Abstracts

Rationale: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) was recently approved in the US for partial onset epilepsy. The original trial (Stimulation of ANT for Epilepsy, SANTÉ) supporting this therapy was initiated in 2003 with results initially published in 2010 (Fisher et al., 2010). At that time, an analysis of DBS lead targeting was conducted, but comparison of active contact positions (relative to AC-PC) and clinical outcomes revealed no apparent pattern. Recently, several groups (Lehtimaki et al., 2016; Krishna et al., 2016) have published ANT-DBS case series using advanced imaging and reported considerable inter-patient variability in the location of the nucleus in stereotactic space. They also identified a sub-region within the ANT, superior to the mammillo-thalamic tract (MTT) termination, that was associated with improved outcomes. Based upon these findings, MR images from the SANTÉ trial were re-evaluated to assess lead position relative to visible anatomic landmarks and to the identified sub-region 'target'. Methods: Per the SANTÉ protocol all subjects (n=110) had post-operative imaging and confirmation of bilateral DBS lead placement in the ANT. For the original assessment, these image sets were used to determine individual contact locations of the DBS leads relative to AC-PC using a StealthStationTM system. Active contact positions were defined in X,Y,Z space for each hemisphere and compared to clinical outcomes.For the recent analysis, lead trajectories were assessed qualitatively for proximity to the ANT sub-region target, using axial, coronal, sagittal, and lead trajectory plane static images. To aid in defining the ANT in cases where visualization of anatomic landmarks was difficult, the thalamus was segmented by defining the anterior-posterior (AP) and dorso-ventral (DV) axes at a para-sagittal plane through the lead trajectory and four quadrants of an ellipse created by outlining the thalamus using these major axes. When this para-sagittal plane is centered on the junction of the MTT with the ventral border of the nucleus, the ANT occupies most of the anterior, superior quadrant and extends to, or just past the AP midpoint of the thalamus. Each lead trajectory was assigned a score from 0 (did not appear to hit the ANT) to 3 (passed thru the target region) based position within the ANT, yielding bilateral scores ranging from 0-6. These qualitative scores were compared to seizure reduction outcomes at one year post-implant. Results: The original analysis revealed that, despite marked variability, on average, active contact locations were comparable to the defined coordinates used for the SANTÉ target (X=5-6 mm, Y=0-2 mm anterior, Z=10-12 mm superior) based on the Schaltenbrand and Wahren atlas. A comparison of active contact position in responders (> 50% seizure reduction) and non-responders at one year showed considerable overlap between groups.The results of the qualitative analysis yielded no correlation between bilateral placement score and seizure reduction (r2= 0.01). However, when assessed categorically, it was found that subjects with a score >4 (i.e., 'good' bilateral placement) had a much higher probability of being a clinical responder than those with a score of <