrode surface area was located with respect to the CM. Participants were divided into LF (N=10) and HF (N= 25) cohorts. The number of electrodes in each anatomical category was calculated across participants for each cohort.

Results: There was a tendency for electrodes in the LF cohort to be lateral to the CM as compared to the HF cohort (43.8% vs 23.5%). Changing from HF to LF stimulation resolved paresthesias in all participants who experienced them.

Conclusions: Based on the results, it is probable that participants experiencing paresthesia with CM targeted stimulation have electrode contacts lateral to the target in the sensorimotor nuclei. The surgical trajectory required to reach the target may necessarily place electrodes lateral to the CM. However, delivering stimulation at a lower frequency provides a resolution that allows these subjects to receive responsive neurostimulation therapy. It is not yet known whether HF or LF stimulation confers any therapeutic advantage, or whether placing a stimulating electrode in a specific location within the CM may confer greater benefit in this population. These competing factors must be balanced in surgical planning.

Funding: n/a